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Sample records for advanced disease stages

  1. Current approaches to the treatment of advanced-stage Hodgkin's disease.

    PubMed Central

    Rusthoven, J J

    1986-01-01

    Combination chemotherapy (CT) has been the mainstay of treatment of advanced-stage Hodgkin's disease since the late 1960s. Although treatment with MOPP (nitrogen mustard, vincristine sulfate [Oncovin], procarbazine and prednisone) has resulted in long-term disease-free survival rates exceeding 50%, newer approaches have been studied to improve on this success rate and to reduce the toxic effects associated with MOPP. Prognostic factors have now been defined that identify patients who may require more aggressive treatment; they include age greater than 40 years, presence of B symptoms and more advanced (especially extranodal) disease. A small number of patients with pathological stage III disease may still be successfully treated with extensive radiotherapy (RT) alone. Among patients with advanced-stage disease, significantly better therapeutic results are being obtained with newer treatment approaches than with MOPP, particularly in patients with factors that predict a poor outcome. These newer approaches include combination CT plus RT, alternating cycles of two non-cross-resistant CT regimens and hybrid regimens, which combine agents from two different CT regimens in one cycle. The prognosis of patients who suffer relapse after combination CT remains poor, even with newer drug regimens. The newer treatment approaches may well lead to better cure rates and fewer short-term and long-term toxic effects. PMID:2427176

  2. Advanced glycation end-products and skin autofluorescence in end-stage renal disease: a review.

    PubMed

    Arsov, Stefan; Graaff, Reindert; van Oeveren, Wim; Stegmayr, Bernd; Sikole, Aleksandar; Rakhorst, Gerhard; Smit, Andries J

    2014-01-01

    Chronic kidney disease (CKD), especially in its end stage, is marked by extremely high cardiovascular rates of morbidity and mortality; hemodialysis patients have a five-fold shorter life expectancy than healthy subjects of the same age. In CKD the metabolic products that accumulate in the body are so-called uremic toxins. These include advanced glycation end-products (AGE). AGE levels are markedly increased in CKD patients not only because of impaired excretion but also because of increased production. AGE formation has initially been described as a non-enzymatic reaction between proteins and glucose in the so-called Maillard reaction, but they are also more rapidly formed during oxidative stress and subsequent formation of reactive carbonyl compounds like (methyl)glyoxal. AGE accumulate in tissue where they cross-link with proteins, e.g., collagen, inducing tissue stiffening of blood vessels and skin. They may also interact with receptor of AGE (RAGE) and other receptors, which lead to activation of intracellular transduction mechanisms resulting in cytokine release and further tissue damage in CKD. The accumulation of AGE in the skin can be measured non-invasively using autofluorescence. The skin autofluorescence is a strong marker of cardiovascular mortality in CKD. The focus of this review is on the role of tissue and plasma AGE, and of skin autofluorescence as a proxy of tissue AGE accumulation, in the increase in cardiovascular disease in end stage renal disease (ESRD). This review will also present the possibility of reducing the AGE accumulation in ESRD patients using the following five methods: 1) use of low AGE peritoneal dialysis solutions; 2) use of advanced hemodialysis techniques; 3) use of AGE reducing drugs; 4) optimizing the nutrition of hemodialysis patients; and 5) renal transplantation. PMID:23612551

  3. Cognitive benefits of memantine in Alzheimer's 5XFAD model mice decline during advanced disease stages.

    PubMed

    Devi, Latha; Ohno, Masuo

    2016-05-01

    Memantine, a noncompetitive NMDA receptor antagonist with neuroprotective properties, has been used for the treatment of Alzheimer's disease (AD). Administration of memantine to various transgenic AD mice has been reported to improve cognitive deficits, very often completely back to normal wild-type control levels. However, such great benefits of memantine in preclinical studies do not translate into clinical results of this drug, showing only marginal and transient efficacy in moderate to severe AD. To further address in vivo efficacy, we compared the effects of memantine at different disease stages in 5XFAD mice, one of the rapid-onset and most aggressive amyloid models. Specifically, we administered memantine once daily for 30days to 5XFAD mice, which showed moderate (6-7months of age) and robust (12-15months) β-amyloid (Aβ) accumulation. Treatments with memantine (10mg/kg, i.p.) reversed memory impairments in the younger 5XFAD mice, as tested by the contextual fear conditioning and spontaneous alternation Y-maze paradigms. Memantine had no effects on soluble Aβ oligomer or total Aβ42 levels in 5XFAD mouse brains. In contrast, subchronic treatments with memantine showed no behavioral benefits in the older 5XFAD group, which exhibited more profound memory deficits concomitant with highly increased concentrations of Aβ as compared with those of the younger 5XFAD group. Since subchronic memantine at the higher dose (30mg/kg) impaired memory performances in wild-type controls, we further tested acute administration of 50mg/kg memantine, which was reported to enhance hippocampal adult neurogenesis and memory function. However, this treatment also failed to rescue memory deficits in 12-15-month-old 5XFAD mice. Collectively, our results demonstrate that cognitive benefits of memantine independent of Aβ reductions were no longer observed in the 5XFAD Alzheimer mouse model during advanced stages, which may be reflective of the limited efficacy of memantine in

  4. Tail-flick test response in 3×Tg-AD mice at early and advanced stages of disease.

    PubMed

    Baeta-Corral, Raquel; Defrin, Ruti; Pick, Chagi G; Giménez-Llort, Lydia

    2015-07-23

    Despite the impact of pain in cognitive dysfunctions and affective disorders has been largely studied, the research that examines pain dimensions in cognitive impairment or dementia is still scarce. In patients with Alzheimer's disease (AD) and related dementias, management of pain is challenging. While the sensory-discriminative dimension of pain is preserved, the cognitive-evaluative and the affective-motivational pain dimensions are affected. Due to the complexity of the disease and the poor self-reports, pain is underdiagnosed and undertreated. In confluence with an impaired thermoregulatory behavior, the patients' ability to confront environmental stressors such as cold temperature can put them at risk of fatal accidental hypothermia. Here, 3xTg-AD mice demonstrate that the sensorial-discriminative threshold to a noxious cold stimulus, as measured by the latency of tail-flicking, was preserved at early and advances stages of disease (7 and 11 month-old, respectively) as compared to age-matched (adulthood and middle aged, respectively) non-transgenic mice (NTg). In both genotypes, the sensory deterioration and poor thermoregulatory behavior associated to age was observed as an increase of tail-flick response and poor sensorimotor performance. At both stages studied, 3xTg-AD mice exhibited BPSD (Behavioral and Psychological Symptoms of Dementia)-like alterations in the corner, open-field, dark-light box and the T-maze tests. In the adult NTg mice, this nociceptive withdrawal response was correlated with copying with stress-related behaviors. This integrative behavioral profile was lost in both groups of 3xTg-AD mice and middle aged controls, suggesting derangements in their subjacent networks and the complex interplay between the pain dimensions in the elderly with dementia. PMID:26091881

  5. Regulation of striatal astrocytic receptor for advanced glycation end-products variants in an early stage of experimental Parkinson's disease.

    PubMed

    Viana, Sofia D; Valero, Jorge; Rodrigues-Santos, Paulo; Couceiro, Patrícia; Silva, Andréa M; Carvalho, Félix; Ali, Syed F; Fontes-Ribeiro, Carlos A; Pereira, Frederico C

    2016-08-01

    Convincing evidence indicates that advanced glycation end-products and danger-associated protein S100B play a role in Parkinson's disease (PD). These agents operate through the receptor for advanced glycation end-products (RAGE), which displays distinct isoforms playing protective/deleterious effects. However, the nature of RAGE variants has been overlooked in PD studies. Hence, we attempted to characterize RAGE regulation in early stages of PD striatal pathology. A neurotoxin-based rodent model of PD was used in this study, through administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57BL/6 mice. Animals were killed 6 h post-MPTP to assess S100B/RAGE contents (RT-qPCR, ELISA) and RAGE isoform density (WB) and cellular distribution (immunohistochemistry). Dopaminergic and gliotic status were also mapped (HPLC-ED, WB, immunohistochemistry). At this preliminary stage of MPTP-induced PD in mice, RAGE inhibitory isoforms were increased whereas full-length RAGE was not affected. This putative cytoprotective RAGE phenotype paired an inflammatory and pro-oxidant setting fueling DAergic denervation. Increased RAGE inhibitory variants occur in astrocytes showing higher S100B density but no overt signs of hypertrophy or NF-κB activation, a canonical effector of RAGE. These findings expand our understanding of the toxic effect of MPTP on striatum and offer first in vivo evidence of RAGE being a responder in early stages of astrogliosis dynamics, supporting a protective rather tissue-destructive phenotype of RAGE in the initial phase of PD degeneration. These data lay the groundwork for future studies on the relevance of astrocytic RAGE in DAergic neuroprotection strategies. We report increased antagonistic RAGE variants paralleling S100B up-regulation in early stages of MPTP-induced astrogliosis dynamics . We propose that selective RAGE regulation reflects a self-protective mechanism to maintain low levels of RAGE ligands , preventing long

  6. Progenitor Hematopoietic Cells Implantation Improves Functional Capacity of End Stage Coronary Artery Disease Patients with Advanced Heart Failure

    PubMed Central

    Yuniadi, Yoga; Kusnadi, Yuyus; Sandhow, Lakshmi; Erika, Rendra; Hanafy, Dicky A.; Sardjono, Caroline; Kaligis, R. W. M.; Kasim, Manoefris; Harimurti, Ganesja M.

    2016-01-01

    Background. Proangiogenic Hematopoietic Cells (PHC) which comprise diverse mixture of cell types are able to secrete proangiogenic factors and interesting candidate for cell therapy. The aim of this study was to seek for benefit in implantation of PHC on functional improvement in end stage coronary artery disease patients with advanced heart failure. Methods. Patients with symptomatic heart failure despite guideline directed medical therapy and LVEF less than 35% were included. Peripheral blood mononuclear cells were isolated, cultivated for 5 days, and then harvested. Flow cytometry and cell surface markers were used to characterize PHC. The PHC were delivered retrogradely via sinus coronarius. Echocardiography, myocardial perfusion, and clinical and functional data were analyzed up to 1-year observation. Results. Of 30 patients (56.4 ± 7.40 yo) preimplant NT proBNP level is 5124.5 ± 4682.50 pmol/L. Harvested cells characterized with CD133, CD34, CD45, and KDR showed 0.87 ± 0.41, 0.63 ± 0.66, 99.00 ± 2.60, and 3.22 ± 3.79%, respectively. LVEF was improved (22 ± 5.68 versus 26.8 ± 7.93, p < 0.001) during short and long term observation. Myocardial perfusion significantly improved 6 months after treatment. NYHA Class and six-minute walk test are improved during short term and long term follow-up. Conclusion. Expanded peripheral blood PHC implantation using retrograde delivery approach improved LV systolic function, myocardial perfusion, and functional capacity. PMID:27148465

  7. Comparison of five models for end-stage liver disease in predicting the survival rate of patients with advanced hepatocellular carcinoma.

    PubMed

    Hong, Ying-Fen; Chen, Zhan-Hong; Ma, Xiao-Kun; Li, Xing; Wu, Dong-Hao; Chen, Jie; Dong, Min; Wei, Li; Wang, Tian-Tian; Ruan, Dan-Yun; Lin, Ze-Xiao; Wen, Jing-Yun; Lin, Qu; Jia, Chang-Chang; Wu, Xiang-Yuan

    2016-04-01

    Prognosis of patients with advanced hepatocellular carcinoma (HCC) is under expectation. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical trials. The main purpose of this research is to compare Model for End-Stage Liver Disease (MELD) and four MELD-based prognostic models in predicting the survival rate of advanced HCC patients. One hundred eighty-three patients with advanced HCC who were not amendable to standard anti-tumor therapy were retrospectively analyzed. Data were collected to classify patients according to MELD, Model for End-Stage Liver Disease with the incorporation of serum sodium (MELD-NA), Model for End-Stage Liver Disease to ascites and sodium (MELD-AS), integrated Model for End-Stage Liver Disease (iMELD), and Model for End-Stage Liver Disease to sodium (MESO) scores at diagnosis. 1-, 3-, and 6-month survivals were the end points used in the analysis. When predicting 1-month survival, MELD-AS, MELD, and MESO were the top 3 ranking staging systems. When predicting 3-month survival, area under the receiver operating characteristic curve (AUC) of MELD-AS is significantly higher than that of the other models (P < 0.05). When predicting 6-month survival, AUCs of MELD-AS and MELD-NA are significantly higher than those of the other models (P < 0.05). Cutoff point of MELD-AS is 23.11 with 40.5 % sensitivity and 93.8 % specificity at 1 month, 9.5 with 76.9 % sensitivity and 59.5 % specificity at 3 months, and 18.5 with 27.0 % sensitivity and 89.1 % specificity at 6 months. MELD-based scores of death group are significantly higher than those of survivors within 1 and 3 months (P < 0.001). Independent prognostic factors identified by multivariate analysis included persistent ascites, serum sodium, and thrombosis. MELD-AS is the best model in the prediction of short and intermediate survival among the five models for end-stage liver disease analyzed for Chinese advanced HCC patients

  8. Diminished production of interleukin-6 in chronic lymphocytic leukaemia (B-CLL) cells from patients at advanced stages of disease. Tampere CLL Group.

    PubMed

    Hulkkonen, J; Vilpo, J; Vilpo, L; Hurme, M

    1998-03-01

    The production of the cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in B-CLL cells from 24 patients at different stages of chronic lymphocytic B-cell leukaemia (B-CLL) was investigated in vitro. In the majority of these cases, low spontaneous IL-6 production was measured. Mitogenic stimulation with phorbol 12-myristate 13-acetate (PMA) or PMA plus interleukin-2 (IL-2) resulted in a tremendous increase in TNF-alpha and IL-6 production in cells representing early stage (Binet A) disease. In contrast, very little, if any, production took place in cells from patients with advanced stage (Binet C) B-CLL. The results from stage B patients were intermediate. The most remarkable difference was recorded in PMA-stimulated (1 ng/ml) IL-6 production. In stimulated 72 h cultures, IL-6 concentrations were 1280 +/- 1080 pg/ml for Binet A (n = 11), 757 +/- 597 pg/ml for Binet B (n = 8) and 46.0 +/- 84.0 pg/ml for Binet C (n = 5). The differences in IL-6 production between stage C v B and stage C v A were both statistically significant (P=0.025). Similar effects, but to a lesser extent, were observed in TNF-alpha production. These results suggest that the varying capacity to produce IL-6 and TNF-alpha may play a role in B-CLL progression and in clinical manifestations of the disease. PMID:9504629

  9. Advanced two-stage incinerator

    SciTech Connect

    Rehmat, A.; Khinkis, M.

    1991-01-01

    The Institute of Gas Technology (IGT) is developing an advanced incinerator that combines the fluidized-bed agglomeration/incineration and cyclonic combustion/incineration technologies that have been developed separately at IGT over many years. This combination results in a unique and extremely flexible incinerator for solid, sludge, liquid, and gaseous wastes. This system can operate over a wide range of conditions in the first stage, from low temperature (desorption) to high temperature (agglomeration), including gasification of high-Btu wastes. In the combined system, solid, liquid, and gaseous organic wastes would be easily and efficiently destroyed (>99.99% destruction and removal efficiency (DRE)), whereas solid inorganic contaminants would be contained within a glassy matrix, rendering them benign and suitable for disposal in an ordinary landfill. This technology is different from other existing technologies because of its agglomeration and encapsulation capability and its flexibility with respect to the types wastes it can handle. Both the fluidized-bed as well as the cyclonic incineration technologies have been fully developed and tested separately at pilot scales. 12 refs., 4 figs., 4 tabs.

  10. Human Leukocyte Antigen G Polymorphism and Expression Are Associated with an Increased Risk of Non-Small-Cell Lung Cancer and Advanced Disease Stage.

    PubMed

    Ben Amor, Amira; Beauchemin, Karine; Faucher, Marie-Claude; Hamzaoui, Agnes; Hamzaoui, Kamel; Roger, Michel

    2016-01-01

    Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression may enable tumor cells to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G allelic variants and serum soluble HLA-G (sHLA-G) levels on risk of non-small-cell lung cancer (NSCLC). We analyzed 191 Caucasian adults with NSCLC and 191 healthy subjects recruited between January 2009 and March 2014 in Ariana (Tunisia). Serum sHLA-G levels were measured by immunoassay and HLA-G alleles were determined using a direct DNA sequencing procedures. The heterozygous genotypes of HLA-G 010101 and -G 010401 were associated with increased risks of both NSCLC and advanced disease stages. In contrast, the heterozygous genotypes of HLA-G 0105N and -G 0106 were associated with decreased risks of NSCC and clinical disease stage IV, respectively. Serum sHLA-G levels were significantly higher in patients with NSCLC and particularly in those with advanced disease stages compared to healthy subjects. The area under the receiver-operating characteristic (ROC) curves was 0.82 for controls vs patients. Given 100% specificity, the highest sensitivity achieved to detect NSCLC was 52.8% at a cutoff value of 24.9 U/ml. Patients with the sHLA-G above median level (≥ 50 U/ml) had a significantly shorter survival time. This study demonstrates that HLA-G allelic variants are independent risk factors for NSCLC. Serum sHLA-G levels in NSCLC patients could be useful biomarkers for the diagnostic and prognosis of NSCLC. PMID:27517300

  11. The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

    SciTech Connect

    Higginson, Daniel S.; Chen, Ronald C.; Tracton, Gregg; Morris, David E.; Halle, Jan; Rosenman, Julian G.; Stefanescu, Mihaela; Pham, Erica; Socinski, Mark A.; Marks, Lawrence B.

    2012-11-01

    Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit. Methods and Materials: We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease. Results: On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard ratio, 1

  12. Activity of muscarinic, galanin and cannabinoid receptors in the prodromal and advanced stages in the triple transgenic mice model of Alzheimer's disease.

    PubMed

    Manuel, Iván; Lombardero, Laura; LaFerla, Frank M; Giménez-Llort, Lydia; Rodríguez-Puertas, Rafael

    2016-08-01

    Neurochemical alterations in Alzheimer's disease (AD) include cholinergic neuronal loss in the nucleus basalis of Meynert (nbM) and a decrease in densities of the M2 muscarinic receptor subtype in areas related to learning and memory. Neuromodulators present in the cholinergic pathways, such as neuropeptides and neurolipids, control these cognitive processes and have become targets of research in order to understand and treat the pathophysiological and clinical stages of the disease. This is the case of the endocannabinoid and galaninergic systems, which have been found to be up-regulated in AD, and could therefore have a neuroprotective role. In the present study, the functional coupling of Gi/o protein-coupled receptors to GalR1, and the CB1 receptor subtype for endocannabinoids were analyzed in the 3xTg-AD mice model of AD. In addition, the activity mediated by Gi/o protein-coupled M2/4 muscarinic receptor subtypes was also analyzed in brain areas involved in anxiety and cognition. Thus, male mice were studied at 4 and 15months of age (prodromal and advanced stages, respectively) and compared to age-matched non-transgenic (NTg) mice (adult and old, respectively). In 4-month-old 3xTg-AD mice, the [(35)S]GTPγS binding stimulated by galanin was significantly increased in the hypothalamus, but a decrease of functional M2/4 receptors was observed in the posterior amygdala. The CB1 cannabinoid receptor activity was up-regulated in the anterior thalamus at that age. In 15-month-old 3xTg-AD mice, muscarinic receptor activity was found to be increased in motor cortex, while CB1 activity was decreased in nbM. No changes were found in GalR1-mediated activity at this age. Our results provide further evidence of the relevance of limbic areas in the prodromal stage of AD, the profile of which is characterized by anxiety. The up-regulation of galaninergic and endocannabinoid systems support the hypothesis of their neuroprotective roles, and these are established prior to the

  13. 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

  14. Treatment of advanced-stage Hodgkin lymphoma.

    PubMed

    Vassilakopoulos, Theodoros P; Johnson, Peter W M

    2016-07-01

    There is now good evidence that the escalated BEACOPP regimen (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone) is more effective in controlling advanced-stage Hodgkin lymphoma (HL) than the widely used ABVD regimen (adriamycin, bleomycin, vinblastine, dacarbazine), but the extra efficacy comes at the expense of both short- and long-term toxicity, and there is debate as to whether overall survival is affected. Baseline prognostic factors have proven of limited utility for determining which patients require more intensive therapy and recent studies have sought to use interim fluoro-deoxyglucose positron emission tomography (FDG-PET) evaluation as a means to guide the modulation of treatment, both upwards and downwards in intensity. These suggest that if treatment starts with ABVD then patients remaining PET-positive after 2 months can be salvaged with escalated BEACOPP in around 65% of cases, but those becoming PET-negative may still experience recurrences in 15%-20%, an event that is more common in those with more advanced disease at presentation. There are early data to suggest that starting with escalated BEACOPP may reduce the rate of recurrence after a negative interim PET to less than 10%. This may be an attractive approach for those with very high-risk features at presentation, but risks overtreating many patients if applied nonselectively. New regimens incorporating antibody-drug conjugates may shift the balance of efficacy and toxicity once again, and further studies are underway to evaluate this. PMID:27496308

  15. Electrochemotherapy in combination with chemoradiotherapy in the treatment of oral carcinomas in advanced stages of disease: efficacy, safety, and clinical outcomes in a small number of selected cases

    PubMed Central

    Domanico, Rossana; Trapasso, Serena; Santoro, Mariaquila; Pingitore, Domenico; Allegra, Eugenia

    2015-01-01

    Introduction Electrochemotherapy (ECT) is a new therapeutic method that is used in oncology as palliative treatment in patients with recurrent head and neck tumors and who are not candidates for standard therapeutic options. The aim of our study was to evaluate the cytoreductive effect of ECT in patients subjected to chemoradiotherapy for squamous cell carcinoma of the oral cavity. The primary endpoint of the study was to verify tumor debulking after ECT treatment as neoadjuvant, before conventional chemoradiotherapy. The secondary endpoint was to assess the safety and tolerability of ECT treatment. Materials and methods This experimental study was conducted at the Division of Otolaryngology, University of Catanzaro, Italy. From February 2013 to February 2014, four patients were enrolled, two males and two females, with a mean age of 56 years (range: 47–65 years), and with squamous cell carcinoma of the oral cavity in advanced stages of disease (T3–T4). All patients, with their informed consent, received ECT treatment in accordance with the Standard Operating Procedures defined in the European Standard Operating Procedures on Electrochemotherapy (ESOPE) study, followed by conventional chemoradiotherapy. Their response to ECT treatment was assessed after 30 days. For each patient, the following parameters were evaluated with the appropriate forms: local tumor control, control of pain (analgesia postsurgery scale [APS]), and quality of life (Short Form [36] Health Survey [SF-36]; v1). Results Three of four patients (75%) showed a partial response, whereas in one patient (25%), the disease remained stable. The treatment was well-tolerated by all patients, according to the APS and SF-36 results. Conclusion Although the study was conducted on a small number of cases, data from this study show that ECT represents a safe and effective treatment in terms of tumor cytoreduction and locoregional control of the disease. It also allows good control of postoperative pain

  16. Advanced Coats' disease.

    PubMed Central

    Haik, B G

    1991-01-01

    Advanced Coats' disease and retinoblastoma can both present with the triad of a retinal detachment, the appearance of a subretinal mass, and dilated retinal vessels. Thus, even the most experienced observer may not be able to differentiate these entities on ophthalmoscopic findings alone. Coats' disease is the most common reason for which eyes are enucleated with the misdiagnosis of retinoblastoma. Ultrasonography is the auxiliary diagnostic test most easily incorporated into the clinical examination, and can be utilized repeatedly without biologic tissue hazard. Ultrasonically identifiable features allowing differentiation between Coats' disease and retinoblastoma include the topography and character of retinal detachment and presence or absence of subretinal calcifications. Ultrasonography is of lesser use in poorly calcified retinoblastoma and in detecting optic nerve or extraocular extension in heavily calcified retinoblastoma. CT is perhaps the single most valuable test because of its ability to: (a) delineate intraocular morphology, (b) quantify subretinal densities, (c) identify vascularities within the subretinal space through the use of contrast enhancement, and (d) detected associated orbital or intracranial abnormalities. Optimal computed tomographic studies, however, require multiple thin slices both before and after contrast introduction and expose the child to low levels of radiation if studies are repeated periodically. MR imaging is valuable for its multiplanar imaging capabilities, its superior contrast resolution, and its ability to provide insights into the biochemical structure and composition of tissues. It is limited in its ability to detect calcium, which is the mainstay of ultrasonic and CT differentiation. Aqueous LDH and isoenzyme levels were not valuable in distinguishing between Coats' disease and retinoblastoma. The value of aqueous NSE levels in the differentiation of advanced Coats' disease and exophytic retinoblastoma deserves

  17. End-stage kidney disease

    MedlinePlus

    ... Transplantation: Principles and Practice . 7th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 3. Inker LA, Astor BC, ... Primer on Kidney Diseases . 6th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 53. Taal M. Risk factors ...

  18. Can advanced-stage ovarian cancer be cured?

    PubMed

    Narod, Steven

    2016-04-01

    Approximately 20% of women with advanced-stage ovarian cancer survive beyond 12 years after treatment and are effectively cured. Initial therapy for ovarian cancer comprises surgery and chemotherapy, and is given with the goal of eradicating as many cancer cells as possible. Indeed, the three phases of therapy are as follows: debulking surgery to remove as much of the cancer as possible, preferably to a state of no visible residual disease; chemotherapy to eradicate any microscopic disease that remains present after surgery; and second-line or maintenance therapy, which is given to delay disease progression among patients with tumour recurrence. If no cancer cells remain after initial therapy is completed, a cure is expected. By contrast, if residual cancer cells are present after initial treatment, then disease recurrence is likely. Thus, the probability of cure is contingent on the combination of surgery and chemotherapy effectively eliminating all cancer cells. In this Perspectives article, I present the case that the probability of achieving a cancer-free state is maximized through a combination of maximal debulking surgery and intraperitoneal chemotherapy. I discuss the evidence indicating that by taking this approach, cures could be achieved in up to 50% of women with advanced-stage ovarian cancer. PMID:26787282

  19. Advanced two-stage compressor program design of inlet stage

    NASA Technical Reports Server (NTRS)

    Bryce, C. A.; Paine, C. J.; Mccutcheon, A. R. S.; Tu, R. K.; Perrone, G. L.

    1973-01-01

    The aerodynamic design of an inlet stage for a two-stage, 10/1 pressure ratio, 2 lb/sec flow rate compressor is discussed. Initially a performance comparison was conducted for an axial, mixed flow and centrifugal second stage. A modified mixed flow configuration with tandem rotors and tandem stators was selected for the inlet stage. The term conical flow compressor was coined to describe a particular type of mixed flow compressor configuration which utilizes axial flow type blading and an increase in radius to increase the work input potential. Design details of the conical flow compressor are described.

  20. The Economic Burden of Chronic Kidney Disease and End-Stage Renal Disease.

    PubMed

    Wang, Virginia; Vilme, Helene; Maciejewski, Matthew L; Boulware, L Ebony

    2016-07-01

    The growing prevalence and progression of chronic kidney disease (CKD) raises concerns about our capacity to manage its economic burden to patients, caregivers, and society. The societal direct and indirect costs of CKD and end-stage renal disease are substantial and increase throughout disease progression. There is significant variability in the evidence about direct and indirect costs attributable to CKD and end-stage renal disease, with the most complete evidence concentrated on direct health care costs of patients with advanced to end-stage CKD. There are substantial gaps in evidence that need to be filled to inform clinical practice and policy. PMID:27475662

  1. Asian gastric cancer patients at a southern California comprehensive cancer center are diagnosed with less advanced disease and have superior stage-stratified survival.

    PubMed

    Theuer, C P

    2000-09-01

    The 5-year overall survival after curative gastrectomy for gastric cancer is markedly different in the West from that in the Far East. Japanese surgeons feel that extended lymphadenectomy contributes to this superior survival, although survival differences may reflect improved staging or less aggressive tumor biology. We analyzed consecutive cases of gastric adenocarcinoma diagnosed and treated at the University of California, Irvine Medical Center from 1989 through 1998 to determine whether patients of Asian descent diagnosed with gastric cancer in Southern California have improved outcome. Fifty-two cases (36%) occurred in patients of Asian descent (39% Vietnamese, 31% Chinese, 13% Korean, 6% Filipino, and 2% Japanese). Only one Asian patient was born in the United States. Non-Asian patients (67% white, 30% Latino, and 3% black) were younger (59 years vs 64 years; P < 0.05) and more likely to have tumors of the gastroesophageal junction (33% vs 4%; P < 0.001). Asian patients were less likely to have distant metastases (24% vs 39%; P = 0.08), were more likely to undergo formal gastrectomy (71% vs 45%; P < 0.01), and were more likely to undergo a curative resection (40% vs 18%; P < 0.01). The overall survival of Asian patients at 3 years was significantly higher than the overall survival of non-Asians (39.4% vs 19.6%, P < 0.05). Asians with regional (node-positive) disease had superior survival (40.2% vs 14.8%, P < 0.05), which can be largely attributed to greater rates of resectability. We conclude that the clinical behavior of gastric cancer in Asians in Southern California differs from that in non-Asians. The increased proportion of resectable disease and improved survival of patients of Asian descent likely reflects less aggressive tumor biology. PMID:10993608

  2. Myeloma today: Disease definitions and treatment advances.

    PubMed

    Rajkumar, S Vincent

    2016-01-01

    There have been major advances in the diagnosis, staging, risk-stratification, and management of multiple myeloma (MM). In addition to established CRAB (hypercalcemia, renal failure, anemia, and lytic bone lesions) features, new diagnostic criteria include three new biomarkers to diagnose the disease: bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain ratio ≥100, and >1 focal lesion on magnetic resonance imaging. MM can be classified into several subtypes based on baseline cytogenetics, and prognosis varies according to underlying cytogenetic abnormalities. A Revised International Staging System has been developed which combines markers of tumor burden (albumin, beta-2 microglobulin) with markers of aggressive disease biology (high-risk cytogenetics and elevated serum lactate dehydrogenase). Although the approach to therapy remains largely the same, the treatment options at every stage of the disease have changed. Carfilzomib, pomalidomide, panobinostat, daratumumab, elotuzumab, and ixazomib have been approved for the treatment of the disease. These drugs combined with older agents such as cyclophosphamide, dexamethasone, thalidomide, bortezomib, and lenalidomide dramatically increase the repertoire of regimens available for the treatment of MM. This review provides a concise overview of recent advances in MM, including updates to diagnostic criteria, staging, risk-stratification, and management. PMID:26565896

  3. Moderate dose escalation for advanced stage Hodgkin's disease using the bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone scheme and adjuvant radiotherapy: a study of the German Hodgkin's Lymphoma Study Group.

    PubMed

    Tesch, H; Diehl, V; Lathan, B; Hasenclever, D; Sieber, M; Rüffer, U; Engert, A; Franklin, J; Pfreundschuh, M; Schalk, K P; Schwieder, G; Wulf, G; Dölken, G; Worst, P; Koch, P; Schmitz, N; Bruntsch, U; Tirier, C; Müller, U; Loeffler, M

    1998-12-15

    The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, a rearranged and accelerated version of the standard COPP/adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, has been shown to be effective and safe in a previous pilot study for advanced stage Hodgkin's disease (HD). The present study aimed to determine a maximum practicable dose of three drugs, ie, etoposide, adriamycin, and cyclophosphamide, for which acute toxicities were acceptable and to assess the feasibility of the escalated scheme. Sixty untreated patients with advanced stage HD were enrolled in this study. Radiotherapy was given in 44 patients (73%) after chemotherapy to initial bulk lesions and residual disease. Granulocyte-colony stimulating factor (G-CSF) was given from day 8 to prevent prolonged neutrocytopenia and severe infections. The intended doses of adriamycin, etoposide, and cyclophosphamide in the BEACOPP schedule could be substantially escalated: adriamycin from 25 to 35, cyclophosphamide from 650 to 1,200, and etoposide from 100 to 200 mg/m2. The major toxicities were leukocytopenia and thrombocytopenia with considerable heterogeneity between individual patients. Of 60 patients, 56 (93%) achieved a complete remission (CR). At a median observation of 32 months, the rates of survival and freedom from treatment failure (FFTF) were estimated to be 91% (95% confidence interval 83% to 99%) and 90% (82% to 98%). These results show that a moderate dose escalation of adriamycin, cyclophosphamide, and etoposide of the baseline BEACOPP regimen is feasible. The escalated BEACOPP regimen shows very encouraging results in advanced stage HD and is now being compared in a randomized phase III study with BEACOPP at baseline dose level. PMID:9845521

  4. Treatment of advanced Parkinson’s disease

    PubMed Central

    Giugni, Juan C.; Okun, Michael S.

    2014-01-01

    Purpose of the review Later stage Parkinson’s disease (PD), sometimes referred to as advanced disease, has been characterized by motor complication, as well as by the potential emergence non-levodopa responsive motor and non-motor symptoms. The management of advanced stage PD can be complex. This review summarizes the currently available treatment strategies for addressing advanced PD. Recent findings We will discuss the latest pharmacological strategies (e.g. inhibitors of dopamine-metabolizing enzymes, dopamine agonists and extended release dopamine formulations) for addressing motor dysfunction. We will summarize the risks and benefits of current invasive treatments. Finally, we will address the current evidence supporting the treatment of non-motor symptoms in the advanced PD patient. We will conclude by detailing the potential non-pharmacological and multidisciplinary approaches for advanced stage PD. Summary The optimization of levodopa is in most cases the most powerful therapeutic option available, however medication optimization requires an advanced understanding of PD. Failure of conventional pharmacotherapy, should precipitate a discussion of the potential risks and benefits of more invasive treatments. Currently, there are no comparative studies of invasive treatment. Among the invasive treatments, deep brain stimulation has the largest amount of existing evidence, but also has the highest individual per patient risk. Non-motor symptoms will affect quality of life more than the motor PD symptoms, and these non-motor symptoms should be aggressively treated. Many advanced PD patients will likely benefit from multi- and interdisciplinary PD teams with multiple professionals collaborating to develop a collective and tailored strategy for an individual patient. PMID:24978634

  5. Treatment results in advanced stage Hodgkin's lymphoma: A retrospective study

    PubMed Central

    Jain, H; Sengar, M; Nair, R; Menon, H; Laskar, S; Shet, T; Gujral, S; Sridhar, E

    2015-01-01

    Background: Hodgkin's lymphoma displays distinct epidemiological attributes in Asian population thus making it relevant to study whether there are any differences in treatment outcomes too when treated with current standard of care. Aim: To evaluate the treatment outcomes of de-novo advanced stage HL in adults. Materials and Methods: This retrospective study included de-novo advanced stage HL patients (≥15 years) registered at our center from January 2004 to December 2007. Treatment outcomes were measured in terms of response rates, overall survival (OS) and progression-free survival (PFS). Overall and PFS were calculated with Kaplan-Meier methodology and Cox-proportional hazards model was used for multivariate analysis to identify prognostic factors. Results: There were 125 patients (males 77%) who received minimum one cycle of chemotherapy with median age of 32 years (Range 15-65 years). Stage IV disease was seen in (46 patients) 37%; 75% (94 patients) patients had B symptoms. International prognostic score (IPS) ≤4 was seen in 95/112 (85%) patients. ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy was given to 94%. Radiation to residual/bulky sites was given to 36% (45 patients). Response data was available for 112 patients; complete response in 76%; partial response in 10 % and progressive disease in 3 patients. Nineteen deaths (progressive disease-7, toxicity-8, unrelated cause-4) were observed. At median follow-up of 28 months, estimated 5-year OS and PFS were 60% and 58%, respectively. On multivariate analysis, IPS and response to treatment were significant factors for both OS and PFS. Conclusions: The treatment outcomes in this study are comparable with the published literature with limited follow-up data. PMID:25766339

  6. Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma

    PubMed Central

    Kato, Hiroyuki; Yoshida, Hideo; Taniguch, Hiroyoshi; Nomura, Ryutaro; Sato, Kengo; Suzuki, Ichiro; Nakata, Ryo

    2015-01-01

    AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher’s exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral

  7. The treatment of stage IIIA Hodgkin's disease

    SciTech Connect

    Lister, T.A.; Dorreen, M.S.; Faux, M.; Jones, A.E.; Wrigley, P.F.

    1983-12-01

    Sixty consecutive previously untreated adults with surgically confirmed stage IIIA Hodgkin's disease (39 stage IIIA1, 21 stage IIIA2) began therapy at St. Bartholomew's Hospital between 1969 and 1981. Prior to 1973, treatment consisted of total nodal irradiation (TNI). From 1973 until 1978 patients were randomly allocated to receive either TNI or cyclic combination chemotherapy of mustine, vinblastine, prednisolone, and procarbazine (MVPP) as part of a Medical Research Council Trial. Since 1978 treatment has been allocated according to substage, those with stage IIIA1 receiving TNI and those with stage IIIA2 receiving MVPP. Seven patients received ''non protocol'' therapy (extended mantle radiotherapy in three patients, mantle and MVPP in four patients), and have been excluded from the study. Complete remission was achieved in 48 of 53 patients regardless of substage or therapy. Seven have relapsed, one after MVPP and six after TNI. The predicted freedom-from-relapse after MVPP was 96% compared with 60% after TNI, both at 10 years (p less than 0.01). The relapse pattern was the same for both substages in the group receiving TNI. Although overall survival of patients receiving TNI was identical to that of those receiving MVPP, TNI must be considered inappropriate therapy for stage IIIA Hodgkin's disease if permanent freedom-from-recurrence is the goal.

  8. Stage I and II subdiaphragmatic Hodgkin's disease.

    PubMed

    Mai, D H; Peschel, R E; Portlock, C; Knowlton, A; Farber, L

    1991-10-01

    From January 1971 to December 1986, 521 patients with Hodgkin's disease were evaluated and treated at the Yale University School of Medicine or one of its close affiliates. A total of 258 patients had pathologic stage (PS) I or II disease, with 239 patients having Hodgkin's disease above the diaphragm (ADHD) and 19 patients having Hodgkin's disease below the diaphragm (BDHD). A comparison of patients with BDHD versus patients with ADHD showed that patients with BDHD were older (mean age, 42 versus 28 years of age, P = 0.005), were initially seen less often with nodular sclerosis subtype (32% versus 77%, P = 0.00001), and had a higher male: female ratio (2.8 versus 1.2, P = 0.12). Ten patients with BDHD (53%) had positive findings at staging laparotomy (0 of 4 clinical stage [CS] IA patients and 10 of 15 (67%) CS II patients). Radiation therapy alone was the initial treatment of choice for 74% of patients with BDHD versus 94% of the patients with ADHD. There was no statistical difference in the overall survival or relapse-free survival rates for patients with BDHD versus ADHD (10-year survival rates, BDHD = 73% and ADHD = 81%). However, patients with BDHD who initially had intra-abdominal disease had a statistically significant increase in death rate (60%) due to Hodgkin's disease compared with patients with BDHD who initially had only peripheral nodal disease (0%). Treatment recommendations for patients with BDHD should be tailored to the specific clinical presentation of each patient. For most PS IA/IIA patients initially seen with peripheral nodal disease, radiation therapy alone is a successful treatment program. However, combined modality therapy should be the treatment of choice for patients with BDHD initially seen with intra-abdominal disease. PMID:1893346

  9. [Primary treatment of advanced Hodgkin's disease].

    PubMed

    Illés, Arpád; Udvardy, Miklós; Molnár, Zsuzsa

    2005-01-30

    Primary treatment of advanced Hodgkin's disease. Hodgkin's disease is one of the few malignant diseases that can be cured even in an advanced stage in the majority of cases. By employing a polychemotherapy containing anthracyclines, a long remission and recovery can be achieved in 60-70% of the patients. At present the standard treatment is ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) scheme for the following reasons: besides good treatment results early side effects are more favourable; sterility and secondary acute leukemia present themselves less often than by employing regimens containing alkylating agents. Unfortunately, some of the patients do not react properly to the treatment and about one third of the patients who are in remission following primary treatment will relapse at a later stage. The main goal is now to further improve treatment (recovery) results without an increase, or even a decrease of early or late side effects. Awareness of prognostic factors should lead to the employment of a less intensive but not toxic therapy in patients with good prognosis to prevent overtreatment, while in cases with bad prognosis a more effective regimen is needed (even for the price of expected complications). The latest meta-analysis on the subject has shown that--similarly to sequential high dose therapy--the addition of radiotherapy to an effective chemotherapy does not seem to prolong the survival of patients. Despite the excellent therapeutic results achieved by the many new "intensive" chemotherapies, there is unfortunately no optimal therapy or protocol available today. The multicentre analysis to confirm these results and to compare them with standard scheme is still under way. It is to be hoped that risk adapted management for advanced stage Hodgkin's disease will also be available soon. PMID:15773586

  10. Management of Stage IIIA Hodgkin's disease

    SciTech Connect

    Timothy, A.R.; Sutcliffe, S.B.J.; Lister, A.; Wrigley, P.F.M.; Jones, A.E.

    1980-02-01

    Forty patients with pathological Stage IIIA Hodgkin's disease were allocated to receive either total modal irradiation (TNI) or 6 cycles of chemotherapy with Nitrogen Mustard (Mustine), Vinblastine, Procarbazine and Prednisolone (MVPP) as initial treatment. The complete remission rate for both groups was 100%, with 5-year actuarial disease-free survival figures of 74 and 87% for TNI and MVPP respectively (median duration of follow-up= 48 months). Eighty-eight percent of TNI treated patients were alive at 5 years compared with 100% in the MVPP group. Three patients died, two who were treated with TNI and one who received MVPP. Treatment related morbidity included one patient with osteonecrosis and one with a second malignancy. Given the length of follow-up available, these results demonstrate no significant difference between TNI and MVPP for patients with Stage IIIA disease; it is unlikely that further patient entry into this particular study will allow any conclusion to be reached regarding the optimal form of management. We would recommend that individual disease characteristics within Stage IIIA be used as a basis for future treatment decisions with the understanding that further information regarding morbidity may become available with prolonged follow-up.

  11. Therapeutic advances in Huntington's Disease.

    PubMed

    Shannon, Kathleen M; Fraint, Avram

    2015-09-15

    Huntington's disease is a rare hereditary degenerative disease with a wide variety of symptoms that encompass movement, cognition, and behavior. The genetic mutation that causes the disease has been known for more than 20 y, and animal models have illuminated a host of intracellular derangements that occur downstream of protein translation. A number of clinical trials targeting these metabolic consequences have failed to produce a single effective therapy, although clinical trials continue. New strategies targeting the protein at the level of transcription, translation, and posttranslational modification and aggregation engender new hope that a successful strategy will emerge, but there is much work ahead. Some of the clinical manifestations of the illness, particularly chorea, affective symptoms, and irritability, are amenable to palliative strategies, but physicians have a poor evidence base on which to select the best agents. Clinical trials since 2013 have dashed hopes that coenzyme Q10 or creatine might have disease-modifying properties but suggested other agents were safe or hinted at efficacy (cysteamine, selisistat, hydroxyquinoline) and could proceed into later-stage disease modification trials. The hunt for effective symptom relief suggested that pridopidine might be shown effective given the right outcome measure. This review summarizes recent progress in HD and highlights promising new strategies for slowing disease progression and relieving suffering in HD. PMID:26226924

  12. Recent Advances in Diverticular Disease.

    PubMed

    Peery, Anne F

    2016-07-01

    Diverticular disease is common and accounts for substantial health care utilization in the USA. Recent publications in the areas of diverticulosis and diverticular disease have highlighted several notable advances that are now changing practice. Despite colonic diverticula being common, only 1-4 % of individuals with colonic diverticula will develop diverticulitis. After a first occurrence of acute diverticulitis, the risk of recurrence is 20 % at 5 years. Complications most commonly occur with the first occurrence of acute diverticulitis and not with recurrent episodes. After an episode of diverticulitis, many patients continue to experience chronic gastrointestinal symptoms. Prophylactic surgery is an option to reduce the risk of recurrence and its negative impact on quality of life. Importantly, the rationale for surgery is no longer to prevent complications because this risk is low. The review concludes with practical recommendations for patients with diverticulosis and diverticular disease. PMID:27241190

  13. Recent Advances in Kawasaki Disease

    PubMed Central

    Kim, Kyu Yeun

    2016-01-01

    Kawasaki disease (KD) is characterized with acute systemic vasculitis, occurs predominantly in children between 6 months to 5 years of age. Patients with this disease recover well and the disease is self-limited in most cases. Since it can lead to devastating cardiovascular complications, KD needs special attention. Recent reports show steady increases in the prevalence of KD in both Japan and Korea. However, specific pathogens have yet to be found. Recent advances in research on KD include searches for genetic susceptibility related to KD and research on immunopathogenesis based on innate and acquired immunity. Also, search for etiopathogenesis and treatment of KD has been actively sought after using animal models. In this paper, the recent progress of research on KD was discussed. PMID:26632378

  14. Persistent hyperactivity and distinctive strategy features in the Morris water maze in 3xTg-AD mice at advanced stages of disease.

    PubMed

    Baeta-Corral, Raquel; Giménez-Llort, Lydia

    2015-04-01

    Search strategies in the Morris water maze provide useful insights on cognitive function that may reveal genotype differences not reflected by escape latency or distance. Its analysis is pointed out as a complementary tool to better define the phenotype and the effect of treatments in animal models in which both cognitive impairment and behavioral symptoms reproduce the clinical complexity of the Alzheimer's disease patient. Here, we studied the performance of 13-month-old male 3xTg-AD mice in 3 different paradigms (cue learning, place task, and probe trial) and as compared with age-matched nontransgenic mice. The quantitative analysis (escape latency, distance, and speed) showed that in all tasks, the cognitive performance of 3xTg-AD mice was interfered with by a persistent hyperactive pattern. Their worse cognitive function was revealed by the qualitative features of nonsearch behaviors (floating and circling) and search strategies (single and /mixed, goal directed and nongoal directed). The search pattern was based on mixed and nongoal-directed strategies, in contrast to the single and goal-directed strategies used by controls. In the place task, poor cognitive flexibility of 3xTg-AD mice was also shown in persistence of search in the cue-trained position and the need to correct the strategy to find the new location. Trials involving a naïve situation (first trial of the cue task) or the difficulty of a new task (first trial of the place task and the probe trial) were the most suitable to show the deficits. This qualitative analysis may also be useful in the assessment of preventive or therapeutical treatments. PMID:25730122

  15. Sleep-Wake Cycle Dysfunction in the TgCRND8 Mouse Model of Alzheimer's Disease: From Early to Advanced Pathological Stages.

    PubMed

    Colby-Milley, Jessica; Cavanagh, Chelsea; Jego, Sonia; Breitner, John C S; Quirion, Rémi; Adamantidis, Antoine

    2015-01-01

    In addition to cognitive decline, individuals affected by Alzheimer's disease (AD) can experience important neuropsychiatric symptoms including sleep disturbances. We characterized the sleep-wake cycle in the TgCRND8 mouse model of AD, which overexpresses a mutant human form of amyloid precursor protein resulting in high levels of β-amyloid and plaque formation by 3 months of age. Polysomnographic recordings in freely-moving mice were conducted to study sleep-wake cycle architecture at 3, 7 and 11 months of age and corresponding levels of β-amyloid in brain regions regulating sleep-wake states were measured. At all ages, TgCRND8 mice showed increased wakefulness and reduced non-rapid eye movement (NREM) sleep during the resting and active phases. Increased wakefulness in TgCRND8 mice was accompanied by a shift in the waking power spectrum towards fast frequency oscillations in the beta (14-20 Hz) and low gamma range (20-50 Hz). Given the phenotype of hyperarousal observed in TgCRND8 mice, the role of noradrenergic transmission in the promotion of arousal, and previous work reporting an early disruption of the noradrenergic system in TgCRND8, we tested the effects of the alpha-1-adrenoreceptor antagonist, prazosin, on sleep-wake patterns in TgCRND8 and non-transgenic (NTg) mice. We found that a lower dose (2 mg/kg) of prazosin increased NREM sleep in NTg but not in TgCRND8 mice, whereas a higher dose (5 mg/kg) increased NREM sleep in both genotypes, suggesting altered sensitivity to noradrenergic blockade in TgCRND8 mice. Collectively our results demonstrate that amyloidosis in TgCRND8 mice is associated with sleep-wake cycle dysfunction, characterized by hyperarousal, validating this model as a tool towards understanding the relationship between β-amyloid overproduction and disrupted sleep-wake patterns in AD. PMID:26076358

  16. Sleep-Wake Cycle Dysfunction in the TgCRND8 Mouse Model of Alzheimer’s Disease: From Early to Advanced Pathological Stages

    PubMed Central

    Colby-Milley, Jessica; Cavanagh, Chelsea; Jego, Sonia; Breitner, John C. S.; Quirion, Rémi; Adamantidis, Antoine

    2015-01-01

    In addition to cognitive decline, individuals affected by Alzheimer’s disease (AD) can experience important neuropsychiatric symptoms including sleep disturbances. We characterized the sleep-wake cycle in the TgCRND8 mouse model of AD, which overexpresses a mutant human form of amyloid precursor protein resulting in high levels of β-amyloid and plaque formation by 3 months of age. Polysomnographic recordings in freely-moving mice were conducted to study sleep-wake cycle architecture at 3, 7 and 11 months of age and corresponding levels of β-amyloid in brain regions regulating sleep-wake states were measured. At all ages, TgCRND8 mice showed increased wakefulness and reduced non-rapid eye movement (NREM) sleep during the resting and active phases. Increased wakefulness in TgCRND8 mice was accompanied by a shift in the waking power spectrum towards fast frequency oscillations in the beta (14-20 Hz) and low gamma range (20-50 Hz). Given the phenotype of hyperarousal observed in TgCRND8 mice, the role of noradrenergic transmission in the promotion of arousal, and previous work reporting an early disruption of the noradrenergic system in TgCRND8, we tested the effects of the alpha-1-adrenoreceptor antagonist, prazosin, on sleep-wake patterns in TgCRND8 and non-transgenic (NTg) mice. We found that a lower dose (2 mg/kg) of prazosin increased NREM sleep in NTg but not in TgCRND8 mice, whereas a higher dose (5 mg/kg) increased NREM sleep in both genotypes, suggesting altered sensitivity to noradrenergic blockade in TgCRND8 mice. Collectively our results demonstrate that amyloidosis in TgCRND8 mice is associated with sleep-wake cycle dysfunction, characterized by hyperarousal, validating this model as a tool towards understanding the relationship between β-amyloid overproduction and disrupted sleep-wake patterns in AD. PMID:26076358

  17. Advanced Therapies For End-Stage Heart Failure

    PubMed Central

    Katz, Jason N; Waters, Sarah B; Hollis, Ian B; Chang, Patricia P

    2015-01-01

    Management of the advanced heart failure patient can be complex. Therapies include cardiac transplantation and mechanical circulatory support, as well inotropic agents for the short-term. Despite a growing armamentarium of resources, the clinician must carefully weigh the risks and benefits of each therapy to develop an optimal treatment strategy. While cardiac transplantation remains the only true “cure” for end-stage disease, this resource is limited and the demand continues to far outpace the supply. For patients who are transplant-ineligible or likely to succumb to their illness prior to transplant, ventricular assist device therapy has now become a viable option for improving morbidity and mortality. Particularly for the non-operative pa-tient, intravenous inotropes can be utilized for symptom control. Regardless of the treatments considered, care of the heart failure patient requires thoughtful dialogue, multidisciplinary collaboration, and individualized care. While survival is important, most patients covet quality of life above all outcomes. An often overlooked component is the patient’s control over the dying process. It is vital that clinicians make goals-of-care discussions a priority when seeing patients with advanced heart failure. The use of palliative care consultation is well-validated and facilitates these difficult conversations to ensure that all patient needs are ultimately met. PMID:24251460

  18. A Stage Model of Stress and Disease.

    PubMed

    Cohen, Sheldon; Gianaros, Peter J; Manuck, Stephen B

    2016-07-01

    In this article, we argued that the term stress has served as a valuable heuristic, helping researchers to integrate traditions that illuminate different stages of the process linking stressful life events to disease. We provided a short history of three traditions in the study of stress: the epidemiological, psychological, and biological. The epidemiological tradition focuses on defining which circumstances and experiences are deemed stressful on the basis of consensual agreement that they constitute threats to social or physical well-being. The psychological tradition focuses on individuals' perceptions of the stress presented by life events on the basis of their appraisals of the threats posed and the availability of effective coping resources. The biological tradition focuses on brain-based perturbations of physiological systems that are otherwise essential for normal homeostatic regulation and metabolic control. The foci of these three traditions have informed elements of a stage model of disease, wherein events appraised as stressful are viewed as triggering affective states that in turn engender behavioral and biological responses having possible downstream implications for disease. PMID:27474134

  19. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    PubMed

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research. PMID:26925962

  20. Joint Leveling for Advanced Kienbock’s Disease

    PubMed Central

    Calfee, Ryan P.; Van Steyn, Marlo O.; Gyuricza, Cassie; Adams, Amelia; Weiland, Andrew J.; Gelberman, Richard H.

    2010-01-01

    PURPOSE The use of joint leveling procedures to treat Kienbock’s disease has been limited by the degree of disease advancement. This study was designed to compare clinical and radiographic outcomes of wrists with more advanced Kienbock’s disease (stage IIIB) to wrists with less advanced disease (stage II/IIIA) following radius shortening osteotomy. METHODS This retrospective study enrolled 31 adult wrists (30 patients, mean age 39 years), treated by radius shortening osteotomy between two institutions for either stage IIIB (n=14) or stage II/IIIA (n=17) disease. Evaluation was carried out at a mean of 74 months (IIIB, 77 months; II/IIIA, 72 months). Radiographic assessment determined disease progression. Clinical outcomes were determined by validated patient-based and objective measures. RESULTS Patient-based outcome ratings of wrists treated for stage IIIB were similar to those with stage II/IIIA [QuickDASH (15 vs 12:p=.63), MMWS (84 vs 87:p=.59), VAS pain (1.2 vs 1.7:p=.45), VAS function (2.6 vs 2.1:p=.59)]. The average flexion/extension arc was 102° for wrists with stage IIIB and 106° for wrists with stage II/IIIA Kienbock’s (p=.70). Grip strength was 77% of the opposite side for stage IIIB wrists versus 85% for stage II/IIIA (p=.25). Postoperative carpal height ratio and radioscaphoid angle were worse (p<.05) for wrists treated for stage IIIB (0.46:65°) than stage II/IIIA (0.53:53°) disease. Radiographic disease progression occurred in 7 wrists (6 stage II/IIIA: 1 stage IIIB). The one stage IIIB wrist that progressed underwent wrist arthrodesis. CONCLUSIONS In this limited series, clinical outcomes of radius shortening using validated, patient-based assessment instruments and objective measures failed to demonstrate predicted “clinically relevant” differences between stage II/IIIA and IIIB Kienbock’s. Provided the high percentage successful clinical outcomes in this case series of 14 stage IIIB wrists, we believe that static carpal malalignment

  1. Initial Staging of Hodgkin’s Disease

    PubMed Central

    Chiaravalloti, Agostino; Danieli, Roberta; Caracciolo, Cristiana Ragano; Travascio, Laura; Cantonetti, Maria; Gallamini, Andrea; Guazzaroni, Manlio; Orlacchio, Antonio; Simonetti, Giovanni; Schillaci, Orazio

    2014-01-01

    Abstract The objective of this study was to compare the diagnostic accuracy of positron emission tomography/low-dose computed tomography (PET/ldCT) versus the same technique implemented by contrast-enhanced computed tomography (ceCT) in staging Hodgkin’s disease (HD). Forty patients (18 men and 22 women, mean age 30 ± 9.6) with biopsy-proven HD underwent a PET/ldCT study for initial staging including an unenhanced low-dose computed tomography for attenuation correction with positron emission tomography acquisition and a ceCT, performed at the end of the PET/ldCT scan, in the same exam session. A detailed datasheet was generated for illness locations for separate imaging modality comparison and then merged in order to compare the separate imaging method results (PET/ldCT and ceCT) versus merged results positron emission tomography/contrast-enhanced computed tomography (PET/ceCT). The nodal and extranodal lesions detected by each technique were then compared with follow-up data that served as the reference standard. No significant differences were found at staging between PET/ldCT and PET/ceCT in our series. One hundred and eighty four stations of nodal involvement have been found with no differences in both modalities. Extranodal involvement was identified in 26 sites by PET/ldCT and in 28 by PET/ceCT. We did not find significant differences concerning the stage (Ann Arbor). Our study shows a good concordance and conjunction between PET/ldCT and ceCT in both nodal and extranodal sites in the initial staging of HD, suggesting that PET/ldCT could suffice in most of these patients. PMID:25121354

  2. Impact of Huntington's across the entire disease spectrum: the phases and stages of disease from the patient perspective

    PubMed Central

    Ho, AK; Hocaoglu, MB

    2011-01-01

    Ho AK, Hocaoglu MB for the European Huntington's Disease Network Quality of Life Working Group. Impact of Huntington disease across the entire disease spectrum: the phases and stages of disease from the patient perspective. Although Huntington's disease (HD) is a neurodegenerative disease characterized by motor, cognitive and behavioural disturbances, there has been little empirical data examining what patients are most concerned about throughout the different stages of disease, which can span many years. Semi-structured face-to-face interviews were individually conducted with 31 people living with different stages of Huntington's, from pre-clinical gene carriers to advanced stage. We examined how often participants raised issues and concerns regarding the impact of Huntington's on everyday life. The Physical/functional theme hardly featured pre-clinically, but was strongly present from Stage 1, rose steadily and peaked at Stage 5. There were no significant changes between stages for the Emotional, Social, and Self themes that all featured across all stages, indicating that these issues were not raised more frequently over the course of the disease. Likewise, the more rarely mentioned Financial and Legal themes also remained similar across stages. However, the Cognitive theme only featured between Stages 1 and 4, and hardly at all pre-clinically and at Stage 5. These findings provide insight into patients' important and unique perspective and have implications for the management and development of interventions across the spectrum of HD stages. Section Editor: Aad Tibben, email: a.Tibben@lumc.nl PMID:21736564

  3. Comparison of staging methods for Hodgkin's disease in children

    SciTech Connect

    Lally, K.P.; Arnstein, M.; Siegel, S.; Miller, J.H.; Gilsanz, V.; Ettinger, L.; Atkinson, J.B.

    1986-10-01

    Potential long-term complications of radiotherapy and chemotherapy in the pediatric patient with Hodgkin's disease necessitate accurate staging. To determine the accuracy of abdominal computed tomography (CT) and gallium citrate Ga 67 scans in staging Hodgkin's disease, we reviewed the charts of all children with Hodgkin's disease seen at Childrens Hospital of Los Angeles from 1975 to 1985. Patients with pathologically proved stage IV disease (ie, bone marrow involvement) and those who only underwent staging laparotomy were excluded. A total of 40 children underwent staging by laparotomy and staging by abdominal CT and/or /sup 67/Ga scan. The CT and /sup 67/Ga scans were reviewed by radiologists in a blinded manner and compared with the results of a formal staging laparotomy. Of the 38 patients whose disease was staged with /sup 67/Ga scan, disease in ten was understaged and in four overstaged, for a 37% incorrect staging rate. Of the 14 patients whose disease was staged by CT scan, disease in three was understaged and in one overstaged, for a 29% incorrect staging rate. In view of the inaccuracy of noninvasive studies and the impact of incorrect staging on treatment, we recommend that a staging laparotomy be performed in all children with Hodgkin's disease who are not proved to have stage IV disease.

  4. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the...

  5. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the...

  6. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the...

  7. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the...

  8. 42 CFR 441.40 - End-stage renal disease.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false End-stage renal disease. 441.40 Section 441.40... General Provisions § 441.40 End-stage renal disease. FFP in expenditures for services described in subpart A of part 440 is available for facility treatment of end-stage renal disease only if the...

  9. [Advances in Surgical Treatment of Early Stage Non-small Cell Lung Cancer].

    PubMed

    Hu, Jian; Bao, Feichao

    2016-06-20

    Lung cancer is the leading cause of cancer-related deaths worldwide, computed tomography screening has made the disease spectrum of lung cancer shift from the previously predominating central local advanced squamous cell carcinoma to early stage lung adenocarcinoma represented by solitary pulmonary nodule, ground-glass opacity (GGO) and sub-centimeter nodule. This paper reviewed the recent proceeding in the surgical management of early stage lung cancer. PMID:27335305

  10. 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.

  11. End-stage renal disease and thrombophilia.

    PubMed

    Bauer, Alexander; Limperger, Verena; Nowak-Göttl, Ulrike

    2016-05-10

    Chronic kidney disease is an established risk factor for arterial and venous thromboembolism (TE). Whereas the overall risk of TE in moderately decreased kidney function is approximately 2.5-fold higher compared to patients with normal renal function, the risk increase is 5.5-fold in patients with severe renal dysfunction. In patients with renal dysfunction and arterial thrombosis (OR: 4.9), malignancy (OR: 5.8) surgery (OR: 14.0) or thrombophilia (OR: 4.3) the risk to suffer from venous TE is higher compared to the risk associated to the baseline renal dysfunction alone. The treatment options for end-stage renal diseases include hemodialysis, peritoneal dialysis and kidney transplantation. During all treatment modalities thrombotic complications have been described, namely catheter malfunction and shunt thrombosis in patients undergoing hemodialysis in up to 25% of patients, and TE, pulmonary embolism or graft vessel thrombosis in approximately 8% of patients. The reported incidence of reno-vascular thrombosis following renal transplantation leading to hemorrhagic infarction with organ rejection or organ loss varied between 2-12%. Keeping in mind the multifactorial etiology of TE in patients with kidney dysfunction a general screening for thrombophilia in this patient group is not indicated. Selected screening on an individual patient basis should be discussed if the family history for TE is positive or the patient itself had suffered one thrombosis before the onset of the renal disease or multiple TEs during hemodialysis or post kidney transplantation in patients waiting for living donor kidney transplantation. PMID:25639843

  12. Transcriptomic analysis of stage 1 versus advanced adult granulosa cell tumors

    PubMed Central

    Leung, Dilys; Gould, Jodee A.; Jobling, Tom; Fuller, Peter J.

    2016-01-01

    Ovarian granulosa cell tumors (GCT) are hormonally-active neoplasms characterized, in the adult-subtype, by a mutation in the FOXL2 gene (C134W). They exhibit an indolent course with an unexplained propensity for late recurrence; ∼80% of patients with aggressive, advanced stage tumors die from their disease; aside from surgery, therapeutic options are limited. To identify the molecular basis of advanced stage disease we have used whole transcriptome analysis of FOXL2 C134W mutation positive adult (a)GCT to identify genes that are differentially expressed between early (stage 1) and advanced (stage 3) aGCT. Transcriptome profiles for early (n = 6) and stage 3 (n = 6) aGCT, and for the aGCT-derived KGN, cell line identified 24 genes whose expression significantly differs between the early and stage 3 aGCT. Of these, 16 were more abundantly expressed in the stage 3 aGCT and 8 were higher in the stage 1 tumors. These changes were further examined for the genes which showed the greatest fold change: the cytokine CXCL14, microfibrillar-associated protein 5, insulin-like 3 and desmin. Gene Set Enrichment Analysis identified overexpression of genes on chromosome 7p15 which includes the homeobox A gene locus. The analysis therefore identifies a small number of genes with clearly discriminate patterns of expression arguing that the clinicopathological-derived distinction of the tumor stage is robust, whilst confirming the relative homogeneity of expression for many genes across the cohort and hence of aGCT. The expression profiles do however identify several overexpressed genes in both stage 1 and/or stage 3 aGCT which warrant further study as possible therapeutic targets. PMID:26893359

  13. Diagnosis, disease stage, and distress of Chinese cancer patients

    PubMed Central

    Huang, Boyan; Chen, Huiping; Deng, Yaotiao; Yi, Tingwu; Wang, Yuqing

    2016-01-01

    Background The objective is to assess how cancer patients know about their diagnosis what they know about their real stage, and the relationship between cancer stage and psychological distress. Methods A questionnaire including the Distress Thermometer was delivered to 422 cancer inpatients. Multivariate logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results Most of patients (68.7%) knew the bad news immediately after diagnosis. Half of patients knew their diagnosis directly from medical reports. Nearly one third of patients were informed by doctors. Cancer stages, which patients believed, differed significantly from their real disease stages (P<0.001). Over half of patients did not know their real disease stages. Patients with stage I–III cancer were more likely to know their real disease stage than patients with stage IV cancer (P<0.001). Distress scores of cancer patients were determined by the real cancer stage (P=0.012), not the stage which patients believed. Conclusions Although most of participants knew the bad news immediately after diagnosis, less than half of them knew their real disease stage. Patient with stage I–III cancer was more likely to know the real disease stage and had a DT score <4 than patient with stage IV disease. PMID:27004220

  14. Recent advances in oesophageal diseases.

    PubMed

    Al Dulaimi, David

    2014-01-01

    -quadrant biopsy protocol which may have led to an underestimation of BE prevalence. The review highlights an increasing incidence of esophageal adenocarcinoma in the West but unclear disease trend in Asia with inter-country variability. Similarly in Asian and Western countries BE is associated with the presence of hiatus hernia, advancing age, male gender, alcohol consumption, smoking, abdominal obesity and longer duration of gastro-esophageal reflux disease. The authors postulate that Helicobacter pylori infection, more prevalent in Asia than the West, may have a protective effect on BE. There is a need for larger, prospective studies to further clarify the disease pattern of BE in Asian countries. Clearly standardisation of the diagnostic process for BE is important to validate the differences in disease trends between Asian and Western countries. Kiadaliri AA. Gender and social disparities in esophagus cancer incidence in Iran, 2003-2009: a time trend province-level study.Asian Pac J Cancer Prev 2014;15(2):623-7 Esophageal cancer (EC) is a major cause of morbidity and mortality particuarly in Iran where the incidence rate exceeds the global average. An understanding of the factors influencing the province-specific incidence of EC in Iran is important to inform disease-prevention strategies and address health inequalities. This ecological study used cancer registry data to investigate the relationship between gender and social class and the incidence of EC in Iran at province-level between 2003 and 2009. The age standardised incidence rates (ASIR) of EC were greatest in the Northern provinces of Iran, specifically Razavi Khorasan in males and Kordestan in females. Overall the EC incidence did not significantly differ according to gender. Interestingly, during the study period the ASIR increased by 4.6% per year in females (p=0.08) and 6.5% per year in males (p=0.02). This may reflect increasing rates of establised risk factors for EC including obsesity and gastro

  15. Hyperphosphatemia in end-stage renal disease.

    PubMed

    Indridason, Olafur S; Quarles, L Darryl

    2002-07-01

    Hyperphosphatemia occurs universally in end-stage renal disease (ESRD) unless efforts are made to prevent positive phosphate balance. Positive phosphate balance results from the loss of renal elimination of phosphate and continued obligatory intestinal absorption of dietary phosphate. Increased efflux of phosphate from bone because of excess parathyroid hormone-mediated bone resorption can also contribute to increased serum phosphate concentrations in the setting of severe hyperparathyroidism. It is important to treat hyperphosphatemia because it contributes to the pathogenesis of hyperparathyroidism, vascular calcifications, and increased cardiovascular mortality in ESRD patients. Attaining a neutral phosphate balance, which is the key to the management of hyperphosphatemia in ESRD, is a challenge. Control of phosphorus depends on its removal during dialysis and the limitation of gastrointestinal absorption by dietary phosphate restriction and chelation of phosphate. Knowledge of the quantitative aspects of phosphate balance is useful in optimizing our use of phosphate binders, dialysis frequency, and vitamin D sterols. The development of new phosphate binders and efforts to find new ways to inhibit gastrointestinal absorption of phosphate will lead to improvements in the control of serum phosphate levels in ESRD. PMID:12203200

  16. Magnetic Resonance Imaging Features of the Nigrostriatal System: Biomarkers of Parkinson’s Disease Stages?

    PubMed Central

    Hopes, Lucie; Grolez, Guillaume; Moreau, Caroline; Lopes, Renaud; Ryckewaert, Gilles; Carrière, Nicolas; Auger, Florent; Laloux, Charlotte; Petrault, Maud; Devedjian, Jean-Christophe; Bordet, Regis; Defebvre, Luc; Jissendi, Patrice; Delmaire, Christine; Devos, David

    2016-01-01

    Introduction Magnetic resonance imaging (MRI) can be used to identify biomarkers in Parkinson’s disease (PD); R2* values reflect iron content related to high levels of oxidative stress, whereas volume and/or shape changes reflect neuronal death. We sought to assess iron overload in the nigrostriatal system and characterize its relationship with focal and overall atrophy of the striatum in the pivotal stages of PD. Methods Twenty controls and 70 PD patients at different disease stages (untreated de novo patients, treated early-stage patients and advanced-stage patients with L-dopa-related motor complications) were included in the study. We determined the R2* values in the substantia nigra, putamen and caudate nucleus, together with striatal volume and shape analysis. We also measured R2* in an acute MPTP mouse model and in a longitudinal follow-up two years later in the early-stage PD patients. Results The R2* values in the substantia nigra, putamen and caudate nucleus were significantly higher in de novo PD patients than in controls. Early-stage patients displayed significantly higher R2* values in the substantia nigra (with changes in striatal shape), relative to de novo patients. Measurements after a two-year follow-up in early-stage patients and characterization of the acute MPTP mouse model confirmed that R2* changed rapidly with disease progression. Advanced-stage patients displayed significant atrophy of striatum, relative to earlier disease stages. Conclusion Each pivotal stage in PD appears to be characterized by putative nigrostriatal MRI biomarkers: iron overload at the de novo stage, striatal shape changes at early-stage disease and generalized striatal atrophy at advanced disease. PMID:27035571

  17. NASA Bioreactors Advance Disease Treatments

    NASA Technical Reports Server (NTRS)

    2009-01-01

    the body. Experiments conducted by Johnson scientist Dr. Thomas Goodwin proved that the NASA bioreactor could successfully cultivate cells using simulated microgravity, resulting in three-dimensional tissues that more closely approximate those in the body. Further experiments conducted on space shuttle missions and by Wolf as an astronaut on the Mir space station demonstrated that the bioreactor s effects were even further expanded in space, resulting in remarkable levels of tissue formation. While the bioreactor may one day culture red blood cells for injured astronauts or single-celled organisms like algae as food or oxygen producers for a Mars colony, the technology s cell growth capability offers significant opportunities for terrestrial medical research right now. A small Texas company is taking advantage of the NASA technology to advance promising treatment applications for diseases both common and obscure.

  18. Advanced technologies for rocket single-stage-to-orbit vehicles

    NASA Technical Reports Server (NTRS)

    Wilhite, Alan W.; Bush, Lance B.; Cruz, Christopher I.; Lepsch, Roger A.; Morris, W. Douglas; Stanley, Douglas O.; Wurster, Kathryn E.

    1991-01-01

    A single-stage-to-orbit vertical takeoff/horizontal landing rocket vehicle was studied to determine the benefits of advanced technology. Advanced technologies that were included in the study were variable mixture ratio oxygen/hydrogen rocket engines and materials, structures, and subsystem technologies currently being developed in the National Aero-Space Plane Program. The application of advanced technology results in an 85 percent reduction in vehicle dry weight. With advanced materials, an external thermal protection system, like the Space Shuttle tiles, was not required. Compared to an all-airbreathing horizontal takeoff/horizontal landing vehicle using the same advanced technologies and mission requirements, the rocket vehicle is lighter in dry weight and has fewer subsystems. To increase reliability and safety, operational features were included in the rocket vehicle-robust subsystems, 5 percent additional margin, no slush hydrogen, fail-operational with an engine out, and a crew escape module. The resulting vehicle grew in dry weight and was still lower in dry weight than the airbreathing vehicle.

  19. Analgesia for patients with advanced disease: 2

    PubMed Central

    Hall, E; Sykes, N

    2004-01-01

    The first article in this series explored epidemiology and patterns of pain in advanced disease, non-pharmacological treatments, and the use of opioids to manage pain. This second article examines the use of non-opioid drugs and anaesthetic interventions for pain relief in advanced disease. It also discusses an approach to managing analgesia in dying patients and finally looks at future developments. PMID:15082837

  20. Advanced Low-Noise Research Fan Stage Design

    NASA Technical Reports Server (NTRS)

    Neubert, Robert; Bock, Larry; Malmborg, Eric; Owen-Peer, William

    1997-01-01

    This report describes the design of the Advanced Low-Noise Research Fan stage. The fan is a variable pitch design, which is designed at the cruise pitch condition. Relative to the cruise setting, the blade is closed at takeoff and opened for reverse thrust operation. The fan stage is a split flow design with fan exit guide vanes (FEGVs) and core stators. The fan stage design is combined with a nacelle and engine core duct to form a powered fan/nacelle subscale model. This model is intended for use in combined aerodynamic, acoustic, and structural testing in a wind tunnel. The fan has an outer diameter of 22 in. and a hub-to-tip of 0.426 in., which allows the use of existing NASA fan and cowl force balance and rig drive systems. The design parameters were selected to permit valid acoustic and aerodynamic comparisons with the Pratt & Whitney (P&W) 17- and 22-in. rigs previously tested under NASA contract. The fan stage design is described in detail. The results of the design axisymmetric and Navier-Stokes aerodynamic analysis are presented at the critical design conditions. The structural analysis of the fan rotor and attachment is included. The blade and attachment are predicted to have adequate low-cycle fatigue life and an acceptable operating range without resonant stress or flutter. The stage was acoustically designed with airfoil counts in the FEGV and core stator to minimize noise. A fan/FEGV tone analysis developed separately under NASA contract was used to determine the optimum airfoil counts. The fan stage was matched to the existing nacelle, designed under the previous P&W low-noise contract, to form a fan/nacelle model for wind tunnel testing. It is an axisymmetric nacelle for convenience in testing and analysis. Previous testing confirmed that the nacelle performed as required at various aircraft operating conditions.

  1. Palliative care in end-stage kidney disease.

    PubMed

    Fassett, Robert G; Robertson, Iain K; Mace, Rose; Youl, Loren; Challenor, Sarah; Bull, Rosalind

    2011-01-01

    Patients with end-stage kidney disease have significantly increased morbidity and mortality. While greater attention has been focused on advanced care planning, end-of-life decisions, conservative therapy and withdrawal from dialysis these must be supported by adequate palliative care incorporating symptom control. With the increase in the elderly, with their inherent comorbidities, accepted onto dialysis, patients, their nephrologists, families and multidisciplinary teams, are often faced with end-of-life decisions and the provision of palliative care. While dialysis may offer a better quality and quantity of life compared with conservative management, this may not always be the case; hence the patient is entitled to be well-informed of all options and potential outcomes before embarking on such therapy. They should be assured of adequate symptom control and palliative care whichever option is selected. No randomized controlled trials have been conducted in this area and only a small number of observational studies provide guidance; thus predicting which patients will have poor outcomes is problematic. Those undertaking dialysis may benefit from being fully aware of their choices between active and conservative treatment should their functional status seriously deteriorate and this should be shared with caregivers. This clarifies treatment pathways and reduces the ambiguity surrounding decision making. If conservative therapy or withdrawal from dialysis is chosen, each should be supported by palliative care. The objective of this review is to summarize published studies and evidence-based guidelines, core curricula, position statements, standards and tools in palliative care in end-stage kidney disease. PMID:21175971

  2. Physical Activity in Patients With Advanced-Stage Cancer: A Systematic Review of the Literature

    PubMed Central

    Albrecht, Tara A.; Taylor, Ann Gill

    2014-01-01

    The importance of physical activity for chronic disease prevention and management has become generally well accepted. The number of research interventions and publications examining the benefits of physical activity for patients with cancer has been rising steadily. However, much of that research has focused on the impact of physical activity either prior to or early in the cancer diagnosis, treatment, and survivorship process. Research focusing on the effects of physical activity, specifically for patients with advanced-stage cancer and poorer prognostic outcomes, has been addressed only recently. The purpose of this article is to examine the state of the science for physical activity in the advanced-stage disease subset of the cancer population. Exercise in a variety of intensities and forms, including yoga, walking, biking, and swimming, has many health benefits for people, including those diagnosed with cancer. Research has shown that, for people with cancer (including advanced-stage cancer), exercise can decrease anxiety, stress, and depression while improving levels of pain, fatigue, shortness of breath, constipation, and insomnia. People diagnosed with cancer should discuss with their oncologist safe, easy ways they can incorporate exercise into their daily lives. PMID:22641322

  3. Physical activity in patients with advanced-stage cancer: a systematic review of the literature.

    PubMed

    Albrecht, Tara A; Taylor, Ann Gill

    2012-06-01

    The importance of physical activity for chronic disease prevention and management has become generally well accepted. The number of research interventions and publications examining the benefits of physical activity for patients with cancer has been rising steadily. However, much of that research has focused on the impact of physical activity either prior to or early in the cancer diagnosis, treatment, and survivorship process. Research focusing on the effects of physical activity, specifically for patients with advanced-stage cancer and poorer prognostic outcomes, has been addressed only recently. The purpose of this article is to examine the state of the science for physical activity in the advanced-stage disease subset of the cancer population. Exercise in a variety of intensities and forms, including yoga, walking, biking, and swimming, has many health benefits for people, including those diagnosed with cancer. Research has shown that, for people with cancer (including advanced-stage cancer), exercise can decrease anxiety, stress, and depression while improving levels of pain, fatigue, shortness of breath, constipation, and insomnia. People diagnosed with cancer should discuss with their oncologist safe, easy ways they can incorporate exercise into their daily lives. PMID:22641322

  4. P08: Somatostatin analogs plus prednisone in aggressive histotype and advanced stage of thymic epithelial tumors

    PubMed Central

    Ottaviano, Margaret; Damiano, Vincenzo; Nappi, Lucia; Rescigno, Pasquale; Marino, Mirella; Del Vecchio, Silvana; Tucci, Irene; von Arx, Claudia; Palumbo, Giuliano; Palmieri, Giovannella

    2015-01-01

    Background Thymic epithelial tumors (TETs) are rare neoplasms characterized by histological variability and different expression at the molecular level. Several biological agents have been evaluated in TETs in small phase II trials. Efficacy of octreotide/lanreotide with or without prednisone in TETs OctreoScan positive has been widely demonstrated in thymoma, but no clearly in thymic carcinoma. Methods Twelve patients (five men, seven women; median age 47 years; range, 27–70 years) with advanced stage disease according to the Masaoka-Koga staging system (seven with IVa stage; five with IVb stage), and aggressive histotype according to WHO classification, revised by central review (two B2/B3; five B3; one B3/thymic carcinoma; four thymic carcinoma) were enrolled in this monocentric referral study. All the patients showed a progressive disease according to RECIST 1.1 criteria to previous conventional chemotherapeutic regimens platinum or not platinum-based. All the patients performed OctreoScan. The schedule includes administration of long-acting analog octreotide (30 mg/every 28 days intramuscularly) plus prednisone 0.2 mg/kg/day until progression of disease was documented. Overall response rate and toxicity were evaluated. Results The median time to progression was 6 months (range, 3–24 months), the overall response rate was 74.9%, particularly three patients (25%) obtained stable disease; four patients (33.3%) partial response; two patients (16.6%) complete response; three patients (25%) progression disease. One patient with Good Syndrome interrupted treatment after 6 months for infection disease. One patient has been lost to follow-up after 24 months of treatment. One patient died after progression disease for PRCA. Treatment was generally well tolerated with acceptable toxicity: no symptomatic cholelithiasis (one patient), grade 1 diarrhea (two patients) hyperglycemia (one patient). One patient with thymic carcinoma and IVB stage had PS improvement from 2

  5. Obstetric outcomes in women with end-stage renal disease on chronic dialysis: a review

    PubMed Central

    Yang, L Y; Thia, E W H; Tan, L K

    2010-01-01

    Pregnancies in women on chronic dialysis for end-stage renal disease are high risk, but outcomes appear to have improved with increasing experience and advances in dialysis care. This paper reviews the existing data on outcomes in such pregnancies to enable evidence-based preconception counselling and anticipation of antenatal complications.

  6. Methods for Surgical Targeting of the STN in Early-Stage Parkinson's Disease.

    PubMed

    Camalier, Corrie R; Konrad, Peter E; Gill, Chandler E; Kao, Chris; Remple, Michael R; Nasr, Hana M; Davis, Thomas L; Hedera, Peter; Phibbs, Fenna T; Molinari, Anna L; Neimat, Joseph S; Charles, David

    2014-01-01

    Patients with Parkinson's disease (PD) experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN) with surgical access. While locating STN in advanced disease patients (Hoehn-Yahr Stage III or IV) is well understood and routinely performed at many centers in the context of deep brain stimulation surgery, the ability to identify this nucleus in early-stage patients has not previously been explored in a sizeable cohort. We report surgical methods used to target the STN in 15 patients with early PD (Hoehn-Yahr Stage II), using a combination of image guided surgery, microelectrode recordings, and clinical responses to macrostimulation of the region surrounding the STN. Measures of electrophysiology (firing rates and root mean squared activity) have previously been found to be lower than in later-stage patients, however, the patterns of electrophysiology seen and dopamimetic macrostimulation effects are qualitatively similar to those seen in advanced stages. Our experience with surgical implantation of Parkinson's patients with minimal motor symptoms suggest that it remains possible to accurately target the STN in early-stage PD using traditional methods. PMID:24678307

  7. Surgical techniques for advanced stage pelvic organ prolapse.

    PubMed

    Brown, Douglas N; Strauchon, Christopher; Gonzalez, Hector; Gruber, Daniel

    2016-02-01

    Pelvic organ prolapse is an extremely common condition, with approximately 12% of women requiring surgical correction over their lifetime. This manuscript reviews the most recent literature regarding the comparative efficacy of various surgical repair techniques in the treatment of advanced stage pelvic organ prolapse. Uterosacral ligament suspension has similar anatomic and subjective outcomes when compared to sacrospinous ligament fixation at 12 months and is considered to be equally effective. The use of transvaginal mesh has been shown to be superior to native tissue vaginal repairs with respect to anatomic outcomes but at the cost of a higher complication rate. Minimally invasive sacrocolpopexy appears to be equivalent to abdominal sacrocolpopexy (ASC). Robot-assisted sacrocolpopexy (RSC) and laparoscopic sacrocolpopexy (LSC) appear as effective as abdominal sacrocolpopexy, however, prospective studies of comparing long-term outcomes of ASC, LSC, and RSC in relation to health care costs is paramount in the near future. Surgical correction of advanced pelvic organ prolapse can be accomplished via a variety of proven techniques. Selection of the correct surgical approach is a complex decision process and involves a multitude of factors. When deciding on the most suitable surgical intervention, the chosen route must be individualized for each patient taking into account the specific risks and benefits of each procedure. PMID:26448444

  8. Comprehension of Complex Discourse in Different Stages of Huntington's Disease

    ERIC Educational Resources Information Center

    Saldert, Charlotta; Fors, Angelika; Stroberg, Sofia; Hartelius, Lena

    2010-01-01

    Background: Huntington's disease not only affects motor speech control, but also may have an impact on the ability to produce and understand language in communication. Aims: The ability to comprehend basic and complex discourse was investigated in three different stages of Huntington's disease. Methods & Procedures: In this experimental group…

  9. Advances in SPECT in evaluating coronary disease.

    PubMed

    Kelion, Andrew D

    2014-07-01

    Myocardial perfusion scintigraphy is the longest established of the functional imaging investigations for patients with known or suspected coronary artery disease. This article describes recent technical and clinical advances that are ensuring that the technique remains relevant some 40 years after its first introduction. PMID:25040515

  10. Does aggressive surgical resection improve survival in advanced stage 3 and 4 neuroblastoma? A systematic review and meta-analysis.

    PubMed

    Mullassery, Dhanya; Farrelly, Paul; Losty, Paul D

    2014-11-01

    The role of surgery in the management of advanced staged neuroblastoma (NBL) is controversial. A systematic review and meta-analysis is reported to address robust evidence for curative "gross total tumor resection" (GTR) in Stage 3 and Stage 4 neuroblastoma. Studies were identified using Medline, Embase, and Cochrane databases using pre-specified search terms. Primary outcomes were 5-year overall (OS) and disease-free survival (DFS) after GTR and subtotal resection (STR) in Stage 3 or 4 NBL. Data were analyzed using Review Manager. The Mantel-Haenszel method and a random effects model was utilized to calculate odds ratios (95% CI). Fifteen studies (five Stage 3 and 13 Stage 4) met full inclusion criteria. The pooled odds ratio for 5 year OS in Stage 3 following GTR compared to STR was 2.4 (95% CI 1.19-4.85). In Stage 4 disease, the pooled odds ratio for 5 year overall survival (OS) following GTR compared to STR was 1.65 (95% CI 0.96-1.91); a pooled odds ratio for 5 year DFS following GTR compared to STR was 1.55 (95% CI 1.12-2.14). A clear survival benefit is shown for GTR over STR in Stage 3 NBL only. Though some advantage can be demonstrated for GTR as defined by DFS in Stage 4 NBL GTR did not significantly improve OS in Stage 4 disease. PMID:25247398

  11. Laboratory Diagnosis of Lyme Disease - Advances and Challenges

    PubMed Central

    Marques, Adriana R.

    2015-01-01

    Synopsis Lyme disease is the most common tick-borne illness in the United States and Europe. Culture for B. burgdorferi is not routinely available. PCR can be helpful in synovial fluid of patients with Lyme arthritis. The majority of laboratory tests performed for the diagnosis of Lyme disease are based on detection of the antibody responses against B. burgdorferi in serum. The sensitivity of antibody-based tests increases with the duration of the infection, and patients who present very early in their illness are more likely to have a negative result. Patients with erythema migrans should receive treatment based on the clinical diagnosis. The current Centers for Disease Control and Prevention recommendations for serodiagnosis of Lyme disease is a 2-tiered algorithm, an initial enzyme immunoassay (EIA) followed by separate IgM and IgG Western blots if the first EIA test result is positive or borderline. The IgM result is only relevant for patients with illness duration of less than a month. While the 2-tier algorithm works well for later stages of the infection, it has low sensitivity during early infection. A major advance has been the discovery of VlsE and its C6 peptide as markers of antibody response in Lyme disease. Specificity is extremely important in Lyme disease testing, as the majority of tests are being performed in situations with low likelihood of the disease, a situation where a positive result is more likely to be a false positive. Current assays do not distinguish between active and inactive infection, and patients may continue to be seropositive for years. There is a need to simplify the testing algorithm for Lyme disease, improving sensitivity in early disease while still maintaining high specificity and providing information about the stage of infection. The development of a point of care assay and biomarkers for active infection would be major advances for the field. PMID:25999225

  12. End stage renal disease and its dental management.

    PubMed

    Sharma, Dileep C G; Pradeep, A R

    2007-01-01

    In recent years, the incidence of renal disease has become more common in middle-aged to geriatric patients. This has led to greater exposure of dental surgeons to patients with renal disease and on hemodialysis. This article highlights the clinical features of patients with end-stage renal disease, the oral manifestations and the precautions to be taken while managing them in a dental setting. PMID:17378316

  13. Advances in Identifying Beryllium Sensitization and Disease

    PubMed Central

    Middleton, Dan; Kowalski, Peter

    2010-01-01

    Beryllium is a lightweight metal with unique qualities related to stiffness, corrosion resistance, and conductivity. While there are many useful applications, researchers in the 1930s and l940s linked beryllium exposure to a progressive occupational lung disease. Acute beryllium disease is a pulmonary irritant response to high exposure levels, whereas chronic beryllium disease (CBD) typically results from a hypersensitivity response to lower exposure levels. A blood test, the beryllium lymphocyte proliferation test (BeLPT), was an important advance in identifying individuals who are sensitized to beryllium (BeS) and thus at risk for developing CBD. While there is no true “gold standard” for BeS, basic epidemiologic concepts have been used to advance our understanding of the different screening algorithms. PMID:20195436

  14. Peyronie's disease: review and recent advances.

    PubMed

    Langston, Joshua P; Carson, Culley C

    2014-08-01

    Peyronie's disease is an incurable, sexually debilitating fibrotic disease of the penis that results in penile curvature, coital failure, and significant psychological stress for patients and their partners. Appropriate treatment should be individualized and tailored to the patient's goals and expectations, disease history, physical exam findings, and erectile function. While medical treatments exist, there is little evidence to support their use. High-quality data supporting more recent advances in injectable therapies, interferon α-2b and collagenase clostridium histolyticum, show great promise for their application. Once the disease has stabilized, surgical correction is also an excellent option for patients with significant Peyronie's disease accompanied by functional impairment. Outcomes are satisfactory when proper treatment decisions are made, with the goal being expected return to normal sexual function following treatment. PMID:24984940

  15. The experience of living with advanced-stage cancer: a thematic synthesis of the literature.

    PubMed

    García-Rueda, N; Carvajal Valcárcel, A; Saracíbar-Razquin, M; Arantzamendi Solabarrieta, M

    2016-07-01

    The aim of the study was to understand the experience of people living with advanced-stage cancer through literature. The search included The Cochrane Library, PubMed, PsycInfo, CINAHL and Cuiden. Thirteen studies were included. A qualitative meta-synthesis was conducted. One thread emerged from the thematic synthesis: the desire to live as normally as possible, despite being aware of the proximity of death. Three themes also emerged: "a process that is unique" with its four sub-themes; "support network" and "health context," each of them having two sub-themes. This study concludes that living with advanced-stage cancer is a unique and complex process which has both positive and negative aspects. The review provides a comprehensive view of the experience, which considers the importance of the support network and the health context in which the person lives. In this study, "normalcy" is the adjustment to the new reality and living as closely as possible to the way one lived before the disease, while developing a new relationship with being finite and death. A better understanding of the experience of living with advanced-stage cancer will help health professionals to identify the needs of the patients in order to plan individual, high-quality care. PMID:27297131

  16. Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer.

    PubMed

    Panis, C; Victorino, V J; Herrera, A C S A; Freitas, L F; De Rossi, T; Campos, F C; Simão, A N Colado; Barbosa, D S; Pinge-Filho, P; Cecchini, R; Cecchini, A L

    2012-06-01

    Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-α, IL-1β, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8-isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure

  17. Questions and Answers for Transplant Candidates about Model for End-Stage Liver Disease (MELD) and Pediatric End-Stage ....

    MedlinePlus

    ... needs a liver transplant most urgently. The MELD (Model for End Stage Liver Disease) is used for ... and the PELD (Pediatric End Stage Liver Disease Model) is used for patients age 11 and younger. ...

  18. Subclinical cardiopulmonary dysfunction in stage 3 chronic kidney disease

    PubMed Central

    Nelson, Alexander; Otto, James; Whittle, John; Stephens, Robert C M; Martin, Daniel S; Prowle, John R

    2016-01-01

    Objective Reduced exercise capacity is well documented in end-stage chronic kidney disease (CKD), preceded by changes in cardiac morphology in CKD stage 3. However, it is unknown whether subclinical cardiopulmonary dysfunction occurs in CKD stage 3 independently of heart failure. Methods Prospective observational cross-sectional study of exercise capacity assessed by cardiopulmonary exercise testing in 993 preoperative patients. Primary outcome was peak oxygen consumption (VO2peak). Anaerobic threshold (AT), oxygen pulse and exercise-evoked measures of autonomic function were analysed, controlling for CKD stage 3, age, gender, diabetes mellitus and hypertension. Results CKD stage 3 was present in 93/993 (9.97%) patients. Diabetes mellitus (RR 2.49 (95% CI 1.59 to 3.89); p<0.001), and hypertension (RR 3.20 (95% CI 2.04 to 5.03); p<0.001)) were more common in CKD stage 3. Cardiac failure (RR 0.83 (95% CI 0.30 to 2.24); p=0.70) and ischaemic heart disease (RR 1.40 (95% CI 0.97 to 2.02); p=0.09) were not more common in CKD stage 3. Patients with CKD stage 3 had lower predicted VO2peak (mean difference: 6% (95% CI 1% to 11%); p=0.02), lower peak heart rate (mean difference:9 bpm (95% CI 3 to 14); p=0.03)), lower AT (mean difference: 1.1 mL/min/kg (95% CI 0.4 to 1.7); p<0.001) and impaired heart rate recovery (mean difference: 4 bpm (95% CI 1 to 7); p<0.001)). Conclusions Subclinical cardiopulmonary dysfunction in CKD stage 3 is common. This study suggests that maladaptive cardiovascular/autonomic dysfunction may be established in CKD stage 3, preceding pathophysiology reported in end-stage CKD. PMID:27127638

  19. Advances in microfluidics in combating infectious diseases.

    PubMed

    Tay, Andy; Pavesi, Andrea; Yazdi, Saeed Rismani; Lim, Chwee Teck; Warkiani, Majid Ebrahimi

    2016-01-01

    One of the important pursuits in science and engineering research today is to develop low-cost and user-friendly technologies to improve the health of people. Over the past decade, research efforts in microfluidics have been made to develop methods that can facilitate low-cost diagnosis of infectious diseases, especially in resource-poor settings. Here, we provide an overview of the recent advances in microfluidic devices for point-of-care (POC) diagnostics for infectious diseases and emphasis is placed on malaria, sepsis and AIDS/HIV. Other infectious diseases such as SARS, tuberculosis, and dengue are also briefly discussed. These infectious diseases are chosen as they contribute the most to disability-adjusted life-years (DALYs) lost according to the World Health Organization (WHO). The current state of research in this area is evaluated and projection toward future applications and accompanying challenges are also discussed. PMID:26854743

  20. Advanced stages of PD: interventional therapies and related patient-centered care.

    PubMed

    Krüger, Rejko; Hilker, Rüdiger; Winkler, Christian; Lorrain, Michael; Hahne, Matthias; Redecker, Christoph; Lingor, Paul; Jost, Wolfgang H

    2016-01-01

    During the last decades, symptomatic treatment of motor symptoms of Parkinson's disease (PD) improved continuously and is reflected by long-range independency of the patient during the disease course. However, advanced stages of PD still represent an important challenge to patients, caregivers and treating physicians. In patients with advanced PD, interventional therapy strategies are increasingly applied. These device-related treatment strategies using pump-based continuous dopaminergic stimulation (CDS) or deep brain stimulation (DBS) opened new treatment options especially if motor complications predominate. Well-designed clinical studies on these interventional therapeutic approaches provided class 1 evidence for the efficacy of DBS and CDS in advanced PD and opened new perspectives for their use in earlier disease stages also. Therefore, careful selection of patients amenable to the (semi)invasive therapy options becomes more and more important and requires an interdisciplinary setting that accounts for (i) optimal patient information and awareness, (ii) selection of best individual treatment modality, (iii) training of relatives and caregivers, (iv) management of complications, and (v) follow-up care. Here, we address these topics by summarizing current state-of-the-art in patient selection, providing specificities of treatment options and troubleshooting, and defining steps towards an optimized patient-centered care. Interventional therapies pioneer in the area of individualized treatment approaches for PD, and may be complemented in the future by biomarker-based improved stratification and by closed-loop systems for adaptive therapeutic strategies. In the present review, we summarize the proceedings of an Expert Workshop on Parkinson's disease held on November 22, 2014 in Frankfurt, Germany. PMID:26138439

  1. Advanced Querying Features for Disease Surveillance Systems

    PubMed Central

    Hashemian, Mohammad R.

    2010-01-01

    Most automated disease surveillance systems notify users of increases in the prevalence of reports in syndrome categories and allow users to view patient level data related to those increases. Occasionally, a more dynamic level of control is required to properly detect an emerging disease in a community. Dynamic querying features are invaluable when using existing surveillance systems to investigate outbreaks of newly emergent diseases or to identify cases of reportable diseases within data being captured for surveillance. The objective of the Advance Querying Tool (AQT) is to build a more flexible query interface for most web-based disease surveillance systems. This interface allows users to define and build their query as if they were writing a logical expression for a mathematical computation. The AQT allows users to develop, investigate, save, and share complex case definitions. It provides a flexible interface that accommodates both advanced and novice users, checks the validity of the expression as it is built, and marks errors for users. PMID:23569575

  2. Sialadenosis in Patients with Advanced Liver Disease

    PubMed Central

    Close, John M.; Eghtesad, Bijan

    2009-01-01

    Sialadenosis (sialosis) has been associated most often with alcoholic liver disease and alcoholic cirrhosis, but a number of nutritional deficiencies, diabetes, and bulimia have also been reported to result in sialadenosis. The aim of this study was to determine the prevalence of sialadenosis in patients with advanced liver disease. Patients in the study group consisted of 300 candidates for liver transplantation. Types of liver disease in subjects with clinical evidence of sialadenosis were compared with diagnoses in cases who had no manifestations of sialadenosis. The data were analyzed for significant association. Sialadenosis was found in 28 of the 300 subjects (9.3%). Among these 28 cases, 11 (39.3%) had alcoholic cirrhosis. The remaining 17 (60.7%) had eight other types of liver disease. There was no significant association between sialadenosis and alcoholic cirrhosis (P = 0.389). These findings suggest that both alcoholic and non-alcoholic cirrhosis may lead to the development of sialadenosis. Advanced liver disease is accompanied by multiple nutritional deficiencies which may be exacerbated by alcohol. Similar metabolic abnormalities may occur in patients with diabetes or bulimia. Malnutrition has been associated with autonomic neuropathy, the pathogenic mechanism that has been proposed for sialadenosis. PMID:19644542

  3. An approach to dyspnea in advanced disease.

    PubMed Central

    Gallagher, Romayne

    2003-01-01

    INTRODUCTION: To describe an approach to assessment and treatment of dyspnea. SOURCES OF INFORMATION: New level I evidence can guide management of dyspnea in advanced illness. Assessment and use of adjuvant medications and oxygen relies on level II and III evidence. MAIN MESSAGE: Opioids are first-line therapy for managing dyspnea in advanced illness. They are safe and effective in reducing shortness of breath. Neuroleptics are useful adjuvant medications. Evidence does not support use of oxygen for every patient experiencing dyspnea; it should be tried for patients who do not benefit from first-line medications and nonmedicinal therapies. CONCLUSION: Opioids relieve dyspnea and are indicated as first-line treatment for dyspnea arising from advanced disease of any cause. PMID:14708926

  4. Bronchial involvement in advanced stage lymphangioleiomyomatosis: histopathologic and molecular analyses.

    PubMed

    Hayashi, Takuo; Kumasaka, Toshio; Mitani, Keiko; Okada, Yoshinori; Kondo, Takashi; Date, Hiroshi; Chen, Fengshi; Oto, Takahiro; Miyoshi, Shinichiro; Shiraishi, Takeshi; Iwasaki, Akinori; Hara, Kieko; Saito, Tsuyoshi; Ando, Katsutoshi; Kobayashi, Etsuko; Gunji-Niitsu, Yoko; Kunogi, Makiko; Takahashi, Kazuhisa; Yao, Takashi; Seyama, Kuniaki

    2016-04-01

    Lymphangioleiomyomatosis (LAM), a rare progressive disease that almost exclusively affects women, is characterized by pulmonary cysts and neoplastic proliferation of smooth muscle-like cells (LAM cells). Airflow obstruction is a physiologic consequence that is commonly observed in LAM and has been attributed to narrowing of peripheral airways. However, histopathologic examinations of the entire airway have been precluded by the limited availability of such specimens. Here, we used explanted lung tissues from 30 LAM patients for a thorough histologic analysis with a special emphasis on the bronchi. We found bronchial involvement by LAM cells and lymphatics in all patients examined. Furthermore, a moderate to severe degree of chronic inflammation (73%), goblet cell hyperplasia (97%), squamous cell metaplasia (83%) of the epithelium, and thickening of basal lamina (93%) were identified in the bronchi. Because LAM cells are transformed by the functional loss of the TSC genes leading to a hyperactivated mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, we confirmed the expression of phospho-p70S6K, phospho-S6, phospho-4E-BP1, and vascular endothelial growth factor (VEGF)-D in LAM cells from all of the patients examined. In contrast, no protein expression of hypoxia-inducible factor 1α, a downstream molecule indicative of mTORC1 activation and leading to VEGF production, was detected in any patient. Our study indicates that late-stage LAM patients commonly have bronchi involved by the proliferation of both LAM cells and lymphatics and that chronic inflammation complicated their disease. Furthermore, the up-regulation of hypoxia-inducible factor 1α, a common event in mTORC1-driven tumor cells, does not occur in LAM cells and plays no role in VEGF-D expression in LAM cells. PMID:26997436

  5. Advanced medical interventions in pleural disease.

    PubMed

    Bhatnagar, Rahul; Corcoran, John P; Maldonado, Fabien; Feller-Kopman, David; Janssen, Julius; Astoul, Philippe; Rahman, Najib M

    2016-06-01

    The burden of a number of pleural diseases continues to increase internationally. Although many pleural procedures have historically been the domain of interventional radiologists or thoracic surgeons, in recent years, there has been a marked expansion in the techniques available to the pulmonologist. This has been due in part to both technological advancements and a greater recognition that pleural disease is an important subspecialty of respiratory medicine. This article summarises the important literature relating to a number of advanced pleural interventions, including medical thoracoscopy, the insertion and use of indwelling pleural catheters, pleural manometry, point-of-care thoracic ultrasound, and image-guided closed pleural biopsy. We also aim to inform the reader regarding the latest updates to more established procedures such as chemical pleurodesis, thoracentesis and the management of chest drains, drawing on contemporary data from recent randomised trials. Finally, we shall look to explore the challenges faced by those practicing pleural medicine, especially relating to training, as well as possible future directions for the use and expansion of advanced medical interventions in pleural disease. PMID:27246597

  6. Current stage in inflammatory bowel disease: What is next?

    PubMed Central

    Gómez-Gómez, Gonzalo Jesús; Masedo, Ángeles; Yela, Carmen; Martínez-Montiel, Maria del Pilar; Casís, Begoña

    2015-01-01

    In recent years, the incidence of inflammatory bowel disease (IBD) has been on the rise, extending to countries where it was infrequent in the past. As a result, the gap between high and low incidence countries is decreasing. The disease, therefore, has an important economic impact on the healthcare system. Advances in recent years in pharmacogenetics and clinical pharmacology have allowed for the development of treatment strategies adjusted to the patient profile. Concurrently, new drugs aimed at inflammatory targets have been developed that may expand future treatment options. This review examines advances in the optimization of existing drug treatments and the development of novel treatment options for IBD. PMID:26525013

  7. Advanced Strategies for End-Stage Heart Failure: Combining Regenerative Approaches with LVAD, a New Horizon?

    PubMed Central

    Tseng, Cheyenne C. S.; Ramjankhan, Faiz Z.; de Jonge, Nicolaas; Chamuleau, Steven A. J.

    2015-01-01

    Despite the improved treatment of cardiovascular diseases, the population with end-stage heart failure (HF) is progressively growing. The scarcity of the gold standard therapy, heart transplantation, demands novel therapeutic approaches. For patients awaiting transplantation, ventricular-assist devices have been of great benefit on survival. To allow explantation of the assist device and obviate heart transplantation, sufficient and durable myocardial recovery is necessary. However, explant rates so far are low. Combining mechanical circulatory support with regenerative therapies such as cell (-based) therapy and biomaterials might give rise to improved long-term results. Although synergistic effects are suggested with mechanical support and stem cell therapy, evidence in both preclinical and clinical setting is lacking. This review focuses on advanced and innovative strategies for the treatment of end-stage HF and furthermore appraises clinical experience with combined strategies. PMID:25905105

  8. Symmetric Dimethylarginine: Improving the Diagnosis and Staging of Chronic Kidney Disease in Small Animals.

    PubMed

    Relford, Roberta; Robertson, Jane; Clements, Celeste

    2016-11-01

    Chronic kidney disease (CKD) is a common condition in cats and dogs, traditionally diagnosed after substantial loss of kidney function when serum creatinine concentrations increase. Symmetric dimethylarginine (SDMA) is a sensitive circulating kidney biomarker whose concentrations increase earlier than creatinine as glomerular filtration rate decreases. Unlike creatinine SDMA is unaffected by lean body mass. The IDEXX SDMA test introduces a clinically relevant and reliable tool for the diagnosis and management of kidney disease. SDMA has been provisionally incorporated into the International Renal Interest Society guidelines for CKD to aid staging and targeted treatment of early and advanced disease. PMID:27499007

  9. Management of glycemia in diabetic patients with stage IV and V chronic kidney disease.

    PubMed

    Roche-Recinos, Andrea; Charlap, Esti; Markell, Mariana

    2015-05-01

    Diabetic kidney disease is a leading cause of end-stage kidney disease worldwide. Data suggest that prevention of progression to end-stage may lie in excellent blood glucose control; however, as kidney disease progresses, the risk of hypoglycemia increases, due to unpredictable insulin kinetics and altered pharmacokinetics of hypoglycemic agents. In addition, whole classes of hypoglycemic agents become contraindicated and regimens must be adjusted for declining kidney function. There is no consensus regarding the best therapy for the patient with advanced chronic kidney disease. In the best of circumstances, the care of these patients will involve intensive monitoring, with the input of a team of health care providers creating a coordinated care plan, including dietary advice and a drug regimen tailored to the specific issues faced by the individual patient. An open dialogue is necessary at all times, as patients may become frustrated and attempt self-treatment using over the counter alternatives. PMID:25772643

  10. Molecular advances in genetic skin diseases.

    PubMed

    Siegel, Dawn H; Howard, Renee

    2002-08-01

    The genes for several genetic skin diseases have been identified in recent years. This development improves diagnostic capabilities and genetic counseling, and investigators can now turn to the molecular mechanisms involved in the pathogenesis of these diseases. The identification of the causative genes has led to the generation of mouse models for some genetic skin diseases. A study of the keratin 10 deficient mouse, a model for epidermolytic hyperkeratosis, and a mouse model for Bloom syndrome are reviewed in this article. Several studies also evaluate the relation between genotype and phenotype. In this article, the clinical findings and molecular advances in tuberous sclerosis complex, neurofibromatosis type 1, Bloom syndrome, epidermolytic hyperkeratosis, X-linked ichthyosis, Netherton syndrome, and Hermansky-Pudlak syndrome are reviewed. PMID:12130905

  11. Selecting the best strategy of treatment in newly diagnosed advanced-stage ovarian cancer patients

    PubMed Central

    Minig, Lucas; Zorrero, Cristina; Iserte, Pablo Padilla; Poveda, Andres

    2015-01-01

    Although it is assumed that the combination of chemotherapy and radical surgery should be indicated in all newly diagnosed advanced-stage ovarian cancer patients, one of the main raised questions is how to select the best strategy of initial treatment in this group of patients, neoadjuvant chemotherapy followed by interval debulking surgery or primary debulking surgery followed by adjuvant chemotherapy. The selection criteria to offer one strategy over the other as well as a stepwise patient selection for initial treatment are described. Selecting the best strategy of treatment in newly diagnosed advanced stage ovarian cancer patients is a multifactorial and multidisciplinary decision. Several factors should be taken into consideration: (1) the disease factor, related to the extension and localization of the disease as well as tumor biology; (2) the patient factor, associated with patient age, poor performance status, and co-morbidities; and (3) institutional infrastructure factor, related to the lack of prolonged operative time, an appropriate surgical armamentarium, as well as well-equipped intensive care units with well-trained personnel. PMID:26713279

  12. Survival Analysis of Patients with End Stage Renal Disease

    NASA Astrophysics Data System (ADS)

    Urrutia, J. D.; Gayo, W. S.; Bautista, L. A.; Baccay, E. B.

    2015-06-01

    This paper provides a survival analysis of End Stage Renal Disease (ESRD) under Kaplan-Meier Estimates and Weibull Distribution. The data were obtained from the records of V. L. MakabaliMemorial Hospital with respect to time t (patient's age), covariates such as developed secondary disease (Pulmonary Congestion and Cardiovascular Disease), gender, and the event of interest: the death of ESRD patients. Survival and hazard rates were estimated using NCSS for Weibull Distribution and SPSS for Kaplan-Meier Estimates. These lead to the same conclusion that hazard rate increases and survival rate decreases of ESRD patient diagnosed with Pulmonary Congestion, Cardiovascular Disease and both diseases with respect to time. It also shows that female patients have a greater risk of death compared to males. The probability risk was given the equation R = 1 — e-H(t) where e-H(t) is the survival function, H(t) the cumulative hazard function which was created using Cox-Regression.

  13. The news advances on Alzheimer's disease's therapeutics.

    PubMed

    Sun, H-Q; Zhang, X; Huang, W-J; Chen, W-W

    2016-05-01

    Alzheimer's disease (AD) is a multifaceted disorder, characterized by the failure of memory and dementia. AD affects mostly elder above 65 years of age and is confirmed by post-mortem detection in the brain, of extracellular senile plaques of amyloid-beta (Aβ) and intracellular neurofibrillary tangles. These pathological hallmarks appear in the brain when the disease is already installed. The difficulty of earlier diagnosis and possibly, the poor understanding of the disease etiology, limit the benefits afforded by available treatments. Indeed, several putative drugs resulting from thorough investigations in preclinical studies have failed to produce clinical results, suggesting the development of further therapeutic alternatives. Recently, the regular practice of physical activity has been shown as one of the effective preventive or curative mean against AD. This finding rekindles the debate on the place of the intrinsic vascular component in the AD pathogenesis which is an aspect of the disease often considered as a distinct pathology. A new integrative conception of the disease may offer an advantage to current therapies which may gain in potency if combined in a multi-target manner to yield true improvements. This review will revisit the pathophysiology of AD and discuss the advanced therapeutics currently in use. PMID:27212186

  14. Coats’ Disease: Very Long-Term Outcome After Early Stage Conventional Treatment

    PubMed Central

    Perrone, Salvatore; Rossetti, Alberto; Sportiello, Patrick; Mirabelli, Pierfrancesco; Cimatti, Pierangela; Doro, Daniele

    2016-01-01

    Purpose: To report on the outcome of conventional therapy in patients with Coats’ disease. Methods: Retrospective analysis of the charts of thirteen patients with Coats’ disease. Results: Mean age of 9 male (70%) and 4 female (30%) patients was 17.7 (range, 5-33) years; one female had bilateral disease. Eleven eyes with retinal telangiectasia and exudation were treated with argon laser photocoagulation alone or photocoagulation associated with cryotherapy; the mean follow up was 32.5 (range,17-41) years. In four eyes without foveal involvement (stage 2a) the mean presenting visual acuity (VA) remained at 0.8 or improved, whereas poor VA in seven stage 2b eyes deteriorated minimally over time. In one and two of the three eyes with total retinal detachment, phthisis or neovascular glaucoma ensued. Conclusion: About three decades after conventional treatment of Coats’ disease stage 2a, treated eyes maintained good VA, and stage 2b eyes did not progress to advanced stages. PMID:27014383

  15. Canine stage 1 periodontal disease: a latent pathology.

    PubMed

    Whyte, A; Bonastre, C; Monteagudo, L V; Les, F; Obon, J; Whyte, J; Tejedor, M T

    2014-07-01

    To evaluate the potential health issues associated with periodontal disease (PD) in dogs, 1004 teeth from 25 dogs were examined. The dogs were randomly selected, aged 2-14 years, and had at least 95% of their teeth at the first PD stage. Significant positive correlations between plaque grade (PG) and gum inflammation, gingival regression, periodontal pocket, age and serum alanine aminotransferase (ALT) activity were identified. In contrast, PG was negatively correlated to total platelet count. Altogether, these findings suggest that prevention and therapy at the first PD stages can have an important impact on the general health condition of dogs. PMID:24878263

  16. Are Early Relapses in Advanced-Stage Ovarian Cancer Doomed to a Poor Prognosis?

    PubMed Central

    Vidal, Fabien; Guerby, Paul; Luyckx, Mathieu; Haddad, Pascale; Stoeckle, Eberhard; Morice, Philippe; Leblanc, Eric; Lecuru, Fabrice; Daraï, Emile; Classe, Jean Marc; Pomel, Christophe; Filleron, Thomas; Ferron, Gwenael; Querleu, Denis; Rafii, Arash

    2016-01-01

    Objective Early recurrence (ER) after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients. Study Design We analyzed a multi-centric database of 527 FIGO stage IIIC and IV ovarian cancer patients. We defined patients relapsing within 12 months as ER and investigated using Cox logistic regression the prognostic factors in ER group. We subsequently divided ER patients into good and poor prognosis groups according to a lower or higher overall survival (OS) at 12 months after relapse and determined parameters associated to poor prognosis. Results The median follow up was 49 months. One hundred and thirty eight patients recurred within 12 months. OS and Disease Free Survival (DFS) were 24.6 and 8.6 months, respectively, in this group of patients. Among the ER patients, 73 had a poor prognosis with an OS after relapse below 12 months (mean OS = 5.2 months) and 65 survived after one year (mean OS = 26.9 months). Residual disease (RD) after debulking surgery and mucinous histological subtype negatively impacted prognosis (HR = 1.758, p = 0.017 and HR = 8.641, p = 0.001 respectively). The relative risk of death within 12 months following relapse in ER patients was 1.61 according to RD status. However, RD did not affect DFS (HR = 0.889, p = 0.5). Conclusion ER in advanced-stage ovarian cancer does not inevitably portend a short-term poor prognosis. RD status after initial cytoreduction strongly modulates OS, that gives additional support to the concept of maximum surgical effort even in patients who will experience early recurrence. The heterogeneity in outcomes within the ER group suggests a role for tumor biology in addition to classical clinical parameters. PMID:26820579

  17. An overview of advance care planning for patients with advanced chronic kidney disease: The basics.

    PubMed

    Wasylynuk, Betty Ann; Davison, Sara N

    2016-01-01

    As the number of Canadians living with end-stage kidney disease (ESKD) continues to grow, even higher numbers are living with advanced chronic kidney disease (CKD). Many of these people will eventually require renal replacement therapy (RRT), either dialysis or transplantation. More than 50% of patients starting RRT today are aged 65 or older, with the fastest growing group being patients 75 years and older. Despite advances to dialysis technology and dialysis care, the mortality rates remain high and dialysis patients' end-of-life care may not align with their preferences or values. Advance care planning (ACP) is an essential component of quality comprehensive kidney care. Kidney care teams develop strong relationships with their patients and are well positioned to integrate ACP into routine kidney care. This article defines ACP, outlines the essential components of ACP, and discusses the benefits, challenges, and special considerations of ACP. By enhancing the kidney care team's understanding of ACP, this article aims to assist in integrating ACP into routine kidney care for patients with advanced CKD. PMID:27215058

  18. Scientifically advanced solutions for chestnut ink disease.

    PubMed

    Choupina, Altino Branco; Estevinho, Letícia; Martins, Ivone M

    2014-05-01

    On the north regions of Portugal and Spain, the Castanea sativa Mill. culture is extremely important. The biggest productivity and yield break occurs due to the ink disease, the causal agent being the oomycete Phytophthora cinnamomi. This oomycete is also responsible for the decline of many other plant species in Europe and worldwide. P. cinnamomi and Phytophthora cambivora are considered, by the generality of the authors, as the C. sativa ink disease causal agents. Most Phytophthora species secrete large amounts of elicitins, a group of unique highly conserved proteins that are able to induce hypersensitive response (HR) and enhances plant defense responses in a systemic acquired resistance (SAR) manner against infection by different pathogens. Some other proteins involved in mechanisms of infection by P. cinnamomi were identified by our group: endo-1,3-beta-glucanase (complete cds); exo-glucanase (partial cds) responsible by adhesion, penetration, and colonization of host tissues; glucanase inhibitor protein (GIP) (complete cds) responsible by the suppression of host defense responses; necrosis-inducing Phytophthora protein 1 (NPP1) (partial cds); and transglutaminase (partial cds) which inducts defense responses and disease-like symptoms. In this mini-review, we present some scientifically advanced solutions that can contribute to the resolution of ink disease. PMID:24622889

  19. A unique description of stage IV extranodal marginal zone lymphoma (EMZL) in an adolescent associated with gamma heavy chain disease.

    PubMed

    Mittal, Nupur; Zhu, Bing; Gaitonde, Sujata; Lu, Yang; Schmidt, Mary Lou

    2015-05-01

    Extranodal Marginal zone lymphoma (EMZL) is a rare, usually localized disease in children. Advanced stage EMZL in adults is considered incurable, with prolonged remissions after chemotherapy. Gamma heavy chain disease (γHCD) is a rare disease of adults associated with lympho-proliferative processes with no comparable reports in children. A case of stage-IV EMZL with γHCD in an adolescent is discussed including treatment with Bendamustine plus Rituximab. The patient remains disease free 18 months from diagnosis. This case highlights necessity for careful diagnostic work-up to identify indolent lymphomas in children which may respond to less toxic chemotherapy than used for common pediatric lymphomas. PMID:25663537

  20. Depression in the early stages of Huntington disease

    PubMed Central

    Epping, Eric A; Paulsen, Jane S

    2012-01-01

    Summary Huntington disease (HD) has traditionally been considered a movement disorder, but cognitive and psychiatric symptoms also prominently factor into its clinical presentation. Depression is one of the most common psychiatric disturbances in HD, with its prevalence highest in manifest disease during stage 2, but it is also present during the illness prodrome (the period before manifestation of motor symptoms). Identification and treatment of depression in individuals with the HD mutation is an essential part of clinical management in this population, especially owing to the high risk of suicide. This article summarizes what is currently known about the presentation and treatment of depression in the early stages of HD and provides advice to clinicians treating this population. PMID:22942903

  1. Psychiatric Symptoms in the Initial Motor Stage of Parkinson's Disease.

    PubMed

    Stanković, Iva; Stefanova, Elka; Tomić, Aleksandra; Lukić, Milica Ječmenica; Stojković, Tanja; Marković, Vladana; Stojmenović, Gorana Mandić; Kresojević, Nikola; Svetel, Marina; Kostić, Vladimir

    2016-01-01

    Neuropsychiatric symptoms (NPS) are common in Parkinson's disease (PD). The aim of this study was to estimate the correlates of NPS in patients with PD in the initial motor stage of the disease (hemiparkinsonism). A total of 111 patients with PD and 105 healthy control participants were assessed. Patients with PD experienced apathy, depression, and anxiety more frequently compared with healthy controls. Sleep disturbances occurred commonly in early PD patients. Patients with PD and mild cognitive impairment (MCI) had depression and anxiety more frequently, but not apathy, compared with patients with PD without MCI. The results of this study confirm a high burden of NPS even in the earliest motor stage of PD. PMID:26900739

  2. Cross-View Neuroimage Pattern Analysis in Alzheimer's Disease Staging

    PubMed Central

    Liu, Sidong; Cai, Weidong; Pujol, Sonia; Kikinis, Ron; Feng, Dagan D.

    2016-01-01

    The research on staging of pre-symptomatic and prodromal phase of neurological disorders, e.g., Alzheimer's disease (AD), is essential for prevention of dementia. New strategies for AD staging with a focus on early detection, are demanded to optimize potential efficacy of disease-modifying therapies that can halt or slow the disease progression. Recently, neuroimaging are increasingly used as additional research-based markers to detect AD onset and predict conversion of MCI and normal control (NC) to AD. Researchers have proposed a variety of neuroimaging biomarkers to characterize the patterns of the pathology of AD and MCI, and suggested that multi-view neuroimaging biomarkers could lead to better performance than single-view biomarkers in AD staging. However, it is still unclear what leads to such synergy and how to preserve or maximize. In an attempt to answer these questions, we proposed a cross-view pattern analysis framework for investigating the synergy between different neuroimaging biomarkers. We quantitatively analyzed nine types of biomarkers derived from FDG-PET and T1-MRI, and evaluated their performance in a task of classifying AD, MCI, and NC subjects obtained from the ADNI baseline cohort. The experiment results showed that these biomarkers could depict the pathology of AD from different perspectives, and output distinct patterns that are significantly associated with the disease progression. Most importantly, we found that these features could be separated into clusters, each depicting a particular aspect; and the inter-cluster features could always achieve better performance than the intra-cluster features in AD staging. PMID:26941639

  3. Stroke and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Management Across Kidney Disease Stages

    PubMed Central

    Weiner, Daniel E.; Dad, Taimur

    2015-01-01

    Summary Cerebrovascular disease and stroke are very common at all stages of chronic kidney disease (CKD), likely representing both shared risk factors as well as synergy among risk factors. More subtle ischemic brain lesions may be particularly common in the CKD population, with subtle manifestations including cognitive impairment. For individuals with nondialysis CKD, the prevention, approach to, diagnosis, and management of stroke is similar to the general, non-CKD population. For individuals with end-stage renal disease, far less is known regarding the prevention of stroke. Stroke prophylaxis using warfarin in dialysis patients with atrial fibrillation in particular remains of uncertain benefit. End-stage renal disease patients can be managed aggressively in the setting of acute stroke. Outcomes after stroke at all stages of CKD are poor, and improving these outcomes should be the subject of future clinical trials. PMID:26355250

  4. Advances in the prevention of Alzheimer's Disease

    PubMed Central

    Mangialasche, Francesca; Kivipelto, Miia

    2015-01-01

    Alzheimer's disease (AD), the leading cause of dementia, has reached epidemic proportions, with major social, medical and economical burdens. With no currently available curative treatments, both the World Health Organization and the G8 Dementia Summit recently identified dementia and AD prevention as a major public health priority. Dementia and AD have a wide range of risk factors (genetic, vascular/metabolic and lifestyle-related), which often co-occur and thus interact with each other. Previous intervention efforts aimed at preventing dementia and AD focused on the management of single risk factors, with relatively modest findings. Also, the effect of risk factors depends on age at exposure, indicating that the timing of preventive interventions needs to be carefully considered. In view of the complex multifactorial nature of AD, as well as its long pre-clinical (asymptomatic) phase, interventions simultaneously targeting multiple risk factors and disease mechanisms at an early stage of the disease are most likely to be effective. Three large European multidomain prevention trials have been launched with the goal of preventing cognitive decline, dementia and AD in older adults with different risk profiles. Pharmacological trials are also shifting towards prevention of Alzheimer dementia, by targeting at-risk individuals prior to the onset of cognitive symptoms. The current review will summarize and discuss the evidence on risk and protective factors from observational studies, ongoing lifestyle-related and pharmacological randomized controlled trials (RCTs), as well as future directions for dementia and AD prevention. PMID:26097723

  5. Advanced two-stage incineration: Research and development

    SciTech Connect

    Rehmat, A.; Khinkis, M.

    1991-01-01

    IGT is currently developing a two-stage fluidized-bed/cyclonic agglomerating incineration system that is based on combining the fluidized-bed agglomeration/incineration and cyclonic combustion technologies, both of which have been developed individually at IGT over many years. This combination has resulted in a unique and extremely flexible incinerator for solid, liquid, and gaseous wastes. The system can operate over a wide range of conditions in the first stage, from low temperature (desorption) to high temperature (agglomeration), including gasification of high-Btu wastes. In the combined system, solid, liquid, and gaseous organic wastes are expected to be easily and efficiently destroyed (>99.99% destruction and removal efficiency (DRE)) while solid inorganic contaminants are expected to be contained within a glassy matrix, rendering them benign and suitable for disposal in an ordinary landfill. The development of the two-stage incinerator is a culmination of extensive research and development efforts on each stage of the incinerator. A variety of data obtained for both stages includes agglomeration of ash, incineration and reclamation of used blast grit and foundry sand, partial combustion of carbonaceous fuels, in-situ desulfurization, combustion of low-Btu gases, incineration of industrial wastewater, and incineration of carbon tetrachloride.

  6. Clinical pathologic correlations of Lyme disease by stage.

    PubMed

    Duray, P H; Steere, A C

    1988-01-01

    Lyme disease is capable of producing a wide variety of clinical pathologic conditions and lesions having in common histologic features of collagen-vascular disease. The plasma cell is an omnipotent inflammatory responder in most tissues involved by Lyme disease, ranging from relatively acute to lesions that have gone on for years. Vascular thickening also seems to be prominent, and in the dermis is accompanied by scleroderma-like collagen expansion. The disease in some ways resembles the responses seen in lupus erythematosus such as mild cerebritis with lymphocytes and plasma cells in the leptomeninges. Lymphoplasmacytic panniculitis of Lyme disease resembles lupus profundus, both in the infiltrate and the plasma cell-blood vessel relationship. The onion skin thickened vessels of the synovia resemble the vessels of lupus spleens, while the scleradermoid thickening of the dermis and various skin lesions of stage III Lyme disease suggest a collagen-vascular disorder. Finally, the perivascular lymphoid infiltrate in clinical myositis does not differ from that seen in polymyositis or dermatomyositis. All of these histologic derangements suggest immunologic damage in response to persistence of the spirochete, however few in number. PMID:2847622

  7. Advanced clinical insights & practice: ischemic heart disease.

    PubMed

    Benner, Randall W; Zavarella, Matthew S

    2008-03-01

    This issue sees the debut of a new series of continuing education articles. The series, Advanced Clinical Insights & Practice, is designed to provide continuing education to an ever-expanding realm of paramedicine that needs more of it: the critical care transport paramedic. Secondly, and equally important, are the benefits that can be reaped by other certification levels reading this feature. For EMT-Basics and Intermediates, it will provide a great enhancement to your core knowledge, although most of the interventions discussed will be beyond your traditional scope. For paramedics, it will augment both your pathophysiological understanding and clinical assessment/management skills of diseases and injuries discussed. Ultimately though, it is hoped that anyone who reads these articles will become a better clinician. The next article will appear in the July issue. PMID:18814637

  8. Potential Biomarkers of the Earliest Clinical Stages of Parkinson's Disease

    PubMed Central

    Alieva, Anelya Kh.; Filatova, Elena V.; Karabanov, Aleksey V.; Illarioshkin, Sergey N.; Slominsky, Petr A.; Shadrina, Maria I.

    2015-01-01

    Parkinson's disease (PD) is a widespread neurodegenerative disorder. Despite the intensive studies of this pathology, in general, the picture of the etiopathogenesis has still not been clarified fully. To understand better the mechanisms underlying the pathogenesis of PD, we analyzed the expression of 10 genes in the peripheral blood of treated and untreated patients with PD. 35 untreated patients with PD and 12 treated patients with Parkinson's disease (Hoehn and Yahr scores 1-2) were studied. An analysis of the mRNA levels of ATP13A2, PARK2, PARK7, PINK1, LRRK2, SNCA, ALDH1A1, PDHB, PPARGC1A, and ZNF746 genes in the peripheral blood of patients was carried out using reverse transcription followed by real-time PCR. A statistically significant and specific increase by more than 1.5-fold in the expression of the ATP13A2, PARK7, and ZNF746 genes was observed in patients with PD. Based on these results, it can be suggested that the upregulation of the mRNA levels of ATP13A2, PARK7, and ZNF746 in untreated patients in the earliest clinical stages can also be observed in the preclinical stages of PD, and that these genes can be considered as potential biomarkers of the preclinical stage of PD. PMID:26483988

  9. Pulp Stone, Haemodialysis, End-stage Renal Disease, Carotid Atherosclerosis

    PubMed Central

    Patil, Santosh; Sinha, Nidhi

    2013-01-01

    Objectives: The aim of this study was to determine the relationship between the presence of pulp calcification and carotid artery calcification on the dental panoramic radiographs in End Stage Renal Disease (ESRD) patients who were on haemodialysis. Methods: A total of 112 End Stage Renal Disease (ESRD) patients on who were haemodialysis participated in this study. The periapical and the panoramic radiographs for all the patients were evaluated for the presence or absence of the narrowing of the dental pulps and for pulp stones in the pulp chambers and the pulp canals. The panoramic radiographs were also evaluated to determine the carotid calcification. Results: Carotid calcifications were detected in none of the patients. 84 (74.99%) patients had dental pulp narrowing, and 38 (33.92%) patients had pulp stones. There was no statistical correlation between pulp narrowing and Carotid Artery Calcification (CAC) in the haemodialysis patient group. There was also no statistical correlation between pulp stones and CAC in the haemodialysis patients. Conclusion: However, the incidental finding of CAC on a panoramic radiograph can provide life-saving information for the vascular disease patients, but in the present study, no significant relationship was found between the presence of the pulpal calcification and CAC in the ESRD patients who were on haemodialysis. Therefore, the presence of pulp calcification does not seem to serve as a diagnostic marker for carotid atherosclerosis. PMID:23905147

  10. Lung microbiota across age and disease stage in cystic fibrosis.

    PubMed

    Coburn, Bryan; Wang, Pauline W; Diaz Caballero, Julio; Clark, Shawn T; Brahma, Vijaya; Donaldson, Sylva; Zhang, Yu; Surendra, Anu; Gong, Yunchen; Elizabeth Tullis, D; Yau, Yvonne C W; Waters, Valerie J; Hwang, David M; Guttman, David S

    2015-01-01

    Understanding the significance of bacterial species that colonize and persist in cystic fibrosis (CF) airways requires a detailed examination of bacterial community structure across a broad range of age and disease stage. We used 16S ribosomal RNA sequencing to characterize the lung microbiota in 269 CF patients spanning a 60 year age range, including 76 pediatric samples from patients of age 4-17, and a broad cross-section of disease status to identify features of bacterial community structure and their relationship to disease stage and age. The CF lung microbiota shows significant inter-individual variability in community structure, composition and diversity. The core microbiota consists of five genera - Streptococcus, Prevotella, Rothia, Veillonella and Actinomyces. CF-associated pathogens such as Pseudomonas, Burkholderia, Stenotrophomonas and Achromobacter are less prevalent than core genera, but have a strong tendency to dominate the bacterial community when present. Community diversity and lung function are greatest in patients less than 10 years of age and lower in older age groups, plateauing at approximately age 25. Lower community diversity correlates with worse lung function in a multivariate regression model. Infection by Pseudomonas correlates with age-associated trends in community diversity and lung function. PMID:25974282

  11. Lung microbiota across age and disease stage in cystic fibrosis

    PubMed Central

    Coburn, Bryan; Wang, Pauline W.; Diaz Caballero, Julio; Clark, Shawn T.; Brahma, Vijaya; Donaldson, Sylva; Zhang, Yu; Surendra, Anu; Gong, Yunchen; Elizabeth Tullis, D.; Yau, Yvonne C. W.; Waters, Valerie J.; Hwang, David M.; Guttman, David S.

    2015-01-01

    Understanding the significance of bacterial species that colonize and persist in cystic fibrosis (CF) airways requires a detailed examination of bacterial community structure across a broad range of age and disease stage. We used 16S ribosomal RNA sequencing to characterize the lung microbiota in 269 CF patients spanning a 60 year age range, including 76 pediatric samples from patients of age 4–17, and a broad cross-section of disease status to identify features of bacterial community structure and their relationship to disease stage and age. The CF lung microbiota shows significant inter-individual variability in community structure, composition and diversity. The core microbiota consists of five genera - Streptococcus, Prevotella, Rothia, Veillonella and Actinomyces. CF-associated pathogens such as Pseudomonas, Burkholderia, Stenotrophomonas and Achromobacter are less prevalent than core genera, but have a strong tendency to dominate the bacterial community when present. Community diversity and lung function are greatest in patients less than 10 years of age and lower in older age groups, plateauing at approximately age 25. Lower community diversity correlates with worse lung function in a multivariate regression model. Infection by Pseudomonas correlates with age-associated trends in community diversity and lung function. PMID:25974282

  12. Liver ultrasound elastography: More than staging the disease

    PubMed Central

    Gherlan, George S

    2015-01-01

    Ultrasound elastography is perhaps the most important breakthrough in the evolution of ultrasonography in the last 15 years. Since transient elastography was introduced, many other methods have been developed and became more and more widely available. The value of ultrasound elastography in staging a chronic liver disease has been established by numerous studies. There have been many studies that have shown that using liver elastography it is possible to predict the presence of the complications of cirrhosis: portal hypertension, presence of esophageal varices (and even their risk of bleeding) and hepatocellular carcinoma. It has been shown that liver elastography can predict the progression of liver fibrosis and also the survival (hepatic events - free) of the patients with chronic liver diseases. These are the real quests of the clinicians, this is the ultimate scope of any medical investigation - to predict the outcome of a patient and to help making therapeutic decisions. I brought together only a small amount of the data that has already been written on this subject to support my affirmation that liver ultrasound elastography is more than a tool for staging the liver disease, but it is also comparable to a crystal ball which in the hands of a skilled clinician can reveal the future of the patient and can help to improve this future. PMID:26140079

  13. Liver ultrasound elastography: More than staging the disease.

    PubMed

    Gherlan, George S

    2015-06-28

    Ultrasound elastography is perhaps the most important breakthrough in the evolution of ultrasonography in the last 15 years. Since transient elastography was introduced, many other methods have been developed and became more and more widely available. The value of ultrasound elastography in staging a chronic liver disease has been established by numerous studies. There have been many studies that have shown that using liver elastography it is possible to predict the presence of the complications of cirrhosis: portal hypertension, presence of esophageal varices (and even their risk of bleeding) and hepatocellular carcinoma. It has been shown that liver elastography can predict the progression of liver fibrosis and also the survival (hepatic events - free) of the patients with chronic liver diseases. These are the real quests of the clinicians, this is the ultimate scope of any medical investigation - to predict the outcome of a patient and to help making therapeutic decisions. I brought together only a small amount of the data that has already been written on this subject to support my affirmation that liver ultrasound elastography is more than a tool for staging the liver disease, but it is also comparable to a crystal ball which in the hands of a skilled clinician can reveal the future of the patient and can help to improve this future. PMID:26140079

  14. Computed tomography, lymphography, and staging laparotomy: correlations in initial staging of Hodgkin disease

    SciTech Connect

    Castellino, R.A.; Hoppe, R.T.; Blank, N.; Young, S.W.; Neumann, C.; Rosenberg, S.A.; Kaplan, H.S.

    1984-07-01

    One hundred twenty-one patients with newly diagnosed, previously untreated Hodgkin disease underwent abdominal and pelvic computed tomographic (CT) scanning and bipedal lymphography. These studies were followed by staging laparotomy, which included biopsy of the liver, retroperitoneal and mesenteric lymph nodes, and splenectomy. Correlation of the results of the imaging studies with the histopathologic diagnoses revealed a small - but significant - increased accuracy of lymphography compared with CT in assessing the retroperitoneal lymph nodes. The theoretical advantages of CT scanning in detecting lymphomatous deposits in lymph nodes about the celiac axis and the mesentery, or in the liver and spleen, were not confirmed.

  15. Multivariate analysis of prognostic factors in early stage Hodgkin's disease

    SciTech Connect

    Tubiana, M.; Henry-Amar, M.; van der Werf-Messing, B.; Henry, J.; Abbatucci, J.; Burgers, M.; Hayat, M.; Somers, R.; Laugier, A.; Carde, P.

    1985-01-01

    A multivariate analysis of the prognostic factors was carried out with a Cox model on 1,139 patients with clinical Stage I + II Hodgkin's disease included in three controlled clinical trials. The following indicators had been prospectively registered: aged, sex, systemic symptoms, erythrocyte sedimentation, results of staging laparotomy when performed, as well as the date and type of treatment. A linear logistic analysis showed that most of the indicators are interrelated. This emphasizes the necessity of a multivariate analysis in order to assess the independent influence of each of them. The two main prognostic indicators for relapse-free survival are systemic symptoms and/or ESR and number of involved areas. The only significant factor for survival after relapse is age. Sex has a small but significant influence on relapse-free survival. The relative influence of each indicator varies with the type of treatment and these variations may help in understanding the biologic significance of the indicators.

  16. Limited health literacy in advanced kidney disease.

    PubMed

    Taylor, Dominic M; Bradley, John A; Bradley, Clare; Draper, Heather; Johnson, Rachel; Metcalfe, Wendy; Oniscu, Gabriel; Robb, Matthew; Tomson, Charles; Watson, Chris; Ravanan, Rommel; Roderick, Paul

    2016-09-01

    Limited health literacy may reduce the ability of patients with advanced kidney disease to understand their disease and treatment and take part in shared decision making. In dialysis and transplant patients, limited health literacy has been associated with low socioeconomic status, comorbidity, and mortality. Here, we investigated the prevalence and associations of limited health literacy using data from the United Kingdom-wide Access to Transplantation and Transplant Outcome Measures (ATTOM) program. Incident dialysis, incident transplant, and transplant wait-listed patients ages 18 to 75 were recruited from 2011 to 2013 and data were collected from patient questionnaires and case notes. A score >2 in the Single-Item Literacy Screener was used to define limited health literacy. Univariate and multivariate analyses were performed to identify patient factors associated with limited health literacy. We studied 6842 patients, 2621 were incident dialysis, 1959 were wait-listed, and 2262 were incident transplant. Limited health literacy prevalence was 20%, 15%, and 12% in each group, respectively. Limited health literacy was independently associated with low socioeconomic status, poor English fluency, and comorbidity. However, transplant wait-listing, preemptive transplantation, and live-donor transplantation were associated with increasing health literacy. PMID:27521115

  17. Point pressure sensitivity in early stage Parkinson's disease.

    PubMed

    Doty, Richard L; Gandhi, Shifa S; Osman, Allen; Hurtig, Howard I; Pawasarat, Ian; Beals, Evan; Chung, Inna; Dubroff, Jacob; Newberg, Andrew; Ying, Gui-Shang; Leon-Sarmiento, Fidias E

    2015-01-01

    A number of sensory changes occur in the earliest stages of Parkinson's disease (PD), some of which precede the expression of the classic motor phenotype by years (e.g., olfactory dysfunction). Whether point pressure sensitivity (PPS), a cutaneous measure of light touch mediated by myelinated Aβ fibers, is altered in early PD is not clear. Prior studies on this point are contradictory and are based on non-forced-choice threshold tests that confound the sensitivity measure with the response criterion. While α-synuclein pathology, a defining feature of PD, is present in the skin of PD patients, it is restricted to unmyelinated nerve fibers, suggesting PPS may be spared in this disease. We determined PPS thresholds using a state-of-the-art forced-choice staircase threshold test paradigm in 29 early stage PD patients and 29 matched controls at 11 body sites: the center of the forehead and the left and right forearms, index fingers, palms, medial soles of the feet, and plantar halluces. The patients were tested, in counterbalanced sessions, both on and off dopamine-related medications (DRMs). PPS was not influenced by PD and did not correlate with DRM l-DOPA equivalents, scores on the Unified Parkinson's Disease Rating Scale, side of the major motor disturbances, or SPECT imaging of the striatal dopamine transporter, as measured by technetium-99m TRODAT. However, PPS thresholds were lower on the left than on the right side of the body (p=0.008) and on the upper extremities relative to the toes and feet (ps<0.0001). Positive correlations were evident among the thresholds obtained across all body sectors, even though disparate regions of the body differed in terms of absolute sensitivity. This study indicates that PPS is not influenced in early stage PD regardless of whether patients are on or off DRMs. PMID:25447476

  18. Medicare end stage renal disease population, 1982-87

    PubMed Central

    Breidenbaugh, M. Zermain; Sarsitis, Ida M.; Milam, Roger A.

    1990-01-01

    A synopsis is given between the relationship of the number of end stage renal disease (ESRD) patients to the total Medicare population and their associated expenditures. The aging trend within the ESRD population is examined in terms of enrollment statistics and incidence (new cases) counts. Also, longitudinal trends in expenditures, program enrollment, and incidence of ESRD are included. Findings indicate that the ESRD population is growing at a faster rate than Medicare in general. Further, within ESRD, the beneficiary population is aging. PMID:10113457

  19. Staging laparoscopy improves treatment decision-making for advanced gastric cancer

    PubMed Central

    Hu, Yan-Feng; Deng, Zhen-Wei; Liu, Hao; Mou, Ting-Yu; Chen, Tao; Lu, Xin; Wang, Da; Yu, Jiang; Li, Guo-Xin

    2016-01-01

    AIM: To evaluate the clinical value of staging laparoscopy in treatment decision-making for advanced gastric cancer (GC). METHODS: Clinical data of 582 patients with advanced GC were retrospectively analyzed. All patients underwent staging laparoscopy. The strength of agreement between computed tomography (CT) stage, endoscopic ultrasound (EUS) stage, laparoscopic stage, and final stage were determined by weighted Kappa statistic (Kw). The number of patients with treatment decision-changes was counted. A χ2 test was used to analyze the correlation between peritoneal metastasis or positive cytology and clinical characteristics. RESULTS: Among the 582 patients, the distributions of pathological T classifications were T2/3 (153, 26.3%), T4a (262, 45.0%), and T4b (167, 28.7%). Treatment plans for 211 (36.3%) patients were changed after staging laparoscopy was performed. Two (10.5%) of 19 patients in M1 regained the opportunity for potential radical resection by staging laparoscopy. Unnecessary laparotomy was avoided in 71 (12.2%) patients. The strength of agreement between preoperative T stage and final T stage was in almost perfect agreement (Kw = 0.838; 95% confidence interval (CI): 0.803-0.872; P < 0.05) for staging laparoscopy; compared with CT and EUS, which was in fair agreement. The strength of agreement between preoperative M stage and final M stage was in almost perfect agreement (Kw = 0.990; 95% CI: 0.977-1.000; P < 0.05) for staging laparoscopy; compared with CT, which was in slight agreement. Multivariate analysis revealed that tumor size (≥ 40 mm), depth of tumor invasion (T4b), and Borrmann type (III or IV) were significantly correlated with either peritoneal metastasis or positive cytology. The best performance in diagnosing P-positive was obtained when two or three risk factors existed. CONCLUSION: Staging laparoscopy can improve treatment decision-making for advanced GC and decrease unnecessary exploratory laparotomy. PMID:26855545

  20. Febuxostat for hyperuricemia in patients with advanced chronic kidney disease.

    PubMed

    Akimoto, Tetsu; Morishita, Yoshiyuki; Ito, Chiharu; Iimura, Osamu; Tsunematsu, Sadao; Watanabe, Yuko; Kusano, Eiji; Nagata, Daisuke

    2014-01-01

    Febuxostat is a nonpurine xanthine oxidase (XO) inhibitor, which recently received marketing approval. However, information regarding the experience with this agent among advanced chronic kidney disease (CKD) patients is limited. In the current study, we investigated the effects of oral febuxostat in patients with advanced CKD with asymptomatic hyperuricemia. We demonstrated, for the first time, that not only the serum levels of uric acid (UA) but also those of 8-hydroxydeoxyguanosine, an oxidative stress marker, were significantly reduced after six months of febuxostat treatment, with no adverse events. These results encouraged us to pursue further investigations regarding the clinical impact of lowering the serum UA levels with febuxostat in advanced CKD patients in terms of concomitantly reducing oxidative stress via the blockade of XO. More detailed studies with a larger number of subjects and assessments of the effects of multiple factors affecting hyperuricemia, such as age, sex, and dietary habits, would shed light on the therapeutic challenges of treating asymptomatic hyperuricemia in patients with various stages of CKD. PMID:25210423

  1. Down syndrome with end-stage renal disease.

    PubMed

    Kute, Vivek B; Vanikar, Aruna V; Shah, Pankaj R; Gumber, Manoj R; Patel, Himanshu V; Engineer, Divyesh P; Thakkar, Umang G; Trivedi, Hargovind L

    2013-10-01

    Down syndrome is one of the most common genetic causes of learning disabilities in children. Although the incidence of renal and urological involvement in Down syndrome is not very common, monitoring of patients with Down syndrome for renal diseases should be done regularly as patient's age into the second and third decades. With increased survival, it appears that a growing number of these patients present with chronic renal failure. Down syndrome patients are apparently not suited for peritoneal dialysis because of lacking cooperation. This procedure can be prone to failure, mainly because of an increased risk of peritonitis. Handling such patients especially those on peritoneal dialysis is challenging. Here we report a case of Down syndrome with end-stage renal disease treated with hemodialysis for 6 months. To the best of our knowledge and current literature review this is the first case report of a patient with Down syndrome undergoing hemodialysis. PMID:24426250

  2. The Seven Stages of Man: The Role of Developmental Stage on Medication Adherence in Respiratory Diseases.

    PubMed

    Costello, Richard W; Foster, Juliet M; Grigg, Jonathan; Eakin, Michelle N; Canonica, Walter; Yunus, Fasail; Ryan, Dermot

    2016-01-01

    The circumstances and drivers of the decision to initiate, implement, or persist with a medication differ for individuals at each developmental stage. For school-age children with asthma, the social environment of their family's cultural beliefs and the influence of peer networks and school policies are strong determinants of medication adherence. The stage of adolescence can be a particularly challenging time because there is a reduction in parental supervision of asthma management as the young person strives to become more autonomous. To illustrate the importance of such factors, adherence interventions in children and young adults with asthma have used peer-based supports and social supports, particularly social media platforms. In older patients, it is internal rather than external factors and age-related decline that pose challenges to medication adherence. Seniors face the challenges of polypharmacy, reduced social support, increased isolation, and loss of cognitive function. Strategies to promote adherence must be tailored to the developmental stage and respective behavioral determinants of the target group. This review considers the different attitudes toward medication and the different adherence behaviors in young and elderly patients with chronic respiratory conditions, specifically asthma and chronic obstructive pulmonary disease. Opportunities to intervene to optimize adherence are suggested. PMID:27587315

  3. The Risk of Peripheral Arterial Disease after Parathyroidectomy in Patients with End-Stage Renal Disease

    PubMed Central

    Chen, Hsuan-Ju; Li, Tsai-Chung; Hsu, Chih-Cheng; Kao, Chia-Hung

    2016-01-01

    Purpose The changes of the risk of peripheral arterial disease (PAD) in patients with end-stage renal disease after parathyroidectomy are scant. Methods We used a nationwide health insurance claims database to select all dialysis-dependent patients with end-stage renal disease aged 18 years and older for the study population in 2000 to 2006. Of the patients with end-stage renal disease, we selected 947 patients who had undergone parathyroidectomy as the parathyroidectomy group and frequency matched 3746 patients with end-stage renal disease by sex, age, years since the disease diagnosis, and the year of index date as the non-parathyroidectomy group. We used a multivariate Cox proportional hazards regression analysis with the use of a robust sandwich covariance matrix estimate, accounting for the intra-cluster dependence of hospitals or clinics, to measure the risk of peripheral arterial disease for the parathyroidectomy group compared with the non-parathyroidectomy group after adjusting for sex, age, premium-based income, urbanization, and comorbidity. Results The mean post-op follow-up periods were 5.08 and 4.52 years for the parathyroidectomy and non-parathyroidectomy groups, respectively; the incidence density rate of PAD in the PTX group was 12.26 per 1000 person-years, significantly lower than the data in the non-PTX group (24.09 per 1000 person-years, adjusted HR = 0.66, 95% CI = 0.46–0.94). Conclusion Parathyroidectomy is associated with reduced risk of peripheral arterial disease in patients with end-stage renal disease complicated with severe secondary hyperparathyroidism. PMID:27284924

  4. Functional assessment staging (FAST) in Korean patients with Alzheimer's disease.

    PubMed

    Na, Hae-Ri; Kim, Sang-Yun; Chang, Young-Hee; Park, Moon-Ho; Cho, Sung-Tae; Han, Il-Woo; Kim, Tae-You; Hwang, Sul-A

    2010-01-01

    Functional Assessment Staging (FAST) was devised to meet the need for a more brief patient-derived rating scale for evaluating changes in functional performance and activities of daily living skills in all the stages of Alzheimer's disease (AD). FAST was administered to 464 patients with probable AD according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. The patients were also evaluated using the Korean version of the Mini-Mental Status Examination (K-MMSE), the Clinical Dementia Rating (CDR), the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Global Deterioration Scale (GDS), the Barthel Activities of Daily Living (B-ADL), and the Seoul-Instrumental Activities of Daily Living (S-IADL). For patients with moderate to severe dementia, the Korean versions of the Severe Impairment Battery (SIB-Ko) and Baylor profound mental status examination (BPMSE-Ko) were also administered. There were significant correlations between the FAST and the K-MMSE scores (r= - 0.71, p< 0.001), between the FAST and the SIB-Ko scores (r= - 0.54, p< 0.001) and between the FAST and the BPMSE-Ko scores (r=- 0.46, p< 0.001). The FAST was also correlated with the CDR, the CDR-SB, the B-ADL, and the S-IADL (p< 0.001). Ultimately, FAST is a reliable and valid assessment technique for evaluating functional deterioration in AD patients throughout the disease course. Moreover, the findings of the present study suggest that the FAST elucidates a characteristic pattern of progressive, ordinal, and functional decline in AD in Korean AD patients with dementia. PMID:20847407

  5. Stage-dependent reduction in T colony formation in Hodgkin's disease. Coincidence with monocyte synthesis of prostaglandins.

    PubMed Central

    Bockman, R S

    1980-01-01

    Prostaglandin synthesis and T lymphocyte colony formation have been examined in previously untreated patients with Hodgkin's disease. Mononuclear cells have been isolated from peripheral blood and spleens of these patients. Significant augmentation in prostaglandin E levels were noted in the mononuclear cell cutures from Hodgkin's disease patients compared with controls (1.64 +/- 0.29 vs. 0.39 +/- 0.09 ng/10(6) cells, P < 0.005). Measured prostaglandin E levels increased with advancing stage of disease. Virtually all of the prostaglandins were synthesized by the adherent monocyte cell population. Prostaglandin E was the major product. Clonal expansion of a T lymphocyte precursor cell, which gives rise to colonies > 50 cells, was determined by a layered soft agar method. T colony formation was significantly reduced in patients with stage II, III, and IV disease. There were progressively reduced colony numbers seen with advancing stage of disease (609 +/- 209, 416 +/- 158, 207 +/- 58 compared with normals 2,274 +/- 360 colonies/10(6) cells plated; P < 0.005). The addition of inhibitors of endogenous prostaglandin synthesis resulted in significant augmentation of T colony number. However, a consistent relative decrease in T colony number was seen even when endogenous prostaglandin E synthesis was blocked. It would appear that both the prostaglandin-dependent and independent T colony precursor cells are lost with progressive stage of disease. A causative role of augmented prostaglandin synthesis in this stage-dependent reduction of T colony formation could not be established. PMID:6967491

  6. Exprimental Results of the First Two Stages of an Advanced Transonic Core Compressor Under Isolated and Multi-Stage Conditions.

    NASA Technical Reports Server (NTRS)

    Prahst, Patricia S.; Kulkarni, Sameer; Sohn, Ki H.

    2015-01-01

    NASA's Environmentally Responsible Aviation (ERA) Program calls for investigation of the technology barriers associated with improved fuel efficiency for large gas turbine engines. Under ERA, the highly loaded core compressor technology program attempts to realize the fuel burn reduction goal by increasing overall pressure ratio of the compressor to increase thermal efficiency of the engine. Study engines with overall pressure ratio of 60 to 70 are now being investigated. This means that the high pressure compressor would have to almost double in pressure ratio while keeping a high level of efficiency. NASA and GE teamed to address this challenge by testing the first two stages of an advanced GE compressor designed to meet the requirements of a very high pressure ratio core compressor. Previous test experience of a compressor which included these front two stages indicated a performance deficit relative to design intent. Therefore, the current rig was designed to run in 1-stage and 2-stage configurations in two separate tests to assess whether the bow shock of the second rotor interacting with the upstream stage contributed to the unpredicted performance deficit, or if the culprit was due to interaction of rotor 1 and stator 1. Thus, the goal was to fully understand the stage 1 performance under isolated and multi-stage conditions, and additionally to provide a detailed aerodynamic data set for CFD validation. Full use was made of steady and unsteady measurement methods to understand fluid dynamics loss source mechanisms due to rotor shock interaction and endwall losses. This paper will present the description of the compressor test article and its measured performance and operability, for both the single stage and two stage configurations. We focus the paper on measurements at 97% corrected speed with design intent vane setting angles.

  7. Visual perception in prediagnostic and early stage Huntington's disease.

    PubMed

    O'Donnell, Brian F; Blekher, Tanya M; Weaver, Marjorie; White, Kerry M; Marshall, Jeanine; Beristain, Xabier; Stout, Julie C; Gray, Jacqueline; Wojcieszek, Joanne M; Foroud, Tatiana M

    2008-05-01

    Disturbances of visual perception frequently accompany neurodegenerative disorders but have been little studied in Huntington's disease (HD) gene carriers. We used psychophysical tests to assess visual perception among individuals in the prediagnostic and early stages of HD. The sample comprised four groups, which included 201 nongene carriers (NG), 32 prediagnostic gene carriers with minimal neurological abnormalities (PD1); 20 prediagnostic gene carriers with moderate neurological abnormalities (PD2), and 36 gene carriers with diagnosed HD. Contrast sensitivity for stationary and moving sinusoidal gratings, and tests of form and motion discrimination, were used to probe different visual pathways. Patients with HD showed impaired contrast sensitivity for moving gratings. For one of the three contrast sensitivity tests, the prediagnostic gene carriers with greater neurological abnormality (PD2) also had impaired performance as compared with NG. These findings suggest that early stage HD disrupts visual functions associated with the magnocellular pathway. However, these changes are only observed in individuals diagnosed with HD or who are in the more symptomatic stages of prediagnostic HD. PMID:18419843

  8. The Critical Technologies and Applications on Advanced Upper Stage Vehicles

    NASA Astrophysics Data System (ADS)

    Qi, Feng; Wang, Guo-hui

    2016-07-01

    Upper Stage Vehicle(USV) is a kind of independent one-stop-into-space launching vehicles. In this article, different new-conception USVs are mentioned and out of them, on basis of the possibility in future application, laser propelling USV and nuclear-thermal propelling USV are selected and discussed in technical details, especially in critical technologies and recent relative technical improvements about new propelling methods within these two kinds. Furthermore, laser propelled USV and nuclear-thermal propelled USV both seem to have important roles to play in future space exploring projects. And several possible applications of the two kinds of USVs emphasized above are carried out at the end of this piece of article.

  9. Management of postural sensory conflict and dynamic balance control in late-stage Parkinson's disease.

    PubMed

    Colnat-Coulbois, S; Gauchard, G C; Maillard, L; Barroche, G; Vespignani, H; Auque, J; Perrin, P P

    2011-10-13

    Parkinson's disease (PD) is known to affect postural control, especially in situations needing a change in balance strategy or when a concurrent task is simultaneously performed. However, few studies assessing postural control in patients with PD included homogeneous population in late stage of the disease. Thus, this study aimed to analyse postural control and strategies in a homogeneous population of patients with idiopathic advanced (late-stage) PD, and to determine the contribution of peripheral inputs in simple and more complex postural tasks, such as sensory conflicting and dynamic tasks. Twenty-four subjects with advanced PD (duration: median (M)=11.0 years, interquartile range (IQR)=4.3 years; Unified Parkinson's Disease Rating Scale (UPDRS): M "on-dopa"=13.5, IQR=7.8; UPDRS: M "off-dopa"=48.5, IQR=16.8; Hoehn and Yahr stage IV in all patients) and 48 age-matched healthy controls underwent static (SPT) and dynamic posturographic (DPT) tests and a sensory organization test (SOT). In SPT, patients with PD showed reduced postural control precision with increased oscillations in both anterior-posterior and medial-lateral planes. In SOT, patients with PD displayed reduced postural performances especially in situations in which visual and vestibular cues became predominant to organize balance control, as was the ability to manage balance in situations for which visual or proprioceptive inputs are disrupted. In DPT, postural restabilization strategies were often inefficient to maintain equilibrium resulting in falls. Postural strategies were often precarious, postural regulation involving more hip joint than ankle joint in patients with advanced PD than in controls. Difficulties in managing complex postural situations, such as sensory conflicting and dynamic situations might reflect an inadequate sensory organization suggesting impairment in central information processing. PMID:21627979

  10. Exon skipping restores dystrophin expression, but fails to prevent disease progression in later stage dystrophic dko mice

    PubMed Central

    Wu, B; Cloer, C; Lu, P; Milazi, S; Shaban, M; Shah, SN; Marston-Poe, L; Moulton, HM; Lu, QL

    2014-01-01

    Antisense therapy with both chemistries of phosphorodiamidate morpholino oligomers (PMOs) and 2′-O-methyl phosphorothioate has demonstrated the capability to induce dystrophin expression in Duchenne muscular dystrophy (DMD) patients in phase II–III clinical trials with benefit in muscle functions. However, potential of the therapy for DMD at different stages of the disease progression is not understood. In this study, we examined the effect of peptide-conjugated PMO (PPMO)-mediated exon skipping on disease progression of utrophin-dystrophin-deficient mice (dko) of four age groups (21–29, 30–39, 40–49 and 50+ days), representing diseases from early stage to advanced stage with severe kyphosis. Biweekly intravenous (i.v.) administration of the PPMO restored the dystrophin expression in nearly 100% skeletal muscle fibers in all age groups. This was associated with the restoration of dystrophin-associated proteins including functional glycosylated dystroglycan and neuronal nitric synthase. However, therapeutic outcomes clearly depended on severity of the disease at the time the treatment started. The PPMO treatment alleviated the disease pathology and significantly prolonged the life span of the mice receiving treatment at younger age with mild phenotype. However, restoration of high levels of dystrophin expression failed to prevent disease progression to the mice receiving treatment when disease was already at advanced stage. The results could be critical for design of clinical trials with antisense therapy to DMD. PMID:24942628

  11. [Chronic Duodenitis and Celiac Disease: a path between the nonspecific and the early stages of Marsh].

    PubMed

    Passera, Andrea Helena; Passera, Mario Luis; Higa, Antonio Luis; Nuñez, Maria; Armando, Lucas; Barzón, Silvia

    2015-01-01

    Given the advances in diagnosis for CD, some patients are detected with symptoms and signs of food intolerance, which have positive antibodies and autoantibodies for coeliac disease, whom present proximal bowel biopsies with chronic nonspecific duodenitis and are not associated with stages 0 and 1 Marsh. On the other hand, patients with bloating, abdominal pain, pondostatural delay, negative antibodies for CD, and chronic nonspecific duodenitis in whom removing cow's milk or gluten, the symptoms remit. There are also celiac patients with biopsies before diagnosis, with chronic nonspecific duodenitis. In this paper, we summarize three brothers with different degrees of chronic duodenitis, one with chronic nonspecific duodenitis, and two with histopathological sings of coeliac disease. It is an invitation to think that chronic nonspecific duodenitis in some patients may be an earlier manifestation of celiac disease. PMID:26544059

  12. The Care Needs of Community-Dwelling Seniors Suffering from Advanced Chronic Obstructive Pulmonary Disease

    ERIC Educational Resources Information Center

    Wilson, Donna M.; Ross, Carolyn; Goodridge, Donna; Davis, Penny; Landreville, Alison; Roebuck, Kim

    2008-01-01

    Aim: This study was undertaken to determine the care needs of Canadian seniors living at home with advanced chronic obstructive pulmonary disease (COPD). Background: COPD is a leading cause of morbidity and mortality worldwide. Although hospitalizations for illness exacerbations and end-stage care may be common, most persons with COPD live out…

  13. End-Stage Renal Disease From Cast Nephropathy in a Teenager With Neuroendocrine Carcinoma.

    PubMed

    Butani, Lavjay; Ducore, Jonathan

    2016-07-01

    Cast nephropathy is the most common manifestation of renal injury in patients with multiple myeloma but is rarely reported in other conditions. We are reporting our experience in caring for a teenager with a metastatic neuroendocrine carcinoma who developed rapidly progressive kidney injury that advanced to end-stage renal disease. On renal biopsy extensive tubular necrosis and intratubular eosinophilic casts were noted. This previously unreported finding should prompt oncologists to closely monitor for such a complication in patients with secretory tumors. Whether early plasmapheresis could be of benefit, as has been tried in multiple myeloma, remains to be determined. PMID:26989910

  14. Experimental Results of the First Two Stages of an Advanced Transonic Core Compressor Under Isolated and Multi-Stage Conditions

    NASA Technical Reports Server (NTRS)

    Prahst, Patricia S.; Kulkarni, Sameer; Sohn, Ki H.

    2015-01-01

    NASA's Environmentally Responsible Aviation (ERA) Program calls for investigation of the technology barriers associated with improved fuel efficiency of large gas turbine engines. Under ERA the task for a High Pressure Ratio Core Technology program calls for a higher overall pressure ratio of 60 to 70. This mean that the HPC would have to almost double in pressure ratio and keep its high level of efficiency. The challenge is how to match the corrected mass flow rate of the front two supersonic high reaction and high corrected tip speed stages with a total pressure ratio of 3.5. NASA and GE teamed to address this challenge by using the initial geometry of an advanced GE compressor design to meet the requirements of the first 2 stages of the very high pressure ratio core compressor. The rig was configured to run as a 2 stage machine, with Strut and IGV, Rotor 1 and Stator 1 run as independent tests which were then followed by adding the second stage. The goal is to fully understand the stage performances under isolated and multi-stage conditions and fully understand any differences and provide a detailed aerodynamic data set for CFD validation. Full use was made of steady and unsteady measurement methods to isolate fluid dynamics loss source mechanisms due to interaction and endwalls. The paper will present the description of the compressor test article, its predicted performance and operability, and the experimental results for both the single stage and two stage configurations. We focus the detailed measurements on 97 and 100 of design speed at 3 vane setting angles.

  15. Advanced MRI and staging of multiple sclerosis lesions.

    PubMed

    Absinta, Martina; Sati, Pascal; Reich, Daniel S

    2016-06-01

    Over the past few decades, MRI-based visualization of demyelinated CNS lesions has become pivotal to the diagnosis and monitoring of multiple sclerosis (MS). In this Review, we outline current efforts to correlate imaging findings with the pathology of lesion development in MS, and the pitfalls that are being encountered in this research. Multimodal imaging at high and ultra-high magnetic field strengths is yielding biologically relevant insights into the pathophysiology of blood-brain barrier dynamics and both active and chronic inflammation, as well as mechanisms of lesion healing and remyelination. Here, we parallel the results in humans with advances in imaging of a primate model of MS - experimental autoimmune encephalomyelitis (EAE) in the common marmoset - in which demyelinated lesions resemble their human counterparts far more closely than do EAE lesions in the rodent. This approach holds promise for the identification of innovative biological markers, and for next-generation clinical trials that will focus more on tissue protection and repair. PMID:27125632

  16. 77 FR 67449 - Medicare Program; End-Stage Renal Disease Prospective Payment System, Quality Incentive Program...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-09

    ...-Stage Renal Disease Bundled FDA Food and Drug Administration FI/MAC Fiscal Intermediary/Medicare..., 2010, we published in the Federal Register a final (75 FR 49030) titled, ``End-Stage Renal Disease... comment period (76 FR 18930) titled, ``Changes in the End-Stage Renal Disease Prospective Payment...

  17. Recent advances in echocardiography for valvular heart disease

    PubMed Central

    Hahn, Rebecca

    2015-01-01

    Echocardiography is the imaging modality of choice for the assessment of patients with valvular heart disease. Echocardiographic advancements may have particular impact on the assessment and management of patients with valvular heart disease. This review will summarize the current literature on advancements, such as three-dimensional echocardiography, strain imaging, intracardiac echocardiography, and fusion imaging, in this patient population. PMID:26594349

  18. Short-term morbidity in transdiaphragmatic cardiophrenic lymph node resection for advanced stage gynecologic cancer.

    PubMed

    LaFargue, C J; Sawyer, B T; Bristow, R E

    2016-08-01

    Ovarian cancer is commonly diagnosed at an advanced stage, with disease involving the upper abdomen. The finding of enlarged cardiophrenic lymph nodes (CPLNs) on pre-operative imaging often indicates the presence of malignant spread to the mediastinum. Surgical resection of CPLN through a transdiaphragmatic approach can help to achieve cytoreduction to no gross residual. A retrospective chart review was conducted on all patients who underwent transdiaphragmatic cardiophrenic lymph node resection from 8/1/11 through 2/1/15. All relevant pre-, intra-, and post-operative characteristics and findings were recorded. A brief description of the surgical technique is included for reference. Eleven patients were identified who had undergone transdiaphragmatic resection of cardiophrenic lymph nodes. Malignancy was identified in 18/21 (86%) of total lymph nodes submitted. The median number of post-operative days was 7. The overall post-operative morbidity associated with CPLN resection was low, with the most common finding being a small pleural effusion present on chest x-ray between POD# 3-5 (55%). Transdiaphragmatic CPLN resection is a feasible procedure with relatively minor short-term post-operative morbidities that can be used to achieve cytoreduction to no gross residual disease. PMID:27354998

  19. Meaningful rehabilitation of the end-stage renal disease patient.

    PubMed

    Thornton, T A; Hakim, R M

    1997-05-01

    In this highly technological age, health care providers are called to attend to the patient as a whole person, with dreams and goals and a desire for purpose and meaning in life. In this article, we propose a broadened definition of rehabilitation and a rehabilitation program designed to effect an improvement in the quality of life of each renal patient by aiming to restore meaningful existence in each of their lives. An individualized plan for rehabilitation can be constructed and implemented with far-reaching success when the focus is on the life goals of the patient, whether physical, social, psychological, or intellectual. These programs not only enhance the quality of life of the patient with end-stage renal disease, but are cost-effective, both at the societal level and at the level of the dialysis clinic. PMID:9165654

  20. Advancing frontiers in Alzheimer's disease research

    SciTech Connect

    Glenner, G.G.; Wurtman, R.J.

    1987-01-01

    This book contain 16 chapters. Some of the titles are: Transmitter Alterations in Alzheimer's Disease: Relation to Cortical Dysfunction as Suggested by Positron Emission Tomography; Single-Photon Emission Computed Tomography in the Clinical Evaluation of Dementia; Clinical Diagnosis of Alzheimer's Disease; Down's Syndrome and Alzheimer's Disease: What is the Relationship; and Beta Protein: A Possible Marker for Alzheimer's Disease.

  1. Obesity end stage renal disease and survival in an elderly cohort with cardiovascular disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity is highly prevalent in African-Americans and is associated with increased risk of end stage renal disease (ESRD) and death. It is not known if the effect of obesity is similar among Blacks and whites. The aim of this study is to examine racial differences in the association of obesity with E...

  2. Neutrophilic leukocytosis in advanced stage polycythemia vera: hematopathologic features and prognostic implications.

    PubMed

    Boiocchi, Leonardo; Gianelli, Umberto; Iurlo, Alessandra; Fend, Falko; Bonzheim, Irina; Cattaneo, Daniele; Knowles, Daniel M; Orazi, Attilio

    2015-11-01

    Polycythemia vera in 20-30% of cases progresses towards post-polycythemic myelofibrosis, an advanced phase characterized by decreased red blood cells counts and increasing splenomegaly with extramedullary hematopoiesis. There is evidence that the presence of neutrophilic leukocytosis at polycythemia vera disease outset is associated with an increased risk of recurrent thrombosis. However, its clinical significance when developing later in the course of the disease is not well defined. Over a period of 8 years we identified from the files of two reference centers 10 patients (7M/3F, median age: 68 years) who developed persistent absolute leukocytosis ≥ 13 × 10⁹/l (median: 25.1 × 10⁹/l; range: 16.1-89.7 × 10⁹/l) at or around the time of diagnosis of post-polycythemic myelofibrosis (median interval from diagnosis:0 months; range: -6/31) and persisted for a median period of 13 months. Peripheral blood smears showed numerous neutrophils without dysplastic features and, in four, ≥ 10% immature myeloid precursors. In five cases, corresponding marrow specimens obtained at or immediately after the onset of leukocytosis showed a markedly increased myeloid:erythroid ratio due to granulocytic proliferation. No change in JAK2 and BCR-ABL1 status or cytogenetic evolution was associated with the development of leukocytosis. The mutational status of CSF3R, SETBP1, and SRSF2, genes associated with other chronic myeloid neoplasms where neutrophilic leukocytosis occurs, was investigated but all cases showed wild-type only alleles. Four patients died after developing leukocytosis and one experienced worsening disease. Compared with a control group of post-polycythemic myelofibrosis patients (n=23) who never developed persistent leukocytosis, patients with leukocytosis showed higher white blood cells counts and a shorter overall survival. This is the first study describing the development of significant neutrophilic leukocytosis during advanced stages of polycythemia vera

  3. Sevelamer carbonate experience in Indian end stage renal disease patients

    PubMed Central

    Abraham, G.; Kher, V.; Saxena, S.; Jayakumar, M.; Chafekar, D.; Pargaonkar, P.; Shetty, M.; Reddy, Y. N. V.; Reddy, Y. N. V.

    2012-01-01

    This open label, multicentric, comparative clinical trial was done to compare the efficacy and tolerability of two sevelamer formulations, sevelamer carbonate, and sevelamer hydrochloride, in the treatment of hyperphosphatemia in Indian end stage renal disease (ESRD) patients. A total of 97 ESRD patients on hemodialysis, were enrolled. Patients were randomized to receive either sevelamer carbonate or sevelamer hydrochloride. All patients were evaluated every week for 6 weeks for efficacy and safety variables. Total 88 patients completed the study. After 6 weeks of therapy, there were similar reductions (P<0.0001) in mean serum phosphorus and the CaxP product both the groups. The responder rates for test and reference groups were 75%, 68.18% respectively (P=0.3474). The adverse events reported were nausea, abdominal pain/discomfort, heartburn, constipation, diarrhea, increased prothrombin time, and severe arthritis. No serious adverse events were reported. There was no significant difference between the groups for adverse events and the laboratory parameters. From the results of this multicentric, comparative, randomized clinical study on sevelamer carbonate we can recommend that sevelamer carbonate may be used as a phosphate binder in Indian chronic kidney disease patients. PMID:23087553

  4. Defining end-stage renal disease in clinical trials: a framework for adjudication.

    PubMed

    Agarwal, Rajiv

    2016-06-01

    Unlike definition of stroke and myocardial infarction, there is no uniformly agreed upon definition to adjudicate end-stage renal disease (ESRD). ESRD remains the most unambiguous and clinically relevant end point for clinical trialists, regulators, payers and patients with chronic kidney disease. The prescription of dialysis to patients with advanced chronic kidney disease is subjective and great variations exist among physicians and countries. Given the difficulties in diagnosing ESRD, the presence of estimated GFR <15 mL/min/1.7 3m(2) itself has been suggested as an end point. However, this definition is still a surrogate since many patients may live years without being symptomatic or needing dialysis. The purpose of this report is to describe a framework to define when the kidney function ends and when ESRD can be adjudicated. Discussed in this report are (i) the importance of diagnosing symptomatic uremia or advanced asymptomatic uremia thus establishing the need for dialysis; (ii) establishing the chronicity of dialysis so as to distinguish it from acute dialysis; (iii) establishing ESRD when dialysis is unavailable, refused or considered futile and (iv) the adjudication process. Several challenges and ambiguities that emerge in clinical trials and their possible solutions are provided. The criteria proposed herein may help to standardize the definition of ESRD and reduce the variability in adjudicating the most important renal end point in clinical trials of chronic kidney disease. PMID:26264780

  5. Advances in the treatment of nonalcoholic fatty liver disease

    PubMed Central

    Mehta, Sanjeev R.

    2010-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world, and its prevalence is predicted to rise in the future in parallel with rising levels of obesity and type 2 diabetes mellitus. It is commonly associated with insulin resistance. Many patients have coexisting obesity, hypertension, dyslipidaemia or hyperglycaemia, and are at increased risk of developing cardiovascular disease. Although patients with simple steatosis have a good prognosis, a significant percentage will develop nonalcoholic steatohepatitis which may progress to cirrhosis, end-stage liver failure and hepatocellular carcinoma. Despite promising results from several pilot studies and small to medium randomized controlled trials, there is currently no pharmacological agent that is licensed for the treatment of NAFLD. At present the mainstay of treatment for all patients is lifestyle modification using a combination of diet, exercise and behavioural therapy. With recent advances in the understanding of the pathogenesis of NAFLD, the goal of treatment has shifted from simply trying to clear fat from the liver and prevent progressive liver damage to addressing and treating the metabolic risk factors for the condition. To reduce liver-related and cardiovascular morbidity and mortality, all patients with NAFLD should be invited to enrol in adequately powered, randomized controlled studies testing novel therapies, many of which are targeted at reducing insulin resistance or preventing progressive liver disease. Coexisting obesity, hypertension, dyslipidaemia or hyperglycaemia should be treated aggressively. Orlistat, bariatric surgery, angiotensin receptor blockers, statins, fibrates, metformin and thiazolidinediones should all be considered, but treatments should be carefully tailored to meet the specific requirements of each patient. The efficacy and safety of any new treatment, as well as its cost-effectiveness, will need to be carefully evaluated

  6. Advanced-stage nodular lymphocyte predominant Hodgkin lymphoma compared with classical Hodgkin lymphoma: a matched pair outcome analysis.

    PubMed

    Xing, Katharine H; Connors, Joseph M; Lai, Anky; Al-Mansour, Mubarak; Sehn, Laurie H; Villa, Diego; Klasa, Richard; Shenkier, Tamara; Gascoyne, Randy D; Skinnider, Brian; Savage, Kerry J

    2014-06-01

    Due to disease rarity, there is limited information regarding the optimal therapy and outcome for patients with advanced-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Forty-two patients with NLPHL by the Revised European-American Lymphoma/World Health Organization classification with advanced-stage disease were identified and paired 1:2 with a matched control with classical Hodgkin lymphoma (CHL) matched by age, gender, stage, decade of diagnosis, and treatment received. The median follow-up was 11.3 years (range, 1.9 to 35.5 years) for NLPHL patients and 10.7 years (range, 1.6 to 26.3 years) for CHL patients. The majority received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-like chemotherapy. Although the 10-year overall survival (OS) (P = .579) and HL freedom from treatment failure (HL-FFTF) were similar between NLPHL and CHL patients (75% vs 73%; P = .610), the time to progression (TTP), which also includes the development of secondary aggressive lymphoma, was inferior in NLPHL (10-year, 63% vs 73%; P = .040). Splenic involvement was associated with an inferior 10-year TTP in patients treated with ABVD (48% vs 71%; P = .049) and an increased cumulative incidence of secondary aggressive lymphoma (P = .014) providing a rationale for further evaluation of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with rituximab in NLPHL. PMID:24713929

  7. Prognosis and Clinicopathologic Features of Patients With Advanced Stage Isocitrate Dehydrogenase (IDH) Mutant and IDH Wild-Type Intrahepatic Cholangiocarcinoma

    PubMed Central

    Goyal, Lipika; Govindan, Aparna; Sheth, Rahul A.; Nardi, Valentina; Blaszkowsky, Lawrence S.; Faris, Jason E.; Clark, Jeffrey W.; Ryan, David P.; Kwak, Eunice L.; Allen, Jill N.; Murphy, Janet E.; Saha, Supriya K.; Hong, Theodore S.; Wo, Jennifer Y.; Ferrone, Cristina R.; Tanabe, Kenneth K.; Chong, Dawn Q.; Deshpande, Vikram; Borger, Darrell R.; Iafrate, A. John; Bardeesy, Nabeel; Zheng, Hui

    2015-01-01

    Background. Conflicting data exist regarding the prognostic impact of the isocitrate dehydrogenase (IDH) mutation in intrahepatic cholangiocarcinoma (ICC), and limited data exist in patients with advanced-stage disease. Similarly, the clinical phenotype of patients with advanced IDH mutant (IDHm) ICC has not been characterized. In this study, we report the correlation of IDH mutation status with prognosis and clinicopathologic features in patients with advanced ICC. Methods. Patients with histologically confirmed advanced ICC who underwent tumor mutational profiling as a routine part of their care between 2009 and 2014 were evaluated. Clinical and pathological data were collected by retrospective chart review for patients with IDHm versus IDH wild-type (IDHwt) ICC. Pretreatment tumor volume was calculated on computed tomography or magnetic resonance imaging. Results. Of the 104 patients with ICC who were evaluated, 30 (28.8%) had an IDH mutation (25.0% IDH1, 3.8% IDH2). The median overall survival did not differ significantly between IDHm and IDHwt patients (15.0 vs. 20.1 months, respectively; p = .17). The pretreatment serum carbohydrate antigen 19-9 (CA19-9) level in IDHm and IDHwt patients was 34.5 and 118.0 U/mL, respectively (p = .04). Age at diagnosis, sex, histologic grade, and pattern of metastasis did not differ significantly by IDH mutation status. Conclusion. The IDH mutation was not associated with prognosis in patients with advanced ICC. The clinical phenotypes of advanced IDHm and IDHwt ICC were similar, but patients with IDHm ICC had a lower median serum CA19-9 level at presentation. Implications for Practice: Previous studies assessing the prognostic impact of the isocitrate dehydrogenase (IDH) gene mutation in intrahepatic cholangiocarcinoma (ICC) mainly focused on patients with early-stage disease who have undergone resection. These studies offer conflicting results. The target population for clinical trials of IDH inhibitors is patients with

  8. Novel therapeutics for primary biliary cholangitis: Toward a disease-stage-based approach.

    PubMed

    Mousa, Hani S; Carbone, Marco; Malinverno, Federica; Ronca, Vincenzo; Gershwin, M Eric; Invernizzi, Pietro

    2016-09-01

    Primary biliary cholangitis (PBC; previously "primary biliary cirrhosis") is a cholestatic, putatively autoimmune-mediated liver disease with a clear female preponderance affecting the intrahepatic small and medium-size bile ducts and resulting in bile duct destruction, ductopenia and portal fibrosis that progresses slowly to biliary cirrhosis. Despite suboptimal response in one third of patients treated with ursodeoxycholic acid (UDCA), this remains the only FDA-approved agent for this disease. In this review, we cover recent advances in research that have yielded numerous agents currently at different stages of the drug pipeline, some of which are expected to be approved in the near future. We also discuss accumulating evidence supporting the use of older agents (fibrates and glucocorticoids) as an adjunctive therapy to UDCA in non-responsive patients. We suggest that with the imminent expansion of the therapeutic armamentarium for PBC, a more comprehensive approach - ideally taking into account not only biochemical markers of disease stage - is needed to better select patients in whom these strategies might be most useful. Studies are also needed to compare the relative efficacy of different proposed second-line treatments not only against UDCA monotherapy. PMID:27393766

  9. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis.

    PubMed

    Weaver, Jamie M J; Ross-Innes, Caryn S; Shannon, Nicholas; Lynch, Andy G; Forshew, Tim; Barbera, Mariagnese; Murtaza, Muhammed; Ong, Chin-Ann J; Lao-Sirieix, Pierre; Dunning, Mark J; Smith, Laura; Smith, Mike L; Anderson, Charlotte L; Carvalho, Benilton; O'Donovan, Maria; Underwood, Timothy J; May, Andrew P; Grehan, Nicola; Hardwick, Richard; Davies, Jim; Oloumi, Arusha; Aparicio, Sam; Caldas, Carlos; Eldridge, Matthew D; Edwards, Paul A W; Rosenfeld, Nitzan; Tavaré, Simon; Fitzgerald, Rebecca C

    2014-08-01

    Cancer genome sequencing studies have identified numerous driver genes, but the relative timing of mutations in carcinogenesis remains unclear. The gradual progression from premalignant Barrett's esophagus to esophageal adenocarcinoma (EAC) provides an ideal model to study the ordering of somatic mutations. We identified recurrently mutated genes and assessed clonal structure using whole-genome sequencing and amplicon resequencing of 112 EACs. We next screened a cohort of 109 biopsies from 2 key transition points in the development of malignancy: benign metaplastic never-dysplastic Barrett's esophagus (NDBE; n=66) and high-grade dysplasia (HGD; n=43). Unexpectedly, the majority of recurrently mutated genes in EAC were also mutated in NDBE. Only TP53 and SMAD4 mutations occurred in a stage-specific manner, confined to HGD and EAC, respectively. Finally, we applied this knowledge to identify high-risk Barrett's esophagus in a new non-endoscopic test. In conclusion, mutations in EAC driver genes generally occur exceptionally early in disease development with profound implications for diagnostic and therapeutic strategies. PMID:24952744

  10. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis

    PubMed Central

    Forshew, Tim; Barbera, Mariagnese; Murtaza, Muhammed; Ong, Chin-Ann J.; Lao-Sirieix, Pierre; Dunning, Mark J; Smith, Laura; Smith, Mike L.; Anderson, Charlotte L.; Carvalho, Benilton; O’Donovan, Maria; Underwood, Timothy J.; May, Andrew P; Grehan, Nicola; Hardwick, Richard; Davies, Jim; Oloumi, Arusha; Aparicio, Sam; Caldas, Carlos; Eldridge, Matthew D.; Edwards, Paul A.W.; Rosenfeld, Nitzan; Tavaré, Simon; Fitzgerald, Rebecca C

    2014-01-01

    Cancer genome sequencing studies have identified numerous driver genes but the relative timing of mutations in carcinogenesis remains unclear. The gradual progression from pre-malignant Barrett’s esophagus to esophageal adenocarcinoma (EAC) provides an ideal model to study the ordering of somatic mutations. We identified recurrently-mutated genes and assessed clonal structure using whole-genome sequencing and amplicon-resequencing of 112 EACs. We next screened a cohort of 109 biopsies from two key transition points in the development of malignancy; benign metaplastic never-dysplastic Barrett’s esophagus (NDBE, n=66), and high-grade dysplasia (HGD, n=43). Unexpectedly, the majority of recurrently mutated genes in EAC were also mutated in NDBE. Only TP53 and SMAD4 were stage-specific, confined to HGD and EAC, respectively. Finally, we applied this knowledge to identify high-risk Barrett’s esophagus in a novel non-endoscopic test. In conclusion, mutations in EAC driver genes generally occur exceptionally early in disease development with profound implications for diagnostic and therapeutic strategies. PMID:24952744

  11. Ethics and decision making in end stage lung disease.

    PubMed

    Simonds, A K

    2003-03-01

    Most physicians believe they do more good than harm, and these duties of helping and not harming the patient are rooted in the Hippocratic oath, the good Samaritan tradition, and the Order of the Knight Hospitallers founded in the 11th century to care for pilgrims and those wounded in the Crusades.(1) In recent times the simple principles of beneficence and non-maleficence have been augmented and sometimes challenged by a rising awareness of patient/consumer rights, and the public expectation of greater involvement in medical, social and scientific affairs which affect them. In a publicly funded healthcare system in which rationing (explicit or otherwise) is inevitable, the additional concepts of utility and distributive justice can easily come into conflict with the individual's right to autonomy. Possible treatment options for end stage lung disease include transplantation and long term invasive ventilation which are challenging in resource terms. Other interventions such as pulmonary rehabilitation and palliative care are relatively low cost but not uniformly accessible. PMID:12612311

  12. Markers of bacterial translocation in end-stage liver disease.

    PubMed

    Koutsounas, Ioannis; Kaltsa, Garyfallia; Siakavellas, Spyros I; Bamias, Giorgos

    2015-09-18

    Bacterial translocation (BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The three principal mechanisms that are thought to be involved in BT include bacterial overgrowth, disruption of the gut mucosal barrier and an impaired host defence. BT is commonly observed in liver cirrhosis and has been shown to play an important role in the pathogenesis of the complications of end stage liver disease, including infections as well as hepatic encephalopathy and hepatorenal syndrome. Due to the importance of BT in the natural history of cirrhosis, there is intense interest for the discovery of biomarkers of BT. To date, several such candidates have been proposed, which include bacterial DNA, soluble CD14, lipopolysaccharides endotoxin, lipopolysaccharide-binding protein, calprotectin and procalcitonin. Studies on the association of these markers with BT have demonstrated not only promising data but, oftentimes, contradictory results. As a consequence, currently, there is no optimal marker that may be used in clinical practice as a surrogate for the presence of BT. PMID:26380651

  13. Markers of bacterial translocation in end-stage liver disease

    PubMed Central

    Koutsounas, Ioannis; Kaltsa, Garyfallia; Siakavellas, Spyros I; Bamias, Giorgos

    2015-01-01

    Bacterial translocation (BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The three principal mechanisms that are thought to be involved in BT include bacterial overgrowth, disruption of the gut mucosal barrier and an impaired host defence. BT is commonly observed in liver cirrhosis and has been shown to play an important role in the pathogenesis of the complications of end stage liver disease, including infections as well as hepatic encephalopathy and hepatorenal syndrome. Due to the importance of BT in the natural history of cirrhosis, there is intense interest for the discovery of biomarkers of BT. To date, several such candidates have been proposed, which include bacterial DNA, soluble CD14, lipopolysaccharides endotoxin, lipopolysaccharide-binding protein, calprotectin and procalcitonin. Studies on the association of these markers with BT have demonstrated not only promising data but, oftentimes, contradictory results. As a consequence, currently, there is no optimal marker that may be used in clinical practice as a surrogate for the presence of BT. PMID:26380651

  14. Antidiabetic Therapy in End-Stage Renal Disease.

    PubMed

    Boyle, Suzanne M; Simon, Barbara; Kobrin, Sidney M

    2015-01-01

    There has been substantial growth in the variety of available antidiabetic agents during the last decade and a half. The role of these newer agents in patients with diabetes and end-stage renal disease (ESRD) population, and their relative benefits and risks in this population compared to patients without ESRD are not yet clear. This stems from the altered state of glucose homeostasis in ESRD, which places patients at high risk for hypoglycemia and, in certain situations, hyperglycemia. In addition, there is a dearth of evidence to support a benefit of tight glycemic control on either micro- or macrovascular outcomes in ESRD patients; furthermore, the metrics by which glycemic control is conventionally measured are less valid in ESRD. In this review, we will discuss noninsulin and insulin-based therapies as well as unique challenges, contraindications, advantages, and disadvantages to their use in ESRD. We will also review issues pertinent to both hemodialysis (HD) and peritoneal dialysis (PD) patients. PMID:25898790

  15. Psychotherapeutic Agents in End-Stage Renal Disease.

    PubMed

    Eyler, Rachel F; Unruh, Mark L; Quinn, Davin K; Vilay, Aloun Mary

    2015-01-01

    Patients with end-stage renal disease (ESRD) are often affected by many comorbid conditions, including mental health disorders. Psychiatric illness among patients with ESRD has been associated with increased risks for nonadherence, hospitalizations, suicide, and all-cause mortality. We reviewed the pharmacokinetic data available with psychotherapeutic agents, focusing on physiologic data rather than specific dosing recommendations. Unfortunately data regarding the pharmacokinetics, efficacy, and safety of psychotherapeutic agents in ESRD remain rather limited. Of the agents available, it appears that the most data in this patient group were found with selective serotonin reuptake inhibitors and benzodiazepines. Given the small number of patients enrolled in many of the studies and the wide inter-individual variability, it was difficult to interpret the significance of results in many instances. A number of agents, such as tricyclic antidepressants, were associated with adverse effects that would be imperative to avoid in patients with ESRD. Psychotherapeutic medications should be started at low doses and titrated carefully, while monitoring the efficacy and safety of each agent. PMID:25857865

  16. Plasma epidermal growth factor decreased in the early stage of Parkinson's disease.

    PubMed

    Jiang, Qian-Wen; Wang, Cheng; Zhou, Yi; Hou, Miao-Miao; Wang, Xi; Tang, Hui-Dong; Wu, Yi-Wen; Ma, Jian-Fang; Chen, Sheng-Di

    2015-06-01

    Epidermal growth factor (EGF) is a neurotrophic factor that plays an important role in Parkinson's disease (PD). We measured plasma EGF level in PD, essential tremor (ET) and normal controls to investigate whether it changes in PD and whether it is associated with motor and non-motor symptoms of PD. 100 patients with PD, 40 patients with ET as disease control and 76 healthy persons were enrolled in the present study. Motor and non-motor symptoms were assessed by different scales. Plasma EGF levels of three groups were measured by enzyme-linked immunosorbent assay kit. Spearman test and linear logistics regression model were used to test the correlation of EGF with motor and non-motor symptoms of PD. Plasma EGF level was significantly decreased in early PD patients compared with normal control, but not in advanced PD patients. Interestingly, plasma EGF level was significantly increased in advanced PD and total PD patients compared with ET patients, but not in early PD patients. In addition, plasma EGF level was correlated with UPDRS-III scores in PD. Also plasma EGF level was correlated with UPDRS-III scores and NMS scores in early PD. Our results suggested that plasma EGF decreased in the early stage of PD and increased later on in the PD disease course. Also, plasma EGF level was increased significantly in PD compared with ET patients and correlated with motor and non-motor symptoms in early PD. PMID:26029474

  17. ADVANCES AND UPDATE ON MAREK'S DISEASE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek's disease virus has evolved toward greater forms of virulence within the last 50 years. The two consequences of such evolution to the poultry industry are the more complicated diagnosis and the lower protection conferred by the currently available vaccines. Diagnosis of Marek's disease has bec...

  18. Dysphagia in stroke, neurodegenerative disease, and advanced dementia.

    PubMed

    Altman, Kenneth W; Richards, Amanda; Goldberg, Leanne; Frucht, Steven; McCabe, Daniel J

    2013-12-01

    Aspiration risk from dysphagia increases with central and peripheral neurologic disease. Stroke, microvascular ischemic disease, a spectrum of neurodegenerative diseases, and advancing dementia all have unique aspects. However, there are distinct commonalities in this population. Increasing nutritional requirements to stave off oropharyngeal muscular atrophy and a sedentary lifestyle further tax the patient's abilities to safely swallow. This article reviews stroke, muscular dystrophy, myasthenia gravis, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and advanced dementia. Approaches to screening and evaluation, recognizing sentinel indicators of decline that increase aspiration risk, and options for managing global laryngeal dysfunction are also presented. PMID:24262965

  19. Early outcomes of one-stage combined osteotomy in Legg-Calve´-Perthes disease

    PubMed Central

    Bhuyan, Basant Kumar

    2016-01-01

    Background: Legg-Calve´-Perthes disease (LCPD) is an idiopathic avascular necrosis of the femoral head. There are multiple approaches to the treatment of LCPD ranging from conservative management to a wide variety of surgical methods. Conservative management necessitates extreme degrees of abduction in an orthosis for a longer period of time which further jeopardize capital femoral head vascularity. Surgical containment methods are used in cases where it is desirable. Initial surgical containment methods are varus or varus-derotational osteotomy of the proximal femur or an innominate osteotomy as described by Salter and other pelvic osteotomies. The purpose of this study was to describe the early results of containment methods by one-stage combined osteotomy (femoral varus osteotomy and Salter innominate osteotomy) in patients with severe LCPD. Materials and Methods: 23 children were operated in the age group of 4–9 years for LCPD by one-stage combined osteotomy procedure between January 2005 and June 2012. There were 19 boys and 4 girls, left hip involved in 10 cases and right in 13 cases. Preoperatively, they were classified according to Catterall, Joseph's stage and lateral pillar (LP) classification. Postoperatively, clinical results were evaluated in accordance with Ratliff classification and radiological assessment was made by Mose's index, modified Stulberg classification and Epiphyseal extrusion index. Results: Seventeen hips were Catterall group III, 6 in group IV and all had two or more “head-at-risk” signs. There were 2 patients with stage IIA, 15 were in stage IIB and 6 were in stage IIIA as classified by Joseph's stage of disease. According to LP classification, 11 patients were group B, 3 were group B/C and 9 were in group C. At an average followup of 5.4 years (range 2–9.5 years), the clinical results were good in 12, fair in 9 and poor in 2. According to Mose scale, 8 patients had good results, 13 fair results and 2 had poor results. Based

  20. Interdisciplinary Management of Patient with Advanced Periodontal Disease.

    PubMed

    Kochar, Gagan Deep; Jayan, B; Chopra, S S; Mechery, Reenesh; Goel, Manish; Verma, Munish

    2016-01-01

    This case report describes the interdisciplinary management of an adult patient with advanced periodontal disease. Treatment involved orthodontic and periodontal management. Good esthetic results and dental relationships were achieved by the treatment. PMID:27319043

  1. [Defining and disease-modifying therapy for the preclinical stages of Alzheimer's disease].

    PubMed

    Sakurai, Hirofumi; Hanyu, Haruo

    2016-03-01

    The pathophysiological process of Alzheimer's disease (AD) is thought to begin more than twenty years before the diagnosis of AD dementia. Recent studies provided the biomarker of AD pathological changes. Biomarkers of brain Aβ amyloidosis include reduction in cerebrospinal fluid (CSF) Aβ42 and increased amyloid tracer retention on positron emission tomography(PET) imaging. Elevated CSF tau is thought to be a biomarker of neuronal injury. The Natinal Institute on Aging and the Alzheimer's Association proposed AD dementia, mild cognitive impairment due to AD, the preclinical stage of AD. These recommendation for the biomarker of AD are intended for research purposes at this time. Some disease-modifying therapies may be effective for the preclinical stage of AD. PMID:27025083

  2. Advancing swine models for human health and diseases.

    PubMed

    Walters, Eric M; Prather, Randall S

    2013-01-01

    Swine models are relatively new kids on the block for modeling human health and diseases when compared to rodents and dogs. Because of the similarity to humans in size, physiology, and genetics, the pig has made significant strides in advancing the understanding of the human condition, and is thus an excellent choice for an animal model. Recent technological advances to genetic engineering of the swine genome enhance the utility of swine as models of human genetic diseases. PMID:23829105

  3. Recent advances in tropical diseases research.

    PubMed

    Lucas, A O

    1983-05-15

    The past few years have witnessed renewed effort to develop new tools for the conquest of parasitic and other infectious tropical diseases. The Special Programme for Research and Training in Tropical Diseases was initiated by the WHO, following a resolution of the World Health Assembly calling for the intensification of research into tropical diseases. The Programme, co-sponsored by UNDP and the World Bank, has developed a network of activities with two inter-related objective: Research and development towards new and improved tools to control six tropical diseases; and Strengthening of national institutions, including training, to increase the research capabilities of the tropical countries effected by the diseases. The six target diseases are: malaria, schistosomiasis, filariasis, trypanosomiasis (both African sleeping sickness and Chagas' disease), leishmaniasis and leprosy. Early scientific results include progress in chemotherapy for malaria, schistosomiasis and filariasis; in the developing and testing of a vaccine against leprosy; in the fundamental knowledge required to develop a vaccine against malaria; and in simple and accurate diagnostic field tests for malaria, leprosy and African trypanosomiasis. In addition, institution strengthening and training support, awarded exclusively to institutions and scientists of developing endemic countries, has increased rapidly. The programme has collaborated with other agencies which are active in this area and with the pharmaceutical industry. Additional scientists and institutions are involved in the planning, implementation and evaluation of the Programme. PMID:6684365

  4. Subthalamic Nucleus Deep Brain Stimulation May Reduce Medication Costs in Early Stage Parkinson’s Disease

    PubMed Central

    Hacker, Mallory L.; Currie, Amanda D.; Molinari, Anna L.; Turchan, Maxim; Millan, Sarah M.; Heusinkveld, Lauren E.; Roach, Jonathon; Konrad, Peter E.; Davis, Thomas L.; Neimat, Joseph S.; Phibbs, Fenna T.; Hedera, Peter; Byrne, Daniel W.; Charles, David

    2016-01-01

    Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is well-known to reduce medication burden in advanced stage Parkinson’s disease (PD). Preliminary data from a prospective, single blind, controlled pilot trial demonstrated that early stage PD subjects treated with STN-DBS also required less medication than those treated with optimal drug therapy (ODT). Objective: The purpose of this study was to analyze medication cost and utilization from the pilot trial of DBS in early stage PD and to project 10 year medication costs. Methods: Medication data collected at each visit were used to calculate medication costs. Medications were converted to levodopa equivalent daily dose, categorized by medication class, and compared. Medication costs were projected to advanced stage PD, the time when a typical patient may be offered DBS. Results: Medication costs increased 72% in the ODT group and decreased 16% in the DBS+ODT group from baseline to 24 months. This cost difference translates into a cumulative savings for the DBS+ODT group of $7,150 over the study period. Projected medication cost savings over 10 years reach $64,590. Additionally, DBS+ODT subjects were 80% less likely to require polypharmacy compared with ODT subjects at 24 months (p <  0.05; OR = 0.2; 95% CI: 0.04–0.97). Conclusions: STN-DBS in early PD reduced medication cost over the two-year study period. DBS may offer substantial long-term reduction in medication cost by maintaining a simplified, low dose medication regimen. Further study is needed to confirm these findings, and the FDA has approved a pivotal, multicenter clinical trial evaluating STN-DBS in early PD. PMID:26967937

  5. Advances in Biomarker Research in Parkinson's Disease.

    PubMed

    Mehta, Shyamal H; Adler, Charles H

    2016-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease, and the numbers are projected to double in the next two decades with the increase in the aging population. An important focus of current research is to develop interventions to slow the progression of the disease. However, prerequisites to it include the development of reliable biomarkers for early diagnosis which would identify at-risk groups and disease progression. In this review, we present updated evidence of already known clinical biomarkers (such as hyposmia and rapid eye movement (REM) sleep behavior disorder (RBD)) and neuroimaging biomarkers, as well as newer possible markers in the blood, CSF, and other tissues. While several promising candidates and methods to assess these biomarkers are on the horizon, it is becoming increasingly clear that no one candidate will clearly fulfill all the roles as a single biomarker. A multimodal and combinatorial approach to develop a battery of biomarkers will likely be necessary in the future. PMID:26711276

  6. Brief chemotherapy (Stanford V) and adjuvant radiotherapy for bulky or advanced Hodgkin's disease: an update.

    PubMed

    Horning, S J; Rosenberg, S A; Hoppe, R T

    1996-01-01

    From May 1989 to August 1995, 94 previously untreated patients with Hodgkin's disease stage II with bulky mediastinal involvement (n = 28) or stage III or IV (n = 66) received an abbreviated chemotherapy regimen, Stanford V, +/-radiotherapy (RT). Chemotherapy was given weekly for 12 weeks followed by consolidative RT to sites of initial bulky disease. With a median follow-up of 3 years, the actuarial 6-year survival is 93% and the freedom from progression is 89%. There have been no relapses or deaths among the 28 patients with stage II bulky mediastinal disease. Eight relapses and three deaths have occurred in the group of 66 patients with stage III-IV disease. The abbreviated chemotherapy regimen, Stanford V, in combination with RT is well tolerated and highly effective therapy for bulky, limited stage and advanced stage HD. Lower cumulative exposure to alkylating agents, doxorubicin, bleomycin and limited use of radiation is expected to improved the prospects for fertility and decrease the risks for second neoplasms and late cardiopulmonary toxicity. PMID:8836420

  7. 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

  8. Predicting utility of a model for end stage liver disease in alcoholic liver disease

    PubMed Central

    Soultati, Aspasia S; Dourakis, Spyridon P; Alexopoulou, Alexandra; Deutsch, Melanie; Vasilieva, Larissa; Archimandritis, Athanasios J

    2006-01-01

    AIM: To validate the statistic utility of both the Maddrey Discriminant Function score and the Model for End-Stage Liver Disease as predictors of short term (30 d and 90 d) mortality in patients with alcoholic hepatitis and to assess prognostic factors among clinical characteristics and laboratory variables of patients with alcoholic hepatitis. METHODS: Thirty-four patients with the diagnosis of alcoholic hepatitis admitted to Hippokration University Hospital of Athens from 2000 to 2005 were assessed in the current retrospective study and a statistical analysis was conducted. RESULTS: 30- and 90-d mortality rates were reported at 5.9% (2/34) and 14.7% (5/34), respectively. Significant correlation was demonstrated for the Model for End-Stage Liver Disease (P30 = 0.094, P90 = 0.046) and the Maddrey Discriminant Function score (P30 = 0.033, P90 = 0.038) with 30- and 90-d mortality whereas a significant association was also established for alanine aminotransferase (P = 0.057), fibrin degradation products (P = 0.048) and C-reactive protein (P = 0.067) with 90-d mortality. For 30-d mortality the Area Under the Curve was 0.969 (95%CI: 0.902-1.036, P = 0.028) for the Model for End-Stage Liver Disease score and 0.984 (95%CI: 0.942-1.027, P = 0.023) for the Maddrey Discriminant Function score with the optimal cut off point of 30.5 (sensitivity 1, specificity 0.937) and 108.68 (sensitivity 1, specificity 0.969), respectively. Accordingly, for 90-d mortality the Area Under the Curve was 0.762 (95%CI: 0.559-0.965, P = 0.065) for the Model for End-Stage Liver Disease score and 0.752 (95%CI: 0.465-1.038, P = 0.076) for the Maddrey Discriminant Function score with the optimal cut off point of 19 (sensitivity 0.6, specificity 0.6) and 92 (sensitivity 0.6, specificity 0.946), respectively. The observed Kaplan Meier survival rates for different score-categories were compared with log-rank tests and higher score values were correlated with a lower survival. CONCLUSION: Equivalency of

  9. Atrophy Patterns in Early Clinical Stages Across Distinct Phenotypes of Alzheimer’s Disease

    PubMed Central

    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.

    2015-01-01

    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

  10. Advances in cardiac magnetic resonance imaging of congenital heart disease.

    PubMed

    Driessen, Mieke M P; Breur, Johannes M P J; Budde, Ricardo P J; van Oorschot, Joep W M; van Kimmenade, Roland R J; Sieswerda, Gertjan Tj; Meijboom, Folkert J; Leiner, Tim

    2015-01-01

    Due to advances in cardiac surgery, survival of patients with congenital heart disease has increased considerably during the past decades. Many of these patients require repeated cardiovascular magnetic resonance imaging to assess cardiac anatomy and function. In the past decade, technological advances have enabled faster and more robust cardiovascular magnetic resonance with improved image quality and spatial as well as temporal resolution. This review aims to provide an overview of advances in cardiovascular magnetic resonance hardware and acquisition techniques relevant to both pediatric and adult patients with congenital heart disease and discusses the techniques used to assess function, anatomy, flow and tissue characterization. PMID:25552386

  11. Overview: end-stage renal disease in the developing world.

    PubMed

    Barsoum, Rashad S

    2002-09-01

    Although the vast majority of patients with end-stage renal disease (ESRD) worldwide live in what is called the developing world, little is known about its epidemiology and management. With the current paucity of credible and adequately representative registries, it is justified to resort to innovative means of obtaining information. In this attempt, world-renowned leading nephrologists in 10 developing countries collaborated in filling a 103-item questionnaire addressing epidemiology, etiology, and management of ESRD in their respective countries on the basis of integrating available data from different sources. Through this joint effort, it was possible to identify a number of important trends. These include the expected high prevalence of ESRD, despite the limited access to renal replacement therapy, and the dependence of prevalence on wealth. Glomerulonephritis, rather than diabetes, remains as the main cause of ESRD with significant geographical variations in the prevailing histopathological types. The implementation of different modalities of renal replacement therapy (RRT) is inhibited by the lack of funding, although governments, insurance companies, and donations usually constitute the major sponsors. Hemodialysis is the preferred modality in most countries with the exception of Mexico where chronic ambulatory peritoneal dialysis (CAPD) takes the lead. In several other countries, dialysis is available only for those on the transplant waiting list. Dialysis is associated with a high frequency of complications particularly HBV and HCV infections. Data on HIV are lacking. Aluminum intoxication remains as a major problem in a number of countries. Treatment withdrawal is common for socioeconomic reasons. Transplantation is offered to an average of 4 per million population (pmp). Recipient exclusion criteria are minimal. Donor selection criteria are generally loose regarding tissue typing, remote viral infection, and, in some countries, blood-relation to the

  12. Staged diabetes management: computerizing a disease state management program.

    PubMed

    Ginsberg, B H; Tan, M H; Mazze, R; Bergelson, A

    1998-04-01

    Recently, the Diabetes Control and Complication Trial (DCCT) and other similar studies have demonstrated that near-normalization of blood glucose in diabetes will reduce complications up to 75% but translation of these results into practice has been difficult. In an attempt to help provide the best possible control of patients with diabetes, we have produced an attempt to help provide the best possible control of patients with diabetes, we have produced a new disease state management system for diabetes, called "Staged Diabetes Management" (SDM), implemented it in over 100 sites worldwide, and developed a computer program to simplify its use. SDM, designed to change the way we deal with patients with diabetes, is based upon five principles: (1) community involvement in setting care guidelines; (2) negotiation of goals with patients; (3) appropriate timelines for therapeutic success; (4) use of flowcharts for medical decisions; and (5) evaluation of the program. SDM is designed to be altered by a community to meet its needs and resources. It encourages primary care physicians to deliver better diabetes care using a team approach and to refer patients with diabetes to specialists when appropriate. It has a complete set of materials for communities, individual health care providers and patients. SDM has been tested for changes in structure, process and outcomes. A meta-analysis of seven clinical trials with over 500 patients has shown a time-weighted average fall in hemoglobin A1c of 1.7 points (equivalent to a drop in mean blood glucose of about 3.5 mM or 60 mg/dL). Preliminary pharmacoeconomic analysis demonstrates a lifetime cost saving of over $27,000 per patient. A computer program has been developed for the Microsoft Windows environment that contains a client-server database, based upon DiabCare, for the data file structure. PMID:9571514

  13. Obesity Paradox in End-Stage Kidney Disease Patients

    PubMed Central

    Park, Jongha; Ahmadi, Seyed-Foad; Streja, Elani; Molnar, Miklos Z; Flegal, Katherine M.; Gillen, Daniel; Kovesdy, Csaba P.; Kalantar-Zadeh, Kamyar

    2016-01-01

    In the general population, obesity is associated with increased cardiovascular risk and decreased survival. In patients with end-stage renal disease (ESRD), however, an “obesity paradox” or “reverse epidemiology” (to include lipid and hypertension paradoxes) has been consistently reported, i.e. a higher body mass index (BMI) is paradoxically associated with better survival. This survival advantage of large body size is relatively consistent for hemodialysis patients across racial and regional differences, although published results are mixed for peritoneal dialysis patients.. Recent data indicate that both higher skeletal muscle mass and increased total body fat are protective, although there are mixed data on visceral (intra-abdominal) fat. The obesity paradox in ESRD is unlikely to be due to residual confounding alone and has biologic plausibility. Possible causes of the obesity paradox include protein-energy wasting and inflammation, time discrepancy among competitive risk factors (undernutrition versus overnutrition), hemodynamic stability, alteration of circulatory cytokines, sequestration of uremic toxin in adipose tissue, and endotoxin-lipoprotein interaction. The obesity paradox may have significant clinical implications in the management of ESRD patients especially if obese dialysis patients are forced to lose weight upon transplant wait-listing. Well-designed studies exploring the causes and consequences of the reverse epidemiology of cardiovascular risk factors, including the obesity paradox, among ESRD patients could provide more information on mechanisms. These could include controlled trials of nutritional and pharmacologic interventions to examine whether gain in lean body mass or even body fat can improve survival and quality of life in these patients. PMID:24438733

  14. The conjoint use of music therapy and reflexology with hospitalized advanced stage cancer patients and their families.

    PubMed

    Magill, Lucanne; Berenson, Susan

    2008-09-01

    Advanced stage cancer patients experience debilitating physical symptoms as well as profound emotional and spiritual struggles. Advanced disease is accompanied by multiple changes and losses for the patient and the family. Palliative care focuses on the relief of overall suffering of patients and families, including symptom control, psychosocial support, and the meeting of spiritual needs. Music therapy and reflexology are complementary therapies that can soothe and provide comfort. When used conjointly, they provide a multifaceted experience that can aid in the reduction of anxiety, pain, and isolation; facilitate communication between patients, family members, and staff; and provide the potential for a more peaceful dying experience for all involved. This article addresses the benefits of the combined use of music therapy and reflexology. Two case studies are presented to illustrate the application and benefits of this dual approach for patients and their families regarding adjustment to the end of life in the presence of anxiety and cognitive impairment. PMID:18662423

  15. Advances in apheresis therapy for glomerular diseases.

    PubMed

    Yokoyama, Hitoshi; Wada, Takashi; Zhang, Wei; Yamaya, Hideki; Asaka, Mitsuhiro

    2007-06-01

    This article is an overview of the immunomodulatory effects of apheresis in renal diseases, especially primary and secondary glomerulonephritis, and the clinical evidence for the efficacy of apheresis therapy. Permeability factor(s) derived from circulating T cells are speculated to have a crucial role in the proteinuria of nephrotic syndrome (NS). Plasma exchange (PE); immunoadsorption plasmapheresis (IAPP), using protein A sepharose cartridges; low-density lipoprotein apheresis; and lymphocytapheresis (LCAP) have been used to remove such factors or pathogenic T cells. Other glomerular diseases induced by specific antibodies such as anti-glomerular basement membrane antibodies, anti-neutrophil cytoplasmic antibodies, and immune-complexes have also been treated with PE, double-filtration plasmapheresis, IAPP, and LCAP. Recommendations, based on the evidence from recent randomized controlled studies, have been established in apheresis therapy for various glomerular diseases. PMID:17593511

  16. [Advances in Genomics Studies for Coronary Artery Disease].

    PubMed

    Wang, Ying; Zhu, Hui-juan; Zeng, Yong

    2015-08-01

    Coronary artery disease (CAD) is one of the major life-threatening diseases. In addition to traditional risk factors including age, sex, smoking, hypertension,and diabetes, genomic studies have shown that CAD has obvious genetic predisposition. In recent years, the rapid advances in genomics shed new light on early diagnosis, risk stratification and new treatment targets. PMID:26564468

  17. Selected aspects of palliative care and quality of life at the terminal stage of neoplastic disease.

    PubMed

    Farbicka, Paulina; Nowicki, Andrzej

    2012-01-01

    Neoplastic diseases are among the most common causes of death. The quality of life in neoplastic disease depends on the type of neoplasm, level of progression, location, treatment possibilities and prognosis. Cancer reduces the quality of life at the advanced stage of disease. At this time patients feel pain and suffering. Palliative care is used in the terminal phase of neoplastic disease. It includes overall care of an incurable patient and her/his family. The main objective of palliative care is meeting somatic and psycho-social requirements. Recently, more and more physicians dealing with oncological patients are moving away from treatment of the patient like an object. They pay attention to a subjective approach to treatment outcomes that are felt by the patient. The model of medicine is becoming a holistic one and during examination physicians pay attention to the patient's physical and mental state, economic condition, social situation, feelings or lack of complaints more often. Research on quality of life is becoming a vital part of medical examination. PMID:23788936

  18. Selected aspects of palliative care and quality of life at the terminal stage of neoplastic disease

    PubMed Central

    Farbicka, Paulina

    2013-01-01

    Neoplastic diseases are among the most common causes of death. The quality of life in neoplastic disease depends on the type of neoplasm, level of progression, location, treatment possibilities and prognosis. Cancer reduces the quality of life at the advanced stage of disease. At this time patients feel pain and suffering. Palliative care is used in the terminal phase of neoplastic disease. It includes overall care of an incurable patient and her/his family. The main objective of palliative care is meeting somatic and psycho-social requirements. Recently, more and more physicians dealing with oncological patients are moving away from treatment of the patient like an object. They pay attention to a subjective approach to treatment outcomes that are felt by the patient. The model of medicine is becoming a holistic one and during examination physicians pay attention to the patient's physical and mental state, economic condition, social situation, feelings or lack of complaints more often. Research on quality of life is becoming a vital part of medical examination. PMID:23788936

  19. Long-term outcome of patients with advanced-stage cutaneous T cell lymphoma treated with gemcitabine.

    PubMed

    Pellegrini, Cinzia; Stefoni, Vittorio; Casadei, Beatrice; Maglie, Roberto; Argnani, Lisa; Zinzani, Pier Luigi

    2014-11-01

    The choice of treatment for cutaneous T cell lymphoma (CTCL) is often determined by institutional experience, particularly as there is a paucity of data from phase III trials and a lack of consensus concerning treatment of the advanced stages. Among the several second-line and experimental drugs, gemcitabine could be considered one of the most suitable options for pretreated CTCL. Since it is difficult to find in literature the long-term outcome regarding the efficacy of a single-agent drug in pretreated patients and, in particular, in rare diseases such as CTCL, a retrospective observational study was conducted with the aim of evaluating the long-term outcome of CTCL patients treated with gemcitabine. Twenty-five patients with at least one therapy (range 1-8) performed prior to gemcitabine were found. After gemcitabine treatment, the overall response was 48 % with a 20 % of complete responses. At 15 years, the estimated overall survival is 47 %, progression-free survival 8.8 %, and disease-free survival 40 % (median reached at 2.9 years). All patients received at least three cycles and no grade 3-4 hematological adverse events occurred. At the latest follow-up, two patients are still in continuous complete response. This long-term update on the role of gemcitabine as a single agent in pretreated advanced-stage CTCL confirms this monotherapy as effective and safe. PMID:24908331

  20. NIH Research: Advances in Parkinson's Disease Research

    MedlinePlus

    ... fundamental contributions to the understanding of nervous system development. Neurological disorders—such as Parkinson's disease (PD)—strike an estimated 50 million Americans each year, exacting an incalculable personal toll and an annual economic cost of hundreds of billions of dollars in ...

  1. Advanced Development Program for a 625 lbf thrust engine for Ares First Stage Roll Control System

    NASA Technical Reports Server (NTRS)

    Dawson, Matt; Chenevert, Blake; Brewster, Gerry; Frei, Tom; Bullard, Brad; Fuller, Ray

    2009-01-01

    NASA's new Ares Launch Vehicle will require twelve thrusters to provide roll control of the vehicle during the first stage firing. All twelve roll control thrusters will be located at the inter-stage segment that separates the solid rocket booster first stage from the second stage. NASA selected a mono propellant hydrazine solution and as a result awarded Aerojet-General a contract in 2007 for an advanced development program for an MR-80- series 625 Ibf vacuum thrust monopropellant hydrazine thruster. This thruster has heritage dating back to the 1976 Viking Landers and most recently for the 2011 Mars Science Laboratory. Prior to the Ares application, the MR-80-series thrusters had been equipped with throttle valves and not typically operated in pulse mode. The primary objective of the advanced development program was to increase the technology readiness level and retire major technical risks for the future flight qualification test program. Aerojet built on their heritage MR-80 rocket engine designs to achieve the design and performance requirements. Significant improvements to cost and lead-time were achieved by applying Design for Manufacturing and Assembly (DFMA) principles. AerojetGeneral has completed Preliminary and Critical Design Reviews, followed by two successful rocket engine development test programs. The test programs included qualification random vibration and firing lite that significantly exceed the flight qualification requirements. This paper discusses the advanced development program and the demonstrated capability of the MR-80C engine. Y;

  2. New NIA Booklet By and For People With Early-Stage Alzheimer's Disease

    MedlinePlus

    ... Booklet By and For People With Early-Stage Alzheimer's Disease Past Issues / Fall 2007 Table of Contents ... you have a family member or friends with Alzheimer's disease? Are you wondering what they're going ...

  3. Sevelamer revisited: pleiotropic effects on endothelial and cardiovascular risk factors in chronic kidney disease and end-stage renal disease

    PubMed Central

    2013-01-01

    Endothelial dysfunction underlies multiple cardiovascular consequences of chronic kidney disease (CKD) and antecedent diabetes or hypertension. Endothelial insults in CKD or end-stage renal disease (ESRD) patients include uremic toxins, serum uric acid, hyperphosphatemia, reactive oxygen species, and advanced glycation endproducts (AGEs). Sevelamer carbonate, a calcium-free intestinally nonabsorbed polymer, is approved for hyperphosphatemic dialysis patients in the US and hyperphosphatemic stage 3–5 CKD patients in many other countries. Sevelamer has been observed investigationally to reduce absorption of AGEs, bacterial toxins, and bile acids, suggesting that it may reduce inflammatory, oxidative, and atherogenic stimuli in addition to its on-label action of lowering serum phosphate. Some studies also suggest that noncalcium binders may contribute less to vascular calcification than calcium-based binders. Exploratory sevelamer carbonate use in patients with stages 2–4 diabetic CKD significantly reduced HbA1c, AGEs, fibroblast growth factor (FGF)-23, and total and low-density lipoprotein (LDL) cholesterol versus calcium carbonate; inflammatory markers decreased and defenses against AGEs increased. Sevelamer has also been observed to reduce circulating FGF-23, potentially reducing risk of left ventricular hypertrophy. Sevelamer but not calcium-based binders in exploratory studies increases flow-mediated vasodilation, a marker of improved endothelial function, in patients with CKD. In contrast, lanthanum carbonate and calcium carbonate effects on FMV did not differ in hemodialysis recipients. The recent INDEPENDENT-CKD randomized trial compared sevelamer versus calcium carbonate in predialysis CKD patients (investigational in the US, on-label in European participants); sevelamer reduced 36-month mortality and the composite endpoint of mortality or dialysis inception. Similarly, INDEPENDENT-HD in incident dialysis patients showed improved survival with 24 months

  4. Reusable launch vehicles, enabling technology for the development of advanced upper stages and payloads

    SciTech Connect

    Metzger, John D.

    1998-01-15

    In the near future there will be classes of upper stages and payloads that will require initial operation at a high-earth orbit to reduce the probability of an inadvertent reentry that could result in a detrimental impact on humans and the biosphere. A nuclear propulsion system, such as was being developed under the Space Nuclear Thermal Propulsion (SNTP) Program, is an example of such a potential payload. This paper uses the results of a reusable launch vehicle (RLV) study to demonstrate the potential importance of a Reusable Launch Vehicle (RLV) to test and implement an advanced upper stage (AUS) or payload in a safe orbit and in a cost effective and reliable manner. The RLV is a horizontal takeoff and horizontal landing (HTHL), two-stage-to-orbit (TSTO) vehicle. The results of the study shows that an HTHL is cost effective because it implements airplane-like operation, infrastructure, and flight operations. The first stage of the TSTO is powered by Rocket-Based-Combined-Cycle (RBCC) engines, the second stage is powered by a LOX/LH rocket engine. The TSTO is used since it most effectively utilizes the capability of the RBCC engine. The analysis uses the NASA code POST (Program to Optimize Simulated Trajectories) to determine trajectories and weight in high-earth orbit for AUS/advanced payloads. Cost and reliability of an RLV versus current generation expandable launch vehicles are presented.

  5. Bone marrow derived stem cells for the treatment of end-stage liver disease.

    PubMed

    Margini, Cristina; Vukotic, Ranka; Brodosi, Lucia; Bernardi, Mauro; Andreone, Pietro

    2014-07-21

    End-stage disease due to liver cirrhosis is an important cause of death worldwide. Cirrhosis results from progressive, extensive fibrosis and impaired hepatocyte regeneration. The only curative treatment is liver transplantation, but due to the several limitations of this procedure, the interest in alternative therapeutic strategies is increasing. In particular, the potential of bone marrow stem cell (BMSC) therapy in cirrhosis has been explored in different trials. In this article, we evaluate the results of 18 prospective clinical trials, and we provide a descriptive overview of recent advances in the research on hepatic regenerative medicine. The main message from the currently available data in the literature is that BMSC therapy is extremely promising in the context of liver cirrhosis. However, its application should be further explored in randomized, controlled trials with large cohorts and long follow-ups. PMID:25083082

  6. The Influence of Social Norms on Advancement Through Bystander Stages for Preventing Interpersonal Violence.

    PubMed

    Deitch-Stackhouse, Jacqueline; Kenneavy, Kristin; Thayer, Richard; Berkowitz, Alan; Mascari, Janine

    2015-10-01

    This research evaluates the impact of social norms on the advancement through the bystander stages toward prosocial (active) intervention in interpersonal violence (IPV): emotional abuse, physical violence, controlling behavior, sexual violence, and stalking. The influence of social norms on bystander behavior across stages and types of violence varies. Accurate social norms perceptions are associated with routine intervention, although social norms misperceptions are not always a strong deterrent to intervention. Interpretation of a violent situation as problematic predicts increased willingness to intervene. Implications for the development of social norms antiviolence campaigns and strategies for reducing barriers to prosocial intervention are discussed. PMID:26175519

  7. Cortical hypometabolism and hypoperfusion in Parkinson's disease is extensive: probably even at early disease stages.

    PubMed

    Borghammer, Per; Chakravarty, Mallar; Jonsdottir, Kristjana Yr; Sato, Noriko; Matsuda, Hiroshi; Ito, Kengo; Arahata, Yutaka; Kato, Takashi; Gjedde, Albert

    2010-05-01

    Recent cerebral blood flow (CBF) and glucose consumption (CMRglc) studies of Parkinson's disease (PD) revealed conflicting results. Using simulated data, we previously demonstrated that the often-reported subcortical hypermetabolism in PD could be explained as an artifact of biased global mean (GM) normalization, and that low-magnitude, extensive cortical hypometabolism is best detected by alternative data-driven normalization methods. Thus, we hypothesized that PD is characterized by extensive cortical hypometabolism but no concurrent widespread subcortical hypermetabolism and tested it on three independent samples of PD patients. We compared SPECT CBF images of 32 early-stage and 33 late-stage PD patients with that of 60 matched controls. We also compared PET FDG images from 23 late-stage PD patients with that of 13 controls. Three different normalization methods were compared: (1) GM normalization, (2) cerebellum normalization, (3) reference cluster normalization (Yakushev et al.). We employed standard voxel-based statistics (fMRIstat) and principal component analysis (SSM). Additionally, we performed a meta-analysis of all quantitative CBF and CMRglc studies in the literature to investigate whether the global mean (GM) values in PD are decreased. Voxel-based analysis with GM normalization and the SSM method performed similarly, i.e., both detected decreases in small cortical clusters and concomitant increases in extensive subcortical regions. Cerebellum normalization revealed more widespread cortical decreases but no subcortical increase. In all comparisons, the Yakushev method detected nearly identical patterns of very extensive cortical hypometabolism. Lastly, the meta-analyses demonstrated that global CBF and CMRglc values are decreased in PD. Based on the results, we conclude that PD most likely has widespread cortical hypometabolism, even at early disease stages. In contrast, extensive subcortical hypermetabolism is probably not a feature of PD. PMID

  8. Primary Tumor Site as a Predictor of Treatment Outcome for Definitive Radiotherapy of Advanced-Stage Oral Cavity Cancers

    SciTech Connect

    Lin, Chien-Yu; Wang, Hung-Ming; Kang, Chung-Jan; Lee, Li-Yu; Huang, Shiang-Fu; Fan, Kang-Hsing; Chen, Eric Yen-Chao

    2010-11-15

    Purpose: To evaluate the outcome of definitive radiotherapy (RT) for oral cavity cancers and to assess prognostic factors. Methods and Materials: Definitive RT was performed on 115 patients with oral cavity cancers at Stages III, IVA, and IVB, with a distribution of 6%, 47%, and 47%, respectively. The median dose of RT was 72Gy (range, 62-76Gy). Cisplatin-based chemotherapy was administered to 95% of the patients. Eleven patients underwent salvage surgery after RT failure. Results: Eight-eight (76.5%) patients responded partially and 23 (20%) completely; of the patients who responded, 18% and 57%, respectively, experienced a durable effect of treatment. The 3-year overall survival, disease-specific survival, and progression-free survival were 22%, 27%, and 25%, respectively. The 3-year PFS rates based on the primary tumor sites were as follows: Group I (buccal, mouth floor, and gum) 51%, Group II (retromolar and hard palate) 18%, and Group III (tongue and lip) 6% (p < 0.0001). The 3-year progression-free survival was 41% for N0 patients and 19% for patients with N+ disease (p = 0.012). The T stage and RT technique did not affect survival. The patients who underwent salvage surgery demonstrated better 3-year overall survival and disease-specific survival (53% vs. 19%, p = 0.015 and 53% vs. 24%, p = 0.029, respectively). Subsite group, N+, and salvage surgery were the only significant prognostic factors for survival after multivariate analysis. Conclusion: The primary tumor site and neck stage are prognostic predictors in advanced-stage oral cancer patients who received radical RT. The primary tumor extension and RT technique did not influence survival.

  9. A comparison of biochemical and histopathologic staging in cats with chronic kidney disease.

    PubMed

    McLeland, S M; Cianciolo, R E; Duncan, C G; Quimby, J M

    2015-05-01

    Chronic kidney disease (CKD) is prevalent in elderly cats. Frequently, a diagnosis is made in later stages of disease, by which time many renal lesions are irreversible. As such, little headway has been made in identifying an etiology and preventing this common disease. The aim of this study was to evaluate the presence and severity of both reversible and irreversible histopathologic changes in the kidneys of cats at each stage of CKD and, in addition, to determine if lesion prevalence and character were different between stages. A total of 46 cats with CKD were classified according to the International Renal Interest Society (IRIS) as stage I (3 cats), stage II (16 cats), stage III (14 cats), and stage IV (13 cats). Eleven young, nonazotemic and 10 geriatric, nonazotemic cats were included as controls. The severity of tubular degeneration, interstitial inflammation, fibrosis, and glomerulosclerosis was significantly greater in later stages of CKD compared with early stages of disease. Proteinuria was associated with increased severity of tubular degeneration, inflammation, fibrosis, tubular epithelial single-cell necrosis, and decreased normal parenchyma. Presence of hyperplastic arteriolosclerosis, fibrointimal hyperplasia, or other vascular lesions were not found to be significantly different between hypertensive and normotensive cats. The greater prevalence and severity of irreversible lesions in stage III and IV CKD implies that therapeutic interventions should be targeted at earlier stages of disease. PMID:25516066

  10. Dynamics of Sleep Stage Transitions in Health and Disease

    NASA Astrophysics Data System (ADS)

    Kishi, Akifumi; Struzik, Zbigniew R.; Natelson, Benjamin H.; Togo, Fumiharu; Yamamoto, Yoshiharu

    2007-07-01

    Sleep dynamics emerges from complex interactions between neuronal populations in many brain regions. Annotated sleep stages from electroencephalography (EEG) recordings could potentially provide a non-invasive way to obtain valuable insights into the mechanisms of these interactions, and ultimately into the very nature of sleep regulation. However, to date, sleep stage analysis has been restricted, only very recently expanding the scope of the traditional descriptive statistics to more dynamical concepts of the duration of and transitions between vigilance states and temporal evaluation of transition probabilities among different stages. Physiological and/or pathological implications of the dynamics of sleep stage transitions have, to date, not been investigated. Here, we study detailed duration and transition statistics among sleep stages in healthy humans and patients with chronic fatigue syndrome, known to be associated with disturbed sleep. We find that the durations of waking and non-REM sleep, in particular deep sleep (Stages III and IV), during the nighttime, follow a power-law probability distribution function, while REM sleep durations follow an exponential function, suggestive of complex underlying mechanisms governing the onset of light sleep. We also find a substantial number of REM to non-REM transitions in humans, while this transition is reported to be virtually non-existent in rats. Interestingly, the probability of this REM to non-REM transition is significantly lower in the patients than in controls, resulting in a significantly greater REM to awake, together with Stage I to awake, transition probability. This might potentially account for the reported poor sleep quality in the patients because the normal continuation of sleep after either the lightest or REM sleep is disrupted. We conclude that the dynamical transition analysis of sleep stages is useful for elucidating yet-to-be-determined human sleep regulation mechanisms with a

  11. Stages of Change for the Component Behaviors of Advance Care Planning

    PubMed Central

    Fried, Terri R.; Redding, Colleen; Robbins, Mark; Paiva, Andrea; O’Leary, John R.; Iannone, Lynne

    2010-01-01

    Objectives 1) To develop stages of change measures for advance care planning (ACP), conceptualized as a group of interrelated but separate behaviors. 2) To use these measures to characterize older persons’ engagement in and factors associated with readiness to participate in ACP. Design Observational cohort study. Setting Community. Participants Persons age ≥ 65 recruited from physician offices and a senior center. Measurements Stages of change for six ACP behaviors: completion of a living will and health care proxy, communication with loved ones regarding use of life-sustaining treatments and quantity versus quality of life (QOL), and communication with physicians about these same issues. Results Readiness to participate in ACP varied widely across behaviors. Whereas between approximately 50–60% of participants were in the action or maintenance stage for communicating with loved ones and completing a living will, 40% were in the precontemplation stage for communicating with loved ones about quantity versus QOL, and 70–75% were in the precontemplation stage for communicating with physicians. Participants were frequently in different stages for the different behaviors. Relatively few sociodemographic, health, or psychosocial factors were associated with stages of change for completing a living will, but a broader range of factors was associated with stages of change for communication with loved ones about quantity versus QOL. Conclusion Older persons show a range of readiness to engage in different aspects of ACP. Individualized assessment and interventions targeted to stage of behavior change for each component of ACP may be an effective strategy to increase participation in ACP. PMID:21143441

  12. Efficacy Comparison Between Total Laryngectomy and Nonsurgical Organ-Preservation Modalities in Treatment of Advanced Stage Laryngeal Cancer

    PubMed Central

    Fu, Xiaoyuan; Zhou, Qi; Zhang, Xianquan

    2016-01-01

    Abstract It remains unclear whether the efficacy of nonsurgical organ-preservation modalities (NOP) in the treatment of advanced-stage laryngeal cancer was noninferiority compared with that of total laryngectomy (TL). The objective of this study was to compare the curative effects between TL and NOP in the treatment of advanced-stage laryngeal cancer through a meta-analysis. Clinical studies were retrieved from the electronic databases of PubMed, Embase, Wanfang, and Chinese National Knowledge infrastructure. A meta-analysis was performed to investigate the differences in the curative efficacy of advanced-stage laryngeal cancer between TL and the nonsurgical method. Two reviewers screened all titles and abstracts, and independently assessed all articles. All identified studies were retrospective. Sixteen retrospective studies involving 8308 patients (4478 in the TL group and 3701 in the nonsurgical group) were included in this meta-analysis. The analysis results displayed the advantage of TL for 2-year and 5-year overall survival (OS)(OR 2.79, 95% CI 1.85–4.23 and OR 1.52, 95% CI 1.09–2.14) as well as in 5-year disease-specific survival (DSS)(OR 1.79, 95% CI 1.61–1.98), but no significant difference in 2-year DSS was detected between the 2 groups (OR = 2.09,95% CI0.69–6.40). Additionally, there were no significant differences between TL and NOP for 5-year local control (LC) either (OR = 1.75, 95% CI 0.87–3.53). When we carried out subgroup analyses, the advantage of TL was especially obvious in T4 subgroups, but not in T3 subgroups. This is the first study to compare the curative effects on advanced-stage laryngeal cancer using meta-analytic methodology. Although there was a trend in favor of TL for OS and DSS, there is no clear difference in oncologic outcome between TL and NOP. Therefore, other factors such as tumor T-stage and size, lymph node metastasis, and physical condition are also important indicators for treatment choice. PMID:27057837

  13. Usefulness of pallidotomy in advanced Parkinson's disease.

    PubMed Central

    Johansson, F; Malm, J; Nordh, E; Hariz, M

    1997-01-01

    OBJECTIVE: The combined effect of posteroventral pallidotomy and optimal medical treatment was assessed in 22 patients with levodopa sensitive Parkinson's disease. METHODS: Timed motor tests, video recordings, and computer assisted optoelectronic movement analysis were used for serial hourly assessments performed preoperatively and four and 12 months after operation. Tests were made while patients were on optimal medical therapy. RESULTS: There were no serious adverse events of surgery. Two of the 22 patients could not complete all the tests after operation. The proportion of dyskinesia periods decreased in the 20 patients and there was a proportional increase in normal or fairly normal occasions. "Off" periods were not significantly affected. In 12 of 13 patients with limb dyskinesia this symptom was completely abolished in the contralateral limbs. There was also some degree of improvement axially and ipsilaterally. Tremor was moderately improved contralaterally. Bradykinesia remained unchanged. Results at 12 months follow up were similar to those at four months. CONCLUSION: Pallidotomy produced a pronounced positive effect on dyskinesia and a moderate effect on tremor. Bradykinesia was not affected. Posteroventral pallidotomy may be useful in patients with Parkinson's disease who have severe motor fluctuations and may allow an increase in levodopa dose to alleviate bradykinesia in "off" states. Images PMID:9048711

  14. Future care planning: a first step to palliative care for all patients with advanced heart disease.

    PubMed

    Denvir, M A; Murray, S A; Boyd, K J

    2015-07-01

    Palliative care is recommended for patients with end-stage heart failure with several recent, randomised trials showing improvements in symptoms and quality of life and more studies underway. Future care planning provides a framework for discussing a range of palliative care problems with patients and their families. This approach can be introduced at any time during the patient's journey of care and ideally well in advance of end-of-life care. Future care planning is applicable to a wide range of patients with advanced heart disease and could be delivered systematically by cardiology teams at the time of an unplanned hospital admission, akin to cardiac rehabilitation for myocardial infarction. Integrating cardiology care and palliative care can benefit many patients with advanced heart disease at increased risk of death or hospitalisation. Larger, randomised trials are needed to assess the impact on patient outcomes and experiences. PMID:25900977

  15. 77 FR 34047 - Medicare Program; Proposal Evaluation Criteria and Standards for End Stage Renal Disease (ESRD...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-08

    ... and Standards for End Stage Renal Disease (ESRD) Network Organizations AGENCY: Centers for Medicare... procedures we will use to evaluate an End-Stage Renal Disease (ESRD) Network Organization's capabilities to perform, and actual performance of, the duties and functions under the ESRD Network Statement of Work...

  16. Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease

    PubMed Central

    Charles, David; Konrad, Peter E.; Neimat, Joseph S.; Molinari, Anna L.; Tramontana, Michael G.; Finder, Stuart G.; Gill, Chandler E.; Bliton, Mark J.; Kao, Chris C.; Phibbs, Fenna T.; Hedera, Peter; Salomon, Ronald M.; Cannard, Kevin R.; Wang, Lily; Song, Yanna; Davis, Thomas L.

    2014-01-01

    Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50–75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. PMID:24768120

  17. PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.

    PubMed

    Barrington, Sally F; Kirkwood, Amy A; Franceschetto, Antonella; Fulham, Michael J; Roberts, Thomas H; Almquist, Helén; Brun, Eva; Hjorthaug, Karin; Viney, Zaid N; Pike, Lucy C; Federico, Massimo; Luminari, Stefano; Radford, John; Trotman, Judith; Fosså, Alexander; Berkahn, Leanne; Molin, Daniel; D'Amore, Francesco; Sinclair, Donald A; Smith, Paul; O'Doherty, Michael J; Stevens, Lindsey; Johnson, Peter W

    2016-03-24

    International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice. PMID:26747247

  18. Early supradiaphragmatic Hodgkin's disease. High-dose gallium scanning obviates the need for staging laparotomy

    SciTech Connect

    Blackwell, E.A.; Joshua, D.E.; McLaughlin, A.F.; Green, D.; Kronenberg, H.; May, J.

    1986-08-15

    Experience with 16 sequential patients with Stage IA/IIA supradiaphragmatic Hodgkin's disease who had no evidence of intra-abdominal disease using high-dose gallium and computerized tomography scanning is reported. Subsequent staging laparotomy also was negative in all these patients and did not alter management decisions. It is suggested that high-dose, whole-body gallium scanning and other noninvasive staging procedures give reliable data for therapeutic decisions.

  19. Recent advances in chronic granulomatous disease.

    PubMed

    Goldblatt, David

    2014-11-01

    Chronic Granulomatous Disease (CGD) is a primary immunodeficiency caused by abnormities in the NADPH Oxidase that is involved in the respiratory burst responsible for initiating the killing of microbes ingested by phagocytic cells. The hallmark of CGD is recurrent infection but the inflammatory complications can prove difficult to treat. New insights into the mechanisms responsible for the inflammatory complications have led to new therapies. The treatment of CGD colitis with an anti-tumour necrosis alpha agent has been shown to be successful but associated with significant infectious complications. Haematopoietic stem cell transplants offer the possibility of cure for those with ether a matched or unrelated donor transplant, with results of the latter improving significantly over recent years. Gene Therapy offers the promise of cure without the need for a transplant but better vectors are required. PMID:25264161

  20. Alzheimer's disease: recent advances and future perspectives.

    PubMed

    Ubhi, Kiren; Masliah, Eliezer

    2013-01-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory deficits and other cognitive disturbances. Neuropathologically, AD is characterized by the progressive loss of basal forebrain cholinergic neurons that innervate the hippocampus and cortex and the abnormal extracellular accumulation of amyloid-β and intracellular tau protein. Current research on AD is focused on the mechanisms underlying the abnormal oligomerization, fibrillation, and accumulation of the amyloid-β and tau proteins, mechanisms that may alter the dynamics of this accumulation and on experimental therapeutics approaches aimed at the clearance of the abnormally folded proteins and other potentially neuroprotective interventions. This review will summarize the main areas of investigation in AD and present ways forward for future work. PMID:22810100

  1. Quality of life of patients with end-stage renal disease at various stages of the illness.

    PubMed

    Frank, Attalya; Auslander, Gail K; Weissgarten, Joshua

    2003-01-01

    This study aimed to examine the quality of life of patients undergoing different types of treatment for End Stage Renal Disease at various points in the course of the disease. The theoretical model that guided the study was based on the work of Rolland (1987) and Wilson and Clearly (1995). Subjects were 72 patients at the largest nephrology center in Israel. Instruments included the SF-36 Health Survey (version 1.0) and Parfrey's health questionnaire for End Stage Renal Disease. The findings indicate that the negative effects of the disease on quality of life can be observed in the pre-dialysis stage, and that the strongest predictor of quality of life were patients' symptom reports, independent of objective indicators of their health state. Social workers play a key role in aiding patients and their families to adjust to the disease and its treatment prior to starting dialysis, and in bringing the importance of patients' subjective assessments to the attention of the treatment team. PMID:15022732

  2. Recent advances in small bowel diseases: Part II

    PubMed Central

    Thomson, Alan BR; Chopra, Angeli; Clandinin, Michael Tom; Freeman, Hugh

    2012-01-01

    As is the case in all areas of gastroenterology and hepatology, in 2009 and 2010 there were many advances in our knowledge and understanding of small intestinal diseases. Over 1000 publications were reviewed, and the important advances in basic science as well as clinical applications were considered. In Part II we review six topics: absorption, short bowel syndrome, smooth muscle function and intestinal motility, tumors, diagnostic imaging, and cystic fibrosis. PMID:22807605

  3. 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

  4. Treatment of Children with Advanced-Stage Lymphoblastic Lymphoma with Pegaspargase

    PubMed Central

    Yu-tong, Zhang; Li-hua, FENG; Xiao-dan, Zhong; Li-zhe, Wang; Jian, Chang

    2014-01-01

    Objective: To evaluate the feasibility of Pegaspargase instead of L-asparaginase to treat children with advanced-stage lymphoblastic lymphoma (LBL) on the Berlin-Frankfurt-Munster (BFM)-95 protocol. Methods: Fifty-four newly diagnosed patients with stage III or IV LBL and without any treatment were enrolled in this study. Pegaspargase took place of L-asparaginase in BFM-95. The complications and treatment responses of patients treated on the BFM-95 protocol and modified BFM-95 protocol were then evaluated respectively. Findings : For LBL patients treated with BFM-95 protocol or modified BFM-95 protocol, the complete response, event-free survival, overall survival were similar. Stage 4 myelosuppression was the most common complication in both groups. Besides that, among 31 patients receiving modified BFM-95 protocol, coagulation defects were the most common complication. In contrast, anaphylactic reaction was the most common complication in the other 23 patients receiving BFM-95 protocol. Conclusion: Modified BFM-95 protocol is available to children with advanced-stage LBL with an equal outcome and enhances its compliance and decreases the incidence of anaphylactic reaction, compared to BFM-95 protocol. Coagulation defects are the major complication and tolerable in modified one. PMID:25793049

  5. Percutaneous Coronary Intervention in Patients With End-Stage Liver Disease.

    PubMed

    Singh, Vikas; Patel, Nileshkumar J; Rodriguez, Alex P; Shantha, Ghanshyam; Arora, Shilpkumar; Deshmukh, Abhishek; Cohen, Mauricio G; Grines, Cindy; De Marchena, Eduardo; Badheka, Apurva; Ghatak, Abhijit

    2016-06-01

    The objective of our study was to assess patients with end-stage liver disease undergoing percutaneous coronary intervention (PCI) and determine the rates and trend of complications and in-hospital outcomes. Data were obtained from the Nationwide Inpatient Sample 2005 to 2012. We identified all PCIs performed in patients with diagnosis of cirrhosis during the study period by the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Preventable procedural complications were identified by Patient Safety Indicators. Propensity scoring method was used to establish matched cohorts to control for imbalances and account for differences that may have influenced treatment outcomes. A total of 1,051,242 PCIs were performed during the study period, of these, 122,342 were done on subjects with a formal diagnosis of cirrhosis. Bare-metal stents (BMS) were more likely to be used in patients who presented with ST-elevation myocardial infarction (19.73 vs 13.58, p <0.001), in cardiogenic shock (5.58, vs 2.81, p <0.001), or required intraaortic balloon pump (4.73 vs 2.38, p <0.001). The overall rate of complications was 7.1%, whereas the overall mortality rate over these years was 3.63%. On a propensity-matched analysis the mortality rate was 2 times higher for BMS (5.18 vs 2.35, p <0.001) compared with drug-eluting stents. PCI remains a safe and plausible option for patients with cirrhosis albeit riskier than for the general population. The use of BMS is associated with increased mortality and bleeding complications compared with drug-eluting stents which likely is representative of preferential use of BMS in patients with more advanced end-stage liver disease who are also likely to experience higher postprocedural complications. PMID:27103158

  6. Autosomal dominant polycystic kidney disease: recent advances in clinical management

    PubMed Central

    Mao, Zhiguo; Chong, Jiehan; Ong, Albert C. M.

    2016-01-01

    The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16 th century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21 st century. In this commentary, we consider how clinical management is likely to change in the coming decade. PMID:27594986

  7. Hypercalcemia of advanced chronic liver disease: a forgotten clinical entity!

    PubMed Central

    Kuchay, Mohammad Shafi; Mishra, Sunil Kumar; Farooqui, Khalid Jamal; Bansal, Beena; Wasir, Jasjeet Singh; Mithal, Ambrish

    2016-01-01

    Summary Hypercalcemia caused by advanced chronic liver disease (CLD) without hepatic neoplasia is uncommonly reported and poorly understood condition. We are reporting two cases of advanced CLD who developed hypercalcemia in the course of the disease. This diagnosis of exclusion was made only after meticulous ruling out of all causes of hypercalcemia. The unique feature of this type of hypercalcemia is its transient nature that may or may not require treatment. This clinical condition in patients with CLD should be kept in mind while evaluating the cause of hypercalcemia in them. PMID:27252737

  8. Autosomal dominant polycystic kidney disease: recent advances in clinical management.

    PubMed

    Mao, Zhiguo; Chong, Jiehan; Ong, Albert C M

    2016-01-01

    The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16 (th) century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21 (st) century. In this commentary, we consider how clinical management is likely to change in the coming decade. PMID:27594986

  9. Task-set switching deficits in early-stage Huntington's disease: implications for basal ganglia function.

    PubMed

    Aron, Adam R; Watkins, Laura; Sahakian, Barbara J; Monsell, Stephen; Barker, Roger A; Robbins, Trevor W

    2003-07-01

    Executive functions are likely mediated by interconnected circuits including frontal lobe and basal ganglia structures. We assessed the executive function of task switching in patients with early-stage Huntington's disease (HD), a neurodegenerative disease affecting the basal ganglia. In two experiments, the HD patients had greater difficulty when switching than when repeating a task than matched controls, and this was true even when scaling for the overall slowing of the patients. In the first experiment, HD patients had a switching deficit even in a "pure" condition where they had to switch, predictably, and with substantial preparation time, between stimuli having only one possible response, indicating a switching deficit different from that for patients with Parkinson's disease or frontal lobe trauma, and possibly relating to inadequate activation of stimulus-response links or "response set." In the more elaborate second experiment, we could not account for the switching deficit of the patients in terms of inadequate preparation in advance of a switch, deficient suppression of task-set processing from the preswitch trial, or impaired suppression of interference due to the presence of a competing task set. Instead, we found that part of the switching deficit was due to elevated reaction time and errors on switch trials for a repeated response (same button press as on preswitch trial) relative to an alternated response (different button press from preswitch trial). We argue that this elevated "repetition effect" for the HD patients is due to excessive inhibition of the just-performed response in advance of a switch. Alterations in the "response-setting" process alone (Experiment 1) and both the response-setting and "response inhibition" process (Experiment 2) probably arise from striatal pathology in HD, thus accounting for the task-switching deficits and showing how basal ganglia implemented response processes may underpin executive function. PMID:12965037

  10. Etiology and management of dyslipidemia in children with chronic kidney disease and end-stage renal disease.

    PubMed

    Khurana, Mona; Silverstein, Douglas M

    2015-12-01

    Lipids are essential components of cell membranes, contributing to cell fuel, myelin formation, subcellular organelle function, and steroid hormone synthesis. Children with chronic kidney disease (CKD) and end-stage renal disease (ESRD) exhibit various co-morbidities, including dyslipidemia. The prevalence of dyslipidemias in children with CKD and ESRD is high, being present in 39-65% of patients. Elevated lipid levels in children without renal disease are a risk factor for cardiovascular disease (CVD), while the risk for CVD in pediatric CKD/ESRD is unclear. The pathogenesis of dyslipidemia in CKD features various factors, including increased levels of triglycerides, triglyceride-rich lipoproteins, apolipoprotein C3 (ApoC-III), decreased levels of cholesterylester transfer protein and high-density lipoproteins, and aberrations in serum very low-density and intermediate-density lipoproteins. If initial risk assessment indicates that a child with advanced CKD has 2 or more co-morbidities for CVD, first-line treatment should consist of non-pharmacologic management such as therapeutic lifestyle changes and dietary counseling. Pharmacologic treatment of dyslipidemia may reduce the incidence of CVD in children with CKD/ESRD, but randomized trials are lacking. Statins are the only class of lipid-lowering drugs currently approved by the U.S. Food and Drug Administration (FDA) for use in the pediatric population. FDA-approved pediatric labeling for these drugs is based on results from placebo-controlled trial results, showing 30-50% reductions in baseline low-density lipoprotein cholesterol. Although statins are generally well tolerated in adults, a spectrum of adverse events has been reported with their use in both the clinical trial and post-marketing settings. PMID:25801207

  11. Diagnosis of cardiac disease in pediatric end-stage renal disease

    PubMed Central

    Chavers, Blanche M.; Solid, Craig A.; Sinaiko, Alan; Daniels, Frank X.; Chen, Shu-Cheng; Collins, Allan J.; Frankenfield, Diane L.; Herzog, Charles A.

    2011-01-01

    Background. Cardiac disease is a significant cause of morbidity and mortality in children with end-stage renal disease (ESRD). This study aimed to report the frequency of cardiac disease diagnostic methods used in US pediatric maintenance hemodialysis patients. Methods. A cross-sectional analysis of all US pediatric (ages 0.7–18 years, n = 656) maintenance hemodialysis patients was performed using data from the Centers for Medicare and Medicaid Services ESRD Clinical Performance Measures Project. Clinical and laboratory information was collected in 2001. Results were analysed by age, sex, race, Hispanic ethnicity, dialysis duration, body mass index (BMI), primary ESRD cause and laboratory data. Results. Ninety-two percent of the patients had a cardiovascular risk factor (63% hypertension, 38% anemia, 11% BMI > 94th percentile, 63% serum phosphorus > 5.5 mg/dL and 55% calcium–phosphorus product ≥ 55 mg2/dL2). A diagnosis of cardiac disease was reported in 24% (n = 155) of all patients: left ventricular hypertrophy/enlargement 17%, congestive heart failure/pulmonary edema 8%, cardiomyopathy 2% and decreased left ventricular function 2%. Thirty-one percent of patients were not tested. Of those tested, the diagnostic methods used were chest X-rays in 60%, echocardiograms in 35% and electrocardiograms in 33%; left ventricular hypertrophy/enlargement was diagnosed using echocardiogram (72%), chest X-ray (20%) and electrocardiogram (15%). Conclusions. Although 92% of patients had cardiovascular risk factors, an echocardiography was performed in only one-third of the patients. Our study raises the question of why echocardiography, considered the gold standard for cardiac disease diagnosis, has been infrequently used in pediatric maintenance dialysis patients, a high-risk patient population. PMID:20861193

  12. 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

  13. Ares First Stage "Systemology" - Combining Advanced Systems Engineering and Planning Tools to Assure Mission Success

    NASA Technical Reports Server (NTRS)

    Seiler, James; Brasfield, Fred; Cannon, Scott

    2008-01-01

    Ares is an integral part of NASA s Constellation architecture that will provide crew and cargo access to the International Space Station as well as low earth orbit support for lunar missions. Ares replaces the Space Shuttle in the post 2010 time frame. Ares I is an in-line, two-stage rocket topped by the Orion Crew Exploration Vehicle, its service module, and a launch abort system. The Ares I first stage is a single, five-segment reusable solid rocket booster derived from the Space Shuttle Program's reusable solid rocket motor. The Ares second or upper stage is propelled by a J-2X main engine fueled with liquid oxygen and liquid hydrogen. This paper describes the advanced systems engineering and planning tools being utilized for the design, test, and qualification of the Ares I first stage element. Included are descriptions of the current first stage design, the milestone schedule requirements, and the marriage of systems engineering, detailed planning efforts, and roadmapping employed to achieve these goals.

  14. Urinary Stone Disease: Advancing Knowledge, Patient Care, and Population Health.

    PubMed

    Scales, Charles D; Tasian, Gregory E; Schwaderer, Andrew L; Goldfarb, David S; Star, Robert A; Kirkali, Ziya

    2016-07-01

    Expanding epidemiologic and physiologic data suggest that urinary stone disease is best conceptualized as a chronic metabolic condition punctuated by symptomatic, preventable stone events. These acute events herald substantial future chronic morbidity, including decreased bone mineral density, cardiovascular disease, and CKD. Urinary stone disease imposes a large and growing public health burden. In the United States, 1 in 11 individuals will experience a urinary stone in their lifetime. Given this high incidence and prevalence, urinary stone disease is one of the most expensive urologic conditions, with health care charges exceeding $10 billion annually. Patient care focuses on management of symptomatic stones rather than prevention; after three decades of innovation, procedural interventions are almost exclusively minimally invasive or noninvasive, and mortality is rare. Despite these advances, the prevalence of stone disease has nearly doubled over the past 15 years, likely secondary to dietary and health trends. The NIDDK recently convened a symposium to assess knowledge and treatment gaps to inform future urinary stone disease research. Reducing the public health burden of urinary stone disease will require key advances in understanding environmental, genetic, and other individual disease determinants; improving secondary prevention; and optimal population health strategies in an increasingly cost-conscious care environment. PMID:26964844

  15. Contemporary Management of Coronary Artery Disease and Acute Coronary Syndrome in Patients with Chronic Kidney Disease and End-Stage Renal Disease

    PubMed Central

    Huang, Chin-Chou; Chen, Jaw-Wen

    2013-01-01

    Chronic kidney disease (CKD) and end-stage renal disease (ESRD) have emerged as a worldwide public health problem. Due to the remarkably higher incidence and prevalence of this chronic disease in Taiwan than in other countries, CKD/ESRD has contributed to a significant health burden in Taiwan. Patients with CKD/ESRD have an increased risk of coronary artery disease (CAD) and acute coronary syndrome (ACS) compared to the normal population. Patients with ACS alone can present differently than patients with ACS and CKD/ESRD. Also, due to the lower prevalence of chest pain and ST-segment elevation, CKD/ESRD patients were more difficult to diagnose than other patients. Furthermore, whether advances in ACS management with medical therapy and an early invasive approach could improve patient outcomes with CKD/ESRD is not known. The use of antiplatelets such as aspirin and other antithrombotic agents might reduce the incidence of ACS or stroke in CKD patients. However, such use could also increase bleeding risk and even increase the likelihood of mortality, especially in dialysis patients. While recent clinical data suggest the potential benefit of aggressive management with coronary intervention for CAD and ACS in this category of patients, further clinical studies are still indicated for the proper medical strategy and revascularization therapy to improve the outcomes of CAD and ACS in CKD/ESRD patients, both in Taiwan and worldwide. PMID:27122697

  16. Two-stage, low noise advanced technology fan. 5: Acoustic final report

    NASA Technical Reports Server (NTRS)

    Sofrin, T. G.; Riloff, N., Jr.

    1975-01-01

    The NASA Q2S(quiet two-stage) fan is a 0.836m (32.9 in.) diameter model of the STF 433 engine fan, selected in a 1972 study for an Advanced Technology Transport (ATT) airplane. Noise-control features include: low tip speed, moderate stage pressure rise, large blade-vane spacings, no inlet guide vanes, and optimum blade and vane numbers. Tests were run on the baseline Q2S fan with standard inlet and discharge ducts. Further tests were made of a translating centerbody sonic inlet device and treated discharge ducts. Results were scaled to JT8D and JT3D engine fan size for comparison with current two-stage fans, and were also scaled to STF 433 fan size to compare calculated ATT flyover noise with FAR 36 limits. Baseline Q2S results scaled to JT8D and JT3D engine fan sizes showed substantial noise reductions. Calculated unsuppressed baseline ATT flyovers averaged about 2.5 EPNdB below FAR 36 limits. Using measured sonic inlet results, scaled baseline Q2S fan results, and calculated attenuations for a 1975 technology duct liner, projected flyover noise calculations for the ATT averaged about FAR 36 limits minus 10 EPNdB. Advances in suppression technology required to meet the 1985 goal of FAR 36 limits minus 20 EPNdB are discussed.

  17. Advances in subtyping methods of foodborne disease pathogens.

    PubMed

    Boxrud, Dave

    2010-04-01

    Current subtyping methods for the detection of foodborne disease outbreaks have limitations that reduce their use by public health laboratories. Recent advances in subtyping of foodborne disease pathogens utilize techniques that identify nucleic acid polymorphisms. Recent methods of nucleic acid characterization such as microarrays and mass spectrometry (MS) may provide improvements such as increasing speed and data portability while decreasing labor compared to current methods. This article discusses multiple-locus variable-number tandem-repeat analysis, single-nucleotide polymorphisms, nucleic acid sequencing, whole genome sequencing, variable absent or present loci, microarrays and MS as potential subtyping methods to enhance our ability to detect foodborne disease outbreaks. PMID:20299203

  18. Baseline characteristics of patients with chronic kidney disease stage 3 and stage 4 in spain: the MERENA observational cohort study

    PubMed Central

    2011-01-01

    Background To obtain information on cardiovascular morbidity, hypertension control, anemia and mineral metabolism based on the analysis of the baseline characteristics of a large cohort of Spanish patients enrolled in an ongoing prospective, observational, multicenter study of patients with stages 3 and 4 chronic kidney diseases (CKD). Methods Multicenter study from Spanish government hospital-based Nephrology outpatient clinics involving 1129 patients with CKD stages 3 (n = 434) and 4 (n = 695) defined by GFR calculated by the MDRD formula. Additional analysis was performed with GFR calculated using the CKD-EPI and Cockcroft-Gault formula. Results In the cohort as a whole, median age 70.9 years, morbidity from all cardiovascular disease (CVD) was very high (39.1%). In CKD stage 4, CVD prevalence was higher than in stage 3 (42.2 vs 35.6% p < 0.024). Subdividing stage 3 in 3a and 3b and after adjusting for age, CVD increased with declining GFR with the hierarchy (stage 3a < stage 3b < stage 4) when calculated by CKD-EPI (31.8, 35.4, 42.1%, p 0.039) and Cockcroft-Gault formula (30.9, 35.6, 43.4%, p 0.010) and MDRD formula (32.5, 36.2, 42.2%,) but with the latter, it did not reach statistical significance (p 0.882). Hypertension was almost universal among those with stages 3 and 4 CKD (91.2% and 94.1%, respectively) despite the use of more than 3 anti-hypertensive agents including widespread use of RAS blockers. Proteinuria (> 300 mg/day) was present in more than 60% of patients and there was no significant differences between stages 3 and 4 CKD (1.2 ± 1.8 and 1.3 ± 1.8 g/day, respectively). A majority of the patients had hemoglobin levels greater than 11 g/dL (91.1 and 85.5% in stages 3 and 4 CKD respectively p < 0.001) while the use of erythropoiesis-stimulating agents (ESA) was limited to 16 and 34.1% in stages 3 and 4 CKD respectively. Intact parathyroid hormone (i-PTH) was elevated in stage 3 and stage 4 CKD patients (121 ± 99 and 166 ± 125 pg/mL p 0

  19. Persistence of Self in Advanced Alzheimer’s Disease

    PubMed Central

    Tappen, Ruth M.; Williams, Christine; Fishman, Sarah; Touhy, Theris

    2007-01-01

    Purpose To determine if evidence of the persistence of a sense of self or personal identity could be found in people in the middle and late stages of Alzheimer’s disease. The theme of diminishing self pervades both the popular and professional literature on Alzheimer’s disease. Design Qualitative using conversational analysis. The purposive sample was 23 residents of two urban nursing homes in the southeastern United States who were in the middle and late stages of Alzheimer’s disease. Their mean Mini-Mental State examination score was 10.65. Nineteen subjects were women, four were men in this 1993-1997 study. Methods Analysis of 45 conversations lasting 30 minutes with nursing home residents with a diagnosis of probable Alzheimer’s disease. Use of the first person indexical and other evidence, such as awareness and reactions to the changes that had taken place, in support of and counter to the notion of persistence of self, were sought in conversational analysis. Findings Respondents used the first person indexical frequently, freely, and coherently. Evidence was also present that participants were aware of their cognitive changes. Many struggled to provide an explanation, but none mentioned Alzheimer’s disease. Conclusions Evidence suggests the persistence of awareness of self into the middle and late stages of Alzheimer’s disease. Failure to recognize the continuing awareness of self and the human experience of the person in the middle and late stages can lead to task-oriented care and low expectations for therapeutic interventions. The bafflement noted in respondents suggests that people should be told their diagnosis and offered an explanation of what this diagnosis means. PMID:10380386

  20. Con: Nutritional vitamin D replacement in chronic kidney disease and end-stage renal disease.

    PubMed

    Agarwal, Rajiv; Georgianos, Panagiotis I

    2016-05-01

    Insufficiency of 25-hydroxyvitamin D [25(OH)D] is highly prevalent among patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD) and is a critical component in the pathogenesis of secondary hyperparathyroidism. Accordingly, current National Kidney Foundation-Kidney Disease Outcomes Quality Initiative and Kidney Disease: Improving Global Outcomes guidelines recommend the correction of hypovitaminosis D through nutritional vitamin D replacement as a first-step therapeutic approach targeting secondary hyperparathyroidism. In this Polar Views debate, we summarize the existing evidence, aiming to defend the position that nutritional vitamin D replacement is not evidence-based and should not be applied to patients with CKD. This position is supported by the following: (i) our meta-analysis of randomized controlled trials shows that whereas nutritional vitamin D significantly increases serum 25(OH)D levels relative to placebo, there is no evidence either in predialysis CKD or in ESRD that parathyroid hormone (PTH) is lowered; (ii) on the other hand, in randomized head-to-head comparisons, nutritional vitamin D is shown to be inferior to activated vitamin D analogs in reducing PTH levels; (iii) nutritional vitamin D is reported to exert minimal to no beneficial actions in a series of surrogate risk factors, including aortic stiffness, left ventricular mass index (LVMI), epoetin utilization and immune function among others; and (iv) there is no evidence to support a benefit of nutritional vitamin D on survival and other 'hard' clinical outcomes. Whereas nutritional vitamin D replacement may restore 25(OH)D concentration to near normal, the real target of treating vitamin D insufficiency is to treat secondary hyperparathyroidism, which is untouched by nutritional vitamin D. Furthermore, the pleotropic benefits of nutritional vitamin D remain to be proven. Thus, there is little, if any, benefit of nutritional vitamin D replacement in CKD. PMID:27190392

  1. Advances in Diagnosis of Respiratory Diseases of Small Ruminants

    PubMed Central

    Chakraborty, Sandip; Kumar, Amit; Tiwari, Ruchi; Rahal, Anu; Malik, Yash; Dhama, Kuldeep; Pal, Amar; Prasad, Minakshi

    2014-01-01

    Irrespective of aetiology, infectious respiratory diseases of sheep and goats contribute to 5.6 percent of the total diseases of small ruminants. These infectious respiratory disorders are divided into two groups: the diseases of upper respiratory tract, namely, nasal myiasis and enzootic nasal tumors, and diseases of lower respiratory tract, namely, peste des petits ruminants (PPR), parainfluenza, Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, caprine arthritis encephalitis virus, caseous lymphadenitis, verminous pneumonia, and many others. Depending upon aetiology, many of them are acute and fatal in nature. Early, rapid, and specific diagnosis of such diseases holds great importance to reduce the losses. The advanced enzyme-linked immunosorbent assays (ELISAs) for the detection of antigen as well as antibodies directly from the samples and molecular diagnostic assays along with microsatellites comprehensively assist in diagnosis as well as treatment and epidemiological studies. The present review discusses the advancements made in the diagnosis of common infectious respiratory diseases of sheep and goats. It would update the knowledge and help in adapting and implementing appropriate, timely, and confirmatory diagnostic procedures. Moreover, it would assist in designing appropriate prevention protocols and devising suitable control strategies to overcome respiratory diseases and alleviate the economic losses. PMID:25028620

  2. Advanced Stage T-Cell Non-Hodgkin lymphoma in an 11-Month-Old Infant and Related Superior Vena Cava Syndrome: Importance of Transthoracic Echocardiography.

    PubMed

    Yilmaz, Osman; Karabag, Kezban; Keskin Yildirim, Zuhal; Calik, Muhammet; Kilic, Omer

    2014-01-01

    Superior vena cava syndrome (SVCS) is rare in infants. Non-Hodgkin lymphoma is the most common cause of SVCS in children. Swelling in the face and neck are the most common clinical symptoms associated with this syndrome. However, these clinical findings are also observed in allergic diseases, which therefore often leads to misdiagnosis. Here, we reported the importance of echocardiography in diagnosing SVCS in an infant with advanced stage non-Hodgkin lymphoma. PMID:24639614

  3. End-stage renal disease in sub-Saharan Africa.

    PubMed

    Naicker, Saraladevi

    2009-01-01

    Chronic kidney disease is at least 3-4 times more frequent in Africa than in developed countries. Hypertension affects approximately 25% of the adult population and is the cause of chronic kidney failure in 21% of patients on renal replacement therapy in the South African Registry. The prevalence of diabetic nephropathy is estimated to be 14%-16% in South Africa, 23.8% in Zambia, 12.4% in Egypt, 9% in Sudan, and 6.1% in Ethiopia. The current dialysis treatment rate ranges from 70 per million population (pmp) in South Africa to < 20 pmp in the most of sub-Saharan Africa. The transplant rate in Africa averages 4 pmp and is 9.2 pmp in South Africa. The goal for sub-Saharan Africa should be to have a circumscribed chronic dialysis program, with as short a time on dialysis as possible, and to increase the availability of transplantation (both living related and cadaver) and promotion of prevention strategies at all levels of health care. Screening for kidney disease in high-risk populations, eg, patients with hypertension and diabetes mellitus and a family history of kidney disease, should be instituted as the first step in kidney disease prevention in developing countries. PMID:19484867

  4. A Two Stage Solution Procedure for Production Planning System with Advance Demand Information

    NASA Astrophysics Data System (ADS)

    Ueno, Nobuyuki; Kadomoto, Kiyotaka; Hasuike, Takashi; Okuhara, Koji

    We model for ‘Naiji System’ which is a unique corporation technique between a manufacturer and suppliers in Japan. We propose a two stage solution procedure for a production planning problem with advance demand information, which is called ‘Naiji’. Under demand uncertainty, this model is formulated as a nonlinear stochastic programming problem which minimizes the sum of production cost and inventory holding cost subject to a probabilistic constraint and some linear production constraints. By the convexity and the special structure of correlation matrix in the problem where inventory for different periods is not independent, we propose a solution procedure with two stages which are named Mass Customization Production Planning & Management System (MCPS) and Variable Mesh Neighborhood Search (VMNS) based on meta-heuristics. It is shown that the proposed solution procedure is available to get a near optimal solution efficiently and practical for making a good master production schedule in the suppliers.

  5. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria.

    PubMed

    Dubois, Bruno; Feldman, Howard H; Jacova, Claudia; Hampel, Harald; Molinuevo, José Luis; Blennow, Kaj; DeKosky, Steven T; Gauthier, Serge; Selkoe, Dennis; Bateman, Randall; Cappa, Stefano; Crutch, Sebastian; Engelborghs, Sebastiaan; Frisoni, Giovanni B; Fox, Nick C; Galasko, Douglas; Habert, Marie-Odile; Jicha, Gregory A; Nordberg, Agneta; Pasquier, Florence; Rabinovici, Gil; Robert, Philippe; Rowe, Christopher; Salloway, Stephen; Sarazin, Marie; Epelbaum, Stéphane; de Souza, Leonardo C; Vellas, Bruno; Visser, Pieter J; Schneider, Lon; Stern, Yaakov; Scheltens, Philip; Cummings, Jeffrey L

    2014-06-01

    In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD. PMID:24849862

  6. Advanced drug delivery and targeting technologies for the ocular diseases

    PubMed Central

    Barar, Jaleh; Aghanejad, Ayuob; Fathi, Marziyeh; Omidi, Yadollah

    2016-01-01

    Introduction: Ocular targeted therapy has enormously been advanced by implementation of new methods of drug delivery and targeting using implantable drug delivery systems (DDSs) or devices (DDDs), stimuli-responsive advanced biomaterials, multimodal nanomedicines, cell therapy modalities and medical bioMEMs. These technologies tackle several ocular diseases such as inflammation-based diseases (e.g., scleritis, keratitis, uveitis, iritis, conjunctivitis, chorioretinitis, choroiditis, retinitis, retinochoroiditis), ocular hypertension and neuropathy, age-related macular degeneration and mucopolysaccharidosis (MPS) due to accumulation of glycosaminoglycans (GAGs). Such therapies appear to provide ultimate treatments, even though much more effective, yet biocompatible, noninvasive therapies are needed to control some disabling ocular diseases/disorders. Methods: In the current study, we have reviewed and discussed recent advancements on ocular targeted therapies. Results: On the ground that the pharmacokinetic and pharmacodynamic analyses of ophthalmic drugs need special techniques, most of ocular DDSs/devices developments have been designed to localized therapy within the eye. Application of advanced DDSs such as Subconjunctival insert/implants (e.g., latanoprost implant, Gamunex-C), episcleral implant (e.g., LX201), cationic emulsions (e.g., Cationorm™, Vekacia™, Cyclokat™), intac/punctal plug DDSs (latanoprost punctal plug delivery system, L-PPDS), and intravitreal implants (I-vitaion™, NT-501, NT- 503, MicroPump, Thethadur, IB-20089 Verisome™, Cortiject, DE-102, Retisert™, Iluvein™ and Ozurdex™) have significantly improved the treatment of ocular diseases. However, most of these DDSs/devices are applied invasively and even need surgical procedures. Of these, use of de novo technologies such as advanced stimuli-responsive nanomaterials, multimodal nanosystems (NSs)/nanoconjugates (NCs), biomacromolecualr scaffolds, and bioengineered cell therapies

  7. Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma

    PubMed Central

    Wang, Xue; Chen, Meng; Wu, Jing; Xu, Jian-Hua; Qian, Pu-Dong; Guo, Wen-Jie; Jiang, Xue-Song; Zhu, Huan-Feng; Gu, Jia-Jia; Wu, Jian-Feng; Zhang, Ye-wei; He, Xia

    2015-01-01

    Background N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). Patients and Methods Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. Results With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3–4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. Conclusion IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute

  8. Recent advances in renal transplantation: antibody-mediated rejection takes center stage

    PubMed Central

    Chen, Chien Chia; Sicard, Antoine; Rabeyrin, Maud; Morelon, Emmanuel; Dubois, Valérie

    2015-01-01

    Overlooked for decades, antibodies have taken center stage in renal transplantation and are now widely recognized as the first cause of allograft failure. Diagnosis of antibody-mediated rejection has considerably improved with identification of antibody-mediated lesions in graft biopsies and advances made in the detection of circulating donor-specific antibodies. Unfortunately, this progress has not yet translated into better outcomes for patients. Indeed, in the absence of a drug able to suppress antibody generation by plasma cells, available therapies can only slow down graft destruction. This review provides an overview of the current knowledge of antibody-mediated rejection and discusses future interesting research directions. PMID:26097724

  9. Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Osti, Mattia Falchetto; Agolli, Linda; Valeriani, Maurizio; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Enrici, Riccardo Maurizi

    2013-03-01

    Purpose: Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. Methods and Materials: Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. Results: The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. Conclusions: Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized

  10. Recent advances in autosomal-dominant polycystic kidney disease.

    PubMed

    Rangan, G K; Tchan, M C; Tong, A; Wong, A T Y; Nankivell, B J

    2016-08-01

    Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease in adults, affecting one in every 1000 Australians. It is caused by loss-of-function heterozygous mutations in either PKD1 or PKD2 , which encode the proteins, polycystin-1 and polycystin-2 respectively. The disease hallmark is the development of hundreds of microscopic fluid-filled cysts in the kidney during early childhood, which grow exponentially and continuously through life at varying rates (between 2% and 10% per year), causing loss of normal renal tissue and up to a 50% lifetime risk of dialysis-dependent kidney failure. Other systemic complications include hypertensive cardiac disease, hepatic cysts, intracranial aneurysms, diverticular disease and hernias. Over the last two decades, advances in the genetics and pathogenesis of this disease have led to novel treatments that reduce the rate of renal cyst growth and may potentially delay the onset of kidney failure. New evidence indicates that conventional therapies (such as angiotensin inhibitors and statins) have mild attenuating effects on renal cyst growth and that systemic levels of vasopressin are critical for promoting renal cyst growth in the postnatal period. Identifying and integrating patient-centred perspectives in clinical trials is also being advocated. This review will provide an update on recent advances in the clinical management of ADPKD. PMID:27553994

  11. Recent Advances in Imaging Alzheimer’s Disease

    PubMed Central

    Braskie, Meredith N.; Toga, Arthur W.; Thompson, Paul M.

    2014-01-01

    Advances in brain imaging technology in the past five years have contributed greatly to the understanding of Alzheimer’s disease (AD). Here, we review recent research related to amyloid imaging, new methods for magnetic resonance imaging analyses, and statistical methods. We also review research that evaluates AD risk factors and brain imaging, in the context of AD prediction and progression. We selected a variety of illustrative studies, describing how they advanced the field and are leading AD research in promising new directions. PMID:22672880

  12. Advances in graft-versus-host disease biology and therapy

    PubMed Central

    Blazar, Bruce R.; Murphy, William J.; Abedi, Mehrdad

    2013-01-01

    Preface Allogeneic haematopoietic stem cell transplantation is used to treat a variety of disorders, but its efficacy is limited by the occurrence of graft-versus-host disease (GVHD). The past decade has brought impressive advances in our understanding of the role of both donor and host adaptive and innate immune stimulatory and immune suppressive factors that influence GVHD pathogenesis. New insights in basic immunology, preclinical models and clinical studies have led to novel prevention or treatment approaches. This review highlights recent advances in GVHD pathophysiology and its treatment with a focus on immune system manipulations that are amenable to clinical application. PMID:22576252

  13. Recent advances in small bowel diseases: Part I

    PubMed Central

    Thomson, Alan BR; Chopra, Angeli; Clandinin, Michael Tom; Freeman, Hugh

    2012-01-01

    As is the case in all parts of gastroenterology and hepatology, there have been many advances in our knowledge and understanding of small intestinal diseases. Over 1000 publications were reviewed for 2008 and 2009, and the important advances in basic science as well as clinical applications were considered. In Part I of this Editorial Review, seven topics are considered: intestinal development; proliferation and repair; intestinal permeability; microbiotica, infectious diarrhea and probiotics; diarrhea; salt and water absorption; necrotizing enterocolitis; and immunology/allergy. These topics were chosen because of their importance to the practicing physician. PMID:22807604

  14. Advances in non-dopaminergic treatments for Parkinson's disease

    PubMed Central

    Stayte, Sandy; Vissel, Bryce

    2014-01-01

    Since the 1960's treatments for Parkinson's disease (PD) have traditionally been directed to restore or replace dopamine, with L-Dopa being the gold standard. However, chronic L-Dopa use is associated with debilitating dyskinesias, limiting its effectiveness. This has resulted in extensive efforts to develop new therapies that work in ways other than restoring or replacing dopamine. Here we describe newly emerging non-dopaminergic therapeutic strategies for PD, including drugs targeting adenosine, glutamate, adrenergic, and serotonin receptors, as well as GLP-1 agonists, calcium channel blockers, iron chelators, anti-inflammatories, neurotrophic factors, and gene therapies. We provide a detailed account of their success in animal models and their translation to human clinical trials. We then consider how advances in understanding the mechanisms of PD, genetics, the possibility that PD may consist of multiple disease states, understanding of the etiology of PD in non-dopaminergic regions as well as advances in clinical trial design will be essential for ongoing advances. We conclude that despite the challenges ahead, patients have much cause for optimism that novel therapeutics that offer better disease management and/or which slow disease progression are inevitable. PMID:24904259

  15. Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease[S

    PubMed Central

    Reis, Ana; Rudnitskaya, Alisa; Chariyavilaskul, Pajaree; Dhaun, Neeraj; Melville, Vanessa; Goddard, Jane; Webb, David J.; Pitt, Andrew R.; Spickett, Corinne M.

    2015-01-01

    This study compared the molecular lipidomic profile of LDL in patients with nondiabetic advanced renal disease and no evidence of CVD to that of age-matched controls, with the hypothesis that it would reveal proatherogenic lipid alterations. LDL was isolated from 10 normocholesterolemic patients with stage 4/5 renal disease and 10 controls, and lipids were analyzed by accurate mass LC/MS. Top-down lipidomics analysis and manual examination of the data identified 352 lipid species, and automated comparative analysis demonstrated alterations in lipid profile in disease. The total lipid and cholesterol content was unchanged, but levels of triacylglycerides and N-acyltaurines were significantly increased, while phosphatidylcholines, plasmenyl ethanolamines, sulfatides, ceramides, and cholesterol sulfate were significantly decreased in chronic kidney disease (CKD) patients. Chemometric analysis of individual lipid species showed very good discrimination of control and disease sample despite the small cohorts and identified individual unsaturated phospholipids and triglycerides mainly responsible for the discrimination. These findings illustrate the point that although the clinical biochemistry parameters may not appear abnormal, there may be important underlying lipidomic changes that contribute to disease pathology. The lipidomic profile of CKD LDL offers potential for new biomarkers and novel insights into lipid metabolism and cardiovascular risk in this disease. PMID:25424003

  16. Transoral Laser Microsurgery (TLM) ± Adjuvant Therapy for Advanced Stage Oropharyngeal Cancer: Outcomes and Prognostic Factors

    PubMed Central

    Rich, Jason T.; Milov, Simon; Lewis, James S.; Thorstad, Wade L.; Adkins, Douglas R.; Haughey, Bruce H.

    2013-01-01

    Objectives/Hypothesis Document survival, prognostic variables, and functional outcomes of patients with AJCC stage III or IV oropharyngeal cancer, treated with transoral laser microsurgery (TLM) ± adjuvant therapy. Study Design Analysis of prospectively assembled data pertaining to the above-described patient cohort. Methods Patients treated with TLM for AJCC stage III or IV oropharyngeal cancer at Washington University School of Medicine from 1996 to 2006 were followed for a minimum of 2 years. Recurrence, survival, functional, and human papilloma virus data were analyzed. Results Eighty-four patients met inclusion criteria. Mean follow-up was 52.6 months. Overall AJCC stages were: III 15% and IV 85%. T stages were T1–2, 74%; T3–4, 26%. Eighty-three patients underwent neck dissection, 50 received adjuvant radiotherapy, and 28 received adjuvant chemoradiotherapy. Overall survival at 2 and 5 years was 94% and 88%, respectively. Disease-specific survival at 2 and 5 years was 96% and 92%, respectively. Six patients recurred (7%): locally (one), regionally (four), and distant (five). T stage, positive margins, and p16 status significantly impacted survival. The addition of adjuvant chemo-therapy in high-risk patients did not significantly impact survival. Five patients (6%) had major surgical complications, but without mortality. Eighty-one percent of patients had acceptable swallowing function at last follow-up. Immediately postoperatively, 17% required G-tubes, which dropped to 3.4% of living patients at 3 years. Conclusions In this population, our findings validate TLM ± adjuvant therapy as a highly effective strategy for survival, locoregional control, and swallowing recovery in AJCC stage III and IV oropharyngeal cancer. Our finding also show that p16 positivity improves survival. PMID:19572271

  17. Advances in combating fungal diseases: vaccines on the threshold

    PubMed Central

    Cutler, Jim E.; Deepe, George S.; Klein, Bruce S.

    2008-01-01

    The dramatic increase in fungal diseases in recent years can be attributed to the increased aggressiveness of medical therapy and other human activities. Immunosuppressed patients are at risk of contracting fungal diseases in healthcare settings and from natural environments. Increased prescribing of antifungals has led to the emergence of resistant fungi, resulting in treatment challenges. These concerns, together with the elucidation of the mechanisms of protective immunity against fungal diseases, have renewed interest in the development of vaccines against the mycoses. Most research has used murine models of human disease and, as we review in this article, the knowledge gained from these studies has advanced to the point where the development of vaccines targeting human fungal pathogens is now a realistic and achievable goal. PMID:17160002

  18. Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson's Disease.

    PubMed

    Claassen, Daniel O; Dobolyi, David G; Isaacs, David A; Roman, Olivia C; Herb, Joshua; Wylie, Scott A; Neimat, Joseph S; Donahue, Manus J; Hedera, Peter; Zald, David H; Landman, Bennett A; Bowman, Aaron B; Dawant, Benoit M; Rane, Swati

    2016-05-01

    Advancing age and disease duration both contribute to cortical thinning in Parkinson's disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson's Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2(nd), or 3(rd) order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning. PMID:27330836

  19. A Multi-institutional Investigation of the Prognostic Value of Lymph Nodal Yield in Advanced Stage Oral Cavity Squamous Cell Carcinoma (OCSCC)

    PubMed Central

    Jaber, James J.; Zender, Chad A.; Mehta, Vikas; Davis, Kara; Ferris, Robert L.; Lavertu, Pierre; Rezaee, Rod; Feustel, Paul J.

    2014-01-01

    Background Although existing literature provides surgical recommendations for treating occult disease (cN0) in early stage oral cavity squamous cell carcinoma, a focus on late stage OCSCC is less pervasive. Methods The records of 162 late stage OCSCC pN0 individuals that underwent primary neck dissections were reviewed. Lymph node yield (LNY) as a prognosticator was examined. Results Despite being staged pN0, patients that had a higher LNY had an improved regional/distant control rates, DFS, DSS, and OS. LNY consistently outperformed all other standard variables as being the single best prognostic factor with a tight risk ratio range (RR = 0.95–0.98) even when correcting for the number of lymph nodes examined. Conclusion The results of this study showed that lower regional recurrence rates and improved survival outcomes were seen as lymph node yield increased for advanced T-stage OCSCC pN0. This suggests that increasing lymph node yield with an extended cervical lymphadenectomy may result in lower recurrence rates and improved survival outcomes for this advanced stage group. PMID:24038739

  20. Treatment strategies in early and advanced Parkinson disease.

    PubMed

    Ossig, Christiana; Reichmann, Heinz

    2015-02-01

    The initiation of therapy in Parkinson disease (PD), altering the medication, adding new substances, and switching to alternative therapies throughout the disease is always a matter of debate. In the past, experts in PD have propagated different medication strategies. Even though there is no new medical treatment on the horizon, much has changed in consideration of the known treatments in the early and advanced therapy for PD. Therapeutic regimens have to be adapted and adjusted on a regular basis to accomplish the best medical care for the predominant symptom of the individual patient with PD. PMID:25432721

  1. The Economics of Late-Stage Chronic Kidney Disease.

    PubMed

    Provenzano, Robert

    2016-07-01

    Health care reimbursement is undergoing a fundamental change from volume-driven to value-driven care. The Patient Protection and Affordable Care Act is marshaling this change and empowering hospitals through Accountable Care Organizations to accept risk. ESRD care/nephrology was awarded the only disease-specific Accountable Care Organization, ESRD Seamless Care Organizations. Dialysis providers in partnership with nephrologists will be exploring how ESRD Seamless Care Organizations will drive improvement in care. CKD care and economics will no longer be isolated from ESRD but possibly more closely linked to global patient outcomes. Preparation for these changes will require unique co-operation and collaboration between nephrologists, dialysis providers, payers, and hospitals/health care systems. Early pilot trials, demonstration projects, and special need programs have suggested value care can be delivered. Whether these results are scalable needs to be determined. PMID:27324674

  2. Alcoholic liver disease. Treatment strategies for the potentially reversible stages.

    PubMed

    Hill, D B; Kugelmas, M

    1998-04-01

    Even modest alcohol ingestion can increase the risk of steatosis, and long-term, excessive consumption can lead to alcoholic hepatitis and eventually cirrhosis. Most patients with clinically significant alcoholic liver disease have histologic findings typical of all three conditions. The only clearly beneficial treatment is abstinence from alcohol. Abstinence in combination with proper nutrition and general supportive care is state of the art. Steatosis is reversible upon withdrawal of alcohol, but alcoholic hepatitis can persist even with abstinence and may progress to cirrhosis. Corticosteroid therapy may reduce short-term mortality rates in patients with moderate or severe alcoholic hepatitis who have hepatic encephalopathy but no evidence of infection or gastrointestinal bleeding. Treatment with colchicine may decrease the risk of cirrhosis; however, once cirrhosis has developed, the liver damage is irreversible. The prognosis is improved with abstinence, but complications (e.g., ascites, gastrointestinal bleeding) often occur. Liver transplantation may be considered in patients with severe complications. PMID:9553600

  3. Genome research in pre-dementia stages of Alzheimer's disease.

    PubMed

    Moreno-Grau, Sonia; Ruiz, Agustín

    2016-01-01

    Genetic characterization of individuals at risk of Alzheimer's disease (AD), i.e. people having amyloid deposits in the brain without symptoms, people suffering from subjective cognitive decline (SCD) or mild cognitive impairment (MCI), has spurred the interests of researchers. However, their pre-dementia genetic profile remains mostly unexplored. In this study, we reviewed the loci related to phenotypes of AD, MCI and SCD from literature and performed the first meta-analyses evaluating the role of apolipoprotein E (APOE) in the risk of conversion from a healthy status to MCI and SCD. For AD dementia risk, an increased number of loci have been identified; to date, 28 genes have been associated with Late Onset AD. In MCI syndrome, APOE is confirmed as a pheno-conversion factor leading from MCI to AD, and clusterin is a promising candidate. Additionally, our meta-analyses revealed APOE as genetic risk factor to convert from a healthy status to MCI [OR = 1.849 (1.587-2.153); P = 2.80  × 10-15] and to a lesser extent from healthy status to SCD [OR = 1.151 (1.015-1.304); P = 0.028]. Thus, we believe that genetic studies in longitudinal SCD and MCI series may provide new therapeutic targets and improve the existing knowledge of AD. This type of studies must be completed on healthy subjects to better understand the natural disease resistance to brain insults and neurodegeneration. PMID:27237222

  4. Two-stage, low noise advanced technology fan. Volume 2: Aerodynamic data

    NASA Technical Reports Server (NTRS)

    Harley, K. G.; Odegard, P. A.

    1975-01-01

    Aerodynamic data from static tests of a two-stage advanced technology fan designed to minimize noise are presented. Fan design conditions include delivery of 209.1kg/sec/sq m (42.85 lbm/sec/sq ft) specific corrected flow at an overall pressure ratio of 1.9 and an adiabatic efficiency of 85.3 percent. The 0.836m (2.74ft) diameter first stage rotor has a hub/tip ratio of 0.4 and 365.8m/sec (1200ft/sec) design tip speed. In addition to the moderate tip speed and pressure rise per stage, other noise control design features involve widely spaced blade rows and proper selection of blade-vane ratios. Aerodynamic data are presented for tests with unifrom and with hub and tip radially distorted inlet flow. Aerodynamic data are also presented for tests of this fan with acoustic treatments, including acoustically treated casing walls, a flowpath exit acoustic ring, and a translating centerbody sonic inlet device. A complete tabulation of the overall performance data, the blade element data, and the power spectral density information relating to turbulence levels generated by the sonic inlet obtained during these tests is included. For vol. 1, see N74-33789.

  5. Advances in computed tomography evaluation of skull base diseases.

    PubMed

    Prevedello, Luciano M

    2014-10-01

    Introduction Computed tomography (CT) is a key component in the evaluation of skull base diseases. With its ability to clearly delineate the osseous anatomy, CT can provide not only important tips to diagnosis but also key information for surgical planning. Objectives The purpose of this article is to describe some of the main CT imaging features that contribute to the diagnosis of skull base tumors, review recent knowledge related to bony manifestations of these conditions, and summarize recent technological advances in CT that contribute to image quality and improved diagnosis. Data Synthesis Recent advances in CT technology allow fine-detailed evaluation of the bony anatomy using submillimetric sections. Dual-energy CT material decomposition capabilities allow clear separation between contrast material, bone, and soft tissues with many clinical applications in the skull base. Dual-energy technology has also the ability to decrease image degradation from metallic hardwares using some techniques that can result in similar or even decreased radiation to patients. Conclusions CT is very useful in the evaluation of skull base diseases, and recent technological advances can increase disease conspicuity resulting in improved diagnostic capabilities and enhanced surgical planning. PMID:25992136

  6. Latest research and clinical treatment of advanced-stage epithelial ovarian cancer

    PubMed Central

    Coleman, Robert L.; Monk, Bradley J.; Sood, Anil K.; Herzog, Thomas J.

    2013-01-01

    The natural history of ovarian cancer continues to be characterized by late-stage presentation, metastatic bulky disease burden and stagnant mortality statistics despite prolific drug development. Robust clinical investigation, particularly with modifications to primary treatment surgical goals and adjuvant therapy are increasing median progression-free and overall survival, although the cure rates have only modestly been affected. Maintenance therapy holds promise, but studies have yet to identify an agent and/or strategy that can affect survival. Recurrent disease is largely an incurable state; however, current intervention with selected surgery, combination and targeted therapy and investigational protocols are impacting progression-free survival. Ovarian cancer is a diverse and genomically complex disease, which commands global attention. Rational investigation must balance the high rate of discovery with lagging clinical investigation and limited patient resources. Nevertheless, armamentarium growth offers unprecedented opportunities for patients suffering with this disease. This Review presents and reviews the contemporary management of the disease spectrum termed epithelial ‘ovarian’ cancer and introduces the direction and early results of clinical investigation. PMID:23381004

  7. Hypertension, End-Stage Renal Disease and Rehabilitation: A Look at Black Americans.

    ERIC Educational Resources Information Center

    Livingston, Ivor Lensworth; Ackah, Samuel

    1992-01-01

    Reviews the important relationship between end-stage renal disease (ESRD) and hypertension for African Americans; and considers issues associated with ESRD and the subsequent need for kidney transplants, including organ availability. Individual and societal implications of these diseases are discussed. (SLD)

  8. 42 CFR 488.60 - Special procedures for approving end stage renal disease facilities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... disease facilities. 488.60 Section 488.60 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... ENFORCEMENT PROCEDURES Special Requirements § 488.60 Special procedures for approving end stage renal disease... achievement of ESRD program objectives. (c) New applicant. A facility which has not previously participated...

  9. 42 CFR 488.60 - Special procedures for approving end stage renal disease facilities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... disease facilities. 488.60 Section 488.60 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... ENFORCEMENT PROCEDURES Special Requirements § 488.60 Special procedures for approving end stage renal disease... achievement of ESRD program objectives. (c) New applicant. A facility which has not previously participated...

  10. 42 CFR 488.60 - Special procedures for approving end stage renal disease facilities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... disease facilities. 488.60 Section 488.60 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... ENFORCEMENT PROCEDURES Special Requirements § 488.60 Special procedures for approving end stage renal disease... achievement of ESRD program objectives. (c) New applicant. A facility which has not previously participated...

  11. 42 CFR 488.60 - Special procedures for approving end stage renal disease facilities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... disease facilities. 488.60 Section 488.60 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... ENFORCEMENT PROCEDURES Special Requirements § 488.60 Special procedures for approving end stage renal disease... achievement of ESRD program objectives. (c) New applicant. A facility which has not previously participated...

  12. 42 CFR 488.60 - Special procedures for approving end stage renal disease facilities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... disease facilities. 488.60 Section 488.60 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... ENFORCEMENT PROCEDURES Special Requirements § 488.60 Special procedures for approving end stage renal disease... achievement of ESRD program objectives. (c) New applicant. A facility which has not previously participated...

  13. Marriage and End-Stage Renal Disease: Implications for African Americans

    ERIC Educational Resources Information Center

    Shortridge, Emily F.; James, Cara V.

    2010-01-01

    African Americans are disproportionately represented among patients with end-stage renal disease (ESRD). ESRD is managed with a strict routine that might include regular dialysis as well as dietary, fluid intake, and other lifestyle changes. In a disease such as this, with such disruptive treatment modalities, marriage, specifically, and its ties…

  14. A Computational Cognitive Biomarker for Early-Stage Huntington's Disease.

    PubMed

    Wiecki, Thomas V; Antoniades, Chrystalina A; Stevenson, Alexander; Kennard, Christopher; Borowsky, Beth; Owen, Gail; Leavitt, Blair; Roos, Raymund; Durr, Alexandra; Tabrizi, Sarah J; Frank, Michael J

    2016-01-01

    Huntington's disease (HD) is genetically determined but with variability in symptom onset, leading to uncertainty as to when pharmacological intervention should be initiated. Here we take a computational approach based on neurocognitive phenotyping, computational modeling, and classification, in an effort to provide quantitative predictors of HD before symptom onset. A large sample of subjects-consisting of both pre-manifest individuals carrying the HD mutation (pre-HD), and early symptomatic-as well as healthy controls performed the antisaccade conflict task, which requires executive control and response inhibition. While symptomatic HD subjects differed substantially from controls in behavioral measures [reaction time (RT) and error rates], there was no such clear behavioral differences in pre-HD. RT distributions and error rates were fit with an accumulator-based model which summarizes the computational processes involved and which are related to identified mechanisms in more detailed neural models of prefrontal cortex and basal ganglia. Classification based on fitted model parameters revealed a key parameter related to executive control differentiated pre-HD from controls, whereas the response inhibition parameter declined only after symptom onset. These findings demonstrate the utility of computational approaches for classification and prediction of brain disorders, and provide clues as to the underlying neural mechanisms. PMID:26872129

  15. Canine lymphomas: association of classification type, disease stage, tumor subtype, mitotic rate, and treatment with survival.

    PubMed

    Valli, V E; Kass, P H; San Myint, M; Scott, F

    2013-09-01

    without hydroxydaunorubicin, and only prednisone. Dogs with low-grade T-cell (T-zone) lymphomas had the longest median survival (622 days), whereas the shortest median survival was in dogs with T-cell high-grade (peripheral T-cell) subtype (162 days). The dogs with centroblastic large B-cell lymphomas had a median survival of 127 days with low stage, 221 days with intermediate stage, and 215 days with advanced stage. Dogs with T-zone lymphoma were probably diagnosed in later stages of disease because of the lack of signs associated with progression. As with human lymphomas, a histological diagnosis with immunophenotyping is a minimal requirement for diagnosis of a specific subtype. PMID:23444036

  16. Nonsurgical Management of Cervical Cancer: Locally Advanced, Recurrent, and Metastatic Disease, Survivorship, and Beyond

    PubMed Central

    Mackay, Helen J.; Wenzel, Lari; Mileshkin, Linda

    2016-01-01

    Overview Despite the declining incidence of cervical cancer as a result of the introduction of screening programs, globally it remains a leading cause of cancer-related death in women. Outcomes for patients who are diagnosed with anything but early-stage disease remain poor. Here we examine emerging strategies to improve the treatment of locally advanced disease. We discuss emerging biologic data, which are informing our investigation of new therapeutic interventions in persistent, recurrent, and metastatic cervical cancer. We recognize the importance of interventions to improve quality of life and to prevent long-term sequelae in women undergoing treatment. Finally, and perhaps most importantly, we recognize the need for global collaboration and advocacy to improve the outcome for all women at risk of and diagnosed with this disease. PMID:25993189

  17. Vascular access in elderly patients with end-stage renal disease.

    PubMed

    Bessias, Nikolaos; Paraskevas, Kosmas I; Tziviskou, Effie; Andrikopoulos, Vassilios

    2008-01-01

    During the last few years, the number of elderly patients with end-stage renal disease (ESRD) has been increasing worldwide. Establishment of a viable vascular access is of primary importance in these patients. This review discusses the advantages and disadvantages of the available vascular access modalities [namely arteriovenous (AV) fistulae, AV grafts, and central venous catheters (CVCs)] in elderly ESRD patients. AV fistulae seem to be superior when compared with other vascular access alternatives with respect to patency, morbidity and mortality rates. On the other hand, due to the age-related advanced atherosclerosis in the elderly, higher failure rates for AV fistulae in this age group have been described. Two controversial issues, namely the higher infection and thrombosis rates in elderly ESRD patients, are also discussed. Current evidence suggests that old age should not comprise a drawback when selecting the appropriate vascular access modality (AV fistula, AV graft or CVC) for the performance of hemodialysis. The possible vascular access options in elderly ESRD patients should not be different from younger individuals. PMID:18792799

  18. Factors Associated with the Choice of Peritoneal Dialysis in Patients with End-Stage Renal Disease.

    PubMed

    Chiang, Pei-Chun; Hou, Jia-Jeng; Jong, Ing-Ching; Hung, Peir-Haur; Hsiao, Chih-Yen; Ma, Tsung-Liang; Hsu, Yueh-Han

    2016-01-01

    Background. The purpose of this study was to analyze the factors associated with receiving peritoneal dialysis (PD) in patients with incident end-stage renal disease (ESRD) in a hospital in Southern Taiwan. Methods. The study included all consecutive patients with incident ESRD who participated in a multidisciplinary predialysis education (MPE) program and started their first dialysis therapy between January 1, 2008, and June 30, 2013, in the study hospital. We provided small group teaching sessions to advanced CKD patients and their family to enhance understanding of various dialysis modalities. Multivariate logistic regression models were used to analyze the association of patient characteristics with the chosen dialysis modality. Results. Of the 656 patients, 524 (80%) chose hemodialysis and 132 chose PD. Our data showed that young age, high education level, and high scores of activities of daily living (ADLs) were positively associated with PD treatment. Patients who received small group teaching sessions had higher percentages of PD treatment (30.5% versus 19.5%; P = 0.108) and preparedness for dialysis (61.1% versus 46.6%; P = 0.090). Conclusion. Young age, high education level, and high ADL score were positively associated with choosing PD. Early creation of vascular access may be a barrier for PD. PMID:27042665

  19. [Adding value to the care at the final stage of chronic diseases].

    PubMed

    Vacas Guerrero, Mercedes

    2014-01-01

    There is a growing number of people with advanced chronic health conditions and with palliative care needs who die without their health and social needs satisfied. This is enough to redefine the traditional models of care in order to focus on the person, rather than on the disease. In these new models, the important role of nursing is unquestionably to promote an approach based on comprehensive care, coordination and continuity, and at a social health level appropriate to respond to the care of patients who require complex long-term care. The nurse contribution in the end stages of chronic conditions must be in the value of care. Taking care of someone is to be concerned about them. And this is related to attitude, commitment and responsibility. In the care of patients who live in a situation of extreme vulnerability, it is possible to help them feel warmth, confident, relieve their suffering, respect their autonomy, and help them them find sense and hope, through daily tasks. With gestures, words and facial expressions that go with this care, it is possible to preserve patient dignity. PMID:24355175

  20. Factors Associated with the Choice of Peritoneal Dialysis in Patients with End-Stage Renal Disease

    PubMed Central

    Chiang, Pei-Chun; Hou, Jia-Jeng; Jong, Ing-Ching; Hung, Peir-Haur; Hsiao, Chih-Yen

    2016-01-01

    Background. The purpose of this study was to analyze the factors associated with receiving peritoneal dialysis (PD) in patients with incident end-stage renal disease (ESRD) in a hospital in Southern Taiwan. Methods. The study included all consecutive patients with incident ESRD who participated in a multidisciplinary predialysis education (MPE) program and started their first dialysis therapy between January 1, 2008, and June 30, 2013, in the study hospital. We provided small group teaching sessions to advanced CKD patients and their family to enhance understanding of various dialysis modalities. Multivariate logistic regression models were used to analyze the association of patient characteristics with the chosen dialysis modality. Results. Of the 656 patients, 524 (80%) chose hemodialysis and 132 chose PD. Our data showed that young age, high education level, and high scores of activities of daily living (ADLs) were positively associated with PD treatment. Patients who received small group teaching sessions had higher percentages of PD treatment (30.5% versus 19.5%; P = 0.108) and preparedness for dialysis (61.1% versus 46.6%; P = 0.090). Conclusion. Young age, high education level, and high ADL score were positively associated with choosing PD. Early creation of vascular access may be a barrier for PD. PMID:27042665

  1. Perspectives in Molecular Imaging Using Staging Biomarkers and Immunotherapies in Alzheimer's Disease

    PubMed Central

    Leclerc, Benoît; Abulrob, Abedelnasser

    2013-01-01

    Sporadic Alzheimer's disease (AD) is an emerging chronic illness characterized by a progressive pleiotropic pathophysiological mode of actions triggered during the senescence process and affecting the elderly worldwide. The complex molecular mechanisms of AD not only are supported by cholinergic, beta-amyloid, and tau theories but also have a genetic basis that accounts for the difference in symptomatology processes activation among human population which will evolve into divergent neuropathological features underlying cognitive and behaviour alterations. Distinct immune system tolerance could also influence divergent responses among AD patients treated by immunotherapy. The complexity in nature increases when taken together the genetic/immune tolerance with the patient's brain reserve and with neuropathological evolution from early till advance AD clinical stages. The most promising diagnostic strategies in today's world would consist in performing high diagnostic accuracy of combined modality imaging technologies using beta-amyloid 42 peptide-cerebrospinal fluid (CSF) positron emission tomography (PET), Pittsburgh compound B-PET, fluorodeoxyglucose-PET, total and phosphorylated tau-CSF, and volumetric magnetic resonance imaging hippocampus biomarkers for criteria evaluation and validation. Early diagnosis is the challenge task that needs to look first at plausible mechanisms of actions behind therapies, and combining them would allow for the development of efficient AD treatment in a near future. PMID:23476143

  2. Whole-body FDG-PET imaging for staging of Hodgkin`s disease and lymphoma

    SciTech Connect

    Hoh, C.K.; Glaspy, J.; Rosen, P.

    1997-03-01

    Accurate staging of Hodgkin`s disease (HD) and non-Hodgkin`s lymphoma (NHL) is important for treatment management. In this study, the utility of 2-[{sup 18}F]fluoro-2-deoxy-D-glucose (FDG) wholebody PET was evaluated as an imaging modality for initial staging or restaging of 7 HD and 11 NHL patients. Whole-body PET-based staging results were compared to the patient`s clinical stage based on conventional staging studies, which included combinations of CT of the chest, abdomen and pelvis, MRI scans, gallium scans, lymphangiograms, staging laparatomies and bone scans. Accurate staging was performed in 17 of 18 patients using a whole-body PET-based staging algorithm compared to the conventional staging algorithm in 15 of 18 patients. In 5 of 18 patients, whole-body PET-based staging showed additional lesions not detected by conventional staging modalities, whereas conventional staging demonstrated additional lesions in 4 of 18 patients not detected by whole-body PET. The total cost of conventional staging was $66,292 for 16 CT chest scans, 16 CT abdominal/pelvis scans, three limited MRI scans, four bone scans, give gallium scans, two laparotomies and one lymphangiogram. In contrast, scans cost $36,250 for 18 whole-body PET studies and additional selected correlative studies: one plain film radiograph, one limited CT, one bone marrow san, one upper GI and one endoscopy. A whole-body FDG-PET-based staging algorithm may be an accurate and cost-effective method for staging or restaging HD and NHL. 10 refs., 7 figs., 2 tabs.

  3. Advances and highlights in mechanisms of allergic disease in 2015.

    PubMed

    Wawrzyniak, Paulina; Akdis, Cezmi A; Finkelman, Fred D; Rothenberg, Marc E

    2016-06-01

    This review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported. PMID:27090934

  4. Recent Advances in the Genetics of Parkinson’s Disease

    PubMed Central

    Martin, Ian; Dawson, Valina L.; Dawson, Ted M.

    2014-01-01

    Genetic studies have provided valuable insight into the pathological mechanisms underlying Parkinson’s disease (PD). The elucidation of the genetic components to what was once largely considered a non-genetic disease has given rise to a multitude of cell and animal models enabling the dissection of molecular pathways involved in disease etiology. Here, we review advances obtained from models of dominant mutations in α-synuclein and LRRK2 as well as recessive PINK1, Parkin and DJ-1 mutations. Recent genome-wide association studies have implicated genetic variability at two of these loci, α-synuclein and LRRK2, as significant risk factors for developing sporadic PD. This, coupled to the established role of mitochondrial impairment in both familial and sporadic PD highlights the likelihood of common mechanisms fundamental to the etiology of both. PMID:21639795

  5. Advanced stage ovarian juvenile granuloza cell tumor causing acute abdomen: a case report.

    PubMed

    Bedir, Recep; Mürtezaoğlu, Afşin Rahman; Calapoğlu, Ahmet Salih; Şehitoğlu, İbrahim; Yurdakul, Cüneyt

    2014-09-01

    Ovary juvenile granulosa cell tumors (JGCT) are rare sex cord-stromal tumors that are most commonly encountered in prepubertal girls. These tumors can be of the adult type (95%) and juvenile type (5%). The main causes of complaint are abdominal distention and abdominal pain. Definitive diagnosis is confirmed by histopathologal and immunohistochemical examinations. A 10-year old girl presented with massive abdominal distention, acute abdomen findings and ascites. Abdominopelvic magnetic resonance imaging showed masses with multiple cysts and solid components in the left ovary. Tumor markers were normal, but serum estradiol level was elevated. The patient underwent mass resection with left salpingo-oophorectomy and total omentectomy. Final histopathological diagnosis was JGCT. We herein reporte an extremely rare case of advanced stage JGCT causing massive ascites and acute abdomen. PMID:25204485

  6. Palliative care for patients with advance chronic kidney disease.

    PubMed

    Douglas, C A

    2014-01-01

    Over the past three decades there has been a dramatic rise in the number of patients with advanced chronic kidney disease. The fastest expanding group receiving dialysis has been the elderly. However, for those patients who are very elderly with co-morbidity, dialysis may not offer a survival advantage. Therefore, active conservative management is a growing service offered by many renal units in the UK and focuses on non-dialytic correction of fluid and electrolyes, management of renal anaemia, and assessment and management of symptoms. The five-year survival of a patient over 75 years of age starting dialysis is 20% and if a patient is over 75 years, has co-morbidity, or a poor performance status, dialysis may not offer any survival advantage. Whether a patient is managed by dialysis or by conservative management the symptom burden suffered is high. These symptoms are under-recognised and often managed poorly because of increased drug toxicity in renal failure. This complex group of patients require close working between renal, palliative care, medicine for the elderly, and community teams, to allow best quality of life and end of life care. This review describes some of the challenges in providing Advanced Care Planning for dialysis and conservatively managed patients, highlights the symptom burden of patients with advanced chronic kidney disease, and offers guidance in how to manage the symptoms effectively. PMID:25318401

  7. MRI Helps Depict Clinically Undetectable Risk Factors in Advanced Stage Retinoblastomas

    PubMed Central

    Hadjistilianou, Theodora; Cerase, Alfonso; Toti, Paolo; Leonini, Sara; Bracco, Sandra; de Francesco, Sonia; Galimberti, Daniela; Balducci, Donatella; Piu, Pietro; Monti, Lucia; Bellini, Matteo; Caini, Mauro; Rossi, Alessandro

    2015-01-01

    SUMMARY This study compared high-resolution MRI with histology in advanced stage retinoblastomas in which ophthalmoscopy and ultrasonography did not give an exhaustive depiction of the tumour and/or its extension. MRI of orbits and head in 28 retinoblastoma patients (28 eyes) treated with primary enucleation were evaluated. Iris neoangiogenesis, infiltrations of optic nerve, choroid, anterior segment and sclera suspected at MR and histology were compared. Abnormal anterior segment enhancement (AASE) was also correlated with histologically proven infiltrations. Brain images were also evaluated. Significant values were obtained for: prelaminar optic nerve (ON) sensitivity (0.88), positive predictive value (PPV) (0.75) and negative predictive value (NPV) (0.71); post-laminar ON sensitivity (0.50), specificity (0.83), PPV (0.50) and NPV (0.83); overall choroid sensitivity (0.82), and massive choroid NPV (0.69); scleral specificity (1), and NPV (1). AASE correlated with iris neoangiogenesis in 14 out of 19 eyes, and showed significant values for: overall ON PPV (0.65), prelaminar ON sensitivity (0.65), and PPV (0.61), post-laminar ON NPV (0.64); overall choroid sensitivity (0.77), PPV (0.59) and NPV (0.73); scleral NPV (0.83); anterior segment sensitivity (1), and NPV (1). Odds ratios (OR) and accuracy were significant in scleral and prelaminar optic nerve infiltration. Brain examination was unremarkable in all cases. High-resolution MRI may add important findings to clinical evaluation of advanced stage retinoblastomas. PMID:25924174

  8. Up-regulation of stromal versican expression in advanced stage serous ovarian cancer

    PubMed Central

    Ghosh, Sue; Albitar, Lina; LeBaron, Richard; Welch, William R.; Samimi, Goli; Birrer, Michael J.; Berkowitz, Ross S.; Mok, Samuel C.

    2010-01-01

    Objective The purpose of this study is to examine the role of versican (VCAN) in advanced stage serous ovarian cancer by investigating its expression, its function, and its correlation with clinical outcomes. Methods Microarray analysis was performed on RNA isolated from tumor and stromal components of advanced stage serous ovarian cancer and normal ovarian epithelial tissue to identify genes up-regulated in ovarian tumor stroma. Validation studies using immunohistochemistry and quantitative real-time PCR (Q-RT-PCR) was performed on one of the up-regulated genes, VCAN. Immunolocalization of VCAN (n=111) and CD31 (n= 56) were done on serous ovarian tumors. CD31 staining was performed to examine microvessel density (MVD). Q-RT-PCR was performed on 65 samples to evaluate the differential expression of VCAN isoforms. Cell proliferation and invasion assays were performed to examine how V1-treated ovarian cancer cell lines and an endothelial cell line would differ from controls. Univariate survival analyses were done with VCAN expression. Correlation analysis was done with CD31, platinum resistance, and clinical data. Results Validation studies using Q-RT-PCR and immunohistochemistry showed significantly higher VCAN V1 isoform expression in ovarian cancer stroma compared with normal ovarian stroma and ovarian cancer cells. Correlation studies showed stromal VCAN expression was associated with poorer overall and progression free survival, platinum resistance, and increased MVD. VCAN-treated ovarian cancer and endothelial cells showed increased invasion potential. Conclusions VCAN overexpression is associated with increased MVD and invasion potential, which may lead to poorer overall and progression free survival and platinum resistance. PMID:20619446

  9. [Application of levodopa/carbidopa intestinal gel in advanced Parkinson's disease].

    PubMed

    Toth, Adrián; Nagy, Helga; Wacha, Judit; Bereczki, Dániel; Takáts, Annamária

    2015-12-01

    Parkinson's disease is the second most common neurodegenerative disorder around the world. Levodopa has remained the "gold standard" of the therapy even several decades after its introduction. Chronic levodopa treatment is associated with the development of motor complications in most patients. Advanced Parkinson's disease is characterized by these complications: motor and non-motor fluctuation and disturbing dyskinesia. Continuous dopaminergic stimulation might reduce these complications. In advanced Parkinson's disease levodopa is still effective. In the treatment of this stage there are several advanced or device-aided therapies: apomorphine pump, deep brain stimulation and levodopa/carbidopa intestinal gel. Levodopa/carbidopa intestinal gel is an aqueous gel that can be delivered to the jejunum via a percutaneous gastrojejunostomy tube which is connected to an infusion pump dosing the levodopa gel continuously to the place of absorption. Levodopa/carbidopa gel infusion can be used as monotherapy, can be tested, can be used individually and this therapy is reversible. Several clinical trials demonstrated that levodopa/carbidopa intestinal gel therapy is of long-term benefit, improves the quality of life of the patients and can reduce motor fluctuation and dyskinesia. PMID:26727723

  10. Radiation therapy in clinical stage I and II Hodgkin's disease. The Princess Margaret Hospital Lymphoma Group.

    PubMed

    Gospodarowicz, M K; Sutcliffe, S B; Bergsagel, D E; Chua, T

    1992-01-01

    A review of the Princess Margaret Hospital experience over the last 20 years in treating clinically staged patients with stage I and II Hodgkin's disease was performed to analyse the impact of patient selection and extended field radiation on relapse and survival. Of the 878 patients with stage I and II Hodgkin's disease, 521 with clinical stages I and II received radiation alone as the initial treatment. The actuarial survival for all stage I and II patients was 85.1% at 5 years and 76.2% at 10 years, and for clinically staged patients treated with radiation alone, 87.2 and 77.6%, respectively. The relapse-free rate (RFR) for all clinical stage I and II patients treated with radiotherapy (RT) alone was 70.1% at 5 years and 65.8% at 10 years. Significant prognostic factors for RFR and survival included age, stage and histology. In addition, the extent of radiation was identified as an independent prognostic factor for survival as well as for relapse. The RFR for those treated with involved field RT was 58.4% at 5 years and 50.5% at 10 years; for patients treated with mantle RT, 69.9 and 65.6%, and those treated with extended field RT 77.4 and 75.8%, respectively. In a highly selected group of patients with no adverse features, i.e. with stages IA-IIA, lymphocyte predominant or nodular sclerosis histology, erythrocyte sedimentation rate < 40, age < 50, no large mediastinal mass, and no E-lesions--the policy of mantle RT (M) and extended field RT (EF) produced comparable 5-year relapse-free rates (M, 84.9%; EF, 87.1%; P = 0.53). We conclude that a policy of treatment selection based upon clinicopathological prognostic factors and the use of extended field RT confers excellent results in the treatment of clinical stage I and II Hodgkin's disease. PMID:1389522

  11. Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization.

    PubMed

    Pomilio, Carlos; Pavia, Patricio; Gorojod, Roxana Mayra; Vinuesa, Angeles; Alaimo, Agustina; Galvan, Veronica; Kotler, Monica Lidia; Beauquis, Juan; Saravia, Flavia

    2016-02-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease without effective therapy. Brain amyloid deposits are classical histopathological hallmarks that generate an inflammatory reaction affecting neuronal and glial function. The identification of early cell responses and of brain areas involved could help to design new successful treatments. Hence, we studied early alterations of hippocampal glia and their progression during the neuropathology in PDAPP-J20 transgenic mice, AD model, at 3, 9, and 15 months (m) of age. At 3 m, before deposits formation, microglial Iba1+ cells from transgenic mice already exhibited signs of activation and larger soma size in the hilus, alterations appearing later on stratum radiatum. Iba1 immunohistochemistry revealed increased cell density and immunoreactive area in PDAPP mice from 9 m onward selectively in the hilus, in coincidence with prominent amyloid Congo red + deposition. At pre-plaque stages, GFAP+ astroglia showed density alterations while, at an advanced age, the presence of deposits was associated with important glial volume changes and apparently being intimately involved in amyloid degradation. Astrocytes around plaques were strongly labeled for LC3 until 15 m in Tg mice, suggestive of increased autophagic flux. Moreover, β-Amyloid fibrils internalization by astrocytes in in vitro conditions was dependent on autophagy. Co-localization of Iba1 with ubiquitin or p62 was exclusively found in microglia contacting deposits from 9 m onward, suggesting torpid autophagy. Our work characterizes glial changes at early stages of the disease in PDAPP-J20 mice, focusing on the hilus as an especially susceptible hippocampal subfield, and provides evidence that glial autophagy could play a role in amyloid processing at advanced stages. PMID:26235241

  12. Deep Brain Stimulation in Early Stage Parkinson’s Disease: Operative Experience from a Prospective, Randomized Clinical Trial

    PubMed Central

    Kahn, Elyne; D'Haese, Pierre-Francois; Dawant, Benoit; Allen, Laura; Kao, Chris; Charles, P. David; Konrad, Peter

    2013-01-01

    Background Recent evidence suggests that STN-DBS may have a disease-modifying effect in early PD. A randomized, prospective study is underway to determine whether STN-DBS in early PD is safe and tolerable. Objectives / Methods Fifteen of thirty early PD patients were randomized to receive STN-DBS implants in an IRB-approved protocol. Operative technique, location of DBS leads, and perioperative adverse events are reported. Active contact used for stimulation in these patients were compared with 47 advanced PD patients undergoing an identical procedure by the same surgeon. Results Fourteen of the 15 patients did not sustain any long-term (> 3 months) complications from the surgery. One subject suffered a stroke resulting in mild cognitive changes and slight right arm and face weakness. The average optimal contact used in symptomatic treatment of early PD patients was: anterior −1.1±1.7mm, lateral 10.7±1.7mm, superior −3.3±2.5mm (AC-PC coordinates). This location is statistically no different (0.77mm, p> 0.05) than the optimal contact used in treatment of 47 advanced PD patients. Conclusions The perioperative adverse events in this trial of subjects with early stage PD are comparable to that reported for STN-DBS in advanced PD. The active contact position used in early PD is not significantly different from that used in late stage disease. This is the first report of the operative experience from a randomized, surgical-versus-best-medical-therapy trial for the early treatment of Parkinson’s disease. PMID:21890575

  13. Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

    PubMed Central

    Scarisbrick, Julia J.; Prince, H. Miles; Vermeer, Maarten H.; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S.; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M.; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L.; Rodríguez-Peralto, Jose L.; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M.; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T.; Duvic, Madeleine; Whittaker, Sean J.; Kim, Youn H.

    2015-01-01

    Purpose Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and Methods Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). Conclusion To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and

  14. Advances in endoscopic ultrasound imaging of colorectal diseases

    PubMed Central

    Cârțână, Elena Tatiana; Gheonea, Dan Ionuț; Săftoiu, Adrian

    2016-01-01

    The development of endoscopic ultrasound (EUS) has had a significant impact for patients with digestive diseases, enabling enhanced diagnostic and therapeutic procedures, with most of the available evidence focusing on upper gastrointestinal (GI) and pancreatico-biliary diseases. For the lower GI tract the main application of EUS has been in staging rectal cancer, as a complementary technique to other cross-sectional imaging methods. EUS can provide highly accurate in-depth assessments of tumour infiltration, performing best in the diagnosis of early rectal tumours. In the light of recent developments other EUS applications for colorectal diseases have been also envisaged and are currently under investigation, including beyond-rectum tumour staging by means of the newly developed forward-viewing radial array echoendoscope. Due to its high resolution, EUS might be also regarded as an ideal method for the evaluation of subepithelial lesions. Their differential diagnosis is possible by imaging the originating wall layer and the associated echostructure, and cytological and histological confirmation can be obtained through EUS-guided fine needle aspiration or trucut biopsy. However, reports on the use of EUS in colorectal subepithelial lesions are currently limited. EUS allows detailed examination of perirectal and perianal complications in Crohn’s disease and, as a safe and less expensive investigation, can be used to monitor therapeutic response of fistulae, which seems to improve outcomes and reduce the need for additional surgery. Furthermore, EUS image enhancement techniques, such as the use of contrast agents or elastography, have recently been evaluated for colorectal indications as well. Possible applications of contrast enhancement include the assessment of tumour angiogenesis in colorectal cancer, the monitoring of disease activity in inflammatory bowel disease based on quantification of bowel wall vascularization, and differentiating between benign and

  15. Advances in endoscopic ultrasound imaging of colorectal diseases.

    PubMed

    Cârțână, Elena Tatiana; Gheonea, Dan Ionuț; Săftoiu, Adrian

    2016-02-01

    The development of endoscopic ultrasound (EUS) has had a significant impact for patients with digestive diseases, enabling enhanced diagnostic and therapeutic procedures, with most of the available evidence focusing on upper gastrointestinal (GI) and pancreatico-biliary diseases. For the lower GI tract the main application of EUS has been in staging rectal cancer, as a complementary technique to other cross-sectional imaging methods. EUS can provide highly accurate in-depth assessments of tumour infiltration, performing best in the diagnosis of early rectal tumours. In the light of recent developments other EUS applications for colorectal diseases have been also envisaged and are currently under investigation, including beyond-rectum tumour staging by means of the newly developed forward-viewing radial array echoendoscope. Due to its high resolution, EUS might be also regarded as an ideal method for the evaluation of subepithelial lesions. Their differential diagnosis is possible by imaging the originating wall layer and the associated echostructure, and cytological and histological confirmation can be obtained through EUS-guided fine needle aspiration or trucut biopsy. However, reports on the use of EUS in colorectal subepithelial lesions are currently limited. EUS allows detailed examination of perirectal and perianal complications in Crohn's disease and, as a safe and less expensive investigation, can be used to monitor therapeutic response of fistulae, which seems to improve outcomes and reduce the need for additional surgery. Furthermore, EUS image enhancement techniques, such as the use of contrast agents or elastography, have recently been evaluated for colorectal indications as well. Possible applications of contrast enhancement include the assessment of tumour angiogenesis in colorectal cancer, the monitoring of disease activity in inflammatory bowel disease based on quantification of bowel wall vascularization, and differentiating between benign and

  16. Single stage, low noise advanced technology fan. Volume 3: Acoustic design

    NASA Technical Reports Server (NTRS)

    Kazin, S. B.; Mishler, R. B.

    1976-01-01

    The acoustic design for a half-scale fan vehicle, which would have application on an advanced transport aircraft, is described. The single stage advanced technology fan was designed to a pressure ratio of 1.8 at a tip speed of 503 m/sec (1,650 ft/sec). The two basic approaches taken in the acoustic design were: (1) minimization of noise at the source, and (2) suppression of the generated noise in the inlet and bypass exhaust duct. Suppression of the generated noise is accomplished in the inlet through use of the hybrid concept (wall acoustic treatment plus airflow acceleration suppression) and in the exhaust duct with extensive acoustic treatment including a splitter. The goal of the design was attainment of twenty effective perceived noise decibels (20 EPNdB) below current Federal Air Regulation noise standards for a full-scale fan at the takeoff, cutback, and approach conditions. Predicted unsuppressed and suppressed fore and aft maximum perceived noise levels indicate that the cutback condition is the most critical with respect to the goal, which is probably unattainable for that condition. This is also true for aft radiated noise in the approach condition.

  17. Single stage, low noise, advanced technology fan. Volume 1: Aerodynamic design

    NASA Technical Reports Server (NTRS)

    Sullivan, T. J.; Younghans, J. L.; Little, D. R.

    1976-01-01

    The aerodynamic design for a half-scale fan vehicle, which would have application on an advanced transport aircraft, is described. The single stage advanced technology fan was designed to a pressure ratio of 1.8 at a tip speed of 503 m/sec 11,650 ft/sec). The fan and booster components are designed in a scale model flow size convenient for testing with existing facility and vehicle hardware. The design corrected flow per unit annulus area at the fan face is 215 kg/sec sq m (44.0 lb m/sec sq ft) with a hub-tip ratio of 0.38 at the leading edge of the fan rotor. This results in an inlet corrected airflow of 117.9 kg/sec (259.9 lb m/sec) for the selected rotor tip diameter if 90.37 cm (35.58 in.). The variable geometry inlet is designed utilizing a combination of high throat Mach number and acoustic treatment in the inlet diffuser for noise suppression (hybrid inlet). A variable fan exhaust nozzle was assumed in conjunction with the variable inlet throat area to limit the required area change of the inlet throat at approach and hence limit the overall diffusion and inlet length. The fan exit duct design was primarily influenced by acoustic requirements, including length of suppressor wall treatment; length, thickness and position on a duct splitter for additional suppressor treatment; and duct surface Mach numbers.

  18. Important predictor of mortality in patients with end-stage liver disease

    PubMed Central

    Lee, Hyun Woong

    2013-01-01

    Prognosis is an essential part of the baseline assessment of any disease. For predicting prognosis of end-stage liver disease, many prognostic models were proposed. Child-Pugh score has been the reference for assessing the prognosis of cirrhosis for about three decades in end-stage liver disease. Despite of several limitations, recent large systematic review showed that Child-Pugh score was still robust predictors and it's components (bilirubin, albumin and prothrombin time) were followed by Child-Pugh score. Recently, Model for end-stage liver disease (MELD) score emerged as a "modern" alternative to Child-Pugh score. The MELD score has been an important role to accurately predict the severity of liver disease and effectively assess the risk of mortality. Due to several weakness of MELD score, new modified MELD scores (MELD-Na, Delta MELD) have been developed and validated. This review summarizes the current knowledge about the prognostic factors in end-stage liver disease, focusing on the role of Child-Pugh and MELD score. PMID:23837134

  19. 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

  20. Initial Stage Affects Survival Even After Complete Pathologic Remission is Achieved in Locally Advanced Esophageal Cancer: Analysis of 70 Patients With Pathologic Major Response After Preoperative Chemoradiotherapy

    SciTech Connect

    Kim, Min Kyoung; Cho, Kyung-Ja; Park, Seung-Il; Kim, Yong Hee; Kim, Jong Hoon; Song, Ho-Young; Shin, Ji Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Song, Ho June; Ryu, Jin-Sook; Kim, Sung-Bae

    2009-09-01

    Purpose: To analyze outcomes and factors predictive for recurrence and survival in patients with operable esophageal carcinoma who achieved pathologic complete response (PCR) or microscopic residual disease (MRD) after preoperative chemoradiotherapy (CRT). Materials and Methods: Outcomes were assessed in 70 patients with locally advanced esophageal cancer who achieved pathologic major response (53 with PCR and 17 with MRD) after preoperative CRT. Results: At a median follow-up of 38.6 months for surviving patients, 17 of 70 patients (24.3%) experienced disease recurrence and 31 (44.3%) died. Clinical stage (II vs III; p = 0.013) and pathologic response (PCR vs. MRD; p = 0.014) were independent predictors of disease recurrence. Median overall survival (OS) was 99.6 months (95% CI, 44.1-155.1 months) and the 5-year OS rate was 57%. Median recurrence-free survival (RFS) was 71.5 months (95% CI, 39.5-103.6 months) and the 5-year RFS rate was 51.3%. Median OS of patients with Stage II and Stage III disease was 108.8 months and 39.9 months, respectively, and the 5-year OS rates were 68.2% and 27.0%, respectively (p = 0.0003). In a subgroup of patients with PCR, median OS and RFS were also significantly different according to clinical stage. Multivariate analysis showed that clinical stage was an independent predictor of RFS (p = 0.01) and OS (p = 0.008). Conclusions: Even though patients achieved major response after preoperative CRT, pretreatment clinical stage is an important prognostic marker for recurrence and survival. Patients with MRD have an increased recurrence risk but similar survival compared with patients achieved PCR.

  1. Partial Characterization of the Molecular Nature of Collagen-Linked Fluorescence: Role of Diabetes and End-Stage Renal Disease

    PubMed Central

    Sell, David R.; Nemet, Ina; Monnier, Vincent M.

    2009-01-01

    Collagen-linked fluorescence at excitation/emission 370/440 nm has widely been used as a marker for advanced glycation in studies of aging, diabetic complications and end-stage renal disease (ESRD). Diagnostic devices measuring skin autofluorescence at this wavelength revealed an association between fluorescence and cardiovascular morbidity and mortality. We now report the presence of a major fluorophore (LW-1) in human skin collagen which increases with age, diabetes and ESRD. It has a molecular weight of 623.2 Da, a UV maximum at 348 nm, and involves a lysine residue in an aromatic ring. LW-1 could not be synthesized using traditional glycation chemistry suggesting a complex mechanism of formation, perhaps related to hypoxia since elevated levels were also found in nondiabetic individuals with chronic lung disease. PMID:19879855

  2. Pair-wise comparison analysis of differential expression of mRNAs in early and advanced stage primary colorectal adenocarcinomas

    PubMed Central

    Lau, Tze Pheng; Roslani, April Camilla; Lian, Lay Hoong; Chai, Hwa Chia; Lee, Ping Chin; Hilmi, Ida; Goh, Khean Lee; Chua, Kek Heng

    2014-01-01

    Objectives To characterise the mRNA expression patterns of early and advanced stage colorectal adenocarcinomas of Malaysian patients. Design Comparative expression analysis. Setting and participants We performed a combination of annealing control primer (ACP)-based PCR and reverse transcription-quantitative real-time PCR for the identification of differentially expressed genes (DEGs) associated with early and advanced stage primary colorectal tumours. We recruited four paired samples from patients with colorectal cancer (CRC) of Dukes’ A and B for the preliminary differential expression study, and a total of 27 paired samples, ranging from CRC stages I to IV, for subsequent confirmatory test. The tumouric samples were obtained from the patients with CRC undergoing curative surgical resection without preoperative chemoradiotherapy. The recruited patients with CRC were newly diagnosed with CRC, and were not associated with any hereditary syndromes, previously diagnosed cancer or positive family history of CRC. The paired non-cancerous tissue specimens were excised from macroscopically normal colonic mucosa distally located from the colorectal tumours. Primary and secondary outcome measures The differential mRNA expression patterns of early and advanced stage colorectal adenocarcinomas compared with macroscopically normal colonic mucosa were characterised by ACP-based PCR and reverse transcription-quantitative real-time PCR. Results The RPL35, RPS23 and TIMP1 genes were found to be overexpressed in both early and advanced stage colorectal adenocarcinomas (p<0.05). However, the ARPC2 gene was significantly underexpressed in early colorectal adenocarcinomas, while the advanced stage primary colorectal tumours exhibited an additional overexpression of the C6orf173 gene (p<0.05). Conclusions We characterised two distinctive gene expression patterns to aid in the stratification of primary colorectal neoplasms among Malaysian patients with CRC. Further work can be done to

  3. A prospective evaluation of the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography staging on survival for patients with locally advanced esophageal cancer

    SciTech Connect

    Blackstock, A. William . E-mail: ablackst@wfubmc.edu; Farmer, Michael R.; Lovato, James; Mishra, Girish; Melin, Susan A.; Oaks, Timothy; Aklilu, Mabea; Clark, Paige B.; Levine, Edward A.

    2006-02-01

    Purpose: To determine the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging and prognosis of patients with locally advanced esophageal cancer (LAEC). Methods and Materials: Between January 2000 and October 2004, all patients with LAEC evaluated in the Department of Radiation Oncology were considered for enrollment into a Phase II trial of preoperative chemoradiation. Entry required a staging whole-body FDG-PET scan. Results: One hundred ten consecutive patients were evaluated; 38 were ineligible for reasons including treatment elsewhere, prior malignancy, or refusal of treatment. After conventional staging (clinical examination, endoscopic ultrasound, and chest/abdominal computerized tomography), 33 patients were ineligible because of metastatic disease or poor performance status. Of the remaining 39 patients, 23 were confirmed to have LAEC after FDG-PET staging and were treated in the Phase II trial (Cohort I). Sixteen patients, however, had FDG-PET findings consistent with occult metastatic disease and were deemed ineligible for the trial but were treated with curative intent (Cohort II). The 2-year survival rate for the 23 patients in Cohort I was 64%, compared with 17% (p = 0.003) for patients in Cohort II (FDG-PET positive). Conclusions: More than one-third of patients determined to have LAEC with conventional staging were upstaged with the use of FDG-PET. Despite comparable therapy, upstaging with FDG-PET predicts poor 2-year survival.

  4. Advanced chronic kidney disease: a strong risk factor for Clostridium difficile infection

    PubMed Central

    Kim, Sun Chul; Seo, Min Young; Lee, Jun Yong; Kim, Ki Tae; Cho, Eunjung; Kim, Myung-Gyu; Jo, Sang-Kyung; Cho, Won-Yong; Kim, Hyoung-Kyu

    2016-01-01

    Background/Aims: It has been suggested that chronic kidney disease (CKD) is a risk factor for Clostridium difficile infection (CDI) and is associated with increased mortality among patients infected with C. difficile. However, recent studies of the clinical impact of CKD on CDI in Asians are still insufficient. We sought to determine the relationship between CKD and CDI in a Korean population. Methods: This was a single-center, retrospective case-control study. In total, 171 patients with CDI were included as cases and 342 age- and gender-matched patients without CDI were used as controls. We compared the prevalence of CKD in the study sample and identified independent risk factors that could predict the development or prognosis of CDI. Results: Independent risk factors for CDI included stage IV to V CKD not requiring dialysis (odds ratio [OR], 2.90) and end-stage renal disease requiring dialysis (OR, 3.34). Patients with more advanced CKD (estimated glomerular filtration rate < 30) and CDI showed higher in-hospital mortality and poorer responses to the initial metronidazole therapy. Conclusions: More advanced CKD is an independent risk factor for CDI and is associated with higher in-hospital mortality and poor treatment responses in CDI patients. Thus, in CKD patients, careful attention should be paid to the occurrence of CDI and its management to improve the outcome of CDI. PMID:26767866

  5. Highlight on Advances in Nontuberculous Mycobacterial Disease in North America

    PubMed Central

    Mirsaeidi, Mehdi; Farshidpour, Maham; Allen, Mary Beth; Ebrahimi, Golnaz; Falkinham, Joseph O.

    2014-01-01

    Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and exist as an important cause of pulmonary infections in humans. Pulmonary involvement is the most common disease manifestation of NTM and the incidence of NTM is growing in North America. Susceptibility to NTM infection is incompletely understood; therefore preventative tools are not well defined. Treatment of pulmonary nontuberculous mycobacterial (NTM) infection is difficult and entails multiple antibiotics and an extended treatment course. Also, there is a considerable variation in treatment management that should be considered before initiating treatment. We highlight the new findings in the epidemiology diagnosis and treatment of mycobacterial infections. We debate new advances regarding NTM infection in cystic fibrosis patients and solid organ transplant recipients. Finally, we introduce a new epidemiologic model for NTM disease based on virulence-exposure-host factors. PMID:25574470

  6. Targeting advanced glycation endproducts and mitochondrial dysfunction in cardiovascular disease.

    PubMed

    Ward, Micheal S; Fortheringham, Amelia K; Cooper, Mark E; Forbes, Josephine M

    2013-08-01

    Cardiovascular disease (CVD) is a leading cause of mortality in the Western World. The development and onset of disease can be attributed to many risk factors including genetic susceptibility, diabetes, obesity and atherosclerosis. Numerous studies highlight the production of advanced glycation endproducts (AGEs) and interaction with their receptor (RAGE) as playing a key pathogenic role. The AGEs-RAGE axis is thought to contribute to a proinflammatory environment inducing cellular dysfunction which cascades towards pathology. Mitochondrial dysfunction concurrently plays a role in these proinflammatory responses presenting excess reactive oxygen species (ROS) production under pathological conditions. This ROS release can exacerbate the production of AGEs fuelling the fire somewhat. However, the AGEs-RAGE axis may influence mitochondrial function independently of inflammation. Therefore instigation of the AGEs-RAGE axis may facilitate spiralling towards pathology on many fronts including CVD development. PMID:23871446

  7. Pregnancy in end-stage renal disease patients on dialysis: how to achieve a successful delivery

    PubMed Central

    Manisco, Gianfranco; Potì’, Marcello; Maggiulli, Giuseppe; Di Tullio, Massimo; Losappio, Vincenzo; Vernaglione, Luigi

    2015-01-01

    Pregnancy in women with chronic kidney disease has always been considered as a challenging event both for the mother and the fetus. Over the years, several improvements have been achieved in the outcome of pregnant chronic renal patients with increasing rates of successful deliveries. To date, evidence suggests that the stage of renal failure is the main predictive factor of worsening residual kidney function and complications in pregnant women. Moreover, the possibility of success of the pregnancy depends on adequate depurative and pharmacological strategies in patients with end-stage renal disease. In this paper, we propose a review of the current literature about this topic presenting our experience as well. PMID:26034591

  8. Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease.

    PubMed

    Schneider, Lon S

    2014-03-01

    The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. PMID:24698029

  9. Advances in nutritional therapy in inflammatory bowel diseases: Review

    PubMed Central

    Wędrychowicz, Andrzej; Zając, Andrzej; Tomasik, Przemysław

    2016-01-01

    Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease are chronic, life-long, and relapsing diseases of the gastrointestinal tract. Currently, there are no complete cure possibilities, but combined pharmacological and nutritional therapy may induce remission of the disease. Malnutrition and specific nutritional deficiencies are frequent among IBD patients, so the majority of them need nutritional treatment, which not only improves the state of nutrition of the patients but has strong anti-inflammatory activity as well. Moreover, some nutrients, from early stages of life are suspected as triggering factors in the etiopathogenesis of IBD. Both parenteral and enteral nutrition is used in IBD therapy, but their practical utility in different populations and in different countries is not clearly established, and there are sometimes conflicting theories concerning the role of nutrition in IBD. This review presents the actual data from research studies on the influence of nutrition on the etiopathogenesis of IBD and the latest findings regarding its mechanisms of action. The use of both parenteral and enteral nutrition as therapeutic methods in induction and maintenance therapy in IBD treatment is also extensively discussed. Comparison of the latest research data, scientific theories concerning the role of nutrition in IBD, and different opinions about them are also presented and discussed. Additionally, some potential future perspectives for nutritional therapy are highlighted. PMID:26811646

  10. Advances in nutritional therapy in inflammatory bowel diseases: Review.

    PubMed

    Wędrychowicz, Andrzej; Zając, Andrzej; Tomasik, Przemysław

    2016-01-21

    Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease are chronic, life-long, and relapsing diseases of the gastrointestinal tract. Currently, there are no complete cure possibilities, but combined pharmacological and nutritional therapy may induce remission of the disease. Malnutrition and specific nutritional deficiencies are frequent among IBD patients, so the majority of them need nutritional treatment, which not only improves the state of nutrition of the patients but has strong anti-inflammatory activity as well. Moreover, some nutrients, from early stages of life are suspected as triggering factors in the etiopathogenesis of IBD. Both parenteral and enteral nutrition is used in IBD therapy, but their practical utility in different populations and in different countries is not clearly established, and there are sometimes conflicting theories concerning the role of nutrition in IBD. This review presents the actual data from research studies on the influence of nutrition on the etiopathogenesis of IBD and the latest findings regarding its mechanisms of action. The use of both parenteral and enteral nutrition as therapeutic methods in induction and maintenance therapy in IBD treatment is also extensively discussed. Comparison of the latest research data, scientific theories concerning the role of nutrition in IBD, and different opinions about them are also presented and discussed. Additionally, some potential future perspectives for nutritional therapy are highlighted. PMID:26811646

  11. 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

  12. Recent Advances and Future Needs in Interstitial Lung Diseases.

    PubMed

    Jones, Mark G; Richeldi, Luca

    2016-06-01

    Interstitial lung diseases (ILDs) are a diverse range of conditions affecting the lung interstitium. The prototypic ILD, idiopathic pulmonary fibrosis (IPF), is a chronic progressive fibrotic lung disease with a median survival of only 3 years from the time of diagnosis. Recently significant progress has been made in both our understanding of the pathogenesis and of the therapeutic targeting of IPF. This culminated in the worldwide approval of the first antifibrotic therapies nintedanib and pirfenidone. While an important first step, patients continue to progress and better therapies are urgently required. The aim of this article is to highlight some of the recent advances that have been made in our understanding of genetics, disease classification, clinical trial design, and novel antifibrotic therapy in IPF. It discusses future priorities if we are to continue to increase the length and quality of life of patients with IPF, and considers possible approaches to translate the progress made in IPF to other progressive fibrotic lung diseases where our understanding remains limited. PMID:27231869

  13. Advanced Nanobiomaterials: Vaccines, Diagnosis and Treatment of Infectious Diseases.

    PubMed

    Torres-Sangiao, Eva; Holban, Alina Maria; Gestal, Monica Cartelle

    2016-01-01

    The use of nanoparticles has contributed to many advances due to their important properties such as, size, shape or biocompatibility. The use of nanotechnology in medicine has great potential, especially in medical microbiology. Promising data show the possibility of shaping immune responses and fighting severe infections using synthetic materials. Different studies have suggested that the addition of synthetic nanoparticles in vaccines and immunotherapy will have a great impact on public health. On the other hand, antibiotic resistance is one of the major concerns worldwide; a recent report of the World Health Organization (WHO) states that antibiotic resistance could cause 300 million deaths by 2050. Nanomedicine offers an innovative tool for combating the high rates of resistance that we are fighting nowadays, by the development of both alternative therapeutic and prophylaxis approaches and also novel diagnosis methods. Early detection of infectious diseases is the key to a successful treatment and the new developed applications based on nanotechnology offer an increased sensibility and efficiency of the diagnosis. The aim of this review is to reveal and discuss the main advances made on the science of nanomaterials for the prevention, diagnosis and treatment of infectious diseases. Highlighting innovative approaches utilized to: (i) increasing the efficiency of vaccines; (ii) obtaining shuttle systems that require lower antibiotic concentrations; (iii) developing coating devices that inhibit microbial colonization and biofilm formation. PMID:27376260

  14. Significance of Cerebral Blood Flow Analysis in the Acute Stage after Revascularization Surgery for Moyamoya Disease

    PubMed Central

    FUJIMURA, Miki; TOMINAGA, Teiji

    2015-01-01

    Moyamoya disease is a chronic, occlusive cerebrovascular disease with unknown etiology characterized by steno-occlusive changes at the terminal portion of the internal carotid artery, either bilaterally or unilaterally, and an abnormal vascular network at the base of the brain. Surgical revascularization such as extracranial-intracranial (EC-IC) bypass is the preferred procedure for moyamoya disease. Despite the favorable long-term outcome, cerebral infarction and hyperperfusion syndrome are potential complications of this procedure, which can lead to neurological deterioration in the acute stage. In light of the similar clinical presentations between perioperative ischemia and hyperperfusion, it is essential to attempt a prompt cerebral blood flow (CBF) measurement in the acute stage after EC-IC bypass for moyamoya disease to differentiate these distinct pathologies, because the management of cerebral ischemia and hyperperfusion is contradictory to each other. Routine CBF analysis by single-photon emission computed tomography and/or magnetic resonance imaging not only facilitated a safer perioperative management but also provided important information about dynamic pathology of the hemodynamic conversion in the acute stage after revascularization surgery for moyamoya disease. We represent the current status of CBF analysis during the perioperative period of revascularization surgery for moyamoya disease, and sought to discuss its significance and efficacy to avoid surgical complications. PMID:26369873

  15. The role of the amygdala during emotional processing in Huntington's disease: From pre-manifest to late stage disease

    PubMed Central

    Mason, Sarah L.; Zhang, Jiaxiang; Begeti, Faye; Guzman, Natalie Valle; Lazar, Alpar S.; Rowe, James B.; Barker, Roger A.; Hampshire, Adam

    2015-01-01

    Background Deficits in emotional processing can be detected in the pre-manifest stage of Huntington's disease and negative emotion recognition has been identified as a predictor of clinical diagnosis. The underlying neuropathological correlates of such deficits are typically established using correlative structural MRI studies. This approach does not take into consideration the impact of disruption to the complex interactions between multiple brain circuits on emotional processing. Therefore, exploration of the neural substrates of emotional processing in pre-manifest HD using fMRI connectivity analysis may be a useful way of evaluating the way brain regions interrelate in the period prior to diagnosis. Methods We investigated the impact of predicted time to disease onset on brain activation when participants were exposed to pictures of faces with angry and neutral expressions, in 20 pre-manifest HD gene carriers and 23 healthy controls. On the basis of the results of this initial study went on to look at amygdala dependent cognitive performance in 79 Huntington's disease patients from a cross-section of disease stages (pre-manifest to late disease) and 26 healthy controls, using a validated theory of mind task: “the Reading the Mind in the Eyes Test” which has been previously been shown to be amygdala dependent. Results Psychophysiological interaction analysis identified reduced connectivity between the left amygdala and right fusiform facial area in pre-manifest HD gene carriers compared to controls when viewing angry compared to neutral faces. Change in PPI connectivity scores correlated with predicted time to disease onset (r=0.45, p<0.05). Furthermore, performance on the “Reading the Mind in the Eyes Test” correlated negatively with proximity to disease onset and became progressively worse with each stage of disease. Conclusion Abnormalities in the neural networks underlying social cognition and emotional processing can be detected prior to clinical

  16. Perioperative Outcomes of Robotic Assisted Laparoscopic Surgery Versus Conventional Laparoscopy Surgery for Advanced-Stage Endometriosis

    PubMed Central

    Sirota, Ido

    2014-01-01

    Background and Objectives: To determine perioperative outcome differences in patients undergoing robotic-assisted laparoscopic surgery (RALS) versus conventional laparoscopic surgery (CLS) for advanced-stage endometriosis. Methods: This retrospective cohort study at a minimally invasive gynecologic surgery center at 2 academically affiliated, urban, nonprofit hospitals included all patients treated by either robotic-assisted or conventional laparoscopic surgery for stage III or IV endometriosis (American Society for Reproductive Medicine criteria) between July 2009 and October 2012 by 1 surgeon experienced in both techniques. The main outcome measures were extent of surgery, estimated blood loss, operating room time, intraoperative and postoperative complications, and length of stay, with medians for continuous measures and distributions for categorical measures, stratified by body mass index values. Robotically assisted laparoscopy and conventional laparoscopy were then compared by use of the Wilcoxon rank sum, χ2, or Fisher exact test, as appropriate. Results: Among 86 conventional laparoscopic and 32 robotically assisted cases, the latter had a higher body mass index (27.36 kg/m2 [range, 23.90–34.09 kg/m2] versus 24.53 kg/m2 [range, 22.27–26.96 kg/m2]; P < .0079) and operating room time (250.50 minutes [range, 176–328.50 minutes] versus 173.50 minutes [range, 123–237 minutes]; P < .0005) than did conventional laparoscopy patients. After body mass index stratification, obese patients varied in operating room time (282.5 minutes [range, 224–342 minutes] for robotic-assisted laparoscopy versus 174 minutes [range, 130–270 minutes] for conventional laparoscopy; P < .05). No other significant differences were noted between the robotic-assisted and conventional laparoscopy groups. Conclusion: Despite a higher operating room time, robotic-assisted laparoscopy appears to be a safe minimally invasive approach for patients, with all other perioperative

  17. 42 CFR 413.210 - Conditions for payment under the end-stage renal disease (ESRD) prospective payment system.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... disease (ESRD) prospective payment system. 413.210 Section 413.210 Public Health CENTERS FOR MEDICARE... REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Payment for End-Stage Renal Disease (ESRD) Services and Organ Procurement...

  18. 42 CFR 413.210 - Conditions for payment under the end-stage renal disease (ESRD) prospective payment system.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... disease (ESRD) prospective payment system. 413.210 Section 413.210 Public Health CENTERS FOR MEDICARE... REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Payment for End-Stage Renal Disease (ESRD) Services and Organ Procurement...

  19. 42 CFR 413.210 - Conditions for payment under the end-stage renal disease (ESRD) prospective payment system.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... disease (ESRD) prospective payment system. 413.210 Section 413.210 Public Health CENTERS FOR MEDICARE... REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Payment for End-Stage Renal Disease (ESRD) Services and Organ Procurement...

  20. 42 CFR 413.210 - Conditions for payment under the end-stage renal disease (ESRD) prospective payment system.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... disease (ESRD) prospective payment system. 413.210 Section 413.210 Public Health CENTERS FOR MEDICARE... REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Payment for End-Stage Renal Disease (ESRD) Services and Organ Procurement...

  1. 42 CFR 413.210 - Conditions for payment under the end-stage renal disease (ESRD) prospective payment system.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... disease (ESRD) prospective payment system. 413.210 Section 413.210 Public Health CENTERS FOR MEDICARE... REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Payment for End-Stage Renal Disease (ESRD) Services and Organ Procurement...

  2. Influence of various operating conditions on advanced PFBC with staged combustion

    SciTech Connect

    Moersch, O.; Nagel, H.; Spliethoff, H.; Hein, K.R.G.

    1999-07-01

    The development of PFBC towards advanced or second generation PFBC focuses on an increase of temperature at the gas turbine inlet to bring forth a substantial improvement of the turbine itself and the overall system performance. Most of such advanced systems described in literature include a carbonizer for partial conversion of coal producing a low calorific pressurized syngas and a PFBC burning the remaining char. After hot gas clean-up the syngas and the O{sub 2}-rich fuel gas from the PFBC are led to the combustion chamber of the gas turbine. In the proposed staged combustion concept (PFBC-SC), which also aims at raising the temperatures at the gas turbine inlet, coal is burned substoichiometrically in a pressurized fluidized bed producing a low calorific gas. After hot gas clean-up the gas undergoes post-combustion with pressurized air and enters the gas turbine at approximately 1,450 K. The advantages of PFBC-SC over APFBC as described above are the lower investment costs and the simpler process, because no separate gasifier including hot gas cleaning device is needed. At the IVD's 50 kWth PFBC test facility, experimental investigations were done into substoichiometrical combustion with regard to composition of the produced gas, carbon-conversion and afterburner temperature. The results of the experiments which were carried out at various temperatures (1,073--1,200 K), pressures (1--13 bar), air ratios (0.5--0.9) and with different coals were compared with chemical equilibrium calculations. In contrast to the operating pressure the heating value of the syngas ({ge}CO, H{sub 2}, CH{sub 4}) could be increased significantly with increasing temperatures. Due to the better gasification behavior of subbituminous coal compared with bituminous coal almost equilibrium conditions were achieved. At high pressures and temperatures (13 bar/1,173 K) the carbon conversion rate 97.5% at all air ratios.

  3. Who will be active? Predicting exercise stage transitions after hospitalization for coronary artery disease.

    PubMed

    Reid, Robert D; Tulloch, Heather; Kocourek, Jana; Morrin, Louise I; Beaton, Louise J; Papadakis, Sophia; Blanchard, Chris M; Riley, Dana L; Pipe, Andrew L

    2007-01-01

    We describe transitions between exercise stages of change in people with coronary artery disease (CAD) over a 6-month period following a CAD-related hospitalization and evaluate constructs from Protection Motivation Theory, Theory of Planned Behavior, Social Cognitive Theory, the Ecological Model, and participation in cardiac rehabilitation as correlates of stage transition. Seven hundred eighty-two adults hospitalized with CAD were recruited and administered a baseline survey including assessments of theory-based constructs and exercise stage of change. Mailed surveys were used to gather information concerning exercise stage of change and participation in cardiac rehabilitation 6 months later. Progression from pre-action stages between baseline and 6 month follow-up was associated with greater perceived efficacy of exercise to reduce risk of future disease, fewer barriers to exercise, more access to home exercise equipment, and participation in cardiac rehabilitation. Regression from already active stages between baseline and 6 month follow-up was associated with increased perceived susceptibility to a future CAD-related event, fewer intentions to exercise, lower self-efficacy, and more barriers to exercise. PMID:17487242

  4. 76 FR 70227 - Medicare Program; End-Stage Renal Disease Prospective Payment System and Quality Incentive...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-10

    ...This final rule updates and makes certain revisions to the End-Stage Renal Disease (ESRD) prospective payment system (PPS) for calendar year (CY) 2012. We are also finalizing the interim final rule with comment period published on April 6, 2011, regarding the transition budget-neutrality adjustment under the ESRD PPS,. This final rule also sets forth requirements for the ESRD quality incentive......

  5. Baclofen-induced neurotoxicity in a patient with end-stage renal disease.

    PubMed

    Radhakrishnan, Hemachandar

    2016-05-01

    Baclofen, predominantly excreted by the kidneys is accumulated in patients with renal insufficiency leading to the central nervous system toxicity. Here the author reports a patient with end-stage renal disease on maintenance hemodialysis (HD) who developed drowsiness and became unresponsive within a day after taking single 10 mg dose of baclofen. Patient improved completely after two sessions of HD. PMID:27215257

  6. 75 FR 49029 - Medicare Program; End-Stage Renal Disease Prospective Payment System

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-12

    ... Federal Register a proposed rule entitled ``End-Stage Renal Disease Prospective Payment System'' (74 FR... separately billable services into a single base rate of $198.64 developed from CY 2007 claims data (74 FR... FR 49949). The case-mix adjusters would include variables for age, body surface area (BSA), low...

  7. How End-Stage Renal Disease Patients Manage the Medicare Part D Coverage Gap

    ERIC Educational Resources Information Center

    Kovacs, Pamela J.; Perkins, Nathan; Nuschke, Elizabeth; Carroll, Norman

    2012-01-01

    Medicare Part D was enacted to help elderly and disabled individuals pay for prescription drugs, but it was structured with a gap providing no coverage in 2010 between $2,830 and $6,440. Patients with end-stage renal disease (ESRD) are especially likely to be affected due to high costs of dialysis-related drugs and the importance of adherence for…

  8. 77 FR 40951 - Medicare Program; End-Stage Renal Disease Prospective Payment System, Quality Incentive Program...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-11

    ... rule (75 FR 49030 through 49214) titled, ``End-Stage Renal Disease Prospective Payment System... November 10, 2011, we published in the Federal Register, a final rule (76 FR 70228 through 70316) titled... the CY 2012 ESRD PPS final rule (76 FR 70228), we clarified the following: For the low-volume...

  9. Amygdalohippocampal MR volume measurements in the early stages of Alzheimer disease

    SciTech Connect

    Lehericy, S.; Baulac, M.; Chiras, J.; Pierot, L.; Martin, N.; Pillon, B.; Deweer, B.; Dubois, B.; Marsault, C.

    1994-05-01

    To evaluate the accuracy of hippocampal and amygdala volume measurements in diagnosing patients in the early stages of Alzheimer disease. Measurements of the hippocampal formation, amygdala, amygdalohippocampal complex (the two measurements summed), caudate nucleus, and ventricles, normalized for total intracranial volume, were obtained on coronal sections (1.5 T, 400/13 [repetition time/echo time], 5 mm) of 13 patients in the mild (minimental status {ge} 21) and five patients in the moderate stages of Alzheimer disease (10 < minimental status < 21), and eight age-matched control subjects. For patients with a minimental status score of 21 or greater, atrophy was significant for the amygdala and hippocampal formation (-36% and -25% for amygdala/total intracranial volume and hippocampal formation/total intracranial volume, respectively), but not for the caudate nucleus. No significant ventricular enlargement was found. For patients with a minimental status score less than 21, atrophy was more severe in all structures studied (amygdala/total intracranial volume -40%; hippocampal formation/total intracranial volume, -45%; caudate nucleus/total intracranial volume, -21%), and ventricles were enlarged (63%). No overlap was found between Alzheimer disease and control values for the amygdalohippocampal volume, even in the mild stages of the disease. In Alzheimer disease patients, hippocampal formation volumes correlated with the minimental status. Hippocampal and amygdala atrophy is marked and significant in the mild stages of Alzheimer disease. Volumetric measurements of the amygdala and the amygdalohippocampal complex appear more accurate than those of the hippocampal formation alone in distinguishing patients with Alzheimer disease. 46 refs., 8 figs., 2 tabs.

  10. From orphan drugs to adopted therapies: Advancing C3-targeted intervention to the clinical stage.

    PubMed

    Mastellos, Dimitrios C; Reis, Edimara S; Yancopoulou, Despina; Hajishengallis, George; Ricklin, Daniel; Lambris, John D

    2016-10-01

    Complement dysregulation is increasingly recognized as an important pathogenic driver in a number of clinical disorders. Complement-triggered pathways intertwine with key inflammatory and tissue destructive processes that can either increase the risk of disease or exacerbate pathology in acute or chronic conditions. The launch of the first complement-targeted drugs in the clinic has undeniably stirred the field of complement therapeutic design, providing new insights into complement's contribution to disease pathogenesis and also helping to leverage a more personalized, comprehensive approach to patient management. In this regard, a rapidly expanding toolbox of complement therapeutics is being developed to address unmet clinical needs in several immune-mediated and inflammatory diseases. Elegant approaches employing both surface-directed and fluid-phase inhibitors have exploited diverse components of the complement cascade as putative points of therapeutic intervention. Targeting C3, the central hub of the system, has proven to be a promising strategy for developing biologics as well as small-molecule inhibitors with clinical potential. Complement modulation at the level of C3 has recently shown promise in preclinical primate models, opening up new avenues for therapeutic intervention in both acute and chronic indications fueled by uncontrolled C3 turnover. This review highlights recent developments in the field of complement therapeutics, focusing on C3-directed inhibitors and alternative pathway (AP) regulator-based approaches. Translational perspectives and considerations are discussed, particularly with regard to the structure-guided drug optimization and clinical advancement of a new generation of C3-targeted peptidic inhibitors. PMID:27353192

  11. Nanocarriers for respiratory diseases treatment: recent advances and current challenges.

    PubMed

    Trapani, Adriana; Gioia, Sante Di; Castellani, Stefano; Carbone, Annalucia; Cavallaro, Gennara; Trapani, Giuseppe; Conese, Massimo

    2014-01-01

    Pulmonary delivery of locally-acting drugs encapsulated in nanocarriers provides several advantages for the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis, tuberculosis and lung cancer. These advantages include, among others, sustained drug delivery to the lungs, reduced therapeutic dose and improved patient compliance. The aim of this review is to give an updated overview on recent advances recorded in the last few years in this field as well as on the major challenges still existing and that remain to be overcome before any clinical application. After an outline on the cellular and extracellular barriers affecting drug delivery to the airways both in physiological and pathological conditions, the significant developments recorded using inhaled polymeric- and lipid-based nanocarriers for drug and gene delivery to the lung are presented. In this discussion, the major challenges existing in the field are evidenced including the understanding of the factors governing the mucus penetration capability of these nanocarriers and the identification of new technologies for delivering drugs to specific regions or cell types of the lungs. In this regard, the recognition of receptor expressed only at lung level may facilitate drug targeting to this organ and it should improve the therapeutic efficacy of nanocarrier-based treatments for respiratory diseases. PMID:24678708

  12. Advances in Epigenetics and Epigenomics for Neurodegenerative Diseases

    PubMed Central

    Qureshi, Irfan A.

    2015-01-01

    In the post-genomic era, epigenetic factors—literally those that are “over” or “above” genetic ones and responsible for controlling the expression and function of genes—have emerged as important mediators of development and aging; gene-gene and gene-environmental interactions; and the pathophysiology of complex disease states. Here, we provide a brief overview of the major epigenetic mechanisms (ie, DNA methylation, histone modifications and chromatin remodeling, and non-coding RNA regulation). We highlight the nearly ubiquitous profiles of epigenetic dysregulation that have been found in Alzheimer’s and other neurodegenerative diseases. We also review innovative methods and technologies that enable the characterization of individual epigenetic modifications and more widespread epigenomic states at high resolution. We conclude that, together with complementary genetic, genomic, and related approaches, interrogating epigenetic and epigenomic profiles in neurodegenerative diseases represent important and increasingly practical strategies for advancing our understanding of and the diagnosis and treatment of these disorders. PMID:21671162

  13. Advances in stem cell therapy for cardiovascular disease (Review)

    PubMed Central

    SUN, RONGRONG; LI, XIANCHI; LIU, MIN; ZENG, YI; CHEN, SHUANG; ZHANG, PEYING

    2016-01-01

    Cardiovascular disease constitutes the primary cause of mortality and morbidity worldwide, and represents a group of disorders associated with the loss of cardiac function. Despite considerable advances in the understanding of the pathologic mechanisms of the disease, the majority of the currently available therapies remain at best palliative, since the problem of cardiac tissue loss has not yet been addressed. Indeed, few therapeutic approaches offer direct tissue repair and regeneration, whereas the majority of treatment options aim to limit scar formation and adverse remodeling, while improving myocardial function. Of all the existing therapeutic approaches, the problem of cardiac tissue loss is addressed uniquely by heart transplantation. Nevertheless, alternative options, particularly stem cell therapy, has emerged as a novel and promising approach. This approach involves the transplantation of healthy and functional cells to promote the renewal of damaged cells and repair injured tissue. Bone marrow precursor cells were the first cell type used in clinical studies, and subsequently, preclinical and clinical investigations have been extended to the use of various populations of stem cells. This review addresses the present state of research as regards stem cell therapy for cardiovascular disease. PMID:27220939

  14. HLA-G Expression and Role in Advanced-Stage Classical Hodgkin Lymphoma

    PubMed Central

    Caocci, G.; Greco, M.; Fanni, D.; Senes, G.; Littera, R.; Lai, S.; Risso, P.; Carcassi, C.; Faa, G.; La Nasa, G.

    2016-01-01

    Non-classical human leucocyte antigen (HLA)-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL), in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp) deletion-insertion (del-ins) polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy) patients with a 2-year progression-free survival rate (PFS) of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS) cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2. PMID:27349312

  15. Advanced Imaging and Receipt of Guideline Concordant Care in Women with Early Stage Breast Cancer.

    PubMed

    Loggers, Elizabeth Trice; Buist, Diana S M; Gold, Laura S; Zeliadt, Steven; Hunter Merrill, Rachel; Etzioni, Ruth; Ramsey, Scott D; Sullivan, Sean D; Kessler, Larry

    2016-01-01

    Objective. It is unknown whether advanced imaging (AI) is associated with higher quality breast cancer (BC) care. Materials and Methods. Claims and Surveillance Epidemiology and End Results data were linked for women diagnosed with incident stage I-III BC between 2002 and 2008 in western Washington State. We examined receipt of preoperative breast magnetic resonance imaging (MRI) or AI (defined as computed tomography [CT]/positron emission tomography [PET]/PET/CT) versus mammogram and/or ultrasound (M-US) alone and receipt of guideline concordant care (GCC) using multivariable logistic regression. Results. Of 5247 women, 67% received M-US, 23% MRI, 8% CT, and 3% PET/PET-CT. In 2002, 5% received MRI and 5% AI compared to 45% and 12%, respectively, in 2008. 79% received GCC, but GCC declined over time and was associated with younger age, urban residence, less comorbidity, shorter time from diagnosis to surgery, and earlier year of diagnosis. Breast MRI was associated with GCC for lumpectomy plus radiation therapy (RT) (OR 1.55, 95% CI 1.08-2.26, and p = 0.02) and AI was associated with GCC for adjuvant chemotherapy for estrogen-receptor positive (ER+) BC (OR 1.74, 95% CI 1.17-2.59, and p = 0.01). Conclusion. GCC was associated with prior receipt of breast MRI and AI for lumpectomy plus RT and adjuvant chemotherapy for ER+ BC, respectively. PMID:27525122

  16. Advanced Imaging and Receipt of Guideline Concordant Care in Women with Early Stage Breast Cancer

    PubMed Central

    Buist, Diana S. M.; Gold, Laura S.; Zeliadt, Steven; Hunter Merrill, Rachel; Etzioni, Ruth; Ramsey, Scott D.; Sullivan, Sean D.; Kessler, Larry

    2016-01-01

    Objective. It is unknown whether advanced imaging (AI) is associated with higher quality breast cancer (BC) care. Materials and Methods. Claims and Surveillance Epidemiology and End Results data were linked for women diagnosed with incident stage I-III BC between 2002 and 2008 in western Washington State. We examined receipt of preoperative breast magnetic resonance imaging (MRI) or AI (defined as computed tomography [CT]/positron emission tomography [PET]/PET/CT) versus mammogram and/or ultrasound (M-US) alone and receipt of guideline concordant care (GCC) using multivariable logistic regression. Results. Of 5247 women, 67% received M-US, 23% MRI, 8% CT, and 3% PET/PET-CT. In 2002, 5% received MRI and 5% AI compared to 45% and 12%, respectively, in 2008. 79% received GCC, but GCC declined over time and was associated with younger age, urban residence, less comorbidity, shorter time from diagnosis to surgery, and earlier year of diagnosis. Breast MRI was associated with GCC for lumpectomy plus radiation therapy (RT) (OR 1.55, 95% CI 1.08–2.26, and p = 0.02) and AI was associated with GCC for adjuvant chemotherapy for estrogen-receptor positive (ER+) BC (OR 1.74, 95% CI 1.17–2.59, and p = 0.01). Conclusion. GCC was associated with prior receipt of breast MRI and AI for lumpectomy plus RT and adjuvant chemotherapy for ER+ BC, respectively. PMID:27525122

  17. 'Making the best you can of it': living with early-stage Alzheimer's disease.

    PubMed

    Macrae, Hazel

    2008-04-01

    Drawing upon data from a qualitative study of persons who are in the early stage of the condition, this paper examines the meaning of Alzheimer's disease. It contrasts the meaning of the disease as portrayed in popular culture with its meaning as interpreted by persons living with it. Findings show that persons with the illness do not necessarily accept the negative cultural meaning of the disease, nor the helpless 'victim' role in which they are generally cast. With a determination to 'make the best of it', strategies such as humour, normalisation, present-time orientation, and life review are employed to create a meaningful life. PMID:18298633

  18. Political, social and technical risks in the last stages of disease eradication campaigns.

    PubMed

    Whitty, Christopher J M

    2015-09-01

    Eradication of a disease is one of the greatest gifts any generation can give to subsequent ones, but most attempts have failed. The biggest challenges occur in the final stages of eradication and elimination campaigns. These include falling public support as a disease becomes less common; the emergence of groups who do not support eradication; spiralling costs; and the evolution of drug, vaccine or insecticide resistance. Mass campaigns become less effective as the disease fragments and modelling becomes less reliable. Optimism bias is the biggest risk to any eradication campaign and the long endgame must be planned for from the beginning. PMID:26311754

  19. Motor Sequence Learning Performance in Parkinson's Disease Patients Depends on the Stage of Disease

    ERIC Educational Resources Information Center

    Stephan, Marianne A.; Meier, Beat; Zaugg, Sabine Weber; Kaelin-Lang, Alain

    2011-01-01

    It is still unclear, whether patients with Parkinson's disease (PD) are impaired in the incidental learning of different motor sequences in short succession, although such a deficit might greatly impact their daily life. The aim of this study was thus to clarify the relation between disease parameters of PD and incidental motor learning of two…

  20. High expression of CAI2, a 9p21-embedded long non-coding RNA, contributes to advanced stage neuroblastoma

    PubMed Central

    Barnhill, Lisa M.; Williams, Richard T.; Cohen, Olga; Kim, Youngjin; Batova, Ayse; Mielke, Jenna A.; Messer, Karen; Pu, Minya; Bao, Lei; Yu, Alice L.; Diccianni, Mitchell B.

    2014-01-01

    Neuroblastoma is a pediatric cancer with significant genomic and biological heterogeneity. p16 and ARF, two important tumor suppressor genes on chromosome 9p21, are inactivated commonly in most cancers but paradoxically overexpressed in neuroblastoma. Here we report that exon γ in p16 is also part of an undescribed long non-coding RNA (lncRNA) that we have termed CAI2 (CDKN2A/ARF Intron 2 lncRNA). CAI2 is a single exon gene with a poly A signal located in but independent of the p16/ARF exon 3. CAI2 is expressed at very low levels in normal tissue but is highly expressed in most tumor cell lines with an intact 9p21 locus. Concordant expression of CAI2 with p16 and ARF in normal tissue along with the ability of CAI2 to induce p16 expression suggested that CAI2 may regulate p16 and/or ARF. In neuroblastoma cells transformed by serial passage in vitro, leading to more rapid proliferation, CAI2, p16 and ARF expression all increased dramatically. A similar relationship was also observed in primary neuroblastomas where CAI2 expression was significantly higher in advanced stage neuroblastoma, independently of MYCN amplification. Consistent with its association with high risk disease, CAI2 expression was also significantly associated with poor clinical outcomes, although this effect was reduced when adjusted for MYCN amplification. Taken together, our findings suggested that CAI2 contributes to the paradoxical overexpression of p16 in neuroblastoma, where CAI2 may offer a useful biomarker of high-risk disease. PMID:25028366

  1. Neuroanatomical Correlates of Recognizing Face Expressions in Mild Stages of Alzheimer's Disease.

    PubMed

    Sapey-Triomphe, Laurie-Anne; Heckemann, Rolf A; Boublay, Nawele; Dorey, Jean-Michel; Hénaff, Marie-Anne; Rouch, Isabelle; Padovan, Catherine; Hammers, Alexander; Krolak-Salmon, Pierre

    2015-01-01

    Early Alzheimer's disease can involve social disinvestment, possibly as a consequence of impairment of nonverbal communication skills. This study explores whether patients with Alzheimer's disease at the mild cognitive impairment or mild dementia stage have impaired recognition of emotions in facial expressions, and describes neuroanatomical correlates of emotion processing impairment. As part of the ongoing PACO study (personality, Alzheimer's disease and behaviour), 39 patients with Alzheimer's disease at the mild cognitive impairment or mild dementia stage and 39 matched controls completed tests involving discrimination of four basic emotions-happiness, fear, anger, and disgust-on photographs of faces. In patients, automatic volumetry of 83 brain regions was performed on structural magnetic resonance images using MAPER (multi-atlas propagation with enhanced registration). From the literature, we identified for each of the four basic emotions one brain region thought to be primarily associated with the function of recognizing that emotion. We hypothesized that the volume of each of these regions would be correlated with subjects' performance in recognizing the associated emotion. Patients showed deficits of basic emotion recognition, and these impairments were correlated with the volumes of the expected regions of interest. Unexpectedly, most of these correlations were negative: better emotional facial recognition was associated with lower brain volume. In particular, recognition of fear was negatively correlated with the volume of amygdala, disgust with pallidum, and happiness with fusiform gyrus. Recognition impairment in mild stages of Alzheimer's disease for a given emotion was thus associated with less visible atrophy of functionally responsible brain structures within the patient group. Possible explanations for this counterintuitive result include neuroinflammation, regional β-amyloid deposition, or transient overcompensation during early stages of

  2. Neuroanatomical Correlates of Recognizing Face Expressions in Mild Stages of Alzheimer’s Disease

    PubMed Central

    Sapey-Triomphe, Laurie-Anne; Heckemann, Rolf A.; Boublay, Nawele; Dorey, Jean-Michel; Hénaff, Marie-Anne; Rouch, Isabelle; Padovan, Catherine; Hammers, Alexander; Krolak-Salmon, Pierre

    2015-01-01

    Early Alzheimer’s disease can involve social disinvestment, possibly as a consequence of impairment of nonverbal communication skills. This study explores whether patients with Alzheimer’s disease at the mild cognitive impairment or mild dementia stage have impaired recognition of emotions in facial expressions, and describes neuroanatomical correlates of emotion processing impairment. As part of the ongoing PACO study (personality, Alzheimer’s disease and behaviour), 39 patients with Alzheimer’s disease at the mild cognitive impairment or mild dementia stage and 39 matched controls completed tests involving discrimination of four basic emotions—happiness, fear, anger, and disgust—on photographs of faces. In patients, automatic volumetry of 83 brain regions was performed on structural magnetic resonance images using MAPER (multi-atlas propagation with enhanced registration). From the literature, we identified for each of the four basic emotions one brain region thought to be primarily associated with the function of recognizing that emotion. We hypothesized that the volume of each of these regions would be correlated with subjects’ performance in recognizing the associated emotion. Patients showed deficits of basic emotion recognition, and these impairments were correlated with the volumes of the expected regions of interest. Unexpectedly, most of these correlations were negative: better emotional facial recognition was associated with lower brain volume. In particular, recognition of fear was negatively correlated with the volume of amygdala, disgust with pallidum, and happiness with fusiform gyrus. Recognition impairment in mild stages of Alzheimer’s disease for a given emotion was thus associated with less visible atrophy of functionally responsible brain structures within the patient group. Possible explanations for this counterintuitive result include neuroinflammation, regional β-amyloid deposition, or transient overcompensation during early

  3. Advanced lung disease: quality of life and role of palliative care.

    PubMed

    Gilbert, Christopher R; Smith, Cecilia M

    2009-02-01

    . Recognition and correction of nocturnal hypoxemia and other sleep disturbances should enhance quality of life in patients with restrictive lung disease; however, there is currently no evidence to support this claim. End-of-life care needs more attention by clinicians in the decision-making and preparatory phase. Physicians need to maintain their focus on quality-of-life issues as medical management shifts from curative therapies to comfort management therapies. Palliative care and hospice appear to be underused in patients with advanced diseases other than cancer. Because the only curative option for some end-stage restrictive lung diseases is lung transplantation, if transplantation is not an option, palliation of symptoms and hospice care may offer patients and families the opportunity to die with dignity and comfort. PMID:19170219

  4. Advances in designs for Alzheimer’s disease clinical trials

    PubMed Central

    Cummings, Jeffrey; Gould, Heath; Zhong, Kate

    2012-01-01

    There is an urgent need to identify new treatments for the rapidly growing population of people with Alzheimer’s disease (AD). Innovations in clinical trial designs many help to reduce development time, provide more definitive answers regarding drug efficacy, and facilitate prioritizing compounds to be advanced to Phase III clinical trials. Standard designs compare drug and placebo changes from baseline on a rating scale. Baysian adaptive clinical trials allow the use of data collected in the trial to modify doses, sample size, trial duration, and entry criteria in an ongoing way as the data are collected. Disease-modification is supported by findings on staggered start and delayed withdrawal designs. Futility designs can use historical controls and may shorten trial duration. Combination therapy designs may allow investigation of additive or synergistic treatment effects. Novel trial selection criteria allow investigation of treatment effects in asymptomatic or minimally symptomatic, prodromal AD populations. The Clinical Dementia Rating-Sum of Boxes (CDR-SOB) can be considered as a single trial outcome in early disease populations. Alternate forms of the Alzheimer’s Disease Assessment Scale-Cognitive Portion (ADAS-cog), computerized measures, and pharmacoeconomic scales provide new and relevant information on drug effects. Comparative dose strategies are used in trials of symptomatic agents, and novel methods including withdrawal designs, symptom emergence analyses, and sequential designs are being utilized to assess the efficacy of putative psychotropic agents. The choice of trial design is driven by the question to be answered by the clinical trial; an increasing number of design approaches are available and may be useful in accelerating and refining AD drug development. PMID:23383393

  5. CAP--advancing the evaluation of preclinical Alzheimer disease treatments.

    PubMed

    Reiman, Eric M; Langbaum, Jessica B; Tariot, Pierre N; Lopera, Francisco; Bateman, Randall J; Morris, John C; Sperling, Reisa A; Aisen, Paul S; Roses, Allen D; Welsh-Bohmer, Kathleen A; Carrillo, Maria C; Weninger, Stacie

    2016-01-01

    If we are to find treatments to postpone, reduce the risk of, or completely prevent the clinical onset of Alzheimer disease (AD), we need faster methods to evaluate promising preclinical AD treatments, new ways to work together in support of common goals, and a determination to expedite the initiation and performance of preclinical AD trials. In this article, we note some of the current challenges, opportunities and emerging strategies in preclinical AD treatment. We describe the Collaboration for Alzheimer's Prevention (CAP)-a convening, harmonizing and consensus-building initiative to help stakeholders advance AD prevention research with rigour, care and maximal impact-and we demonstrate the impact of CAP on the goals and design of new preclinical AD trials. PMID:26416539

  6. Advances in nanotechnology for the management of coronary artery disease.

    PubMed

    Rhee, June-Wha; Wu, Joseph C

    2013-02-01

    Nanotechnology holds tremendous potential to advance the current treatment of coronary artery disease. Nanotechnology may assist medical therapies by providing a safe and efficacious delivery platform for a variety of drugs aimed at modulating lipid disorders, decreasing inflammation and angiogenesis within atherosclerotic plaques, and preventing plaque thrombosis. Nanotechnology may improve coronary stent applications by promoting endothelial recovery on a stent surface utilizing bio-mimetic nanofibrous scaffolds, and also by preventing in-stent restenosis using nanoparticle-based delivery of drugs that are decoupled from stents. Additionally, nanotechnology may enhance tissue-engineered graft materials for application in coronary artery bypass grafting by facilitating cellular infiltration and remodeling of a graft matrix. PMID:23245913

  7. Advanced gastrointestinal endoscopic imaging for inflammatory bowel diseases

    PubMed Central

    Tontini, Gian Eugenio; Rath, Timo; Neumann, Helmut

    2016-01-01

    Gastrointestinal luminal endoscopy is of paramount importance for diagnosis, monitoring and dysplasia surveillance in patients with both, Crohn’s disease and ulcerative colitis. Moreover, with the recent recognition that mucosal healing is directly linked to the clinical outcome of patients with inflammatory bowel disorders, a growing demand exists for the precise, timely and detailed endoscopic assessment of superficial mucosal layer. Further, the novel field of molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy, now encompassing not only diagnosis, surveillance, and treatment but also the prediction of individual therapeutic responses. Within this review, we describe how novel endoscopic approaches and advanced endoscopic imaging methods such as high definition and high magnification endoscopy, dye-based and dye-less chromoendoscopy, confocal laser endomicroscopy, endocytoscopy and molecular imaging now allow for the precise and ultrastructural assessment of mucosal inflammation and describe the potential of these techniques for dysplasia detection. PMID:26811662

  8. Recent advancement of therapeutic endoscopy in the esophageal benign diseases.

    PubMed

    Bechara, Robert; Inoue, Haruhiro

    2015-05-16

    Over the past 30 years, the field of endoscopy has witnessed several advances. With the advent of endoscopic mucosal resection, removal of large mucosal lesions have become possible. Thereafter, endoscopic submucosal resection was refined, permitting en bloc removal of large superficial neoplasms. Such techniques have facilitated the development of antireflux mucosectomy, a promising novel treatment for gastroesophageal reflux. The introduction and use of over the scope clips has allowed for endoscopic closure of defects in the gastrointestinal tract, which were traditionally treated with surgical intervention. With the development of per-oral endoscopic myotomy (POEM), the treatment of achalasia and spastic disorders of the esophagus have been revolutionized. From the submucosal tunnelling technique developed for POEM, Per oral endoscopic tumor resection of subepithelial tumors was made possible. Simultaneously, advances in biotechnology have expanded esophageal stenting capabilities with the introduction of fully covered metal and plastic stents, as well as biodegradable stents. Once deemed a primarily diagnostic tool, endoscopy has quickly transcended to a minimally invasive intervention and therapeutic tool. These techniques are reviewed with regards to their application to benign disease of the esophagus. PMID:25992187

  9. Recent advancement of therapeutic endoscopy in the esophageal benign diseases

    PubMed Central

    Bechara, Robert; Inoue, Haruhiro

    2015-01-01

    Over the past 30 years, the field of endoscopy has witnessed several advances. With the advent of endoscopic mucosal resection, removal of large mucosal lesions have become possible. Thereafter, endoscopic submucosal resection was refined, permitting en bloc removal of large superficial neoplasms. Such techniques have facilitated the development of antireflux mucosectomy, a promising novel treatment for gastroesophageal reflux. The introduction and use of over the scope clips has allowed for endoscopic closure of defects in the gastrointestinal tract, which were traditionally treated with surgical intervention. With the development of per-oral endoscopic myotomy (POEM), the treatment of achalasia and spastic disorders of the esophagus have been revolutionized. From the submucosal tunnelling technique developed for POEM, Per oral endoscopic tumor resection of subepithelial tumors was made possible. Simultaneously, advances in biotechnology have expanded esophageal stenting capabilities with the introduction of fully covered metal and plastic stents, as well as biodegradable stents. Once deemed a primarily diagnostic tool, endoscopy has quickly transcended to a minimally invasive intervention and therapeutic tool. These techniques are reviewed with regards to their application to benign disease of the esophagus. PMID:25992187

  10. Soluble cell adhesion molecules in human Chagas' disease: association with disease severity and stage of infection.

    PubMed

    Laucella, S; De Titto, E H; Segura, E L; Orn, A; Rottenberg, M E

    1996-12-01

    Formation of inflammatory lesions, one of the pathologic consequences of infection with Trypanosoma cruzi, involves intricate cell-cell interactions in which cell adhesion molecules (CAMs) are involved. Sera from 56 Chagas' disease patients grouped according to disease severity were studied for the presence of soluble intercellular adhesion molecule-1 (s-ICAM-1), soluble endothelial selectin (s-E-selectin), soluble vascular cell adhesion molecule-1 (s-VCAM-1), soluble platelet selectin (s-P-selectin), and s-CD44 were studied to determine if they could be used alone or in different combinations as markers for specific diagnostic procedures. Comparisons were made between congenitally, acutely, and chronically infected patients and aged-matched, noninfected individuals, as well as between patients with chronic Chagas' disease grouped according to the severity of their heart-related pathology. No differences in levels of s-CAMs were detected between sera from children with congenital T. cruzi infection and sera from noninfected infants born from chagasic mothers. In contrast, titers of s-ICAM-1, s-VCAM-1, s-selectin, and s-CD44 but not s-P-selectin were significantly increased in sera from patients during the acute phase of infection with T. cruzi. Titers of s-VCAM-1 and s-P-selectin were increased in chronically infected patients. A positive association with disease severity in sera from patients with chronic disease was observed for the levels of s-P-selectin. In contrast, we found no association between clinical symptoms and levels of s-VCAM-1. Patients with chronic disease with severe cardiopathy also showed diminished levels of s-CD44 in comparison with healthy controls or patients with mild disease. The results are discussed in the context of pathology of Chagas' disease. PMID:9025689

  11. Evaluation of mean platelet volume, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in advanced stage endometriosis with endometrioma

    PubMed Central

    Yavuzcan, Ali; Çağlar, Mete; Üstün, Yusuf; Dilbaz, Serdar; Özdemir, İsmail; Yıldız, Elif; Özkara, Atilla; Kumru, Selahattin

    2013-01-01

    Objective We compared the preoperative values of mean platelet volume (MPV) and peripheral systemic inflammatory response (SIR) markers (neutrophil/lymphocyte ratio and platelet/lymphocyte ratio) between patients with advanced-stage (stage 3/4) endometriosis having endometrioma (OMA) and patients with a non-neoplastic adnexal mass other than endometrioma (non-OMA). Material and Methods Patients who underwent operations with the pre-diagnosis of infertility or adnexal mass and who underwent laparoscopic tubal ligation were included. Results Haemoglobin levels, leucocyte count, platelet count, neutrophil count and lymphocyte count were not significantly different between patients with advanced stage endometriosis having OMA, patients with non-OMA and patients in the control group (p=0.970, p=0.902, p=0.373, p=0.501 and p=0.463, respectively). Patients with stage 3/4 endometriosis having OMA, patients with non-OMA and control patients were also not significantly different in terms of MPV (p=0.836), neutrophil/lymphocyte ratio (NLR) (p=0.555) and platelet/lymphocyte ratio (PLR) (p=0.358). Preoperative cancer antigen 125 (Ca-125) levels were significantly higher in patients with OMA (p=0.006). Mean size of the OMAs was significantly lower than non-OMAs (p=0.000). Conclusion It is very important to determine advanced stage endometriosis and OMAs during preoperative evaluation in order to inform patients and plan an appropriate surgical approach. We demonstrate that MPV, NLR and PLR values are not useful for this purpose in patients with advanced stage endometriosis that are proven to develop severe inflammation at either the cellular or molecular level. PMID:24592108

  12. Recent Advances in Surgery of Congenital Heart Disease

    PubMed Central

    Gerbode, Frank; Sharma, Giridhari

    1970-01-01

    In the cyanotic group palliative procedures for transposition of the great arteries are frequently life-saving in infancy, and the definitive operations such as the atrial baffle, and the Rastelli procedure for those with ventricular septal defect and pulmonic stenosis, are now firmly established. In tetralogy of Fallot shunting procedures continue to be employed in infancy and early childhood, and the complete repair is usually done after the age of five. Corrective operations for total anomalous venous return may have to be staged, and the results are more satisfactory in older children. The various forms of endocardial cushion defects can usually be recognized accurately preoperatively, and where the normal anatomical relationships can be restored, excellent results obtained. Brilliant operative success can now be had in some forms of truncus arteriosus and double outlet right ventricle. It is quite common to find congenital heart disease in adults, frequently after many years of having been treated as rheumatic heart disease. The operative risk in this group is less than 10 percent, and in most instances such patients are restored to their normal physiological age after operation. PMID:4926370

  13. Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Viola, Kirsten L.; Sbarboro, James; Sureka, Ruchi; de, Mrinmoy; Bicca, Maíra A.; Wang, Jane; Vasavada, Shaleen; Satpathy, Sreyesh; Wu, Summer; Joshi, Hrushikesh; Velasco, Pauline T.; Macrenaris, Keith; Waters, E. Alex; Lu, Chang; Phan, Joseph; Lacor, Pascale; Prasad, Pottumarthi; Dravid, Vinayak P.; Klein, William L.

    2015-01-01

    One way to image the molecular pathology in Alzheimer's disease is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early-stage biomarkers that instigate memory loss are composed of Aβ oligomers. Here, we report a sensitive molecular magnetic resonance imaging contrast probe that is specific for Aβ oligomers. We attach oligomer-specific antibodies onto magnetic nanostructures and show that the complex is stable and binds to Aβ oligomers on cells and brain tissues to give a magnetic resonance imaging signal. When intranasally administered to an Alzheimer's disease mouse model, the probe readily reached hippocampal Aβ oligomers. In isolated samples of human brain tissue, we observed a magnetic resonance imaging signal that distinguished Alzheimer's disease from controls. Such nanostructures that target neurotoxic Aβ oligomers are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage Alzheimer's disease diagnosis and disease management.

  14. Solid rocket technology advancement for Space Tug and IUS applications. [Interim Upper Stage

    NASA Technical Reports Server (NTRS)

    Ascher, W.; Bailey, R. L.; Behm, J. W.; Gin, W.

    1975-01-01

    Two-burn restartable solid propellant rocket motors for the kick stage (auxiliary stage) of the Shuttle Tug, or Interim Upper Stage, are described, with details on features and test results of the ignition and quench (thrust termination) systems and procedures, fabrication of propellant and insulation, explosion hazards of propellants, and comparative data on present and future motor design. These rocket motor systems are designed for upper stage augmentation of launch vehicles and possible service in Shuttle-launched outer planet spacecraft.

  15. Acylated Cholesteryl Galactosides Are Specific Antigens of Borrelia Causing Lyme Disease and Frequently Induce Antibodies in Late Stages of Disease

    PubMed Central

    Stübs, Gunthard; Fingerle, Volker; Wilske, Bettina; Göbel, Ulf B.; Zähringer, Ulrich; Schumann, Ralf R.; Schröder, Nicolas W. J.

    2009-01-01

    Borrelia burgdorferi sensu lato is the causative agent of Lyme disease (LD), an infectious disease occurring in North America, Europe, and Asia in different clinical stages. B. burgdorferi sensu lato encompasses at least 12 species, with B. burgdorferi sensu stricto, B. garinii, and B. afzelii being of highest clinical importance. Immunologic testing for LD as well as recent vaccination strategies exclusively refer to proteinaceous antigens. However, B. burgdorferi sensu stricto exhibits glycolipid antigens, including 6-O-acylated cholesteryl β-d-galactopyranoside (ACGal), and first the data indicated that this compound may act as an immunogen. Here we investigated whether B. garinii and B. afzelii also possess this antigen, and whether antibodies directed against these compounds are abundant among patients suffering from different stages of LD. Gas-liquid chromatography/mass spectroscopy and NMR spectroscopy showed that both B. garinii and B. afzelii exhibit ACGal in high quantities. In contrast, B. hermsii causing relapsing fever features 6-O-acylated cholesteryl β-d-glucopyranoside (ACGlc). Sera derived from patients diagnosed for LD contained antibodies against ACGal, with 80% of patients suffering from late stage disease exhibiting this feature. Antibodies reacted with ACGal from all three B. burgdorferi species tested, but not with ACGlc from B. hermsii. These data show that ACGal is present in all clinically important B. burgdorferi species, and that specific antibodies against this compound are frequently found during LD. ACGal may thus be an interesting tool for improving diagnostics as well as for novel vaccination strategies. PMID:19307181

  16. New Targeted Treatment May Slow Disease in Patients with Advanced GIST

    MedlinePlus

    ... Patients with Advanced GIST A new oral drug, regorafenib (Stivarga®), may delay the progression of advanced gastrointestinal ... in The Lancet demonstrated that patients treated with regorafenib lived longer without their disease progressing than patients ...

  17. Trousseau’s syndrome in a patient with advanced stage gastric cancer

    PubMed Central

    Chien, Tai-Long; Rau, Kung-Ming; Chung, Wen-Jung; Tai, Wei-Chen; Wang, Shih-Ho; Chiu, Yi-Chun; Wu, Keng-Liang; Chou, Yeh-Pin; Wu, Chia-Che; Chen, Yen-Hao; Chuah, Seng-Kee

    2015-01-01

    Patients with cancer are at high risk for thrombotic events, which are known collectively as Trousseau’s syndrome. Herein, we report a 66-year-old male patient who was diagnosed with terminal stage gastric cancer and liver metastasis and who had an initial clinical presentation of upper gastrointestinal bleeding. Acute ischemia of the left lower leg that resulted in gangrenous changes occurred during admission. Subsequent angiography of the left lower limb was then performed. This procedure revealed arterial thrombosis of the left common iliac artery with extension to the external iliac artery, the left common iliac artery, the posterior tibial artery, and the peroneal artery, which were occluded by thrombi. Aspiration of the thrombi demonstrated that these were not tumor thrombi. The interesting aspect of our case was that the disease it presented as arterial thrombotic events, which may correlate with gastric adenocarcinoma. In summary, we suggested that the unexplained thrombotic events might be one of the initial presentations of occult malignancy and that thromboprophylaxis should always be considered. PMID:26379411

  18. Prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage

    PubMed Central

    Verhey, Frans; Frölich, Lutz; Kornhuber, Johannes; Wiltfang, Jens; Maier, Wolfgang; Peters, Oliver; Rüther, Eckart; Nobili, Flavio; Morbelli, Silvia; Frisoni, Giovanni B.; Drzezga, Alexander; Didic, Mira; van Berckel, Bart N. M.; Simmons, Andrew; Soininen, Hilkka; Kłoszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon; Muscio, Cristina; Herukka, Sanna-Kaisa; Salmon, Eric; Bastin, Christine; Wallin, Anders; Nordlund, Arto; de Mendonça, Alexandre; Silva, Dina; Santana, Isabel; Lemos, Raquel; Engelborghs, Sebastiaan; Van der Mussele, Stefan; Freund-Levi, Yvonne; Wallin, Åsa K.; Hampel, Harald; van der Flier, Wiesje; Scheltens, Philip; Visser, Pieter Jelle

    2015-01-01

    Three sets of research criteria are available for diagnosis of Alzheimer’s disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer’s disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer’s disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer’s disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer’s disease at the mild cognitive impairment stage and progression to Alzheimer’s disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer’s disease. Their 3-year progression rate to Alzheimer’s disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer’s disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer’s disease. Their 3-year progression rate to Alzheimer’s disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer’s disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer’s disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in

  19. Inflammatory Markers and Procoagulants in Chronic Renal Disease Stages 1-4

    PubMed Central

    Muslimovic, Alma; Rasic, Senija; Tulumovic, Denijal; Hasanspahic, Senad; Rebic, Damir

    2015-01-01

    Introduction: Starting from the point that the chronic kidney disease (CKD) is chronic, inflammatory and hypercoagulable state characterized by an increase in procoagulant and inflammatory markers high cardiovascular morbidity and mortality in these patients could be explained. Aim: The aim of the research was to monitor inflammatory markers and procoagulants in various stages of kidney disease (stage 1-4). Materials and Methods: The research included 120 subjects older than 18 years with CKD stages 1-4 examined and monitored in Clinic of Nephrology, University Clinical Centre Sarajevo over a period of 24 months. The research included determining the following laboratory parameters: serum creatinine, serum albumin, C-reactive protein, leukocytes in the blood, plasma fibrinogen, D-dimer, antithrombin III, coagulation factors VII (FC VII) and coagulation factor VIII (FC VIII). Results: With the progression of kidney disease (CKD stages 1-4), there was a significant increase of inflammatory and procoagulant markers: CRP, fibrinogen and coagulation factor VIII, and an increase in the average values of leukocytes and a reduction in the value of antithrombin III, but without statistical significance. Also, there were no significant differences in the values of D-dimer and coagulation factor VII. Conclusion: The progression of kidney disease is significantly associated with inflammation, which could in the future be useful in prognostic and therapeutic purposes. Connection of CKD with inflammation and proven connection of inflammation with cardiovascular risk indicates the potential value of some biomarkers, which could in the future identify as predictors of outcome and could have the benefit in the early diagnosis and treatment of cardiovascular disease in CKD. PMID:26622082

  20. MOLECULAR ADVANCES IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

    PubMed Central

    Gallagher, Anna Rachel; Germino, Gregory G.; Somlo, Stefan

    2010-01-01

    Autosomal dominant polycystic disease (ADPKD) is the most common form of inherited kidney disease that results renal failure. The understanding the pathogenesis of ADPKD has advanced significantly since the discovery of the two causative genes, PKD1 or PKD2. Dominantly inherited gene mutations followed by somatic second hit mutations inactivating the normal copy of the respective gene result in renal tubular cyst formation that deforms the kidney and eventually impairs its function. The respective gene products, polycystin-1 and polycystin-2, work together in a common cellular pathway. Polycystin-1, a large receptor molecule, forms a receptor-channel complex with polycystin-2, which is a cation channel belonging to the TRP family. Both polycystin proteins have been localized to the primary cilium, a non-motile microtubule based structure that extends from the apical membrane of tubular cells into the lumen. Here we discuss recent insights in the pathogenesis of ADPKD including the genetics of ADPKD, the properties of the respective polycystin proteins, the role of cilia, and some cell signaling pathways that have been implicated in the pathways related to PKD1 and PKD2. PMID:20219615

  1. Recent Advances in Conjugated Polymer Materials for Disease Diagnosis.

    PubMed

    Lv, Fengting; Qiu, Tian; Liu, Libing; Ying, Jianming; Wang, Shu

    2016-02-10

    The extraordinary optical amplification and light-harvesting properties of conjugated polymers impart sensing systems with higher sensitivity, which meets the primary demands of early cancer diagnosis. Recent advances in the detection of DNA methylation and mutation with polyfluorene derivatives based fluorescence resonance energy transfer (FRET) as a means to modulate fluorescent responses attest to the great promise of conjugated polymers as powerful tools for the clinical diagnosis of diseases. To facilitate the ever-changing needs of diagnosis, the development of detection approaches and FRET signal analysis are highlighted in this review. Due to their exceptional brightness, excellent photostability, and low or absent toxicity, conjugated polymers are verified as superior materials for in-vivo imaging, and provide feasibility for future clinical molecular-imaging applications. The integration of conjugated polymers with clinical research has shown profound effects on diagnosis for the early detection of disease-related biomarkers, as well as in-vivo imaging, which leads to a multidisciplinary scientific field with perspectives in both basic research and application issues. PMID:26679834

  2. Circulating APRIL levels are correlated with advanced disease and prognosis in rectal cancer patients.

    PubMed

    Lascano, V; Hahne, M; Papon, L; Cameron, K; Röeder, C; Schafmayer, C; Driessen, L; van Eenennaam, H; Kalthoff, H; Medema, J P

    2015-01-01

    We have previously shown that the tumor necrosis factor family member a proliferation-inducing ligand (APRIL) enhances intestinal tumor growth in various preclinical tumor models. Here, we have investigated whether APRIL serum levels at time of surgery predict survival in a large cohort of colorectal cancer (CRC) patients. We measured circulating APRIL levels in a cohort of CRC patients (n=432) using a novel validated monoclonal APRIL antibody (hAPRIL.133) in an enzyme-linked immunosorbent assay (ELISA) setup. APRIL levels were correlated with clinicopathological features and outcome. Overall survival was examined with Kaplan-Meier survival analysis, and Cox proportional hazards ratios were calculated. We observed that circulating APRIL levels were normally distributed among CRC patients. High APRIL expression correlated significantly with poor outcome measures, such as higher stage at presentation and development of lymphatic and distant metastases. Within the group of rectal cancer patients, higher circulating APRIL levels at time of surgery were correlated with poor survival (log-rank analysis P-value 0.008). Univariate Cox regression analysis for overall survival in rectal cancer patients showed that patients with elevated circulating APRIL levels had an increased risk of poor outcome (hazard ratio (HR) 1.79; 95% confidence interval (CI) 1.16-2.76; P-value 0.009). Multivariate analysis in rectal cancer patients showed that APRIL as a prognostic factor was dependent on stage of disease (HR 1.25; 95% CI 0.79-1.99; P-value 0.340), which was related to the fact that stage IV rectal cancer patients had significantly higher levels of APRIL. Our results revealed that APRIL serum levels at time of surgery were associated with features of advanced disease and prognosis in rectal cancer patients, which strengthens the previously reported preclinical observation of increased APRIL levels correlating with disease progression. PMID:25622308

  3. Why musical memory can be preserved in advanced Alzheimer's disease.

    PubMed

    Jacobsen, Jörn-Henrik; Stelzer, Johannes; Fritz, Thomas Hans; Chételat, Gael; La Joie, Renaud; Turner, Robert

    2015-08-01

    Musical memory is considered to be partly independent from other memory systems. In Alzheimer's disease and different types of dementia, musical memory is surprisingly robust, and likewise for brain lesions affecting other kinds of memory. However, the mechanisms and neural substrates of musical memory remain poorly understood. In a group of 32 normal young human subjects (16 male and 16 female, mean age of 28.0 ± 2.2 years), we performed a 7 T functional magnetic resonance imaging study of brain responses to music excerpts that were unknown, recently known (heard an hour before scanning), and long-known. We used multivariate pattern classification to identify brain regions that encode long-term musical memory. The results showed a crucial role for the caudal anterior cingulate and the ventral pre-supplementary motor area in the neural encoding of long-known as compared with recently known and unknown music. In the second part of the study, we analysed data of three essential Alzheimer's disease biomarkers in a region of interest derived from our musical memory findings (caudal anterior cingulate cortex and ventral pre-supplementary motor area) in 20 patients with Alzheimer's disease (10 male and 10 female, mean age of 68.9 ± 9.0 years) and 34 healthy control subjects (14 male and 20 female, mean age of 68.1 ± 7.2 years). Interestingly, the regions identified to encode musical memory corresponded to areas that showed substantially minimal cortical atrophy (as measured with magnetic resonance imaging), and minimal disruption of glucose-metabolism (as measured with (18)F-fluorodeoxyglucose positron emission tomography), as compared to the rest of the brain. However, amyloid-β deposition (as measured with (18)F-flobetapir positron emission tomography) within the currently observed regions of interest was not substantially less than in the rest of the brain, which suggests that the regions of interest were still in a very early stage of the expected course of

  4. HLA-G expression and role in advanced-stage classical Hodgkin lymphoma.

    PubMed

    Caocci, G; Greco, M; Fanni, D; Senes, G; Littera, R; Lai, S; Risso, P; Carcassi, C; Faa, G; La Nasa, G

    2016-01-01

    Non-classical human leucocyte antigen (HLA)-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL), in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp) deletion-insertion (del-ins) polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy) patients with a 2-year progression-free survival rate (PFS) of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS) cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2.These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2. PMID:27349312

  5. Risk of Tractional Retinal Detachment Following Intravitreal Bevacizumab Along with Subretinal Fluid Drainage and Cryotherapy for Stage 3B Coats’ Disease

    PubMed Central

    Bhat, Vishalakshi; D’Souza, Palmeera; Shah, Parag K.; Narendran, V.

    2016-01-01

    Purpose: To review the surgical outcomes of intravitreal bevacizumab (IVB) along with subretinal fluid drainage with cryotherapy in patients with stage 3B Coats’ disease. Materials and Methods: A retrospective study of seven cases of stage 3B Coats’ disease, who underwent subretinal fluid drainage with cryopexy, from May 2011 to March 2014. Five eyes received additional IVB at the end of surgery. Green laser therapy was performed on telangiectatic vessels postoperatively. Results: The mean age was 34 months (range, 10-84 months). Mean follow-up was 19 months. Six patients (85.7%) had an attached retina at final follow-up. Three out of four patients (75%) that received IVB developed tractional retinal detachments (TRDs). Two eyes that did not receive bevacizumab did not develop any traction. None progressed to neovascular glaucoma or phthisis bulbi. Conclusion: Simultaneous injection of bevacizumab along with subretinal drainage and cryotherapy for advanced Coats’ disease could not avoid TRD. PMID:27162454

  6. Impact of model for end-stage liver disease (MELD) scoring system on pathological findings at and after liver transplantation.

    PubMed

    Khettry, Urmila; Azabdaftari, Gissou; Simpson, Mary Ann; Pomfret, Elizabeth A; Pomposelli, James J; Lewis, W David; Jenkins, Roger L; Gordon, Fredric D

    2006-06-01

    The Model for End-Stage Liver Disease (MELD) scoring system, a validated objective liver disease severity scale, was adopted in February 2002 to allocate cadaveric organs for liver transplantation (LT). To improve transplantability before succumbing to advanced disease, patients with low-stage hepatocellular carcinoma (HCC) are given extra points in this system commensurate with their predicted mortality. Our aims were to determine 1) any change in the pathological findings at LT following the implementation of this system and 2) the impact of scoring advantage given to early-stage HCC. Clinicopathologic findings were compared before (pre-MELD, n = 87) and after (MELD, n = 58) the introduction of the MELD system. The findings in the pre-MELD vs. MELD groups were as follows: HCC, 27.5% vs. 48.3% (P = 0.001); portal vein thrombosis (PVT), 13.7% vs. 25.9% (P = 0.08); cholestasis, 16.1% vs. 32.7% (P = 0.026); inflammation grade of 2 or more, 43.7% vs. 48.3% (P = not significant); hepatitis C (HCV), 45.9% vs. 51.7% (P = not significant); HCV with lymphoid aggregates, 25% vs. 60% (P = 0.003); HCV with hyperplastic hilar nodes, 15.0% vs. 36.6% (P = 0.001); and post-LT HCC recurrence, 4.1% vs. 3.4% (P = not significant). Non-HCC-related findings were further compared in the 2 subgroups of pre-MELD (n = 57) and MELD (n = 31) after exclusion of HCC and fulminant hepatic failure (FHF) cases, and only cholestasis was significantly increased in the subgroup MELD. In conclusion, increased incidence of native liver cholestasis in the MELD era may be the histologic correlate of clinically severe liver disease. The scoring advantage given to low-stage HCC did result in a significantly increased incidence of HCC in the MELD group, but it did not adversely affect the post-LT recurrence rate. PMID:16598742

  7. Once-Weekly, High-Dose Stereotactic Body Radiotherapy for Lung Cancer: 6-Year Analysis of 60 Early-Stage, 42 Locally Advanced, and 7 Metastatic Lung Cancers

    SciTech Connect

    Salazar, Omar M. Sandhu, Taljit S.; Lattin, Paul B.; Chang, Jung H.; Lee, Choon K.; Groshko, Gayle A.; Lattin, Cheryl J.

    2008-11-01

    Purpose: To explore once-weekly stereotactic body radiotherapy (SBRT) in nonoperable patients with localized, locally advanced, or metastatic lung cancer. Methods and Materials: A total of 102 primary (89 untreated plus 13 recurrent) and 7 metastatic tumors were studied. The median follow-up was 38 months, the average patient age was 75 years. Of the 109 tumors studied, 60 were Stage I (45 IA and 15 IB), 9 were Stage II, 30 were Stage III, 3 were Stage IV, and 7 were metastases. SBRT only was given in 73% (40 Gy in four fractions to the planning target volume to a total dose of 53 Gy to the isocenter for a biologically effective dose of 120 Gy{sub 10}). SBRT was given as a boost in 27% (22.5 Gy in three fractions once weekly for a dose of 32 Gy at the isocenter) after 45 Gy in 25 fractions to the primary plus the mediastinum. The total biologically effective dose was 120 Gy{sub 10}. Respiration gating was used in 46%. Results: The overall response rate was 75%; 33% had a complete response. The overall response rate was 89% for Stage IA patients (40% had a complete response). The local control rate was 82%; it was 100% and 93% for Stage IA and IB patients, respectively. The failure rate was 37%, with 17% within the planning target volume. No Grade 3-4 acute toxicities developed in any patient; 12% and 7% of patients developed Grade 1 and 2 toxicities, respectively. Late toxicity, all Grade 2, developed in 3% of patients. The 5-year cause-specific survival rate for Stage I was 70% and was 74% and 64% for Stage IA and IB patients, respectively. The 3-year Stage III cause-specific survival rate was 30%. The patients with metastatic lung cancer had a 57% response rate, a 27% complete response rate, an 86% local control rate, a median survival time of 19 months, and 23% 3-year survival rate. Conclusions: SBRT is noninvasive, convenient, fast, and economically attractive; it achieves results similar to surgery for early or metastatic lung cancer patients who are older

  8. Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage I-II Hodgkin's disease.

    PubMed

    Pavlovsky, S; Maschio, M; Santarelli, M T; Muriel, F S; Corrado, C; Garcia, I; Schwartz, L; Montero, C; Sanahuja, F L; Magnasco, O

    1988-11-16

    A total of 277 patients with untreated Hodgkin's disease, clinical stages I-II, were randomized to cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) alone for 6 monthly cycles or to CVPP plus radiation therapy (RT), 3,000 rad, to involved areas (CVPP plus RT). One or more of the following factors were considered as unfavorable prognosis: age greater than 45 years, more than two lymph node areas involved, or bulky disease. In the favorable group, disease-free survival (77% vs. 70%) or overall survival (92% vs. 91%) at 84 months for CVPP versus RT plus CVPP was similar. Patients with unfavorable prognosis treated with RT plus CVPP had longer disease-free survival (75% vs. 34%) (P = .001) and overall survival (84% vs. 66%) than patients treated with CVPP alone. PMID:3184196

  9. Time-to-Progression of NSCLC from Early to Advanced Stages: An Analysis of data from SEER Registry and a Single Institute

    PubMed Central

    Yuan, Ping; Cao, Jin Lin; Rustam, Azmat; Zhang, Chong; Yuan, Xiao Shuai; Bao, Fei Chao; Lv, Wang; Hu, Jian

    2016-01-01

    The average time required for cancers to progress through stages can be reflected in the average age of the patients diagnosed at each stage of disease. To estimate the time it takes for non-small-cell lung cancer (NSCLC) to progress through different tumor, node and metastasis (TNM) stages and sizes, we compared the mean adjusted age of 45904 NSCLC patients with different stages and tumor sizes from Surveillance, Epidemiology and End Results (SEER) cancer registry database and our institute. Multiple-linear-regression models for age were generated adjusting for various factors. Caucasian, African-American and Asian patients with stage IA cancers were on average 0.8, 1.0 and 1.38 adjusted years younger, respectively, than those with stage IIIB cancers (p < 0.001). And these with T1a cancers were on average 0.84, 0.92 and 1.21 adjusted years younger, respectively, than patients with T3 cancers (p < 0.001). Patients with tumors measuring larger than 8 cm in diameter were on average 0.85 adjusted years older than these with tumors smaller than 1 cm (p < 0.001), with Caucasian demonstrating the shortest age span (0.79 years, P < 0.001). In conclusion, the time-to-progression of NSCLC from early to advanced stages varied among ethnicities, Caucasian patients demonstrating a more rapid progression nature of tumor than their African-American and Asian counterparts. PMID:27346236

  10. Proteinuria as a Therapeutic Target in Advanced Chronic Kidney Disease: a Retrospective Multicenter Cohort Study.

    PubMed

    Chen, Chang-Hsu; Wu, Hon-Yen; Wang, Chieh-Li; Yang, Feng-Jung; Wu, Pei-Chen; Hung, Szu-Chun; Kan, Wei-Chih; Yang, Chung-Wei; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2016-01-01

    Current evidence of proteinuria reduction as a surrogate target in advanced chronic kidney disease (CKD) is incomplete due to lack of patient-pooled database. We retrospectively studied a multicenter cohort of 1891 patients who were enrolled in the nationwide multidisciplinary pre-end stage renal disease care program with a baseline glomerular filtration rate (GFR) <45 mL/min/1.73 m(2) and followed longitudinally to investigate the effect of the change in proteinuria on renal death (defined as composite of dialysis and death occurring before initiation of dialysis). The group with a change in proteinuria ≤0.30 g/g (n = 1261) had lower cumulative probabilities of renal death (p < 0.001). In a linear regression model, a higher baseline proteinuria and a greater increase in proteinuria were associated with faster annual GFR decline. Cox's analysis showed that every 1 unit increase in natural log(baseline proteinuria, 10 g/g) and every 0.1 g/g increase in the change in proteinuria resulted in 67% (HR = 1.67, 95% CI: 1.46-1.91) and 1% (HR = 1.01, 95% CI: 1.01-1.01) greater risk of renal death respectively after adjusting for the effects of the other covariates. Our study provided a patient-based evidence to support proteinuria as a therapeutic target in advanced CKD. PMID:27198863

  11. Proteinuria as a Therapeutic Target in Advanced Chronic Kidney Disease: a Retrospective Multicenter Cohort Study

    PubMed Central

    Chen, Chang-Hsu; Wu, Hon-Yen; Wang, Chieh-Li; Yang, Feng-Jung; Wu, Pei-Chen; Hung, Szu-Chun; Kan, Wei-Chih; Yang, Chung-Wei; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2016-01-01

    Current evidence of proteinuria reduction as a surrogate target in advanced chronic kidney disease (CKD) is incomplete due to lack of patient-pooled database. We retrospectively studied a multicenter cohort of 1891 patients who were enrolled in the nationwide multidisciplinary pre-end stage renal disease care program with a baseline glomerular filtration rate (GFR) <45 mL/min/1.73 m2 and followed longitudinally to investigate the effect of the change in proteinuria on renal death (defined as composite of dialysis and death occurring before initiation of dialysis). The group with a change in proteinuria ≤0.30 g/g (n = 1261) had lower cumulative probabilities of renal death (p < 0.001). In a linear regression model, a higher baseline proteinuria and a greater increase in proteinuria were associated with faster annual GFR decline. Cox’s analysis showed that every 1 unit increase in natural log(baseline proteinuria, 10 g/g) and every 0.1 g/g increase in the change in proteinuria resulted in 67% (HR = 1.67, 95% CI: 1.46–1.91) and 1% (HR = 1.01, 95% CI: 1.01–1.01) greater risk of renal death respectively after adjusting for the effects of the other covariates. Our study provided a patient-based evidence to support proteinuria as a therapeutic target in advanced CKD. PMID:27198863

  12. [Increased IL-4 production in response to virulent Mycobacterium tuberculosis in tuberculosis patients with advanced disease].

    PubMed

    Ordway, Diane J; Martins, Marta S; Costa, Leonor M; Freire, Mónica S; Arroz, Maria J; Dockrell, Hazel M; Ventura, Fernando A

    2005-01-01

    The study was designed to compare immune responses to Mycobacterium tuberculosis bacilli and antigens in healthy Portuguese subjects and pulmonary tuberculosis patients (TB), and to correlate immune status with clinical severity of tuberculosis disease. PBMC were cultured and stimulated with live and killed M. tuberculosis H37Rv and purified protein derivative (PPD) and lymphoproliferation and production of IFN-gamma and IL-5/IL-4 by these cultures were evaluated by the use of ELISA and multi-parameter flow cytometry. PBMC from 30 tuberculosis patients demonstrated significantly reduced amounts of proliferation and IFN-gamma when stimulated with live M. tuberculosis compared the control group. Of 15 tuberculosis patients tested for intracellular IL-4 following stimulation with M. tuberculosis, 7 showed greatly increased IL-4 production in CD8+ and gammadelta+ T cells. Tuberculosis patients demonstrated an increase of intracellular IL-4 after PBMC were stimulated with live M. tuberculosis in the CD4+ phenotype, but more notably in CD8+ and gammadelta TCR+ subsets. Increased production of IL-4 in tuberculosis patients was primarily in individuals with advanced involvement of lung parenchymal with high bacterial loads in sputum. These results suggest that an alteration in type 1 and type 2 cytokine balance can occur in patients with tuberculosis at an advanced clinical stage of disease. PMID:16202332

  13. Postoperative oxycodone toxicity in a patient with chronic pain and end-stage renal disease.

    PubMed

    Tran, Bryant W; Kohan, Lynn R; Vorenkamp, Kevin E

    2015-02-15

    We present this case to review the metabolism of oxycodone and the effects of end-stage renal disease on the elimination of oxycodone and its metabolites. A 42-year-old female with end-stage renal disease who was dependent on hemodialysis presented for left hamstring posterior capsule release. She had been receiving methadone for 2 years for chronic leg pain. On postoperative day 1, the patient's medication was changed from IV hydromorphone to oral oxycodone to treat breakthrough pain. By the next day, the patient was unarousable with notable respiratory depression. She did not fully recover after urgent hemodialysis but did have full recovery after receiving an IV naloxone infusion for 22 hours. Further study of the safety of oxycodone in hemodialysis patients is warranted. PMID:25689360

  14. Asymptomatic pontine and extra-pontine lesions in a patient with end-stage renal disease.

    PubMed

    Yadav, Raj Kanwar; Das, Chandan J; Bagchi, Soumita; Agarwal, Sanjay

    2016-03-01

    Osmotic demyelination syndrome leading to central pontine/extra-pontine myelinolysis (CPM/EPM) occurs mainly in patients with history of alcohol abuse, malnourishment, following liver transplantation and less commonly, in association with other systemic diseases. Asymptomatic CPM/EPM is rare. Patients with end-stage renal disease (ESRD) who develop CPM/EPM are usually symptomatic with florid neurologic manifestations. Herein, we present a patient with ESRD on maintenance hemodialysis who was incidentally detected to have pontine and extra-pontine lesions suggestive of myelinolysis without any neurologic signs or symptoms. PMID:26997398

  15. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

    PubMed

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-10-28

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

  16. Low-Noise Potential of Advanced Fan Stage Stator Vane Designs Verified in NASA Lewis Wind Tunnel Test

    NASA Technical Reports Server (NTRS)

    Hughes, Christopher E.

    1999-01-01

    With the advent of new, more stringent noise regulations in the next century, aircraft engine manufacturers are investigating new technologies to make the current generation of aircraft engines as well as the next generation of advanced engines quieter without sacrificing operating performance. A current NASA initiative called the Advanced Subsonic Technology (AST) Program has set as a goal a 6-EPNdB (effective perceived noise) reduction in aircraft engine noise relative to 1992 technology levels by the year 2000. As part of this noise program, and in cooperation with the Allison Engine Company, an advanced, low-noise, high-bypass-ratio fan stage design and several advanced technology stator vane designs were recently tested in NASA Lewis Research Center's 9- by 15-Foot Low-Speed Wind Tunnel (an anechoic facility). The project was called the NASA/Allison Low Noise Fan.

  17. Advanced Launch Vehicle Upper Stages Using Liquid Propulsion and Metallized Propellants

    NASA Technical Reports Server (NTRS)

    Palaszewski, Bryan A.

    1990-01-01

    Metallized propellants are liquid propellants with a metal additive suspended in a gelled fuel or oxidizer. Typically, aluminum (Al) particles are the metal additive. These propellants provide increase in the density and/or the specific impulse of the propulsion system. Using metallized propellant for volume-and mass-constrained upper stages can deliver modest increases in performance for low earth orbit to geosynchronous earth orbit (LEO-GEO) and other earth orbital transfer missions. Metallized propellants, however, can enable very fast planetary missions with a single-stage upper stage system. Trade studies comparing metallized propellant stage performance with non-metallized upper stages and the Inertial Upper Stage (IUS) are presented. These upper stages are both one- and two-stage vehicles that provide the added energy to send payloads to altitudes and onto trajectories that are unattainable with only the launch vehicle. The stage designs are controlled by the volume and the mass constraints of the Space Transportation System (STS) and Space Transportation System-Cargo (STS-C) launch vehicles. The influences of the density and specific impulse increases enabled by metallized propellants are examined for a variety of different stage and propellant combinations.

  18. Diagnostic value of Cyfra21-1, SCC and CEA for differentiation of early-stage NSCLC from benign lung disease.

    PubMed

    Chen, Feng; Wang, Xiu-Ying; Han, Xiao-Hong; Wang, Hai; Qi, Jun

    2015-01-01

    Non-small cell lung cancer (NSCLC), which account for the most of lung carcinoma, is sometimes difficult to differentiate from benign lung diseases presented with nodular shadow in imaging scan. There is a need to find another non-invasive way to diagnosis early-stage NSCLC. To examine the potential diagnostic value of SCC, CFYRA 21-1 and CEA for the differentiation of early-stage NCSCL from benign lung diseases, we analyzed serum levels of tumor markers in 278 patients, including 248 patients with NSCLC and 30 patients with benign lung diseases. These benign lung diseases were presented with evidence of a high likelihood of having lung cancer. After surgical operation, diagnosis of lung cancer and benign lung disease were confirmed by histological examination. Preoperative tumor marker levels were quantified. Mann-Whitney U test was used to compare median levels of SCC, CFYRA 21-1 and CEA between the benign group and lung cancer group. Analysis of variance results were used for differences between different clinical stages of NSCLC. ROC was used to evaluate the diagnostic value of tumor markers. The median levels of Cyfra21-1, SCC and CEA were much higher in NSCLC than those in benign lung diseases. And we found that the mean levels of tumor marker were higher in advanced stage of NSCLC. The combination of tumor markers resulted in a higher sensitivity (91.3%) and a lower specificity (86.7%). In conclusion, the combination of positive SCC, positive CEA and positive Cyfra21-1 appear to be helpful in distinguishing early-stage NSCLC from benign lung disease which presented with suspicious pulmonary masses. PMID:26379938

  19. Diagnostic value of Cyfra21-1, SCC and CEA for differentiation of early-stage NSCLC from benign lung disease

    PubMed Central

    Chen, Feng; Wang, Xiu-Ying; Han, Xiao-Hong; Wang, Hai; Qi, Jun

    2015-01-01

    Non-small cell lung cancer (NSCLC), which account for the most of lung carcinoma, is sometimes difficult to differentiate from benign lung diseases presented with nodular shadow in imaging scan. There is a need to find another non-invasive way to diagnosis early-stage NSCLC. To examine the potential diagnostic value of SCC, CFYRA 21-1 and CEA for the differentiation of early-stage NCSCL from benign lung diseases, we analyzed serum levels of tumor markers in 278 patients, including 248 patients with NSCLC and 30 patients with benign lung diseases. These benign lung diseases were presented with evidence of a high likelihood of having lung cancer. After surgical operation, diagnosis of lung cancer and benign lung disease were confirmed by histological examination. Preoperative tumor marker levels were quantified. Mann-Whitney U test was used to compare median levels of SCC, CFYRA 21-1 and CEA between the benign group and lung cancer group. Analysis of variance results were used for differences between different clinical stages of NSCLC. ROC was used to evaluate the diagnostic value of tumor markers. The median levels of Cyfra21-1, SCC and CEA were much higher in NSCLC than those in benign lung diseases. And we found that the mean levels of tumor marker were higher in advanced stage of NSCLC. The combination of tumor markers resulted in a higher sensitivity (91.3%) and a lower specificity (86.7%). In conclusion, the combination of positive SCC, positive CEA and positive Cyfra21-1 appear to be helpful in distinguishing early-stage NSCLC from benign lung disease which presented with suspicious pulmonary masses. PMID:26379938

  20. NIA-AA staging of preclinical Alzheimer disease: discordance and concordance of CSF and imaging biomarkers.

    PubMed

    Vos, Stephanie J B; Gordon, Brian A; Su, Yi; Visser, Pieter Jelle; Holtzman, David M; Morris, John C; Fagan, Anne M; Benzinger, Tammie L S

    2016-08-01

    The National Institute of Aging and Alzheimer's Association (NIA-AA) criteria for Alzheimer disease (AD) treat neuroimaging and cerebrospinal fluid (CSF) markers of AD pathology as if they would be interchangeable. We tested this assumption in 212 cognitively normal participants who have both neuroimaging and CSF measures of β-amyloid (CSF Aβ1-42 and positron emission tomography imaging with Pittsburgh Compound B) and neuronal injury (CSF t-tau and p-tau and structural magnetic resonance imaging) with longitudinal clinical follow-up. Participants were classified in preclinical AD stage 1 (β-amyloidosis) or preclinical AD stage 2+ (β-amyloidosis and neuronal injury) using the NIA-AA criteria, or in the normal or suspected non-Alzheimer disease pathophysiology group (neuronal injury without β-amyloidosis). At baseline, 21% of participants had preclinical AD based on CSF and 28% based on neuroimaging. Between modalities, staging was concordant in only 47% of participants. Disagreement resulted from low concordance between biomarkers of neuronal injury. Still, individuals in stage 2+ using either criterion had an increased risk for clinical decline. This highlights the heterogeneity of the definition of neuronal injury and has important implications for clinical trials using biomarkers for enrollment or as surrogate end point measures. PMID:27318129

  1. Supradiaphragmatic early stage Hodgkin's disease: does mantle radiation therapy still have a role?

    PubMed

    Frezza, G; Barbieri, E; Zinzani, P L; Babini, L; Tura, S

    1996-01-01

    Extended field radiation therapy represents the main therapeutic option in early stage Hodgkin's disease with favorable prognostic features. Its role however has recently been criticized, mainly due to the high incidence of late complications in irradiated tissues. Furthermore, surgical staging, which in the opinion of many is mandatory for proper selection of patients for radiotherapy alone, has a well-known morbidity, and splenectomy has been associated with a high risk of secondary leukemias. Lastly, the failure rate after radiotherapy only is not negligible and second-line treatment is not always successful. A review of our experience and of the recent literature has allowed us to refute these objections. The results of radiotherapy, when properly performed, are highly reliable and have been reproducible in many Institutions. Chemotherapy alone cannot yet be regarded as an alternative to radiotherapy in these patients since data reported on this issue are conflicting. Present knowledge regarding the relationship between clinical features and the risk of occult subdiaphragmatic spread allows patients with localized disease to be selected without surgical staging; the results of radiotherapy in clinically staged patients confirm this statement. Concern for the late effects in irradiated tissues is justified, and future efforts should be directed at reducing the toxicity of this treatment. Associating a short chemotherapy course with low-dose radiotherapy to involved sites could help to achieve this goal. PMID:8641642

  2. Functional thiamine deficiency in end-stage renal disease: malnutrition despite ample nutrients.

    PubMed

    Moradi, Hamid; Said, Hamid M

    2016-08-01

    Zhang et al. found that plasma concentrations of the thiamine antimetabolite oxythiamine are significantly increased in patients with end-stage renal disease. These investigators discuss the potential sources of oxythiamine and the consequences of its plasma elevation. This commentary addresses the significance of these findings and expands on the potential role of gut microbiome in the generation of this antithiamine metabolite. PMID:27418090

  3. Risk of Bleeding in End-Stage Liver Disease Patients Undergoing Cardiac Catheterization

    PubMed Central

    Mahmoud, Ahmed M.; Elgendy, Islam Y.; Choi, Calvin Y.

    2015-01-01

    Patients with end-stage liver disease frequently have baseline coagulopathies. The international normalized ratio is in common use for the estimation of bleeding tendency in such patients, especially those undergoing an invasive procedure like cardiac catheterization. The practice of international normalized ratio measurement—followed by pharmacologic (for example, vitamin K or fresh frozen plasma) or nonpharmacologic intervention—is still debatable. The results of multiple randomized trials have shown the superiority of the radial approach over femoral access in reducing catheterization bleeding. This reduction in bleeding in turn decreases the risk and cost of blood-product transfusion. However, there is little evidence regarding the use of the radial approach in the end-stage liver disease patient population specifically. In this review, we summarize the studies that have dealt with cardiac catheterization in patients who have end-stage liver disease. We also discuss the role of the current measurements that are used to reduce the risk of bleeding in these same patients. PMID:26504433

  4. Staging of osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease.

    PubMed

    Bedogni, Alberto; Fedele, Stefano; Bedogni, Giorgio; Scoletta, Matteo; Favia, Gianfranco; Colella, Giuseppe; Agrillo, Alessandro; Bettini, Giordana; Di Fede, Olga; Oteri, Giacomo; Fusco, Vittorio; Gabriele, Mario; Ottolenghi, Livia; Valsecchi, Stefano; Porter, Stephen; Petruzzi, Massimo; Arduino, Paolo; D'Amato, Salvatore; Ungari, Claudio; Fung Polly, Pok-Lam; Saia, Giorgia; Campisi, Giuseppina

    2014-09-01

    Management of osteonecrosis of the jaw associated with antiresorptive agents is challenging, and outcomes are unpredictable. The severity of disease is the main guide to management, and can help to predict prognosis. Most available staging systems for osteonecrosis, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of clinical and radiographic findings. However, clinical inspection and radiography are limited in their ability to identify the extent of necrotic bone disease compared with computed tomography (CT). We have organised a large multicentre retrospective study (known as MISSION) to investigate the agreement between the AAOMS staging system and the extent of osteonecrosis of the jaw (focal compared with diffuse involvement of bone) as detected on CT. We studied 799 patients with detailed clinical phenotyping who had CT images taken. Features of diffuse bone disease were identified on CT within all AAOMS stages (20%, 8%, 48%, and 24% of patients in stages 0, 1, 2, and 3, respectively). Of the patients classified as stage 0, 110/192 (57%) had diffuse disease on CT, and about 1 in 3 with CT evidence of diffuse bone disease was misclassified by the AAOMS system as having stages 0 and 1 osteonecrosis. In addition, more than a third of patients with AAOMS stage 2 (142/405, 35%) had focal bone disease on CT. We conclude that the AAOMS staging system does not correctly identify the extent of bony disease in patients with osteonecrosis of the jaw. PMID:24856927

  5. Recent Advances in Traditional Chinese Medicine for Kidney Disease.

    PubMed

    Zhong, Yifei; Menon, Madhav C; Deng, Yueyi; Chen, Yiping; He, John Cijiang

    2015-09-01

    Because current treatment options for chronic kidney disease (CKD) are limited, many patients seek out alternative therapies such as traditional Chinese medicine. However, there is a lack of evidence from large clinical trials to support the use of traditional medicines in patients with CKD. Many active components of traditional medicine formulas are undetermined and their toxicities are unknown. Therefore, there is a need for research to identify active compounds from traditional medicines and understand the mechanisms of action of these compounds, as well as their potential toxicity, and subsequently perform well-designed, randomized, controlled, clinical trials to study the efficacy and safety of their use in patients with CKD. Significant progress has been made in this field within the last several years. Many active compounds have been identified by applying sophisticated techniques such as mass spectrometry, and more mechanistic studies of these compounds have been performed using both in vitro and in vivo models. In addition, several well-designed, large, randomized, clinical trials have recently been published. We summarize these recent advances in the field of traditional medicines as they apply to CKD. In addition, current barriers for further research are also discussed. Due to the ongoing research in this field, we believe that stronger evidence to support the use of traditional medicines for CKD will emerge in the near future. PMID:26015275

  6. Aortic Stenosis, a Left Ventricular Disease: Insights from Advanced Imaging.

    PubMed

    Badiani, Sveeta; van Zalen, Jet; Treibel, Thomas A; Bhattacharyya, Sanjeev; Moon, James C; Lloyd, Guy

    2016-08-01

    Aortic stenosis (AS) is the most common primary valve disorder in the elderly with an increasing prevalence. It is increasingly clear that it is also a disease of the left ventricle (LV) rather than purely the aortic valve. The transition from left ventricular hypertrophy to fibrosis results in the eventual adverse effects on systolic and diastolic function. Appropriate selection of patients for aortic valve intervention is crucial, and current guidelines recommend aortic valve replacement in severe AS with symptoms or in asymptomatic patients with left ventricular ejection fraction (LVEF) <50 %. LVEF is not a sensitive marker and there are other parameters used in multimodality imaging techniques, including longitudinal strain, exercise stress echo and cardiac MRI that may assist in detecting subclinical and subtle LV dysfunction. These findings offer potentially better ways to evaluate patients, time surgery, predict recovery and potentially offer targets for specific therapies. This article outlines the pathophysiology behind the LV response to aortic stenosis and the role of advanced multimodality imaging in describing it. PMID:27384950

  7. Efficacy Comparison Between Total Laryngectomy and Nonsurgical Organ-Preservation Modalities in Treatment of Advanced Stage Laryngeal Cancer: A Meta-Analysis.

    PubMed

    Fu, Xiaoyuan; Zhou, Qi; Zhang, Xianquan

    2016-04-01

    It remains unclear whether the efficacy of nonsurgical organ-preservation modalities (NOP) in the treatment of advanced-stage laryngeal cancer was noninferiority compared with that of total laryngectomy (TL). The objective of this study was to compare the curative effects between TL and NOP in the treatment of advanced-stage laryngeal cancer through a meta-analysis.Clinical studies were retrieved from the electronic databases of PubMed, Embase, Wanfang, and Chinese National Knowledge infrastructure. A meta-analysis was performed to investigate the differences in the curative efficacy of advanced-stage laryngeal cancer between TL and the nonsurgical method. Two reviewers screened all titles and abstracts, and independently assessed all articles. All identified studies were retrospective.Sixteen retrospective studies involving 8308 patients (4478 in the TL group and 3701 in the nonsurgical group) were included in this meta-analysis. The analysis results displayed the advantage of TL for 2-year and 5-year overall survival (OS)(OR 2.79, 95% CI 1.85-4.23 and OR 1.52, 95% CI 1.09-2.14) as well as in 5-year disease-specific survival (DSS)(OR 1.79, 95% CI 1.61-1.98), but no significant difference in 2-year DSS was detected between the 2 groups (OR = 2.09,95% CI0.69-6.40). Additionally, there were no significant differences between TL and NOP for 5-year local control (LC) either (OR = 1.75, 95% CI 0.87-3.53). When we carried out subgroup analyses, the advantage of TL was especially obvious in T4 subgroups, but not in T3 subgroups.This is the first study to compare the curative effects on advanced-stage laryngeal cancer using meta-analytic methodology. Although there was a trend in favor of TL for OS and DSS, there is no clear difference in oncologic outcome between TL and NOP. Therefore, other factors such as tumor T-stage and size, lymph node metastasis, and physical condition are also important indicators for treatment choice. PMID:27057837

  8. Method and apparatus for advanced staged combustion utilizing forced internal recirculation

    DOEpatents

    Rabovitser, Iosif K.; Knight, Richard A.; Cygan, David F.; Nester, Serguei; Abbasi, Hamid A.

    2003-12-16

    A method and apparatus for combustion of a fuel in which a first-stage fuel and a first-stage oxidant are introduced into a combustion chamber and ignited, forming a primary combustion zone. At least about 5% of the total heat output produced by combustion of the first-stage fuel and the first-stage oxidant is removed from the primary combustion zone, forming cooled first-stage combustion products. A portion of the cooled first-stage combustion products from a downstream region of the primary combustion zone is recirculated to an upstream region of primary combustion zone. A second-stage fuel is introduced into the combustion chamber downstream of the primary combustion zone and ignited, forming a secondary combustion zone. At least about 5% of the heat from the secondary combustion zone is removed. In accordance with one embodiment, a third-stage oxidant is introduced into the combustion chamber downstream of the secondary combustion zone, forming a tertiary combustion zone.

  9. Attention deficit hyperactivity disorder in children with early stages of chronic kidney disease

    PubMed Central

    Yousefi Chaijan, Parsa; Sharafkhah, Mojtaba; Salehi, Bahman; Rafiei, Mohammad

    2015-01-01

    Background: Attention Deficit Hyperactivity Disorder (ADHD) is the most common childhood neurological disorder. This disorder is more prevalent in some chronic diseases. The aim of this study was to investigate ADHD in children with early stages of chronic kidney disease (CKD) and to compare it with healthy children. Methods: Seventy five 5-16-year-old children with early stages of CKD (stage 1, 2 and 3) and 75 healthy children without CKD were included in this case – control study as case and control groups, respectively. The participants were selected from those children who were referred to the pediatric clinic of Amir Kabir Hospital of Arak (Iran) in the form of simple probability and based on inclusion and exclusion criteria. ADHD was diagnosed using Conner's Parent Rating Scale – 48 (CPRS-48) and DSM-IV criteria and was confirmed by a psychologist consultant. Data were analyzed by Binomial test in SPSS18. Results: ADHD inattentive type was observed in 8 cases (10.6%) with CKD and 2 controls (2.6%) (p= 0.109). Moreover, in the case and control groups, 7 (9.3%) and 6 (8%) children were affected by ADHD hyperactiveimpulsive type (p= 0.997), and 9 (12%) and 12 (16%) children were affected by ADHD mixed type (p= 0.664), respectively. Conclusion: No differences were found between the prevalence of ADHD in the children with early stages of CKD and the control group. However, due to the importance of the relationships between different types of psychiatric disorders and CKD and lack of enough evidence concerning the relationship between ADHD and different stages of CKD in children, conducting further studies in this field is recommended. PMID:26034734

  10. Protein Kinase Activity Decreases with Higher Braak Stages of Alzheimer’s Disease Pathology

    PubMed Central

    Rosenberger, Andrea F.N.; Hilhorst, Riet; Coart, Elisabeth; García Barrado, Leandro; Naji, Faris; Rozemuller, Annemieke J.M.; van der Flier, Wiesje M.; Scheltens, Philip; Hoozemans, Jeroen J.M.; van der Vies, Saskia M.

    2015-01-01

    Alzheimer’s disease (AD) is characterized by a long pre-clinical phase (20–30 years), during which significant brain pathology manifests itself. Disease mechanisms associated with pathological hallmarks remain elusive. Most processes associated with AD pathogenesis, such as inflammation, synaptic dysfunction, and hyper-phosphorylation of tau are dependent on protein kinase activity. The objective of this study was to determine the involvement of protein kinases in AD pathogenesis. Protein kinase activity was determined in postmortem hippocampal brain tissue of 60 patients at various stages of AD and 40 non-demented controls (Braak stages 0-VI) using a peptide-based microarray platform. We observed an overall decrease of protein kinase activity that correlated with disease progression. The phosphorylation of 96.7% of the serine/threonine peptides and 37.5% of the tyrosine peptides on the microarray decreased significantly with increased Braak stage (p-value <0.01). Decreased activity was evident at pre-clinical stages of AD pathology (Braak I-II). Increased phosphorylation was not observed for any peptide. STRING analysis in combination with pathway analysis and identification of kinases responsible for peptide phosphorylation showed the interactions between well-known proteins in AD pathology, including the Ephrin-receptor A1 (EphA1), a risk gene for AD, and sarcoma tyrosine kinase (Src), which is involved in memory formation. Additionally, kinases that have not previously been associated with AD were identified, e.g., protein tyrosine kinase 6 (PTK6/BRK), feline sarcoma oncogene kinase (FES), and fyn-associated tyrosine kinase (FRK). The identified protein kinases are new biomarkers and potential drug targets for early (pre-clinical) intervention. PMID:26519433

  11. Clinical heterogeneity in patients with early-stage Parkinson's disease: a cluster analysis.

    PubMed

    Liu, Ping; Feng, Tao; Wang, Yong-jun; Zhang, Xuan; Chen, Biao

    2011-09-01

    The aim of this study was to investigate the clinical heterogeneity of Parkinson's disease (PD) among a cohort of Chinese patients in early stages. Clinical data on demographics, motor variables, motor phenotypes, disease progression, global cognitive function, depression, apathy, sleep quality, constipation, fatigue, and L-dopa complications were collected from 138 Chinese PD subjects in early stages (Hoehn and Yahr stages 1-3). The PD subject subtypes were classified using k-means cluster analysis according to the clinical data from five- to three-cluster consecutively. Kappa statistical analysis was performed to evaluate the consistency among different subtype solutions. The cluster analysis indicated four main subtypes: the non-tremor dominant subtype (NTD, n=28, 20.3%), rapid disease progression subtype (RDP, n=7, 5.1%), young-onset subtype (YO, n=50, 36.2%), and tremor dominant subtype (TD, n=53, 38.4%). Overall, 78.3% (108/138) of subjects were always classified between the same three groups (52 always in TD, 7 in RDP, and 49 in NTD), and 98.6% (136/138) between five- and four-cluster solutions. However, subjects classified as NTD in the four-cluster analysis were dispersed into different subtypes in the three-cluster analysis, with low concordance between four- and three-cluster solutions (kappa value=-0.139, P=0.001). This study defines clinical heterogeneity of PD patients in early stages using a data-driven approach. The subtypes generated by the four-cluster solution appear to exhibit ideal internal cohesion and external isolation. PMID:21887844

  12. Gene Expression Profile for Predicting Survival in Advanced-Stage Serous Ovarian Cancer Across Two Independent Datasets

    PubMed Central

    Yoshihara, Kosuke; Tajima, Atsushi; Yahata, Tetsuro; Kodama, Shoji; Fujiwara, Hiroyuki; Suzuki, Mitsuaki; Onishi, Yoshitaka; Hatae, Masayuki; Sueyoshi, Kazunobu; Fujiwara, Hisaya; Kudo, Yoshiki; Kotera, Kohei; Masuzaki, Hideaki; Tashiro, Hironori; Katabuchi, Hidetaka; Inoue, Ituro; Tanaka, Kenichi

    2010-01-01

    Background Advanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. Our aim is to identify a progression-free survival (PFS)-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer. Methodology/Principal Findings Advanced-stage serous ovarian cancer tissues from 110 Japanese patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We selected 88 PFS-related genes by a univariate Cox model (p<0.01) and generated the prognostic index based on 88 PFS-related genes after adjustment of regression coefficients of the respective genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66–5.43; p<0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20–1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008). Conclusions/Significance The prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer. PMID:20300634

  13. Effect of rifaximin on gut microbiota composition in advanced liver disease and its complications

    PubMed Central

    Ponziani, Francesca Romana; Gerardi, Viviana; Pecere, Silvia; D’Aversa, Francesca; Lopetuso, Loris; Zocco, Maria Assunta; Pompili, Maurizio; Gasbarrini, Antonio

    2015-01-01

    Liver cirrhosis is a paradigm of intestinal dysbiosis. The qualitative and quantitative derangement of intestinal microbial community reported in cirrhotic patients seems to be strictly related with the impairment of liver function. A kind of gut microbial “fingerprint”, characterized by the reduced ratio of “good” to “potentially pathogenic” bacteria has recently been outlined, and is associated with the increase in Model for End-Stage Liver Disease and Child Pugh scores. Moreover, in patients presenting with cirrhosis complications such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and, portal hypertension intestinal microbiota modifications or the isolation of bacteria deriving from the gut are commonly reported. Rifaximin is a non-absorbable antibiotic used in the management of several gastrointestinal diseases. Beyond bactericidal/bacteriostatic, immune-modulating and anti-inflammatory activity, a little is known about its interaction with gut microbial environment. Rifaximin has been demonstrated to exert beneficial effects on cognitive function in patients with HE, and also to prevent the development of SBP, to reduce endotoxemia and to improve hemodynamics in cirrhotics. These results are linked to a shift in gut microbes functionality, triggering the production of favorable metabolites. The low incidence of drug-related adverse events due to the small amount of circulating drug makes rifaximin a relatively safe antibiotic for the modulation of gut microbiota in advanced liver disease. PMID:26604640

  14. Effect of rifaximin on gut microbiota composition in advanced liver disease and its complications.

    PubMed

    Ponziani, Francesca Romana; Gerardi, Viviana; Pecere, Silvia; D'Aversa, Francesca; Lopetuso, Loris; Zocco, Maria Assunta; Pompili, Maurizio; Gasbarrini, Antonio

    2015-11-21

    Liver cirrhosis is a paradigm of intestinal dysbiosis. The qualitative and quantitative derangement of intestinal microbial community reported in cirrhotic patients seems to be strictly related with the impairment of liver function. A kind of gut microbial "fingerprint", characterized by the reduced ratio of "good" to "potentially pathogenic" bacteria has recently been outlined, and is associated with the increase in Model for End-Stage Liver Disease and Child Pugh scores. Moreover, in patients presenting with cirrhosis complications such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and, portal hypertension intestinal microbiota modifications or the isolation of bacteria deriving from the gut are commonly reported. Rifaximin is a non-absorbable antibiotic used in the management of several gastrointestinal diseases. Beyond bactericidal/bacteriostatic, immune-modulating and anti-inflammatory activity, a little is known about its interaction with gut microbial environment. Rifaximin has been demonstrated to exert beneficial effects on cognitive function in patients with HE, and also to prevent the development of SBP, to reduce endotoxemia and to improve hemodynamics in cirrhotics. These results are linked to a shift in gut microbes functionality, triggering the production of favorable metabolites. The low incidence of drug-related adverse events due to the small amount of circulating drug makes rifaximin a relatively safe antibiotic for the modulation of gut microbiota in advanced liver disease. PMID:26604640

  15. Changes in inflorescence protein during advanced stages of floret development in Buchloe dactyloides (Poaceae).

    PubMed

    Zhou, Y-J; Xue, J-G; Wang, X-G; Zhang, X-Q

    2012-01-01

    Buffalograss, Buchloe dactyloides, is a dioecious species native to the Great Plains of North America. The florets at the early stages of development possess both gynoecium and androecium organ primordia but later become unisexual. Very little is known about the proteomic changes that occur when the florets change from hermaphroditism to unisexuality. We compared the protein composition of florets at the hermaphroditic stage with that at the unisexual stage. The development stage of the floret was determined by stereomicroscopic observation. Two-dimensional gel electrophoresis was used to separate the proteins extracted from female and male inflorescences. Stage- specific protein maps, with an average of about 400 spots per map, were analyzed with the protein analysis software. Eighteen spots were found to be differentially expressed between the hermaphrodite and unisexual stages. Of these, 12 were present at both stages but with a different expression value. Four specific spots appeared at the hermaphrodite stage and disappeared at the unisexual stage. Two specific protein spots were associated with female and male floret differentiation. One appears to be associated with contabescence in the female floret and the final protein appears to lead to the abortion of gynoecium in the male floret. The MALDI TOF/TOF technique was used for peptide mass fingerprinting of the differentially expressed proteins and the MASCOT software was used to search the protein database. However, only two protein spots were identified from the database. These were aldolase1 and Os05g0574400 (similar to malate dehydrogenase). This type of proteomic study can help to identify novel protein products and determine the mechanisms involved in the floral sex differentiation process in buffalo grass. PMID:22930428

  16. Art in Alzheimer's care: promoting well-being in people with late-stage Alzheimer's disease.

    PubMed

    Walsh, Sandra M; Lamet, Ann R; Lindgren, Carolyn L; Rillstone, Pam; Little, Daniel J; Steffey, Christine M; Rafalko, Sharon Y; Sonshine, Rosanne

    2011-01-01

    The purpose of this qualitative study was to explore the responses of people with late-stage Alzheimer's disease (AD) to a creative bonding intervention (CBI). The CBI consisted of simple art activities. Guided by Reed's self-transcendence theory, research questions were "Will persons with late-stage AD show evidence of self-transcendence during the CBI?" and "Will persons with late-stage AD show evidence of well-being during the CBI?" Twelve CBI sessions, documented by videotape and field notes, were conducted with four participants. Themes emerged within two clusters: trusting/thirsting/following and choosing/connecting/reminiscing. An overarching category of "cocooning" described participants' world during the CBI as they displayed evidence of self-transcendence and well-being. The CBI is a strategy that can be implemented by staff families, and volunteers. Nurses are positioned to provide transformation leadership for implementation of creative approaches during care of people with late-stage AD, but administrative and financial support are needed. PMID:21473563

  17. Sexual dysfunction in men and women with chronic kidney disease and end-stage kidney disease.

    PubMed

    Palmer, Biff F

    2003-01-01

    Sexual dysfunction is a common finding in both men and women with chronic kidney failure. Common disturbances include erectile dysfunction in men, menstrual abnormalities in women, and decreased libido and fertility in both sexes. These abnormalities are primarily organic in nature and are related to uremia as well as the other comorbid conditions that frequently occur in the chronic kidney failure patient. Fatigue and psychosocial factors related to the presence of a chronic disease are also contributory factors. Disturbances in the hypothalamic-pituitary-gonadal axis can be detected before the need for dialysis but continue to worsen once dialytic therapy is initiated. Impaired gonadal function is prominent in uremic men, whereas the disturbances in the hypothalamic-pituitary axis are more subtle. By contrast, central disturbances are more prominent in uremic women. Therapy is initially directed toward optimizing the delivery of dialysis, correcting anemia with recombinant erythropoietin, and controlling the degree of secondary hyperparathyroidism with vitamin D. For many practicing nephrologists, sildenafil has become the first line therapy in the treatment of impotence. In the hypogonadal man whose only complaint is decreased libido, testosterone may be of benefit. Regular gynecologic follow-up is required in uremic women to guard against potential complications of unopposed estrogen effect. Uremic women should be advised against pregnancy while on dialysis. Successful transplantation is the most effective means of restoring normal sexual function in both men and women with chronic kidney failure. PMID:12616463

  18. Low acute hematological toxicity during chemotherapy predicts reduced disease control in advanced Hodgkin's disease.

    PubMed

    Brosteanu, O; Hasenclever, D; Loeffler, M; Diehl, V

    2004-03-01

    Chemotherapy-treated patients with advanced Hodgkin's disease (HD) differ considerably in acute hematotoxicity. Hematotoxicity may be indicative of pharmacological and metabolic heterogeneity. We hypothesized that low hematotoxicity might correlate with reduced systemic dose and thus reduced disease control. A total of 266 patients with advanced HD treated with cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP-ABVD) were analyzed (HD6 trial of the German Hodgkin's Lymphoma Study Group). The reported WHO grade of leukocytopenia was averaged over chemotherapy cycles given and weighted with the reciprocal dose intensity of the corresponding cycle. The low and high toxicity groups were defined in retrospect as having had an averaged WHO grade of leukocytopenia 2.1, respectively. The independent impact of low hematological toxicity on freedom from treatment failure (FFTF) was assessed multivariately adjusting for the international prognostic score for advanced HD. The results were validated in two independent cohorts [181 patients treated with COPP-ABVD (HD9-trial) and 250 patients treated with COPP-ABV-ifosfamide, methotrexate, etoposide, and prednisone (IMEP) (HD6 trial)]. The 5-year FFTF rates were 68% for patients with high toxicity vs 47% for patients with low toxicity [multivariate relative risk (RR) 2.0, 95% confidence interval (CI) 1.4-3.0, p=0.0002]. Patients with low toxicity received significantly higher nominal dose ( p=0.02) and dose intensity ( p<0.0001). This finding was confirmed in both validation cohorts (multivariate RR 2.1, 95% CI 1.2-3.8, p=0.01 and RR 1.5, 95% CI 1.01-2.26, p=0.04, respectively). Patients with low hematotoxicity have significantly higher failure rates despite higher doses and dose intensity. Hematotoxicity is an independent prognostic factor for treatment outcome. This observation suggests a strategy of individualized dosing adapted to hematotoxicity

  19. Predictors of cognitive decline in the early stage of probable Alzheimer's disease.

    PubMed

    Marra, C; Silveri, M C; Gainotti, G

    2000-01-01

    Several papers have attempted to find neurological and neuropsychological predictors of progression in Alzheimer's disease (AD) till now. Despite this quite large amount of works, different and not univocal conclusions have been reported in this field. Different study samples, different end-points and differences in statistical methods can explain much of the inconsistency in the results obtained. In our study, AD patients were examined in a very early stage of the disease to avoid any possible risk to examine subjects at different times of evolution. All the patients underwent an extensive neuropsychological test battery twice (baseline and follow-up) spaced out over about 1 year and were divided into two groups of fast decliners (FD) and slow decliners (SD) on the basis of their rate of decay at the MMSE score. Verbal memory tests, mental control abilities and attention-demanding tasks seem to play a pivotal role in distinguishing the two groups of subjects in the early stage of the disease. Moreover, FD patients show a worse performance than SD at the baseline in most of the cognitive domains explored. In conclusion, different subtypes of AD do exist and an important predictor of progression is represented by the severity of the cognitive impairment at the onset. PMID:10867447

  20. Advances in the management of patients with thyroid disease.

    PubMed

    Dworkin, H J; Meier, D A; Kaplan, M

    1995-07-01

    Discoveries related to thyroid immunology, especially concerning the thyroid-stimulating hormone (TSH) receptor, may facilitate new immunologic approaches to the therapy of Graves' disease and the thyroiditis syndromes. Advances in genetics are being applied to the thyroid hormone resistance syndromes and papillary and medullary carcinomas. The development of ever more sensitive TSH assays has led to the detection of subclinical thyroid disease, which has special implications for the sick and elderly patients. Sensitive TSH assays also allow more precise titration of levothyroxine (T4) dosages, especially for patients with a past history of thyroid cancer. Evidence continues to accumulate suggesting that postmenopausal women on T4 doses that suppress the TSH level below 0.1 ulU/mL have lower bone mineral density than matched patients with healthy TSH levels. Also, pregnant hypothyroid women need higher T4 doses to normalize the TSH levels. In the evaluation of thyroid nodules, fine-needle aspiration biopsy is the single most definitive modality in selecting the patients for surgery. Scintigraphy provides a complimentary role, especially in defining autonomously functioning thyroid adenomas (AFTA), because these should not be treated with T4 suppression. Ultrasound-guided needle biopsy is occasionally helpful with nodules that are difficult to palpate. Concern for possible tracheal compression after treatment of toxic multinodular goiter with large doses of radioactive iodine (I-131) in the range of 50 to 150 mCi (1.85 to 5.5 GBq) does not seem warranted. Work, primarily out of Italy, suggests AFTA can be ablated with repeat ethanol injections. Residual tissues after thyroidectomy for differentiated carcinoma can be "stunned" by tracer doses of 131I greater than 3.0 mCi (111 MBq), which diminishes the uptake and effectiveness of a subsequent therapy dose. Positron emission tomograph, imaging with thallium-201, and Technetium 99m Sestamibi can identify a small number

  1. Relationship of dietary phosphate intake with risk of end stage renal disease and mortality in chronic kidney disease stage 3-5: A Modification of Diet in Renal Disease study

    PubMed Central

    Selamet, Umut; Tighiouart, Hocine; Sarnak, Mark J.; Beck, Gerald; Levey, Andrew S.; Block, Geoffrey; Ix, Joachim H.

    2015-01-01

    KDIGO guidelines recommend dietary phosphate restriction to lower serum phosphate levels in CKD stage 3-5. Recent studies suggest that dietary phosphate intake is only weakly linked to its serum concentration, and the relationship of phosphate intake with adverse outcomes is uncertain. To further evaluate this, we used Cox proportional hazards models to assess associations of baseline 24 hour urine phosphate excretion with risk of end stage renal disease (ESRD), all-cause mortality, and mortality subtypes (cardiovascular disease (CVD) and non-CVD) using the Modification of Diet in Renal Disease data. Models were adjusted for demographics, CVD risk factors, iothalamate GFR, and urine protein and nitrogen excretion. Phosphate excretion was modestly inversely correlated with serum phosphate concentrations. There was no association of 24 hour urinary phosphate excretion with risk of ESRD, CVD-, non-CVD- or all-cause mortality. For comparison, higher serum phosphate concentrations were associated with all-cause mortality (hazard ratio per 0.7 mg/dL higher, 1.15 [95% CI 1.01, 1.30]). Thus, phosphate intake is not tightly linked with serum phosphate concentrations in CKD stage 3-5, and there was no evidence that greater phosphate intake, assessed by 24 hour phosphate excretion, is associated with ESRD, CVD-, non CVD-, or all-cause mortality in CKD stage 3-5. Hence, factors other than dietary intake may be key determinants of serum phosphate concentrations and require additional investigation. PMID:26422502

  2. Metastatic Neuroblastoma Confined to Distant Lymph Nodes (stage 4N) Predicts Outcome in Patients With Stage 4 Disease: A Study From the International Neuroblastoma Risk Group Database

    PubMed Central

    Morgenstern, Daniel A.; London, Wendy B.; Stephens, Derek; Volchenboum, Samuel L.; Hero, Barbara; Di Cataldo, Andrea; Nakagawara, Akira; Shimada, Hiroyuki; Ambros, Peter F.; Matthay, Katherine K.; Cohn, Susan L.; Pearson, Andrew D.J.; Irwin, Meredith S.

    2014-01-01

    Purpose The presence of distant metastases is one of the most powerful predictors of outcome in patients with neuroblastoma. However, the pattern of metastatic spread is not incorporated into current risk stratification systems. Small case series have suggested that patients with neuroblastoma who have metastatic disease limited to distant lymph nodes (4N disease) may have improved outcomes. Patients and Methods We analyzed retrospective data from the International Neuroblastoma Risk Group database for patients diagnosed from 1990 to 2002. 4N patients were compared with the remaining stage 4 patients (non-4N), excluding those with missing metastatic site data. Results In all, 2,250 International Neuroblastoma Staging System stage 4 patients with complete data were identified, of whom 146 (6.5%) had 4N disease. For 4N patients, event-free survival (EFS; 5-year, 77% ± 4%) and overall survival (OS; 5-year, 85% ± 3%) were significantly better than EFS (5-year, 35% ± 1%) and OS (5-year, 42% ± 1%) for non-4N stage 4 patients (P < .001). 4N patients were more likely to be younger (P < .001) and have tumors with favorable characteristics, including absence of MYCN amplification (89% v 69%; P < .001). In a multivariable analysis, 4N disease remained a significant predictor of outcome (hazard ratio for non-4N v 4N: 3.40 for EFS and 3.69 for OS). Within subgroups defined by age at diagnosis and tumor MYCN status, 4N disease was significantly associated with improved outcomes. Conclusion 4N represents a subgroup with better outcome than that of other patients with metastatic disease. These findings suggest that the biology and treatment response of 4N tumors differ from other stage 4 tumors, and less intensive therapy should be considered for this cohort. Future exploration of biologic factors determining the pattern of metastatic spread is warranted. PMID:24663047

  3. Chronic obstructive pulmonary disease in patients with end-stage kidney disease on hemodialysis.

    PubMed

    Plesner, Louis L; Warming, Peder E; Nielsen, Ture L; Dalsgaard, Morten; Schou, Morten; Høst, Ulla; Rydahl, Casper; Brandi, Lisbet; Køber, Lars; Vestbo, Jørgen; Iversen, Kasper

    2016-01-01

    The objectives of this study were to assess the prevalence of chronic obstructive pulmonary disease (COPD) in hemodialysis patients with spirometry and to examine the effects of fluid removal by hemodialysis on lung volumes. Patients ≥18 years at two Danish hemodialysis centers were included. Forced expiratory volume in one second (FEV1 ), forced vital capacity (FVC), and FEV1 /FVC ratio were measured with spirometry before and after hemodialysis. The diagnosis of COPD was based on both the GOLD criteria and the lower limit of normal criteria. There were 372 patients in treatment at the two centers, 255 patients (69%) completed spirometry before dialysis and 242 of these (65%) repeated the test after. In the initial test, 117 subjects (46%) had airflow limitation indicative of COPD with GOLD criteria and 103 subjects (40.4%) with lower limit of normal criteria; COPD was previously diagnosed in 24 patients (9%). Mean FVC and FEV1 decreased mildly after dialysis (FVC: 2.84 to 2.79 L, P < 0.01. FEV1 : 1.97 to 1.93 L, P < 0.01) Hemodialysis did not affect the FEV1 /FVC ratio or number of subjects with airflow limitation indicative of COPD (113 vs. 120, P = 0.324; n = 242). COPD is a frequent and underdiagnosed comorbidity in patients on chronic hemodialysis. Spirometry should be considered in all patients on dialysis in order to address dyspnea adequately. Hemodialysis induced a small fall in mean FEV1 and FVC, which was more pronounced in patients with little or no fluid removal, but the FEV1 /FVC ratio and the number of subjects with airflow limitation indicative of COPD were not affected by dialysis. PMID:26245152

  4. Antiplatelet Management for Coronary Heart Disease: Advances and Challenges.

    PubMed

    Gillette, Michael; Morneau, Kathleen; Hoang, Vu; Virani, Salim; Jneid, Hani

    2016-06-01

    Coronary heart disease (CHD) remains the leading cause of death in the USA. CHD accounts for 48 % of all cardiovascular mortality or approximately one of every seven deaths. Disruption of atherosclerotic plaques-usually by rupture or erosion-and superimposed thrombosis can result in acute coronary syndromes and sudden cardiac death. Silent plaque disruption may also occur and result in coronary plaque progression and ultimately the symptomatic manifestations of stable CHD. Antiplatelet agents remain the cornerstone therapy for acute thrombotic coronary syndromes and are essential for thromboprophylaxis against these events in patients with stable CHD. Antiplatelet drugs are also important adjunct therapies during percutaneous coronary intervention (PCI) as they mitigate equipment-associated thrombotic complications that are partially induced by iatrogenic plaque rupture by interventionalists during balloon angioplasty in the cardiac catheterization laboratory. Since the introduction of clopidogrel, there has been considerable development in this field with at least three novel P2Y12 antagonists approved by the Food and Drug Administration (FDA) over the past decade. Rapidly accumulating evidence is helping to guide the optimal duration of treatment with dual antiplatelet therapy after stenting, especially with the newer drug-eluting stents. More data are also emerging on the hazards and long-term safety of these agents. It is therefore prudent for clinicians to remain current on treatment options and recent advances in this area. We herein review current and emerging antiplatelet therapies and summarize their characteristics and indications of use as well as challenges and areas of ongoing research. PMID:27139709

  5. Parkinson's Disease and Cognitive-Motor Dual-Task: Is Motor Prioritization Possible in the Early Stages of the Disease?

    PubMed

    Fernandes, Ângela; Sousa, Andreia S P; Rocha, Nuno; Tavares, João Manuel R S

    2016-01-01

    The authors aimed to compare the postural phase of gait initiation under single-task (gait initiation) and dual-task (gait initiation plus Stroop test) conditions in healthy subjects and in subjects with Parkinson's disease (PD) in the early stages (Hoehn and Yahr scale < 3). The postural phase of gait initiation was assessed through the centre of pressure in single and dual task in 10 healthy subjects and 9 with PD. The analysis indicated that in the early stages of PD, an additional cognitive task did not affect the displacement of the gait initiation. No significant effects occurred between the groups and within-subjects (p > .05). Also, no interaction was found between the groups and the conditions (single- and dual-task). Differences were found in the duration of the mediolateral postural phase (p = .003), which was higher in PD subjects than in healthy subjects. The findings suggest that subjects in the early stages of PD prioritize gait initiation, as their motor performance was similar to that of healthy subjects. PMID:27159414

  6. α-Synuclein staging in the amygdala of a Parkinson's disease model: cell types involved.

    PubMed

    Flores-Cuadrado, Alicia; Ubeda-Bañon, Isabel; Saiz-Sanchez, Daniel; de la Rosa-Prieto, Carlos; Martinez-Marcos, Alino

    2015-01-01

    Lewy bodies (ubiquitin and α-synuclein aggregates) can be detected in brain areas in a predictable sequence of six neuropathological stages in Parkinson's disease. Brainstem and olfactory structures are involved in stage 1, whereas the substantia nigra and amygdala are involved in stage 3, prior to cortical spreading. Amygdaloid pathology has been suggested to contribute to non-motor symptoms such as olfactory dysfunction and emotional impairment. This work analysed the distribution of α-synuclein at 16, 30, 43 and 56 weeks in the basolateral, central and cortical amygdaloid complexes of A53T transgenic mice. The expression of calbindin, calretinin and somatostatin was compared in control and transgenic animals. Co-localisation of these markers with α-synuclein was performed. Triple labeling of calbindin, somatostatin and α-synuclein was also investigated. Quantification was carried out using an optical dissector, ImageJ software and confocal microscopy. α-Synuclein-positive cells were mainly concentrated in the basolateral and cortical amygdaloid complexes with a non-significant increase over time from 16 to 30-43 weeks and a significant decrease thereafter. The expression of interneuron markers showed a significant decrease with aging in control animals. When comparing these markers between control and transgenic mice, calretinin was moderately decreased, but calbindin and somatostatin were highly reduced, particularly in the cortical amygdaloid complex. α-Synuclein mostly co-localised with calbindin and a number of these cells also co-expressed somatostatin. These data on α-synucleinopathy staging in the amygdala could help to explain non-motor symptoms as well as to understand the progression of Parkinson's disease in the brain. PMID:25345880

  7. Knowledge-based compact disease models identify new molecular players contributing to early-stage Alzheimer’s disease

    PubMed Central

    2013-01-01

    Background High-throughput profiling of human tissues typically yield as results the gene lists comprised of a mix of relevant molecular entities with multiple false positives that obstruct the translation of such results into mechanistic hypotheses. From general probabilistic considerations, gene lists distilled for the mechanistically relevant components can be far more useful for subsequent experimental design or data interpretation. Results The input candidate gene lists were processed into different tiers of evidence consistency established by enrichment analysis across subsets of the same experiments and across different experiments and platforms. The cut-offs were established empirically through ontological and semantic enrichment; resultant shortened gene list was re-expanded by Ingenuity Pathway Assistant tool. The resulting sub-networks provided the basis for generating mechanistic hypotheses that were partially validated by literature search. This approach differs from previous consistency-based studies in that the cut-off on the Receiver Operating Characteristic of the true-false separation process is optimized by flexible selection of the consistency building procedure. The gene list distilled by this analytic technique and its network representation were termed Compact Disease Model (CDM). Here we present the CDM signature for the study of early-stage Alzheimer’s disease. The integrated analysis of this gene signature allowed us to identify the protein traffic vesicles as prominent players in the pathogenesis of Alzheimer’s. Considering the distances and complexity of protein trafficking in neurons, it is plausible that spontaneous protein misfolding along with a shortage of growth stimulation result in neurodegeneration. Several potentially overlapping scenarios of early-stage Alzheimer pathogenesis have been discussed, with an emphasis on the protective effects of AT-1 mediated antihypertensive response on cytoskeleton remodeling, along with

  8. [Importance of selenium homeostasis in chronic and end-stage kidney diseases].

    PubMed

    Kiss, István

    2013-10-13

    Selenium is an essential trace element for the human body with a significant antioxidant effect. Selenium deficiency and excess are both detrimental for proper functioning of the human body. The possible association between selenium deficiency and acute or chronic renal disease, along with their complications has been less intensively investigated, however, there are firm data showing that selenium deficiency and renal failure increase the risk of both coronary artery disease and total mortality. Further studies revealed that selenium deficiency increases the risk of death due to infection in patients treated with hemodialysis through dysfunction of the immune system. However, there are no data whether the imbalance of selenium metabolism, especially selenium deficiency, could cause chronic kidney disease or renal failure. As far as results of selenium measurements, there is convincing evidence that protein loss and renal replacement treatment reduce serum selenium levels. Despite some contradictory results obtained from various studies regarding selenium deficiency in chronic kidney diseases, it seems that selenium supplementation may be beneficial in many patients with severe or end-stage kidney disease including those treated with dialysis. PMID:24095914

  9. Frontal functions in depressed and nondepressed Parkinson's disease patients: impact of severity stages.

    PubMed

    Silberman, Cláudia Débora; Laks, Jerson; Capitão, Cláudia Figueiredo; Rodrigues, Cláudia Soares; Moreira, Irene; Vasconcellos, Luiz Felipe Rocha; Engelhardt, Eliasz

    2007-01-15

    Severity of Parkinson's disease (PD) and frontal impairment are positively correlated. Testing frontal functions in depressed/nondepressed PD patients with different severity stages may reveal whether depression leads to this impairment. We aimed to relate severity of PD to frontal functional impairment and to test if negative stimuli/depressive symptoms interfered with frontal tasks. The Stroop test and the Emotional Stroop test were performed by 46 PD patients, 18 of whom were depressed. The Hoehn and Yahr scale assessed severity of the disease. We calculated the difference in seconds for each Stroop card and the interference index (C/D) between depressed and nondepressed patients sharing the same severity of disease. The differences among the groups (depressed and nondepressed) according to the severity of the disease (mild and moderate) were compared using the Mann-Whitney test. The depressed patients had a poorer performance on the test than the nondepressed PD patients, although the difference was not statistically significant. In conclusion, there is a clinically relevant but not statistically significant difference on the performance of frontal tasks between depressed and nondepressed PD patients. Neither depression nor the severity of the disease were determinant to the poorer performance on the Stroop and the Emotional Stroop tests. PMID:17113157

  10. The evolving role of the total artificial heart in the management of end-stage congenital heart disease and adolescents.

    PubMed

    Ryan, Thomas D; Jefferies, John L; Zafar, Farhan; Lorts, Angela; Morales, David L S

    2015-01-01

    Advances in medical therapies have yielded improvement in morbidity and a decrease in mortality for patients with congenital heart disease, both surgically palliated and uncorrected. An unintended consequence is a cohort of adolescent and adult patients with heart failure who require alternative therapies. One intriguing option is placement of a total artificial heart (TAH) either as a bridge to transplant or as a destination therapy. Of the 1091 Jarvik-7 type TAH (Symbion, CardioWest and SynCardia) placed between 1985 and 2012, only 24 have been performed in patients with congenital heart disease, and a total of 51 were placed in patients younger than 21. At our institution, the SynCardia TAH was implanted in a 19-year-old patient with cardiac allograft failure because of chronic rejection and related multisystem organ failure including need for hemodialysis. Over the next year, she was nutritionally and physically rehabilitated, as were her end organs, allowing her to come off dialysis, achieve normal renal function and eventually be successfully transplanted. Given the continued growth of adolescent and adult congenital heart disease populations with end-stage heart failure, the TAH may offer therapeutic options where previously there were few. In addition, smaller devices such as the SynCardia 50/50 will open the door for applications in smaller children. The Freedom Driver offers the chance for patients to leave the hospital with a TAH, as does the AbioCor, which is a fully implantable TAH option. In this report, we review the history of the TAH and potential applications in adolescent patients and congenital heart disease. PMID:25248044

  11. An update of the effect of far infrared therapy on arteriovenous access in end-stage renal disease patients.

    PubMed

    Chen, Chun-Fan; Yang, Wu-Chang; Lin, Chih-Ching

    2016-07-12

    The life qualities of end-stage renal disease (ESRD) patients rely largely on adequate dialysis, and a well-functioning vascular access is indispensable for high quality hemodialysis. Despite the advancement of surgical skills and the optimal maintenance of arteriovenous fistula (AVF), malfunction of AVF is still frequently encountered and has great impact on the life of ESRD patients. Several medical, mechanical and genetic prognostic factors are documented to affect the patency of AVF and arteriovenous graft (AVG). Heme oxygenase-1 (HO-1) is one of the genetic factors reported to play a role in cardiovascular disease and the patency of vascular access. Far infrared (FIR), a novel therapeutic modality, can not only conduct heat energy to AVF but also stimulate the non-thermal reactions mediated by HO-1. The use of FIR therapy significantly enhances the primary patency rate and maturation of AVF with fewer unfavorable adverse effects, and also achieves higher post-angioplasty patency rate for AVG. The only limitation in proving the effectiveness of FIR therapy in enhancing patency of AVF is that all the studies were conducted in Chinese people in Taiwan and thus, there is a lack of evidence and experience in people of other ethnicities. PMID:27312759

  12. 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

  13. Advanced Tracers in PET Imaging of Cardiovascular Disease

    PubMed Central

    Zhang, Wei; Wu, Hua; Liu, Gang

    2014-01-01

    Cardiovascular disease is the leading cause of death worldwide. Molecular imaging with targeted tracers by positron emission tomography (PET) allows for the noninvasive detection and characterization of biological changes at the molecular level, leading to earlier disease detection, objective monitoring of therapies, and better prognostication of cardiovascular diseases progression. Here we review, the current role of PET in cardiovascular disease, with emphasize on tracers developed for PET imaging of cardiovascular diseases. PMID:25389529

  14. Gender difference in advanced HIV disease and late presentation according to European consensus definitions

    PubMed Central

    Jiang, Hongbo; Yin, Jieyun; Fan, Yunzhou; Liu, Jianhua; Zhang, Zhixia; Liu, Li; Nie, Shaofa

    2015-01-01

    Effectiveness of highly active antiretroviral therapy is limited for a large proportion of individuals living with HIV presenting for medical care at an advanced stage. Controversial results of gender differences in risk of late HIV diagnosis were reported among existing literatures. Therefore, we conducted this meta-analysis to synthesize a summary of gender differences in risk of advanced HIV disease (AHD) and late presentation (LP) according to European consensus definitions. Totally, 32 studies were included based on predetermined selection criteria. The pooled adjusted odds ratios of males presenting with AHD and LP compared with females were 1.73 (95% confidence interval [CI], 1.59–1.89) and 1.38 (95% CI, 1.18–1.62) with significant heterogeneity observed (I2 = 78.50%, and I2 = 85.60%, respectively). Subgroup analysis revealed that time lag, study location, number of patients, proportion of females, study design, number of adjusted variables might be potential source of heterogeneity. Sensitivity analysis showed robustness of the results. No publication bias was observed in studies on AHD or LP. The current meta-analysis indicated that males are at higher risk of AHD or LP compared with females. More attention should be paid to males to make sure early testing, diagnosis, and treatment, and ultimately improve individual and population health. PMID:26412578

  15. Control-relevant erythropoiesis modeling in end-stage renal disease.

    PubMed

    Chait, Yossi; Horowitz, Joseph; Nichols, Brendan; Shrestha, Rajiv P; Hollot, C V; Germain, Michael J

    2014-03-01

    Anemia is prevalent in end-stage renal disease (ESRD). The discovery of recombinant human erythropoietin (rHuEPO) over 30 years ago has shifted the treatment of anemia for patients on dialysis from blood transfusions to rHuEPO therapy. Many anemia management protocols (AMPs) used by clinicians comprise a set of experience-based rules for weekly-to-monthly titration of rHuEPO doses based on hemoglobin (Hb) measurements. In order to facilitate the design of an AMP using model-based feedback control theory, we present a physiologically relevant erythropoiesis model and demonstrate its applicability using clinical data. PMID:24235247

  16. Removal of Dolutegravir by Hemodialysis in HIV-Infected Patients with End-Stage Renal Disease.

    PubMed

    Moltó, José; Graterol, Fredzzia; Miranda, Cristina; Khoo, Saye; Bancu, Ioana; Amara, Alieu; Bonjoch, Anna; Clotet, Bonaventura

    2016-04-01

    Data on dolutegravir removal by hemodialysis are lacking. To study this, we measured dolutegravir plasma concentrations in samples of blood entering and leaving the dialyzer and of the resulting dialysate from 5 HIV-infected patients with end-stage renal disease. The median dolutegravir hemodialysis extraction ratio was 7%. The dolutegravir concentrations after the dialysis session remained far above the protein-binding-adjusted inhibitory concentration. Our results show minimal dolutegravir removal by hemodialysis, with no specific dolutegravir dosage adjustments required in this setting. (This study is registered at ClinicalTrials.gov under registration number NCT02487706.). PMID:26856824

  17. Prostate cancer with a pseudocapsule at MR imaging: a marker of high grade and stage disease?

    PubMed

    Bonde, Apurva A; Korngold, Elena K; Foster, Bryan R; Westphalen, Antonio C; Pettersson, David R; Troxell, Megan L; Simko, Jeffry P; Coakley, Fergus V

    2016-01-01

    Clinicopathological correlates of prostate cancer associated with a pseudocapsule at T2-weighted magnetic resonance (MR) imaging are presented in a retrospective series of 15 patients. Of 15 tumors, 14 involved the peripheral zone. Extracapsular extension was seen in 14 cases. Tumor Gleason score was 8 or above in 12 of 15 cases, and ductal type adenocarcinoma was identified in 4 cases. Step section histopathological correlation (n=5) demonstrated that the pseudocapsule corresponded with dense compressive or reactive peritumoral fibrosis. A pseudocapsule around prostate cancer at T2-weighted MR imaging is a rare finding that appears to be associated with high grade and stage disease. PMID:27133669

  18. [Notalgia paresthetica, "posterior pigmented pruritic patch" and macular amyloidosis. Three stages of a disease].

    PubMed

    Cerroni, L; Kopera, D; Soyer, H P; Kerl, H

    1993-12-01

    We report on nine cases of notalgia paresthetica, a cutaneous condition that has rarely been described in the dermatological literature and is characterized by localized pruritus, burning and hyperesthesia and/or paresthesia on the back. Histological and immunohistochemical studies have not clarified the pathogenesis of this disease. Several factors might be involved in various cases, including increased cutaneous innervation and neuropathy. The so-called posterior pigmented pruritic patch and macular amyloidosis may be considered as progressive evolutional stages of notalgia paresthetica. PMID:8113041

  19. Pregnancy and Chronic Kidney Disease: A Challenge in All CKD Stages

    PubMed Central

    Attini, Rossella; Vasario, Elena; Conijn, Anne; Biolcati, Marilisa; D'Amico, Federica; Consiglio, Valentina; Bontempo, Salvatore; Todros, Tullia

    2010-01-01

    Background and objectives: Chronic kidney disease (CKD) is a challenge for pregnancy. Its recent classification underlines the importance of its early phases. This study's aim was to evaluate outcomes of pregnancy according to CKD stage versus low-risk pregnancies followed in the same center. Design, setting, participants, & measurements: The prospective analysis was conducted from January 2000 to May 2009 with the start of observation at referral and end of observation 1 month after delivery. Ninety-one singleton deliveries were studied; 267 “low-risk” singleton pregnancies served as controls. Because of the lack of hard end points (death, start of dialysis), surrogate end points were analyzed (cesarean section, prematurity, neonatal intensive care). Results: CKD outcome was worse than physiologic pregnancies: preterm delivery (44% versus 5%); cesarean section (44% versus 25%); and need for neonatal intensive care (26% versus 1%). The differences were highly significant in stage 1 CKD (61 cases) versus controls (CKD stage 1: cesarean sections = 57%, preterm delivery = 33%, intensive care = 18%). In CKD, proteinuria and hypertension were correlated with outcomes [proteinuria dichotomized at 1 g/24 h at referral: need for intensive care, relative risk (RR) = 4.16 (1.05 to 16.46); hypertension: preterm delivery, RR = 7.24 (2.30 to 22.79); cesarean section, RR = 5.70 (1.69 to 19.24)]. Statistical significance across stages was reached for preterm delivery [RR = 3.32 (1.09 to 10.13)]. Conclusions: CKD is a challenge for pregnancy from early stages. Strict follow-up is needed for CKD patients, even when there is normal renal function. PMID:20413442

  20. Initial staging of Hodgkin's disease: role of contrast-enhanced 18F FDG PET/CT.

    PubMed

    Chiaravalloti, Agostino; Danieli, Roberta; Caracciolo, Cristiana Ragano; Travascio, Laura; Cantonetti, Maria; Gallamini, Andrea; Guazzaroni, Manlio; Orlacchio, Antonio; Simonetti, Giovanni; Schillaci, Orazio

    2014-08-01

    The objective of this study was to compare the diagnostic accuracy of positron emission tomography/low-dose computed tomography (PET/ldCT) versus the same technique implemented by contrast-enhanced computed tomography (ceCT) in staging Hodgkin's disease (HD).Forty patients (18 men and 22 women, mean age 30 ± 9.6) with biopsy-proven HD underwent a PET/ldCT study for initial staging including an unenhanced low-dose computed tomography for attenuation correction with positron emission tomography acquisition and a ceCT, performed at the end of the PET/ldCT scan, in the same exam session. A detailed datasheet was generated for illness locations for separate imaging modality comparison and then merged in order to compare the separate imaging method results (PET/ldCT and ceCT) versus merged results positron emission tomography/contrast-enhanced computed tomography (PET/ceCT). The nodal and extranodal lesions detected by each technique were then compared with follow-up data that served as the reference standard.No significant differences were found at staging between PET/ldCT and PET/ceCT in our series. One hundred and eighty four stations of nodal involvement have been found with no differences in both modalities. Extranodal involvement was identified in 26 sites by PET/ldCT and in 28 by PET/ceCT. We did not find significant differences concerning the stage (Ann Arbor).Our study shows a good concordance and conjunction between PET/ldCT and ceCT in both nodal and extranodal sites in the initial staging of HD, suggesting that PET/ldCT could suffice in most of these patients. PMID:25121354

  1. Improvement with ongoing Enzyme Replacement Therapy in advanced late-onset Pompe disease: a case study.

    PubMed

    Case, Laura E; Koeberl, Dwight D; Young, Sarah P; Bali, Deeksha; DeArmey, Stephanie M; Mackey, Joanne; Kishnani, Priya S

    2008-12-01

    Benefits of enzyme replacement therapy with Myozyme (alglucosidase alfa), anecdotally reported in late-onset Pompe disease, range from motor and pulmonary improvement in less severely affected patients, to stabilization with minimal improvement in those with advanced disease. We report a case of a 63-year-old patient with significant morbidity who made notable motor and pulmonary function gains after two years on therapy. Thus, improvements in those with advanced disease may be possible after long-term treatment. PMID:18930676

  2. Stroke and Risks of Development and Progression of Kidney Diseases and End-Stage Renal Disease: A Nationwide Population-Based Cohort Study

    PubMed Central

    Wu, Chia-Lin; Tsai, Chun-Chieh; Kor, Chew-Teng; Tarng, Der-Cherng; Lian, Ie-Bin; Yang, Tao-Hsiang; Chiu, Ping-Fang; Chang, Chia-Chu

    2016-01-01

    Background There is little information about the association between stroke and kidney diseases. We aimed to investigate the impact of stroke on long-term renal outcomes. Methods In this large population-based retrospective cohort study, we identified 100,353 subjects registered in the National Health Insurance Research Database of Taiwan from January 1, 2000, through December 31, 2012, including 33,451 stroke patients and 66,902 age-, sex- and Charlson’s comorbidity index score-matched controls. Results The incidence rate of chronic kidney disease (CKD) was higher in the stroke than in the control cohort (17.5 vs. 9.06 per 1000 person-years). After multivariate adjustment, the risk of developing CKD was significantly higher in patients with stroke (adjusted hazard ratio [aHR] 1.43, 95% confidence interval [CI] 1.36–1.50, P<0.001). Subgroup analysis showed that stroke patients <50 years (aHR 1.61, P<0.001) and those with concomitant diabetes mellitus (aHR 2.12, P<0.001), hyperlipidemia (aHR 1.53, P<0.001) or gout (aHR 1.84, P<0.001) were at higher risk of incident CKD. Additionally, the risks of progression to advanced CKD and end-stage renal disease (ESRD) were significantly higher for stroke patients (aHRs, 1.22 and 1.30; P = 0.04 and P = 0.008, respectively), independent of age, sex, comorbidities and long-term medications. Conclusions Stroke is associated with higher risks for incident CKD, decline in renal function and ESRD. Younger stroke patients, as well as those with concomitant diabetes mellitus, hyperlipidemia or gout are at greater risk for kidney diseases. PMID:27355475

  3. Effects of Renin-Angiotensin-Aldosterone System Blockade in Patients with End-Stage Renal Disease.

    PubMed

    Slomka, Teresa; Lennon, Emily S; Akbar, Hina; Gosmanova, Elvira O; Bhattacharya, Syamal K; Oliphant, Carrie S; Khouzam, Rami N

    2016-03-01

    Blockers of the renin-angiotensin-aldosterone system (RAAS), such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are routinely used in patients with chronic kidney disease because of their cardiovascular (CV) and renoprotective effects. However, there are no uniform recommendations about RAAS blockers for CV protection in the end-stage renal disease (ESRD) population other than the preferred drug class for blood pressure control. This uncertainty stems from the fact that patients with ESRD were generally excluded from randomized controlled trials evaluating the cardioprotective benefits of RAAS blockers. It is important to weigh the potential harms associated with the use of RAAS blockers, such as electrolyte disturbances and worsening anemia, with their role in protection of residual kidney function, alleviation of thirst and potential CV benefits. The objective of this review is to summarize the current knowledge about the use of RAAS blockers in patients with ESRD. PMID:26992264

  4. Therapeutic Challenges to End-Stage Kidney Disease in a Patient with Tetralogy of Fallot

    PubMed Central

    Ohara, Ken; Akimoto, Tetsu; Miki, Takuya; Otani, Naoko; Sugase, Taro; Masuda, Takahiro; Murakami, Takuya; Imai, Toshimi; Takeda, Shin-ichi; Ando, Yasuhiro; Muto, Shigeaki; Nagata, Daisuke

    2015-01-01

    In this report, we describe the case of an end-stage kidney disease patient with tetralogy of Fallot (TOF). A 33-year-old female with TOF was admitted to our hospital with complaints of general fatigue and appetite loss probably due to uremic milieu. She was ultimately treated with peritoneal dialysis (PD) with a favorable clinical course. TOF patients with chronic kidney disease are not exceptional, although the currently available information regarding the association between TOF and renal failure severe enough to require dialysis treatment is limited. We also discuss the complex processes of how and why PD was selected as a mode of chronic renal replacement therapy in this case. PMID:26609249

  5. Exact alpha-error determination for two-stage sampling strategies to substantiate freedom from disease.

    PubMed

    Kopacka, I; Hofrichter, J; Fuchs, K

    2013-05-01

    Sampling strategies to substantiate freedom from disease are important when it comes to the trade of animals and animal products. When considering imperfect tests and finite populations, sample size calculation can, however, be a challenging task. The generalized hypergeometric formula developed by Cameron and Baldock (1998a) offers a framework that can elegantly be extended to multi-stage sampling strategies, which are widely used to account for disease clustering at herd-level. The achieved alpha-error of such surveys, however, typically depends on the realization of the sample and can differ from the pre-calculated value. In this paper, we introduce a new formula to evaluate the exact alpha-error induced by a specific sample. We further give a numerically viable approximation formula and analyze its properties using a data example of Brucella melitensis in the Austrian sheep population. PMID:23103193

  6. Periodontitis and the end-stage renal disease patient receiving hemodialysis maintenance therapy.

    PubMed

    Craig, Ronald G; Kotanko, Peter

    2009-10-01

    Atherosclerotic complications, including myocardial infarction and stroke, are highly prevalent and associated with increased systemic inflammation in patients who have end-stage renal disease (ESRD) and are receiving renal hemodialysis maintenance therapy. In the general population, an increasing body of evidence suggests periodontitis can contribute to systemic inflammation and may contribute to atherosclerotic complications. In addition, results of recent interventional trials suggest effective periodontal therapy may decrease systemic inflammation as well as endothelial dysfunction, an early predictor of atherosclerotic complications. Because moderate-to-severe periodontitis appears to be highly prevalent in the renal hemodialysis population, effective periodontal therapy may reduce systemic inflammation and thereby become a treatment consideration for this population. This article will acquaint dental practitioners with ESRD and the association between systemic inflammation and mortality. Also discussed are the possible contributions of destructive periodontal diseases to systemic inflammation and the dental management of patients receiving renal replacement therapies. PMID:19824568

  7. Correlation of mast cells in different stages of human periodontal diseases: Pilot study

    PubMed Central

    Agrawal, Raina; Gupta, Jagriti; Gupta, Krishna Kumar; Kumar, Vinod

    2016-01-01

    Aims and Objectives: The aim of this study was to evaluate and correlate the relationship between mast cells counts and different stages of human periodontal diseases. Materials and Methods: The study sample comprised 50 patients, which were divided into three groups, consisting of 10 cases of clinically healthy gingival tissues (control group) 20 cases of dental plaque-induced gingivitis with no attachment loss and 20 cases of localized chronic periodontitis (LCP) characterized by the loss of periodontal support. The samples for control group were obtained during tooth extractions for orthodontic reasons. The specimens were immediately fixed in 10% neutral buffered formalin. Conclusion: In this study, LCP cases had higher mast cell counts compared to gingivitis sites or healthy tissues. Increased mast cell counts in the progressing sites of periodontal diseases may indicate the importance of these cells in the progression of chronic periodontitis. PMID:27194868

  8. Non-pharmacological interventions and neuroplasticity in early stage Alzheimer's disease.

    PubMed

    Herholz, Sibylle C; Herholz, Regina S; Herholz, Karl

    2013-11-01

    Non-pharmacological interventions have the potential to reduce cognitive decline and to improve psychosocial aspects in mild cognitive impairment and Alzheimer's dementia, and the absence of side effects makes them a favorable option also for preventive strategies. We provide an overview on recent studies involving cognitive training and reminiscence, stimulating and challenging experiences such as visual art and music, physical activities, and electromagnetic stimulation. We review findings on neuroplasticity in the aging brain and their relevance for cognitive improvement in patients with neurodegenerative diseases. We discuss cognitive reserve and possible mechanisms that drive neuroplasticity and new learning. Finally, we identify promising avenues for future intervention strategies and research, such as combinations of cognitive and pharmaceutical interventions, and individual strategies adapted to the disease stage and tailored to the needs, predispositions and preferences of patients. PMID:24134650

  9. A retrospective study of end-stage renal disease in captive polar bears (Ursus maritimus).

    PubMed

    LaDouceur, Elise E B; Davis, Barbara; Tseng, Flo

    2014-03-01

    This retrospective study summarizes 11 cases of end-stage renal disease (ESRD) in captive polar bears (Ursus maritimus) from eight zoologic institutions across the United States and Canada. Ten bears were female, one was male, and the mean age at the time of death was 24 yr old. The most common clinical signs were lethargy, inappetence, and polyuria-polydipsia. Biochemical findings included azotemia, anemia, hyperphosphatemia, and isosthenuria. Histologic examination commonly showed glomerulonephropathies and interstitial fibrosis. Based on submissions to a private diagnostic institution over a 16-yr period, ESRD was the most commonly diagnosed cause of death or euthanasia in captive polar bears in the United States, with an estimated prevalence of over 20%. Further research is needed to discern the etiology of this apparently common disease of captive polar bears. PMID:24712164

  10. Phosphate control in end-stage renal disease: barriers and opportunities

    PubMed Central

    Waheed, Ahmed A.; Pedraza, Fernando; Lenz, Oliver; Isakova, Tamara

    2013-01-01

    Hyperphosphatemia is a nearly universal complication of end-stage renal disease that is widely recognized as one of the most important and most challenging clinical targets to meet in the care of dialysis patients. Left untreated, it can lead to bone pain, pruritus and worsening secondary hyperparathyroidism. Data from observational studies demonstrate that an elevated serum phosphorus level is an independent risk factor for mortality, and that treatment with phosphate binders is independently associated with improved survival. Experimental studies provide support for the epidemiologic findings: phosphate excess promotes vascular calcification, induces endothelial dysfunction and may contribute to other emerging chronic kidney disease-specific mechanisms of cardiovascular toxicity. On the basis of this evidence, clinical practice guidelines recommend specific targets for serum phosphorus levels in the dialysis population. The purpose of this review is to summarize common challenges in meeting these targets and to identify potential opportunities for improvement. PMID:23901051

  11. Modeling of an advanced concept of a double stage Hall effect thruster

    SciTech Connect

    Garrigues, L.; Boniface, C.; Hagelaar, G. J. M.; Boeuf, J. P.

    2008-11-15

    We present a study of the principle and operation of a two-stage Hall effect thruster, the SPT-MAG, using a two-dimensional quasineutral hybrid model coupled with a Monte Carlo simulation of electron transport. The purpose of the two-stage design is the separation of ion production and acceleration in two separate chambers, the ionization stage and the acceleration stage, with separate control of acceleration voltage and total ionization. The originality of the SPT-MAG lies in the magnetic field configuration in the ionization chamber. Electrons are confined by this magnetic field while ions are supposed to be trapped in the electric potential well supposedly resulting from the magnetic configuration, and guided toward the acceleration stage. The acceleration stage is similar to the channel of a conventional Hall effect thruster. The purpose of this paper is to clarify the physics of the SPT-MAG and to understand the formation of the positive ion trap in the ionization chamber. Using a hybrid model and a Monte Carlo simulation we show that under typical operating conditions most of the ionization in the chamber is due to high energy electrons accelerated in the channel and entering the chamber rather than to electrons accelerated by the voltage applied in the ionization chamber. We also raise the question of the possible role of an additional emissive cathode inside the ionization chamber. The model predicts that an electric potential well guiding the ions to the channel entrance forms in the chamber only if the intermediate electrode inside the chamber is an emissive cathode (which is not the case in recent configurations used for this thruster)

  12. Evidence of Altered Corticomotor System Connectivity in Early-Stage Alzheimer’s Disease

    PubMed Central

    Vidoni, Eric D.; Thomas, George P.; Honea, Robyn A.; Loskutova, Natalia; Burns, Jeffrey M.

    2012-01-01

    Background and Purpose There is increasing evidence for subtle motor dysfunction early in Alzheimer’s Disease (AD), including common motor behaviors that were once considered unaffected early in the disease process. Our objective was to assess if functional neural networks underlying motor behavior are altered by AD. Methods We investigated AD-related differences in regional brain activation during motor performance. Nine older adults with early-stage AD and 10 without dementia underwent fMRI while performing a visually-directed simple motor task (hand squeeze). Results Despite some similarity in brain activation during motor performance, we found that individuals without dementia exhibited greater activation in accessory motor regions supplementary motor area and cerebellum compared to those with AD. We also assessed disease-related differences in regions where activity was functionally integrated with primary motor cortex. Using a psycho-physiological interaction analysis, we found that those with AD displayed increased co-activation with primary motor cortex of bilateral motor and visual regions. Discussion and Conclusions These AD-related changes in regional co-activation during motor execution in may represent inefficiency in the motor network as a consequence of the disease process. Alternatively, they may represent compensatory activation. These findings provide further evidence that in early-stages of AD, neuromotor function is altered in AD even during simple motor behaviors. The results may have implications for performance of more complex tasks, and may be associated with the well-characterized decline in dual task performance in those with AD. PMID:22333920

  13. Radiofrequency Ablation in the Management of Advanced Stage Thymomas: A Case Report on a Novel Multidisciplinary Therapeutic Approach

    PubMed Central

    Pala, Carlo; Versace, Renato

    2014-01-01

    We describe in this report a case of successful radiofrequency ablation of an unresectable stage III-type B3 thymoma, and we discuss the role of this novel approach in the management of patients with advanced stage thymoma. The patient, a 59-year-old Caucasian male underwent neoadjuvant chemotherapy with only a slight reduction of the mass. Subsequently, an explorative sternotomy and debulking were performed; before closing the thorax, radiofrequency ablation of the residual tumor was carried out and a partial necrosis of the mass was achieved. A further percutaneous radiofrequency ablation was performed subsequently, obtaining complete necrosis of the lesion. Successively, the patient underwent adjuvant radiotherapy. As a result of this multidisciplinary treatment, complete and stable response was obtained. It is hard to say which of the single treatments had the major impact on cure; nevertheless, the results obtained suggest that radiofrequency ablation must be taken into account for the treatment of advanced stage thymomas, and its effectiveness must be further assessed in future studies. PMID:25574416

  14. A heartrending burden of gynaecological cancers in advance stage at nuclear institute of medicine and radiotherapy Jamshoro Sindh

    PubMed Central

    Bibi, Seema; Ashfaque, Sanober; Laghari, Naeem Ahmed

    2016-01-01

    Objectives: In Pakistan gynaecological cancers are among the leading causes of women’s morbidity and mortality posing huge financial burden on families, communities and state. Due to lack of national cancer registry exact facts and figures are unknown therefore this study was planned to find out prevalence, age, site and stage of presentation of gynaecological cancers at Nuclear Institute of Medicine and Radiotherapy (NIMRA), Jamshoro. Methods: A retrospective, cross sectional study was conducted from 1st January 2011 to 31st December 2011 at NIMRA Jamshoro. All cases of genital tract cancers were evaluated, required data was entered on predesigned performa and results were analyzed manually. Results: Out of 2401 total registered cancer cases, 231 (9.6%) patients were suffering from gynaecological cancer making it third most common cancer. Ovary was commonest site followed by cervix and uterus. More than 60% cases presented in advanced stage, mostly during 4th and 5th decade of life. Conclusion: Gynecological cancer was among top three cancers at one of the busiest public sector cancer institute in Sindh province and significant number presented in advance stage making treatment difficult and expensive. There is urgent need for development and implementation of an effective health policy regarding cancer prevention and treatment. PMID:27022358

  15. Advanced Parkinson's disease effect on goal-directed and habitual processes involved in visuomotor associative learning

    PubMed Central

    Hadj-Bouziane, Fadila; Benatru, Isabelle; Brovelli, Andrea; Klinger, Hélène; Thobois, Stéphane; Broussolle, Emmanuel; Boussaoud, Driss; Meunier, Martine

    2013-01-01

    The present behavioral study re-addresses the question of habit learning in Parkinson's disease (PD). Patients were early onset, non-demented, dopa-responsive, candidates for surgical treatment, similar to those we found earlier as suffering greater dopamine depletion in the putamen than in the caudate nucleus. The task was the same conditional associative learning task as that used previously in monkeys and healthy humans to unveil the striatum involvement in habit learning. Sixteen patients and 20 age- and education-matched healthy control subjects learned sets of 3 visuo-motor associations between complex patterns and joystick displacements during two testing sessions separated by a few hours. We distinguished errors preceding vs. following the first correct response to compare patients' performance during the earliest phase of learning dominated by goal-directed actions with that observed later on, when responses start to become habitual. The disease significantly retarded both learning phases, especially in patients under 60 years of age. However, only the late phase deficit was disease severity-dependent and persisted on the second testing session. These findings provide the first corroboration in Parkinson patients of two ideas well-established in the animal literature. The first is the idea that associating visual stimuli to motor acts is a form of habit learning that engages the striatum. It is confirmed here by the global impairment in visuo-motor learning induced by PD. The second idea is that goal-directed behaviors are predominantly caudate-dependent whereas habitual responses are primarily putamen-dependent. At the advanced PD stages tested here, dopamine depletion is greater in the putamen than in the caudate nucleus. Accordingly, the late phase of learning corresponding to the emergence of habitual responses was more vulnerable to the disease than the early phase dominated by goal-directed actions. PMID:23386815

  16. Advances of molecular imaging probes for the diagnosis of Alzheimer's disease.

    PubMed

    Zhou, Ming; Wang, Xiaobo; Liu, Zhiguo; Yu, Lun; Hu, Shuo; Chen, Lizhang; Zeng, Wenbin

    2014-03-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in multiple cognitive domains and it becomes the most common cause of dementia in the elderly. There is an urgent need for the early diagnosis and treatment of AD to ease caregiver burden and medical costs, as well as improve patients' living activities associated with the dramatic increasing number of affected individuals. Molecular imaging with target-specific probes is contributing to identify the underlying biology in AD, which benefits to the early diagnosis of AD and the evaluation of anti-AD therapy. Molecular imaging probes, such as (11)C-PIB, (11)C-MP4A, (18)F-AV-45, and (11)F-FDG, can selectively bind to special bimolecular of AD or accurately accumulate at the location of damage areas, thus become an edge tool for a better management of the diseases in the clinical practice and new drug development. In the past decades, a large variety of probes is being developed and tested to be useful for the early and accurate diagnosis of Alzheimer's disease, patient selection for disease-modifying therapeutic trials and monitoring the effect of anti-amyloid therapy. Since imaging probes may also help to guide physicians to identify those patients that could best benefit from a given therapeutic regimen, dose, or duration of drug, this paper is to present a perspective of the available imaging probes for AD, classified on different modalities. Meanwhile, recent advances of those probes that have been selected for clinical trials and are at the different stages of the US Food and Drugs Administration (FDA) approval are outlined. Additionally, future directions and specific application of imaging strategies designed for both diagnosis and treatment for AD are discussed. PMID:24484277

  17. [Treatment of pain in advanced-stage intra-abdominal neoplasms].

    PubMed

    Polati, E; Finco, G; Rigo, V; Gottin, L; Pinaroli, A M; Iacono, C; Mangiante, G; Serio, G; Ischia, S

    1993-01-01

    Different types of pain are present in far advanced intra-abdominal cancer, sometimes in the same site too. An accurate semeiological analysis of pain is important because different types of pain often differently respond to the available therapeutical tools. In this paper the results and the complications of the most important methods of pain management in far advanced intra-abdominal cancer are examined. Analysis of the data reveals that the association of more methods, pharmacological and non, should be a rule rather than the exception. PMID:7923502

  18. Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets

    PubMed Central

    Ramji, Dipak P.; Davies, Thomas S.

    2015-01-01

    Atherosclerosis, a chronic inflammatory disorder of the arteries, is responsible for most deaths in westernized societies with numbers increasing at a marked rate in developing countries. The disease is initiated by the activation of the endothelium by various risk factors leading to chemokine-mediated recruitment of immune cells. The uptake of modified lipoproteins by macrophages along with defective cholesterol efflux gives rise to foam cells associated with the fatty streak in the early phase of the disease. As the disease progresses, complex fibrotic plaques are produced as a result of lysis of foam cells, migration and proliferation of vascular smooth muscle cells and continued inflammatory response. Such plaques are stabilized by the extracellular matrix produced by smooth muscle cells and destabilized by matrix metalloproteinase from macrophages. Rupture of unstable plaques and subsequent thrombosis leads to clinical complications such as myocardial infarction. Cytokines are involved in all stages of atherosclerosis and have a profound influence on the pathogenesis of this disease. This review will describe our current understanding of the roles of different cytokines in atherosclerosis together with therapeutic approaches aimed at manipulating their actions. PMID:26005197

  19. Genetics, Environment, and Diabetes-Related End-Stage Renal Disease in the Canary Islands

    PubMed Central

    González, Ana M.; Maceira, Benito M.; Pérez, Estefanía; Cabrera, Vicente M.; López, Alfonso J.

    2012-01-01

    Aims: Type 1 and type 2 diabetes, complicated with renal disease, have a significantly higher incidence in the Canary Islands than in mainland Spain and other European countries. Present-day Canarian inhabitants consist of a mixed population with North African indigenous and European colonizer ancestors who have rapidly evolved from a rural to an urban life style. The aim of this work was to assess the possible role of genetic and environmental factors on diabetes-related end-stage renal disease incidence in the Canary Islands. Results: For both types of diabetes there is an ethnic susceptibility increased by diabetes family history. Whereas the Y-chromosome does not play a significant role, mitochondrial DNA (mtDNA) haplogroup differences point to a maternal origin for this ethnic predisposition, confirming susceptible and protective effects for haplogroups J and T, respectively. In addition, urban life style seems to be an additional risk factor for type 1 diabetes. Conclusions: The maternal ethnic predisposition to diabetes complicated with kidney disease detected in the Canary Islands signals mtDNA and X-chromosome markers as the best candidates to uncover the genetic predisposition to this disease. PMID:22480375

  20. Current advances on genetic resistance to rice blast disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rice blast disease caused by the fungal pathogen Magnaporthe oryzae is one of the most threatening fungal diseases resulting in significant annual crop losses worldwide. Blast disease has been effectively managed by a combination of resistant (R) gene deployment, application of fungicides, and suita...

  1. Visual perception in prediagnostic and early stage Huntington’s disease

    PubMed Central

    O’DONNELL, BRIAN F.; BLEKHER, TANYA M.; WEAVER, MARJORIE; WHITE, KERRY M.; MARSHALL, JEANINE; BERISTAIN, XABIER; STOUT, JULIE C.; GRAY, JACQUELINE; WOJCIESZEK, JOANNE M.; FOROUD, TATIANA M.

    2009-01-01

    Disturbances of visual perception frequently accompany neurodegenerative disorders but have been little studied in Huntington’s disease (HD) gene carriers. We used psychophysical tests to assess visual perception among individuals in the prediagnostic and early stages of HD. The sample comprised four groups, which included 201 nongene carriers (NG), 32 prediagnostic gene carriers with minimal neurological abnormalities (PD1); 20 prediagnostic gene carriers with moderate neurological abnormalities (PD2), and 36 gene carriers with diagnosed HD. Contrast sensitivity for stationary and moving sinusoidal gratings, and tests of form and motion discrimination, were used to probe different visual pathways. Patients with HD showed impaired contrast sensitivity for moving gratings. For one of the three contrast sensitivity tests, the prediagnostic gene carriers with greater neurological abnormality (PD2) also had impaired performance as compared with NG. These findings suggest that early stage HD disrupts visual functions associated with the magnocellular pathway. However, these changes are only observed in individuals diagnosed with HD or who are in the more symptomatic stages of prediagnostic HD. PMID:18419843

  2. A metabolomics-based approach for predicting stages of chronic kidney disease.

    PubMed

    Kobayashi, Toshihiro; Yoshida, Tatsunari; Fujisawa, Tatsuya; Matsumura, Yuriko; Ozawa, Toshihiko; Yanai, Hiroyuki; Iwasawa, Atsuo; Kamachi, Toshiaki; Fujiwara, Kouichi; Kohno, Masahiro; Tanaka, Noriaki

    2014-03-01

    Chronic kidney disease (CKD) is a major epidemiologic problem and a risk factor for cardiovascular events and cerebrovascular accidents. Because CKD shows irreversible progression, early diagnosis is desirable. Renal function can be evaluated by measuring creatinine-based estimated glomerular filtration rate (eGFR). This method, however, has low sensitivity during early phases of CKD. Cystatin C (CysC) may be a more sensitive predictor. Using a metabolomic method, we previously identified metabolites in CKD and hemodialysis patients. To develop a new index of renal hypofunction, plasma samples were collected from volunteers with and without CKD and metabolite concentrations were assayed by quantitative liquid chromatography/mass spectrometry. These results were used to construct a multivariate regression equation for an inverse of CysC-based eGFR, with eGFR and CKD stage calculated from concentrations of blood metabolites. This equation was able to predict CKD stages with 81.3% accuracy (range, 73.9-87.0% during 20 repeats). This procedure may become a novel method of identifying patients with early-stage CKD. PMID:24530913

  3. [Working memory for music in patients with mild cognitive impairment and early stage Alzheimer's disease].

    PubMed

    Kerer, Manuela; Marksteiner, Josef; Hinterhuber, Hartmann; Mazzola, Guerino; Kemmler, Georg; Bliem, Harald R; Weiss, Elisabeth M

    2013-01-01

    A variety of studies demonstrated that some forms of memory for music are spared in dementia, but only few studies have investigated patients with early stages of dementia. In this pilot-study we tested working memory for music in patients with mild cognitive impairment (MCI) and early stage Alzheimer's disease (AD) with a newly created test. The test probed working memory using 7 gradually elongated tone-lines and 6 chords which were each followed by 3 similar items and 1 identical item. The participants of the study, namely 10 patients with MCI, 10 patients with early stage AD and 23 healthy subjects were instructed to select the identical tone-line or chord. Subjects with MCI and early AD showed significantly reduced performance than controls in most of the presented tasks. In recognizing chords MCI- participants surprisingly showed an unimpaired performance. The gradual increase of the impairment during the preclinical phase of AD seems to spare this special ability in MCI. PMID:23329298

  4. First Human Treatment With Investigational rhGUS Enzyme Replacement Therapy in an Advanced Stage MPS VII Patient

    PubMed Central

    Fox, Joyce E; Volpe, Linda; Bullaro, Josephine; Kakkis, Emil D; Sly, William S

    2015-01-01

    Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is a very rare lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase (GUS), which is required for the degradation of three glycosaminoglycans (GAGs): dermatan sulfate, heparan sulfate and chondroitin sulfate. Progressive accumulation of these GAGs in lysosomes leads to increasing dysfunction in numerous tissues and organs. Enzyme replacement therapy (ERT) has been used successfully for other MPS disorders, but there is no approved treatment for MPS VII. Here we describe the first human treatment with recombinant human GUS (rhGUS), an investigational therapy for MPS VII, in a 12-year old boy with advanced stage MPS VII. Despite a tracheostomy, nocturnal continuous positive airway pressure, and oxygen therapy, significant pulmonary restriction and obstruction led to oxygen dependence and end-tidal carbon dioxide (ETCO2) levels in the 60-80 mmHg range, eventually approaching respiratory failure (ETCO2 of 100 mmHg) and the need for full-time ventilation. Since no additional medical measures could improve his function, we implemented experimental ERT by infusing rhGUS at 2 mg/kg over 4 hours every 2 weeks for 24 weeks. Safety was evaluated by standard assessments and observance for any infusion associated reactions (IARs). Urinary GAG (uGAG) levels, pulmonary function, oxygen dependence, CO2 levels, cardiac valve function, liver and spleen size, and growth velocity were assessed to evaluate response to therapy. rhGUS infusions were well tolerated. No serious adverse events (SAEs) or IARs were observed. After initiation of rhGUS infusions, the patient's uGAG excretion decreased by more than 50%. Liver and spleen size were reduced within 2 weeks of the first infusion and reached normal size by 24 weeks. Pulmonary function appeared to improve during the course of treatment based on reduced changes in ETCO2 after off-ventilator challenges and a reduced oxygen requirement. The patient regained

  5. First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient.

    PubMed

    Fox, Joyce E; Volpe, Linda; Bullaro, Josephine; Kakkis, Emil D; Sly, William S

    2015-02-01

    Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is a very rare lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase (GUS), which is required for the degradation of three glycosaminoglycans (GAGs): dermatan sulfate, heparan sulfate, and chondroitin sulfate. Progressive accumulation of these GAGs in lysosomes leads to increasing dysfunction in numerous tissues and organs. Enzyme replacement therapy (ERT) has been used successfully for other MPS disorders, but there is no approved treatment for MPS VII. Here we describe the first human treatment with recombinant human GUS (rhGUS), an investigational therapy for MPS VII, in a 12-year old boy with advanced stage MPS VII. Despite a tracheostomy, nocturnal continuous positive airway pressure, and oxygen therapy, significant pulmonary restriction and obstruction led to oxygen dependence and end-tidal carbon dioxide (ETCO2) levels in the 60-80mmHg range, eventually approaching respiratory failure (ETCO2 of 100mmHg) and the need for full-time ventilation. Since no additional medical measures could improve his function, we implemented experimental ERT by infusing rhGUS at 2mg/kg over 4h every 2 weeks for 24 weeks. Safety was evaluated by standard assessments and observance for any infusion associated reactions (IARs). Urinary GAG (uGAG) levels, pulmonary function, oxygen dependence, CO2 levels, cardiac valve function, liver and spleen size, and growth velocity were assessed to evaluate response to therapy. rhGUS infusions were well tolerated. No serious adverse events (SAEs) or IARs were observed. After initiation of rhGUS infusions, the patient's uGAG excretion decreased by more than 50%. Liver and spleen size were reduced within 2 weeks of the first infusion and reached normal size by 24 weeks. Pulmonary function appeared to improve during the course of treatment based on reduced changes in ETCO2 after off-ventilator challenges and a reduced oxygen requirement. The patient regained the

  6. Assessing the outcome of rehabilitation in patients with end-stage renal disease.

    PubMed

    Porter, G A

    1994-07-01

    Assessing the rehabilitative/restorative process requires the definition of desired outcome. Traditionally, medicine has defined the desired outcome of treatment as curing disease. End-stage renal disease (ESRD) cannot be cured by applying current biotechnology. Thus, to assess treatment interventions in patients with ESRD, the desired outcome must be expanded to incorporate the broader components of health, which include physical, mental, and social well-being or quality of life. Based on this expanded definition of health, desirable treatment outcomes in patients with ESRD include employment of those able to work, individual control over the effects of kidney disease and dialysis, enhanced fitness, improved communications with caregivers and family, improved compliance with the dialysis regimen, and resumption of many activities enjoyed before the initiation of dialysis. Broadening the definition of desired outcome requires new measurement techniques. Measurement instruments for health status must evaluate fixed disease, which imposes certain limits on expected outcome; mutable health status, which represents the focus of intervention; and factors unrelated to healthcare, which will modify the scope of intervention that can be prescribed. Health-care status involves both self-reported evaluation and physical assessment. The reporting forms should be comprehensive, convenient, controlled, and valid. Such forms can be targeted to gain information about the natural evolution of a disease or disability process, to evaluate the effectiveness of treatment or other intervention on altering the disease or disability outcome, and to measure the quality of care. Two examples of the application of health status assessment will be reviewed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8023836

  7. Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease

    PubMed Central

    An, Chansik; Choi, Youn Ah; Choi, Dongil; Paik, Yong Han; Ahn, Sang Hoon; Kim, Myeong-Jin; Paik, Seung Woon; Han, Kwang-Hyub

    2015-01-01

    Background/Aims The goal of this study was to estimate the growth rate of hepatocellular carcinoma (HCC) and identify the host factors that significantly affect this rate. Methods Patients with early-stage HCC (n=175) who underwent two or more serial dynamic imaging studies without any anticancer treatment at two tertiary care hospitals in Korea were identified. For each patient, the tumor volume doubling time (TVDT) of HCC was calculated by comparing tumor volumes between serial imaging studies. Clinical and laboratory data were obtained from the medical records of the patients. Results The median TVDT was 85.7 days, with a range of 11 to 851.2 days. Multiple linear regression revealed that the initial tumor diameter (a tumor factor) and the etiology of chronic liver disease (a host factor) were significantly associated with the TVDT. The TVDT was shorter when the initial tumor diameter was smaller, and was shorter in HCC related to hepatitis B virus (HBV) infection than in HCC related to hepatitis C virus (HCV) infection (median, 76.8 days vs. 137.2 days; P=0.0234). Conclusions The etiology of chronic liver disease is a host factor that may significantly affect the growth rate of early-stage HCC, since HBV-associated HCC grows faster than HCV-associated HCC. PMID:26523271

  8. Pilot study of modified LMB-based therapy for children with ataxia-telangiectasia and advanced stage high grade mature b-cell malignancies

    PubMed Central

    Sandlund, J. T.; Hudson, M. M.; Kennedy, W.; Onciu, M.; Kastan, M. B.

    2014-01-01

    Children with ataxia-telangiectasia (A-T) and cancer have a poorer prognosis due in part to increased treatment-related toxicity. We piloted a curative intent approach in five children with A-T who presented with advanced stage (III, n=2; IV, n=3) B-NHL (diffuse large B-cell lymphoma, n=4; Burkitt leukemia, n=1) using a modified LMB-based protocol. Two achieved sustained CCR (one, CCR at 6 years; one, pulmonary death after 3 years in CCR). Two died from toxicity during induction and 1 failed induction with progressive disease. Novel therapeutic approaches which overcome drug resistance and are less toxic are needed for children with A-T and B-NHL. PMID:23900766

  9. Impact of Pretreatment Combined {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Staging on Radiation Therapy Treatment Decisions in Locally Advanced Breast Cancer

    SciTech Connect

    Ng, Sweet Ping; David, Steven; Alamgeer, Muhammad; Ganju, Vinod

    2015-09-01

    Purpose: To assess the diagnostic performance of pretreatment {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) and its impact on radiation therapy treatment decisions in patients with locally advanced breast cancer (LABC). Methods and Materials: Patients with LABC with Eastern Cooperative Oncology Group performance status <2 and no contraindication to neoadjuvant chemotherapy, surgery, and adjuvant radiation therapy were enrolled on a prospective trial. All patients had pretreatment conventional imaging (CI) performed, including bilateral breast mammography and ultrasound, bone scan, and CT chest, abdomen, and pelvis scans performed. Informed consent was obtained before enrolment. Pretreatment whole-body {sup 18}F-FDG PET/CT scans were performed on all patients, and results were compared with CI findings. Results: A total of 154 patients with LABC with no clinical or radiologic evidence of distant metastases on CI were enrolled. Median age was 49 years (range, 26-70 years). Imaging with PET/CT detected distant metastatic disease and/or locoregional disease not visualized on CI in 32 patients (20.8%). Distant metastatic disease was detected in 17 patients (11.0%): 6 had bony metastases, 5 had intrathoracic metastases (pulmonary/mediastinal), 2 had distant nodal metastases, 2 had liver metastases, 1 had pulmonary and bony metastases, and 1 had mediastinal and distant nodal metastases. Of the remaining 139 patients, nodal disease outside conventional radiation therapy fields was detected on PET/CT in 15 patients (10.8%), with involvement of ipsilateral internal mammary nodes in 13 and ipsilateral level 5 cervical nodes in 2. Conclusions: Imaging with PET/CT provides superior diagnostic and staging information in patients with LABC compared with CI, which has significant therapeutic implications with respect to radiation therapy management. Imaging with PET/CT should be considered in all patients undergoing primary

  10. Molecular Classification of Endometriosis and Disease Stage Using High-Dimensional Genomic Data

    PubMed Central

    Tamaresis, John S.; Irwin, Juan C.; Goldfien, Gabriel A.; Rabban, Joseph T.; Burney, Richard O.; Nezhat, Camran; DePaolo, Louis V.

    2014-01-01

    Endometriosis (E), an estrogen-dependent, progesterone-resistant, inflammatory disorder, affects 10% of reproductive-age women. It is diagnosed and staged at surgery, resulting in an 11-year latency from symptom onset to diagnosis, underscoring the need for less invasive, less expensive approaches. Because the uterine lining (endometrium) in women with E has altered molecular profiles, we tested whether molecular classification of this tissue can distinguish and stage disease. We developed classifiers using genomic data from n = 148 archived endometrial samples from women with E or without E (normal controls or with other common uterine/pelvic pathologies) across the menstrual cycle and evaluated their performance on independent sample sets. Classifiers were trained separately on samples in specific hormonal milieu, using margin tree classification, and accuracies were scored on independent validation samples. Classification of samples from women with E or no E involved 2 binary decisions, each based on expression of specific genes. These first distinguished presence or absence of uterine/pelvic pathology and then no E from E, with the latter further classified according to severity (minimal/mild or moderate/severe). Best performing classifiers identified E with 90%–100% accuracy, were cycle phase-specific or independent, and used relatively few genes to determine disease and severity. Differential gene expression and pathway analyses revealed immune activation, altered steroid and thyroid hormone signaling/metabolism, and growth factor signaling in endometrium of women with E. Similar findings were observed with other disorders vs controls. Thus, classifier analysis of genomic data from endometrium can detect and stage pelvic E with high accuracy, dependent or independent of hormonal milieu. We propose that limited classifier candidate genes are of high value in developing diagnostics and identifying therapeutic targets. Discovery of endometrial molecular

  11. Central pontine myelinolysis in advanced HIV infection with tuberculosis and multicentric Castleman's disease.

    PubMed

    Katchanov, J; Branding, G; Stocker, H

    2013-07-01

    We present a case of central pontine myelinolysis (CPM) in a patient with advanced HIV infection and miliary tuberculosis. While hospitalized the patient developed an unusual ataxic variant of CPM with full clinical recovery. Follow-up imaging revealed resolution of pontine lesions. To our knowledge, this is the first report of a clinical and radiological recovery from CPM in advanced HIV disease. Our report extends our knowledge of neurological presentations in patients with advanced HIV infection. It highlights the importance of considering CPM in patients with advanced HIV disease presenting with an ataxic syndrome, even in the absence of an electrolyte derangement. PMID:23970776

  12. Bardoxolone Methyl in Type 2 Diabetes and Stage 4 Chronic Kidney Disease

    PubMed Central

    de Zeeuw, Dick; Akizawa, Tadao; Audhya, Paul; Bakris, George L.; Chin, Melanie; Christ-Schmidt, Heidi; Goldsberry, Angie; Houser, Mark; Krauth, Melissa; Heerspink, Hiddo J. Lambers; McMurray, John J.; Meyer, Colin J.; Parving, Hans-Henrik; Remuzzi, Giuseppe; Toto, Robert D.; Vaziri, Nosratola D.; Wanner, Christoph; Wittes, Janet; Wrolstad, Danielle; Chertow, Glenn M.

    2015-01-01

    BACKGROUND Although inhibitors of the renin–angiotensin–aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)–related factor 2 activators further reduce this risk is unknown. METHODS We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 to <30 ml per minute per 1.73 m2 of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes. RESULTS The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6%) randomly assigned to bardoxolone methyl and 69 of 1097 (6%) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95% confidence interval [CI], 0.70 to 1.37; P = 0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95% CI, 1.32 to 2.55; P<0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group. CONCLUSIONS Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl

  13. Verbal Play as an Interactional Discourse Resource in Early Stage Alzheimer’s Disease

    PubMed Central

    Shune, Samantha; Duff, Melissa C.

    2012-01-01

    Background Verbal play, the creative and playful use of language to make puns, rhyme words, and tease, is a pervasive and enjoyable component of social communication and serves important interpersonal functions. The current study examines the use of verbal play in the communicative interactions of individuals with Alzheimer’s disease as part of a broader program of research on language-and-memory-in-use. Aims To document the frequency of verbal play in the communicative interactions of individuals with very mild Alzheimer’s disease (AD) and their familiar communication partners. To characterize the interactional forms, resources, and functions of playful episodes. Methods Using quantitative group comparisons and detailed discourse analysis, we analyzed verbal play in the interactional discourse of five participants with very mild AD and five healthy (demographically matched) comparison participants. Each participant interacted with a familiar partner while completing a collaborative referencing task, and with a researcher between task trials. Results A total of 1,098 verbal play episodes were coded. Despite being in the early stages of AD, all the AD participants used verbal play. There were no significant group differences in the frequency of verbal play episodes or in the interactional forms, resources, or functions of those playful episodes between AD and healthy comparison pair sessions. Conclusions The successful use of verbal play in the interactions of individuals with very mild AD and their partners highlights an area of preserved social communication. These findings represent an important step, both clinically and for research, in documenting the rich ways that individuals with early stage AD orchestrate interactionally meaningful communication with their partners through the use of interactional discourse resources like verbal play. This work also offers a promising clinical tool for tracking and targeting verbal play across disease progression. PMID

  14. Two stage low noise advanced technology fan. 1: Aerodynamic, structural, and acoustic design

    NASA Technical Reports Server (NTRS)

    Messenger, H. E.; Ruschak, J. T.; Sofrin, T. G.

    1974-01-01

    A two-stage fan was designed to reduce noise 20 db below current requirements. The first-stage rotor has a design tip speed of 365.8 m/sec and a hub/tip ratio of 0.4. The fan was designed to deliver a pressure ratio of 1.9 with an adiabatic efficiency of 85.3 percent at a specific inlet corrected flow of 209.2kg/sec/sq m. Noise reduction devices include acoustically treated casing walls, a flowpath exit acoustic splitter, a translating centerbody sonic inlet device, widely spaced blade rows, and the proper ratio of blades and vanes. Multiple-circular-arc rotor airfoils, resettable stators, split outer casings, and capability to go to close blade-row spacing are also included.

  15. Expression of caveolin-1 is correlated with disease stage and survival in lung adenocarcinomas.

    PubMed

    Zhan, Ping; Shen, Xiao-Kun; Qian, Qian; Wang, Qin; Zhu, Ji-Ping; Zhang, Yu; Xie, Hai-Yan; Xu, Chuen-Hua; Hao, Ke-Ke; Hu, Wei; Xia, Ning; Lu, Guo-Jun; Yu, Li-Ke

    2012-04-01

    Caveolin-1 (cav-1) has been implicated in the development of human cancers. However, the distribution of cav-1 in non-small cell lung cancer (NSCLC) and its significance require further study. Real-time PCR and Western blot assays were performed to detect cav-1 mRNA and protein levels in tumor tissues (TT) and matched tumor-free tissues (TF). The protein expression in 115 paraffin-embedded blocks was examined by immunohistochemical staining (IHC). Correlations between cav-1 mRNA and protein expression by IHC and clinicopathological features were statistically evaluated. For the 136 patients examined, the levels of cav-1 mRNA and protein expression were significantly lower in lung TT compared to matched TF (P<0.05). High cav-1 expression was detected in 60 of 115 (52.2%) NSCLC tissues and this level was significantly lower than cav-1 expression in non-cancerous lung tissues (15 of 19, 78.9%, P<0.05). Up-regulation of cav-1 mRNA expression in lung adenocarcinoma (AC) (29.7%) was higher than that observed in lung squamous cell carcinoma (SCC) (15.8%). Statistical analysis of the correlation between cav-1 protein expression and clinical features showed a statistical association with poorer N-stage (P=0.032) and higher pathological TNM stage (P=0.012) in lung AC patients, that was not found in lung SCC patients. Moreover, lung AC patients with higher cav-1 expression showed significantly shorter life-spans than those with lower cav-1 expression (P=0.032, log-rank test). The levels of cav-1 mRNA and protein expression were significantly lower in lung cancers when compared to matched TF or non-cancerous lung tissues. The higher protein expression correlated with the advanced pathological stage and shorter survival rates in lung AC patients. PMID:22200856

  16. What is the correct staging and treatment strategy for locally advanced prostate cancer extending to the bladder?

    PubMed

    Yüksel, Özgür Haki; Verit, Ayhan; Ürkmez, Ahmet

    2015-06-01

    In locally advanced prostate cancer with bladder invasion, frequently encountered problems such as bleeding, urinary retention, hydronephrosis, and pain create distress for the patients. Therefore patients' quality of life is disrupted and duration of hospitalization is prolonged. Relevant literature about accurate staging and treatment of locally advanced prostate cancer with bladder invasion was investigated. Locally advanced prostate cancer can present as a large-volume aggressive tumor extending beyond boundaries of prostate gland, and involving neighboring structures which can be involved as recurrence(s) following initial local therapy. Survival times of these patients can range between 5 and 8 years. Their common characteristics are adverse and severe local symptoms unfavorably affecting quality of life Control of local symptoms and their effective palliation are independent clinical targets influencing survival outcomes of these patients. The treatment outcomes of locally advanced prostate cancer into the bladder are currently debatable. Although in the current TNM classification, it is defined in T4a, we think that this may be categorized as a subgroup of T3 and thus encourage surgeons for the indication of radical surgeries (radical prostatectomy, radical cystoprostatectomy) in selected patient populations after discussing issues concerning consequences of the treatment alternatives, and expectations with the patients. Cystoprostatectomy followed by immediate androgen deprivation therapy may be a feasible option for selected patients with previously untreated prostate cancer involving the bladder neck because of excellent local control and long term survival. PMID:26150029

  17. 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

  18. 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

  19. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure for hepatocellular carcinoma with chronic liver disease: a case report and review of literature.

    PubMed

    Papamichail, Michail; Pizanias, Michail; Yip, Vincent; Prassas, Evangellos; Prachalias, Andreas; Quaglia, Alberto; Peddu, Praveen; Heaton, Nigel; Srinivasan, Parthi

    2016-05-01

    The incidence of complications after liver resection is closely related to functional future liver remnant (FLR). The standard approach to augment FLR is surgical or radiological occlusion of the artery or portal vein on the tumor side. Associated liver partition and portal vein ligation for staged hepatectomy (ALLPS) has been introduced as an alternative method to augment FLR. It offers rapid and effective hypertrophy for resecting liver metastases. However, data regarding its application in patients with hepatocellular carcinoma (HCC) with a background of chronic liver disease are limited. Here we describe the use of ALPPS procedure to manage a large solitary HCC with a background of chronic liver disease. The rising incidence of HCC has increased the number of surgical resections in patients with advanced stage liver disease not considered for liver transplantation. We reviewed reported experience of ALPPS in established chronic liver disease and current therapeutic modalities for HCC on a background of chronic liver disease in patients with potential liver insufficiency where tumor burden is beyond liver transplant criteria. PMID:27212995

  20. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure for hepatocellular carcinoma with chronic liver disease: a case report and review of literature

    PubMed Central

    Pizanias, Michail; Yip, Vincent; Prassas, Evangellos; Prachalias, Andreas; Quaglia, Alberto; Peddu, Praveen; Heaton, Nigel; Srinivasan, Parthi

    2016-01-01

    The incidence of complications after liver resection is closely related to functional future liver remnant (FLR). The standard approach to augment FLR is surgical or radiological occlusion of the artery or portal vein on the tumor side. Associated liver partition and portal vein ligation for staged hepatectomy (ALLPS) has been introduced as an alternative method to augment FLR. It offers rapid and effective hypertrophy for resecting liver metastases. However, data regarding its application in patients with hepatocellular carcinoma (HCC) with a background of chronic liver disease are limited. Here we describe the use of ALPPS procedure to manage a large solitary HCC with a background of chronic liver disease. The rising incidence of HCC has increased the number of surgical resections in patients with advanced stage liver disease not considered for liver transplantation. We reviewed reported experience of ALPPS in established chronic liver disease and current therapeutic modalities for HCC on a background of chronic liver disease in patients with potential liver insufficiency where tumor burden is beyond liver transplant criteria. PMID:27212995

  1. Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson’s Disease

    PubMed Central

    Claassen, Daniel O.; Dobolyi, David G.; Isaacs, David A.; Roman, Olivia C.; Herb, Joshua; Wylie, Scott A.; Neimat, Joseph S.; Donahue, Manus J.; Hedera, Peter; Zald, David H.; Landman, Bennett A.; Bowman, Aaron B.; Dawant, Benoit M.; Rane, Swati

    2016-01-01

    Advancing age and disease duration both contribute to cortical thinning in Parkinson’s disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson’s Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2nd, or 3rd order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning. PMID:27330836

  2. Technology requirements for advanced earth-orbital transportation systems: Summary report. [single stage to orbit vehicles

    NASA Technical Reports Server (NTRS)

    Haefeli, R. C.; Littler, E. G.; Hurley, J. B.; Winter, M. G.

    1977-01-01

    Areas of advanced technology that are either critical or offer significant benefits to the development of future Earth-orbit transportation systems were identified. Technology assessment was based on the application of these technologies to fully reusable, single-state-to-orbit (SSTO) vehicle concepts with horizontal landing capability. Study guidelines included mission requirements similar to space shuttle, an operational capability beginning in 1995, and main propulsion to be advanced hydrogen-fueled rocket engines. The technical and economic feasibility of this class of SSTO concepts were evaluated as well as the comparative features of three operational take-off modes, which were vertical boost, horizontal sled launch, and horizontal take-off with subsequent inflight fueling. Projections of both normal and accelerated technology growth were made. Figures of merit were derived to provide relative rankings of technology areas. The influence of selected accelerated areas on vehicle design and program costs was analyzed by developing near-optimum point designs.

  3. Relative risks of Chronic Kidney Disease for mortality and End Stage Renal Disease across races is similar

    PubMed Central

    Wen, Chi-Pang; Matsushita, Kunihiro; Coresh, Josef; Iseki, Kunitoshi; Islam, Muhammad; Katz, Ronit; McClellan, William; Peralta, Carmen A; Wang, HaiYan; de Zeeuw, Dick; Astor, Brad C; Gansevoort, Ron T; Levey, Andrew S; Levin, Adeera

    2014-01-01

    Some suggest race-specific cutpoints for kidney measures to define and stage chronic kidney disease (CKD), but evidence for race-specific clinical impact is limited. To address this issue, we compared hazard ratios of estimated glomerular filtration rates (eGFR) and albuminuria across races using meta-regression in 1.1 million adults (75% Asians, 21% whites, and 4% blacks) from 45 cohorts. Results came mainly from 25 general population cohorts comprising 0.9 million individuals. The associations of lower eGFR and higher albuminuria with mortality and end-stage renal disease (ESRD) were largely similar across races. For example, in Asians, whites, and blacks, the adjusted hazard ratios (95% confidence interval) for eGFR 45–59 vs. 90–104 ml/min/1.73m2 were 1.3 (1.2–1.3), 1.1 (1.0–1.2) and 1.3 (1.1–1.7) for all-cause mortality, 1.6 (1.5–1.8), 1.4 (1.2–1.7), and 1.4 (0.7–2.9) for cardiovascular mortality, and 27.6 (11.1–68.7), 11.2 (6.0–20.9), and 4.1 (2.2–7.5) for ESRD, respectively. The corresponding hazard ratios for urine albumin-to-creatinine ratio 30–299 mg/g or dipstick 1-positive vs. an albumin-to-creatinine ratio under 10 or dipstick negative were 1.6 (1.4–1.8), 1.7 (1.5–1.9) and 1.8 (1.7–2.1) for all-cause mortality, 1.7 (1.4–2.0), 1.8 (1.5–2.1), and 2.8 (2.2–3.6) for cardiovascular mortality, and 7.4 (2.0–27.6), 4.0 (2.8–5.9), and 5.6 (3.4–9.2) for ESRD, respectively. Thus, the relative mortality or ESRD risks of lower eGFR and higher albuminuria were largely similar among three major races, supporting similar clinical approach to CKD definition and staging, across races. PMID:24522492

  4. Urinary ferritin and cystatin C concentrations at different stages of kidney disease in leishmaniotic dogs.

    PubMed

    García-Martínez, J D; Martinez-Subiela, S; Tvarijonaviciute, A; Caldin, M; Ceron, J J

    2015-04-01

    Traditional analytes do not detect early renal disease; therefore there is a need to find new early markers of chronic kidney disease (CKD) in dogs to avoid the progression to irreversible renal damage. Our objective was to evaluate the presence of ferritin and cystatin C in urine of dogs with CKD and to relate their concentrations with the severity of the disease. Samples obtained from dogs naturally infected with Leishmania infantum were classified into four groups on the basis of the results of urinary protein/creatinine ratio and serum creatinine. This study shows that ferritin and cystatin C concentrations were increased in the urine of dogs with renal damage. Cystatin C value in urine only increased in severe stages of CKD with serum creatinine values >1.4 mg/dL, while the urinary ferritin concentration increased in dogs with proteinuria and serum creatinine <1.4 mg/dL, being, therefore, a renal biomarker earlier than creatinemia. PMID:25639693

  5. Subsets of a Large Cognitive Battery Better Power Clinical Trials on Early Stage Alzheimer Disease

    PubMed Central

    Xiong, Chengjie; Weng, Hua; Bennett, David A.; Boyle, Patricia A.; Shah, Raj C.; Fague, Scot; Hall, Charles B.; Lipton, Richard B.; Morris, John C.

    2014-01-01

    Background/Aims Cognitive batteries routinely used by the Alzheimer disease (AD) research community may contain items uninformative for tracking disease progression to power clinical trials on early stage AD. We aim to identify subsets of the most informative items from an existing cognitive battery for better powering clinical trials on early AD. Methods Longitudinal change in item scores from the battery was associated with the onset of Mild Cognitive Impairment (MCI) in 1513 elderly individuals. Items whose longitudinal changes were correlated with the onset of MCI were selected as informative for tracking the early cognitive progression. Results 226 items in the battery were annually assessed over a follow-up of up to 13 years. Changes of item scores over time from 187 items were significantly correlated with the onset of MCI. For clinical trials on preclinical AD and on MCI, informative items permit smaller or similar sample sizes as compared to the entire battery, whereas uninformative items require much larger sample sizes. Conclusions Longitudinal changes in item scores from about 17% of items in the cognitive battery are uninformative for tracking early disease progression. Clinical trials on early AD can be better powered using informative items rather than the entire battery. PMID:25376544

  6. Discrete epidemic models with arbitrary stage distributions and applications to disease control

    PubMed Central

    Hernandez-Ceron, Nancy; Feng, Zhilan; Castillo-Chavez, Carlos

    2014-01-01

    W. O. Kermack and A. G. McKendrick introduced in their fundamental paper, A Contribution to the Mathematical Theory of Epidemics, published in 1927, a simple deterministic model that captured the qualitative dynamic behavior of single infectious disease outbreaks. A Kermack-McKendrick discrete-time general framework, motivated by the emergence of a multitude of models used to forecast the dynamics of SARS and influenza outbreaks, is introduced in this manuscript. Results that allow us to measure quantitatively the role of classical and general distributions on disease dynamics are presented. The case of the geometric distribution is used to evaluate the impact of waiting-time distributions on epidemiological processes or public health interventions. In short, the geometric distribution is used to set up the baseline or null epidemiological model used to test the relevance of realistic stage-period distribution on the dynamics of single epidemic outbreaks. A final size relationship involving the control reproduction number, a function of transmission parameters and the means of distributions used to model disease or intervention control measures, is computed. Model results and simulations highlight the inconsistencies in forecasting that emerge from the use of specific parametric distributions. Examples, using the geometric, Poisson and binomial distributions, are used to highlight the impact of the choices made in quantifying the risk posed by single outbreaks and the relative importance of various control measures. PMID:23797790

  7. Estimating the prevalence of multiple diseases from two-stage hierarchical pooling.

    PubMed

    Warasi, Md S; Tebbs, Joshua M; McMahan, Christopher S; Bilder, Christopher R

    2016-09-20

    Testing protocols in large-scale sexually transmitted disease screening applications often involve pooling biospecimens (e.g., blood, urine, and swabs) to lower costs and to increase the number of individuals who can be tested. With the recent development of assays that detect multiple diseases, it is now common to test biospecimen pools for multiple infections simultaneously. Recent work has developed an expectation-maximization algorithm to estimate the prevalence of two infections using a two-stage, Dorfman-type testing algorithm motivated by current screening practices for chlamydia and gonorrhea in the USA. In this article, we have the same goal but instead take a more flexible Bayesian approach. Doing so allows us to incorporate information about assay uncertainty during the testing process, which involves testing both pools and individuals, and also to update information as individuals are tested. Overall, our approach provides reliable inference for disease probabilities and accurately estimates assay sensitivity and specificity even when little or no information is provided in the prior distributions. We illustrate the performance of our estimation methods using simulation and by applying them to chlamydia and gonorrhea data collected in Nebraska. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27090057

  8. Cardiovascular complications in patients with end stage renal disease on maintenance haemodialysis.

    PubMed

    Sweety, S A; Arzu, J; Rahman, M; Salim, M A; Mahmood, M

    2014-04-01

    This cross-sectional study was carried out at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka Medical College Hospital (DMCH), National Institute of Kidney Diseases & Urology (NIKDU) and Kidney Foundation from July 2005 to June 2007 to find the cardiovascular complications in end stage renal disease (ESRD) patients on maintenance haemodialysis. Patients of both sexes with age ranging from 18-59 years and getting at least 8 hours of haemodialysis per week for the last 3 months were enrolled in the study. A total of 126 such patients were included in the study. Among 126 patients 77(61.1%) developed some types of cardiovascular complications. In terms of type of complications 63.6% of the patients had LVH, 23.4% had ischemic heart disease (IHD) and 10.4% had congestive heart failure (CCF) and 2.6% cardiomyopathy. Over 96% patients were hypertensive, followed by 46.8% diabetics and 42.1% smokers. Presence of hypertension, diabetes, family history of diabetes and hypertension were observed to be significantly higher in patients who developed cardiovascular complications (p<0.05). It is deserved that cardiovascular complications (CVC) are very common in ESRD patients on maintenance haemodialysis (MHD). Poor control of blood pressure, low Haemoglobin level and poor glycaemic control are higher in ESRD patients on MHD and are possibly related to the development of cardiovascular complications. PMID:24858162

  9. Depression and Frailty in Patients With End-Stage Liver Disease Referred for Transplant Evaluation.

    PubMed

    Cron, D C; Friedman, J F; Winder, G S; Thelen, A E; Derck, J E; Fakhoury, J W; Gerebics, A D; Englesbe, M J; Sonnenday, C J

    2016-06-01

    End-stage liver disease (ESLD) patients are believed to have a high prevalence of depression, although mental health in ESLD has not been studied comprehensively. Further, the relationship between depression and severity of liver disease is unclear. Using baseline data from a large prospective cohort study (N = 500) of frailty in ESLD patients, we studied the association of frailty with depression. Frailty was assessed with the five-component Fried Frailty Index. Patients were assigned a composite score of 0 to 5, with scores ≥3 considered frail. Depression was assessed using the 15-question Geriatric Depression Scale, with a threshold of ≥6 indicating depression; 43.2% of patients were frail and 39.4% of patients were depressed (median score 4, range 0-15). In multivariate analysis, frailty was significantly associated with depression (odds ratio 2.78, 95% confidence interval 1.87-4.15, p < 0.001), whereas model for ESLD score was not associated with depression. After covariate adjustment, depression prevalence was 3.6 times higher in the most-frail patients than the least-frail patients. In conclusion, depression is common in ESLD patients and is strongly associated with frailty but not with severity of liver disease. Transplant centers should address mental health issues and frailty; targeted interventions may lower the burden of mental illness in this population. PMID:26613640

  10. Cognitive rehabilitation for elderly people with early-stage Alzheimer’s disease

    PubMed Central

    Kim, Seyun

    2015-01-01

    [Purpose] The purpose of this study was to investigate the effect of cognitive rehabilitation including tasks of cognitive training on performance of everyday activities in elderly people with early-stage Alzheimer’s disease. [Subjects and Methods] Forty-three elderly people (15 men, 28 women) with a diagnosis of Alzheimer’s disease who had a Mini-Mental State Examination (MMSE) score of 18 or above were randomly assigned to two groups: the cognitive rehabilitation group (experimental) and control group. This study used a randomized controlled trial design. Cognitive rehabilitation is consisted of 8 sessions, each lasting 60 minutes (individual 30 min, group 30 min). The eight weekly individual sessions of cognitive rehabilitation were performed consisting of an individualized intervention focusing on a personally meaningful goal. The eight weekly group sessions involved practicing time-and-place orientation, matching faces and names, and learning memory and sustaining attention. [Results] Significant improvements were observed in rating of occupation performance and satisfaction, Quality of Life in Alzheimer’s Disease (QOL-AD), and the orientation subscale of the MMSE in the experimental group, whereas participants in the control group did not show any significant difference in any tests between before and after the intervention. [Conclusion] Cognitive rehabilitation including tasks of cognitive training is an effective intervention for improving performance and satisfaction with respect to activities of daily living and specific cognitive functions. PMID:25729212

  11. Brain Microstructural Abnormalities Are Related to Physiological Alterations in End-Stage Renal Disease

    PubMed Central

    Tian, Junzhang; Dong, Jianwei; He, Jinlong; Zhan, Wenfeng; Xu, Lijuan; Xu, Yikai; Jiang, Guihua

    2016-01-01

    Purpose To study whole-brain microstructural alterations in patients with end-stage renal disease (ESRD) and examine the relationship between brain microstructure and physiological indictors in the disease. Materials and Methods Diffusion tensor imaging data were collected from 35 patients with ESRD (28 men, 18–61 years) and 40 age- and gender-matched healthy controls (HCs, 32 men, 22–58 years). A voxel-wise analysis was then used to identify microstructural alterations over the whole brain in the ESRD patients compared with the HCs. Multiple biochemical measures of renal metabolin, vascular risk factors, general cognitive ability and dialysis duration were correlated with microstructural integrity for the patients. Results Compared to the HCs, the ESRD patients exhibited disrupted microstructural integrity in not only white matter (WM) but also gray matter (GM) regions, as characterized by decreased fractional anisotropy (FA) and increased mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). Further correlation analyses revealed that the in MD, AD and RD values showed significantly positive correlations with the blood urea nitrogen in the left superior temporal gyrus and significantly negative correlations with the calcium levels in the left superior frontal gyrus (orbital part) in the patients. Conclusion Our findings suggest that ESRD is associated with widespread diffusion abnormalities in both WM and GM regions in the brain, and microstructural integrity of several GM regions are related to biochemical alterations in the disease. PMID:27227649

  12. Clinical and neuroimaging differences between posterior cortical atrophy and typical amnestic Alzheimer's disease patients at an early disease stage.

    PubMed

    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

  13. Identification of biomarkers for development of end-stage kidney disease in chronic kidney disease by metabolomic profiling

    PubMed Central

    Kimura, Tomonori; Yasuda, Keiko; Yamamoto, Ryohei; Soga, Tomoyoshi; Rakugi, Hiromi; Hayashi, Terumasa; Isaka, Yoshitaka

    2016-01-01

    A critical issue in the management of chronic kidney disease (CKD) is to prevent patients from the progression to end-stage kidney disease (ESKD), however, there is only limited number of biomarkers for the discrimination of the high-risk CKD patients. We aimed to identify the metabolites which possess the ability to predict the earlier kidney deterioration. We performed capillary electrophoresis and liquid chromatography mass spectrometry (CE-MS)-based metabolic profiling in a prospective cohort, which consisted of referred 112 CKD patients with median follow-up period of 4.4 years. The association between the levels of candidate metabolites and the outcomes (progression to ESKD alone or in combination with death before ESKD) were assessed by multivariate Cox proportional hazard models after adjusting for the baseline covariates. A total of 218 metabolites were detected in the plasma of CKD patients. We identified 16 metabolites which have predictive values for the composite outcome: The risk for composite outcome was elevated from 2.0- to 8.0-fold in those with higher levels of 16 plasma metabolites. Our results suggest that the measurement of these metabolites may facilitate CKD management by predicting the risk of progression to ESKD. PMID:27188985

  14. Identification of biomarkers for development of end-stage kidney disease in chronic kidney disease by metabolomic profiling.

    PubMed

    Kimura, Tomonori; Yasuda, Keiko; Yamamoto, Ryohei; Soga, Tomoyoshi; Rakugi, Hiromi; Hayashi, Terumasa; Isaka, Yoshitaka

    2016-01-01

    A critical issue in the management of chronic kidney disease (CKD) is to prevent patients from the progression to end-stage kidney disease (ESKD), however, there is only limited number of biomarkers for the discrimination of the high-risk CKD patients. We aimed to identify the metabolites which possess the ability to predict the earlier kidney deterioration. We performed capillary electrophoresis and liquid chromatography mass spectrometry (CE-MS)-based metabolic profiling in a prospective cohort, which consisted of referred 112 CKD patients with median follow-up period of 4.4 years. The association between the levels of candidate metabolites and the outcomes (progression to ESKD alone or in combination with death before ESKD) were assessed by multivariate Cox proportional hazard models after adjusting for the baseline covariates. A total of 218 metabolites were detected in the plasma of CKD patients. We identified 16 metabolites which have predictive values for the composite outcome: The risk for composite outcome was elevated from 2.0- to 8.0-fold in those with higher levels of 16 plasma metabolites. Our results suggest that the measurement of these metabolites may facilitate CKD management by predicting the risk of progression to ESKD. PMID:27188985

  15. A voice that wraps around the body--communication problems in the advanced stages of non-small cell lung cancer.

    PubMed Central

    Moore, R. J.; Chamberlain, R. M.; Khuri, F. R.

    2001-01-01

    INTRODUCTION: Significant problems in clinician-patient communication have been described in the oncology literatures. Advanced stage non-small lung cancer a devastating disease, can cause the communication between survivors, significant others, and clinicians to falter. To date, however, no studies have used qualitative methods to examine experiential aspects of living with non-small cell lung cancer. Nor have any studies evaluated the tools survivors might use to repair some of the damage caused by living with this disease. METHODS: Exploratory, two-part qualitative design. RESULTS: Survivors of non-small cell lung cancer live with multiple fears and losses. These include a diminished sense of self, the loss of health, fears of pain in a future tainted by the threat of death, and increased feelings of alienation due to the loss of previous sources of meaning in life. These experiences significantly affect cancer survivors abilities to communicate with clinicians and significant others. CONCLUSIONS: Survivors of non-small cell lung cancer often have difficulty sharing their experiences with others not suffering a similar affliction. Through their narratives with other survivors, however, patients are better able to initiate a biopsychosocial mechanism which enables them to create a cognitive map. This cognitive map helps survivors share their experiences with others, thereby repairing some of the damage caused by this disease, including the harm done to their communication with other people. PMID:11922184

  16. Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling.

    PubMed

    Escobar, Luis E; Craft, Meggan E

    2016-01-01

    Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks. PMID:27547199

  17. Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling

    PubMed Central

    Escobar, Luis E.; Craft, Meggan E.

    2016-01-01

    Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks. PMID:27547199

  18. ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis

    ClinicalTrials.gov

    2014-07-14

    Chronic Kidney Disease; End Stage Renal Disease; Coronary Artery Calcification; Vascular Calcification; Calcification; Cardiovascular Disease; Chronic Renal Failure; Hyperparathyroidism; Kidney Disease; Nephrology; Secondary Hyperparathyroidism

  19. Advances in Raman spectroscopy for the diagnosis of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Sudworth, Caroline D.; Archer, John K. J.; Black, Richard A.; Mann, David

    2006-02-01

    Within the next 50 years Alzheimer's disease is expected to affect 100 million people worldwide. The progressive decline in the mental health of the patient is caused by severe brain atrophy generated by the breakdown and aggregation of proteins, resulting in β-amyloid plaques and neurofibrillary tangles. The greatest challenge to Alzheimer's disease lies in the pursuit of an early and definitive diagnosis, in order that suitable treatment can be administered. At the present time, definitive diagnosis is restricted to post-mortem examination. Alzheimer's disease also remains without a long-term cure. This research demonstrates the potential role of Raman spectroscopy, combined with principle components analysis (PCA), as a diagnostic method. Analyses of ethically approved ex vivo post-mortem brain tissues (originating from frontal and occipital lobes) from control (3 normal elderly subjects and 3 Huntingdon's disease subjects) and Alzheimer's disease (12 subjects) brain sections, and a further set of 12 blinded samples are presented. Spectra originating from these tissues are highly reproducible, and initial results indicate a vital difference in protein content and conformation, relating to the abnormally high levels of aggregated proteins in the diseased tissues. Further examination of these spectra using PCA allows for the separation of control from diseased tissues. The validation of the PCA models using blinded samples also displays promise for the identification of Alzheimer's disease, in conjunction with secondary information regarding other brain diseases and dementias. These results provide a route for Raman spectroscopy as a possible non-invasive, non-destructive tool for the early diagnosis of Alzheimer's disease.

  20. 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

  1. Advances of multidetector computed tomography in the characterization and staging of renal cell carcinoma

    PubMed Central

    Tsili, Athina C; Argyropoulou, Maria I

    2015-01-01

    Renal cell carcinoma (RCC) accounts for approximately 90%-95% of kidney tumors. With the widespread use of cross-sectional imaging modalities, more than half of RCCs are detected incidentally, often diagnosed at an early stage. This may allow the planning of more conservative treatment strategies. Computed tomography (CT) is considered the examination of choice for the detection and staging of RCC. Multidetector CT (MDCT) with the improvement of spatial resolution and the ability to obtain multiphase imaging, multiplanar and three-dimensional reconstructions in any desired plane brought about further improvement in the evaluation of RCC. Differentiation of RCC from benign renal tumors based on MDCT features is improved. Tumor enhancement characteristics on MDCT have been found closely to correlate with the histologic subtype of RCC, the nuclear grade and the cytogenetic characteristics of clear cell RCC. Important information, including tumor size, localization, and organ involvement, presence and extent of venous thrombus, possible invasion of adjacent organs or lymph nodes, and presence of distant metastases are provided by MDCT examination. The preoperative evaluation of patients with RCC was improved by depicting the presence or absence of renal pseudocapsule and by assessing the possible neoplastic infiltration of the perirenal fat tissue and/or renal sinus fat compartment. PMID:26120380

  2. Is living kidney donation the answer to the economic problem of end-stage renal disease?

    PubMed

    Klarenbach, Scott; Barnieh, Lianne; Gill, John

    2009-09-01

    The escalating number and cost of treating patients with end-stage renal disease is a considerable economic concern for health care systems and societies globally. Compared with dialysis, kidney transplantation leads to improved patient survival and quality of life, as well as cost savings to the health payer. Despite efforts to increase kidney transplantation, the gap between supply and demand continues to grow. In this article we explore the economic consideration of both living and deceased transplantation. Although living kidney donation has several advantages from an economic perspective, efforts to increase both deceased and living donation are required. Strategies to increase kidney donation are underfunded, and even costly strategies are likely to lead to net health care savings. However, demonstration of efficacy of these strategies is required to ensure efficient use of resources. PMID:19751899

  3. Simplification of an erythropoiesis model for design of anemia management protocols in end stage renal disease.

    PubMed

    Nichols, B; Shrestha, R P; Horowitz, J; Hollot, C V; Germain, M J; Gaweda, A E; Chait, Y

    2011-01-01

    Many end stage renal disease (ESRD) patients suffer from anemia due to insufficient endogenous production of erythropoietin (EPO). The discovery of recombinant human EPO (rHuEPO) over 30 years ago has shifted the treatment of anemia for patients on dialysis from blood transfusions to rHuEPO therapy. Many anemia management protocols (AMPs) used by clinicians comprise a set of experience-based rules for weekly-to-monthly titration of rHuEPO doses based on hemoglobin (Hgb) measurements. In order to facilitate the design of an AMP based on formal control design methods, we present a physiologically-relevant erythropoiesis model, and show that its nonlinear dynamics can be approximated using a static nonlinearity, a step that greatly simplifies AMP design. We demonstrate applicability of our results using clinical data. PMID:22254256

  4. Polymorphisms of the ELANE Gene Promoter Region in End-Stage Chronic Kidney Disease Patients

    PubMed Central

    Fernandes, Rafael; Freitas, Bruno; Miranda, Vasco; Costa, Elísio; Santos-Silva, Alice; Bronze-da-Rocha, Elsa

    2016-01-01

    End-stage renal disease (ESRD) patients have a high mortality rate that exceeds that of non-ESRD population. The hemodialysis procedure induces neutrophil activation and elastase release, which might have a role in the inflammatory process and in the development of oxidative stress. The ELANE gene encodes the neutrophil elastase. We analyzed the effect of ELANE promoter region polymorphisms and its relation with the circulating levels of elastase, as well as several clinical, biochemical and inflammatory markers in 123 ESRD patients. We found two duplications in heterozygosity in the promoter region and a new polymorphism, the c.-801G>A. ESRD patients heterozygous for the c.-903T>G polymorphism had no changes in the circulating levels of elastase or other evaluated variables, and those homozygous for the c.-741G>A polymorphism showed significant effects on neutrophils count, as well as in neutrophils/lymphocytes ratio, which might be associated with an increased inflammatory process. PMID:27136588

  5. The end-stage renal disease industry and exit strategies for nephrologists.

    PubMed

    Sullivan, John D

    2006-01-01

    The purpose of this presentation is to identify exit strategies for nephrologists under changing conditions in the dialysis market. The end-stage renal disease service provider market continues to be highly receptive to consolidation. Taking advantage of large economies of scale, large for-profit dialysis chains have surpassed independent operators in both number of clinics and total patients. With relatively low barriers to entry, new smaller clinics continue to open, serving a niche outside the larger chains. Additional competition comes in the form of medium players funded by venture capitalists with the added pressure of rapid growth and financial return. To ensure market power in both dialysis products and managed care negotiation leverage, medium and large service providers will continue to seek out attractive acquisition targets. For nephrologists to capitalize on investment, clinic and business preparation will continue to be the driving force for these divestitures. PMID:17202963

  6. Measuring Physical Activity in Older Adults with and without Early Stage Alzheimer’s Disease

    PubMed Central

    Watts, Amber S.; Vidoni, Eric D.; Loskutova, Natalia; Johnson, David K.; Burns, Jeffrey M.

    2013-01-01

    We compared subjective reports of physical activity with objective measures of physical fitness including cardiorespiratory capacity, body composition, and physical performance in 146 older adults with and without early stage Alzheimer’s disease (ESAD). Respondents reported primarily unstructured and low-intensity activities, including walking and housework. Individuals with ESAD participated in fewer and lower intensity physical activities than those without ESAD. In those without ESAD, housework was related to lower body mass index, leisure walking was related to faster speed on a timed walking test, and participation in sports was related to higher peak oxygen intake. In individuals with ESAD, reported physical activities did not predict any of the physical fitness, body composition, or physical performance measures. We conclude that measures of physical activity require expansion of unstructured and low intensity activities to improve sensitivity in sedentary populations, especially in older adults with ESAD. PMID:24062599

  7. Captopril-induced sialadenitis in a patient with end-stage renal disease

    PubMed Central

    Mahdiabadi, Fatemeh Musavi; Nikvarz, Naemeh

    2016-01-01

    Sialadenitis is a rare adverse effect of captopril. We report a case of captopril-induced sialadenitis in a patient with end-stage renal disease (ESRD). A 20-year-old man with ESRD encountered parotid and submandibular swelling after receiving two doses of captopril, administered sublingually. Despite of prescribing dexamethasone, resuming hemodialysis, and discontinuing other drugs that also can cause parotitis, he improved later than what was reported in patients with normal renal function. In conclusion recovery from captopril-induced sialadenitis in patients with ESRD may be more prolonged than that of patients with normal renal function; moreover, early hemodialysis which helps in drug removal may be the most effective treatment. PMID:27162811

  8. Quantitative EEG: investigation in children with end stage renal disease before and after haemodialysis.

    PubMed

    Balzar, E; Saletu, B; Khoss, A; Wagner, U

    1986-10-01

    Changes in brain function of 9 children (6 males and 3 females) ages 7 to 14 years (mean 12 years) with end stage renal disease (ESRD) were investigated before and after haemodialysis treatment, utilizing computer assisted spectral analysis of the scalp-recorded EEG. A control group of age-matched healthy children was studied as well. Statistical analyses demonstrated that ESRD children exhibited more Delta and Theta activity, less Beta activity, a slower dominant frequency of the Alpha activity as well as a slower centroid of the total activity before treatment than the controls. These findings suggest a deterioration of vigilance as characterized by Head. Haemodialysis decreased slow activity and increased Alpha and Beta activity, thereby inducing an improvement of brain function. PMID:3791647

  9. Continuous intestinal infusion of levodopa/carbidopa in advanced Parkinson's disease: efficacy, safety and patient selection.

    PubMed

    Abbruzzese, Giovanni; Barone, Paolo; Bonuccelli, Ubaldo; Lopiano, Leonardo; Antonini, Angelo

    2012-01-01

    Long-term oral therapy with levodopa is associated with the development of motor fluctuations and dyskinesia in a large percentage of patients with Parkinson's disease (PD). Motor complications are associated with a number of non-motor symptoms and have a negative impact on disability and quality of life. There are three therapeutic options available for the management of patients at this advanced stage: high frequency deep brain stimulation, continuous subcutaneous infusion of apomorphine, and continuous intestinal infusion of levodopa/carbidopa. On the basis of published data and in consideration of the risk-benefit profile of current therapeutic strategies, we here propose an algorithm to help clinicians select the most suitable treatment option for patients with advanced PD. PMID:23402675

  10. Erythropoiesis-stimulating agents for the management of anemia of chronic kidney disease: past advancements and current innovations.

    PubMed

    Dutka, Paula

    2012-01-01

    Over the last century, remarkable advances have been made in the care of patients with end stage renal disease (ESRD), resulting in improved prognosis. However, for decades after the advent of dialysis, anemia-associated symptoms continued to adversely affect patients' daily lives. The identification, isolation, and eventual cloning of erythropoietin and its receptor led to development of erythropoiesis stimulating agents, revolutionizing anemia management. Continued advancements have paved the way for the discovery of novel erythropoiesis stimulating agents with enhanced properties. This article charts the history of anemia management in patients with ESRD, including the discovery of erythropoietin, and briefly reviews the development, mechanism of action, and select attributes of erythropoiesis-stimulating agents. PMID:23469411

  11. Percutaneous coronary intervention in patients with end-stage renal disease.

    PubMed

    Bocksch, Wolfgang; Fateh-Moghadam, Suzanne; Mueller, Eda; Huehns, Sonja; Waigand, Juergen; Dietz, Rainer

    2005-01-01

    Patients with end-stage renal disease (ESRD) represent a growing number of patients in the cardiac catheterization laboratories worldwide. This is a consequence of the growing absolute number of ESRD patients in developed countries, better noninvasive diagnostic tools, better catheterization facilities and last-but-not-least better education of referring physicians about the incidence and prognosis of coronary artery disease (CAD) for patients with ESRD. There is growing evidence of the positive impact of coronary revascularization on long-term outcome of these patients. ESRD patients have a high comorbidity and are therefore better candidates for the less invasive approach using percutaneous coronary intervention (PCI) rather than coronary artery bypass surgery (CABG). From the view of the interventional cardiologist, ESRD patients represent one of the most challenging patient cohort concerning technical challenges and potential risk of complication for the patient. Percutaneous coronary intervention (PCI) including debulking techniques and stent implantation is the current standard therapy for patients with symptomatic single-vessel disease (SVD) and the preferred therapy for most patients with focal, polyfocal or even diffuse multi-vessel disease (MVD). Coronary bypass surgery is reserved for a decreasing number of patients with mechanically untreatable coronary lesions and unprotected left main stem stenosis. The problem of restenosis and subsequent target lesion revascularization has been decreased to a minimum by the use of drug-eluting stents (DES), even though prospective randomized trials including ESRD patients are lacking. In case of acute coronary syndromes, the need for immediate coronary angiography and subsequent revascularization by means of PCI should be pointed out. PMID:16534221

  12. Formal literature review of quality-of-life instruments used in end-stage renal disease.

    PubMed

    Cagney, K A; Wu, A W; Fink, N E; Jenckes, M W; Meyer, K B; Bass, E B; Powe, N R

    2000-08-01

    Although quality-of-life assessment is an important complement to conventional clinical evaluation, there are limited opportunities for researchers in end-stage renal disease (ESRD) to examine evidence for a range of quality-of-life measures. To better understand how quality of life has been conceptualized, measured, and evaluated for ESRD, we conducted a structured literature review. Eligible articles were identified from a MEDLINE search, expert input, and review of references from eligible articles. A standardized instrument was created for article review and included type of measure, instrument development process, study sample characteristics, quality-of-life domains, and reliability and validity testing. From 436 citations, 78 articles were eligible for final review, and of those, 47 articles contained evidence of reliability or validity testing. Within this set, there were 113 uses of 53 different instruments: 82% were generic and 18% were disease specific. Only 32% defined quality of life. The most frequently assessed domains were depression (41%), social functioning (32%), positive affect (30%), and role functioning (27%). Testing was completed for test-retest reliability (20%), interrater reliability (13%), internal consistency (22%), content validity (24%), construct validity (41%), criterion validity (55%), and responsiveness (59%). Few articles measuring quality of life in ESRD defined quality-of-life domains or adequately described instrument development and testing. Generic measures, such as the Sickness Impact Profile, and disease-specific measures, such as the Kidney Disease Questionnaire, had been tested more thoroughly than others. Standardized reporting and more rigorous testing could help researchers make informed choices about instruments that would best serve their own and their patients' needs. PMID:10922311

  13. Continuous ambulatory peritoneal dialysis and survival of HIV infected patients with end-stage renal disease.

    PubMed

    Kimmel, P L; Umana, W O; Simmens, S J; Watson, J; Bosch, J P

    1993-08-01

    As the number of human immunodeficiency virus (HIV) infected patients has increased in the U.S., the number of infected patients treated for end-stage renal disease (ESRD) has stabilized at about 1 to 2% of the hemodialyzed population. Little has been written regarding the role of continuous ambulatory peritoneal dialysis (CAPD) in the treatment of HIV infected patients with ESRD. To evaluate the effectiveness of CAPD as a long term therapy for HIV infected patients with ESRD, we reviewed our ESRD program's experience. We entered 392 patients from its inception in February 1984 until April 1992. Thirty-one, or 7.9% of our population were HIV infected. Twenty, or 64.5% had stage IV infection. Patients were entered into our chronic hemodialysis (HD) or CAPD program according to standard clinical criteria. Eight HIV infected patients elected to start CAPD, while 23 patients were treated exclusively with HD. The proportion of stage IV infected patients was similar in both treatment modality groups. HIV infected ESRD patients were younger than non-HIV infected patients (37.5 +/- 9.7 vs. 49.8 +/- 15.7 years, respectively, P < 0.0001) at the start of treatment. We used Cox regression techniques to analyze survival data. Mean survival time for our entire non-HIV infected ESRD population (N = 361) was 44.0 +/- 33.9 months. Mean survival time for HIV infected patients with ESRD was 15.5 +/- 9.9 months. Median survival for HIV infected ESRD patients was 13 months compared to 38 months for the non-infected population. As expected, mean survival time in HIV infected ESRD patients was significantly diminished compared to non-infected ESRD patients (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8377381

  14. The Level of Cholesterol in COPD Patients with Severe and Very Severe Stage of the Disease

    PubMed Central

    Zafirova-Ivanovska, Beti; Stojkovikj, Jagoda; Dokikj, Dejan; Anastasova, Sasha; Debresliovska, Angela; Zejnel, Sead; Stojkovikj, Dragana

    2016-01-01

    BACKGROUND: High blood cholesterol is part of metabolic syndrome and can be caused by medical conditions or bad dietary habits. AIM: The aim of the study was to investigate the prevalence of hypercholesterolemia in privies diagnosed patients with the severe and very severe stage of COPD, which were stable. MATERIAL AND METHODS: We investigated 100 subjects, all of them smokers, with smoking status >10 years, stratified into two groups: with severe and very severe stage of the disease. It was clinical, randomized, cross-sectional study. Besides demographic parameters and functional parameters, body mass index, cholesterol, LDL, and HDL were investigated. RESULTS: In the group of patients with very severe COPD were recorded significantly higher average values of cholesterol (6.16 ± 1.5 vs. 5.61 ± 1.1, p = 0.039). As independent significant factors influencing cholesterol in the group with a very severe COPD were confirmed the age of the patients (p = 0.005), LDL (p = 0.004) and HDL (p = 0.002). In the group with severe COPD, only LDL was confirmed as an independent significant factor that has an impact on cholesterol (p < 0.0001). CONCLUSION: The results of our survey demonstrated a high level of blood cholesterol and LDL, and low level of blood HDL in both investigated group’s patients with COPD. PMID:27335600

  15. What can we learn from the U.S. expanded end-stage renal disease bundle?

    PubMed

    Chambers, James D; Weiner, Daniel E; Bliss, Sarah K; Neumann, Peter J

    2013-05-01

    Episode-based payment, commonly referred to as bundled payment, has emerged as a key component of U.S. health care payment reform. Bundled payments are appealing as they share the financial risk of treating patients between payers and providers, encouraging the delivery of cost-effective care. A closely watched example is the U.S. End Stage Renal Disease (ESRD) Prospective Payment System, known as the 'expanded ESRD bundle.' In this paper we consider the expanded ESRD bundle 2 years after its implementation. First, we discuss emerging lessons, including how implementation has changed dialysis care with respect to the use of erythropoietin stimulating agents, how implementation has led to an increase in the use of home-based peritoneal dialysis, and how it may have contributed to the market consolidation of dialysis providers. Second, we use the expanded ESRD bundle to illustrate the importance of accounting for stakeholder input and staging policy implementation. Third, we highlight the need to consider system-wide consequences of implementing bundled payment policies. Fourth, we suggest how bundled payments may create research opportunities. Bundled payment policies offer opportunities and challenges. Their success will be determined not only by impacts on cost containment, but also to the extent they encourage high quality care. PMID:23419419

  16. Gene Expression Profiling during Early Acute Febrile Stage of Dengue Infection Can Predict the Disease Outcome

    PubMed Central

    Calzavara-Silva, Carlos E.; Gomes, Ana L. V.; Brito, Carlos A. A.; Cordeiro, Marli T.; Silva, Ana M.; Magalhães, Cecilia; Andrade, Raoni; Gil, Laura H. V. G.; Marques, Ernesto T. A.

    2009-01-01

    Background We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data, validated by quantitative PCR and tested in independent samples. Methodology/Principal Findings The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity: classic dengue fever or dengue hemorrhagic fever (DHF) samples were compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2–3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels. Conclusions/Significance Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection. PMID:19936257

  17. Comparison of the outcomes of three surgical treatments for end-stage temporomandibular joint disease.

    PubMed

    Dimitroulis, G

    2014-08-01

    The aim of this study was to determine whether there are any differences between condylectomy, rib grafts, and prosthetic joints (Biomet TMJ stock prosthesis) with regard to outcomes for patients with end-stage temporomandibular joint (TMJ) disease. Fifty-six of a total 127 patients who presented with category 5 end-stage TMJ disease over 3 years (2010-2013) agreed to participate in this retrospective, comparative, cohort study. Patients were divided into four groups: preoperative (n=16), condylectomy (n=8), rib graft (n=16), and prosthetic joint (n=16). They were assessed for major postoperative complications (i.e., return to theatre) and maximum range of mandibular motion, and all completed a specific quality of life (QOL) questionnaire. Whilst the condylectomy group demonstrated the best mandibular range of motion (P<0.01), rib graft patients were more likely to experience complications (43.8%) necessitating a return to theatre. The prosthesis group recorded the best mean aggregate QOL score, but the difference compared to the rib graft and condylectomy groups was not statistically significant. The results of this study suggest that for dentate patients, prosthetic joints are highly dependable with no returns to theatre and favourable QOL outcomes. For edentulous patients, condylectomies alone also appear to work well. Future TMJ prosthetic designs should focus on improving mandibular range of motion, as the current stock prosthesis allows only a restricted range, no better than that achieved with rib graft (P>0.05) and far less than that achieved with condylectomy (P<0.01). PMID:24629849

  18. Integrative EEG biomarkers predict progression to Alzheimer's disease at the MCI stage

    PubMed Central

    Poil, Simon-Shlomo; de Haan, Willem; van der Flier, Wiesje M.; Mansvelder, Huibert D.; Scheltens, Philip; Linkenkaer-Hansen, Klaus

    2013-01-01

    Alzheimer's disease (AD) is a devastating disorder of increasing prevalence in modern society. Mild cognitive impairment (MCI) is considered a transitional stage between normal aging and AD; however, not all subjects with MCI progress to AD. Prediction of conversion to AD at an early stage would enable an earlier, and potentially more effective, treatment of AD. Electroencephalography (EEG) biomarkers would provide a non-invasive and relatively cheap screening tool to predict conversion to AD; however, traditional EEG biomarkers have not been considered accurate enough to be useful in clinical practice. Here, we aim to combine the information from multiple EEG biomarkers into a diagnostic classification index in order to improve the accuracy of predicting conversion from MCI to AD within a 2-year period. We followed 86 patients initially diagnosed with MCI for 2 years during which 25 patients converted to AD. We show that multiple EEG biomarkers mainly related to activity in the beta-frequency range (13–30 Hz) can predict conversion from MCI to AD. Importantly, by integrating six EEG biomarkers into a diagnostic index using logistic regression the prediction improved compared with the classification using the individual biomarkers, with a sensitivity of 88% and specificity of 82%, compared with a sensitivity of 64% and specificity of 62% of the best individual biomarker in this index. In order to identify this diagnostic index we developed a data mining approach implemented in the Neurophysiological Biomarker Toolbox (http://www.nbtwiki.net/). We suggest that this approach can be used to identify optimal combinations of biomarkers (integrative biomarkers) also in other modalities. Potentially, these integrative biomarkers could be more sensitive to disease progression and response to therapeutic intervention. PMID:24106478

  19. Plasma Amino Acid Concentrations Predict Mortality in Patients with End-Stage Liver Disease

    PubMed Central

    Kinny-Köster, Benedict; Bartels, Michael; Becker, Susen; Scholz, Markus; Thiery, Joachim

    2016-01-01

    Background The liver plays a key role in amino acid metabolism. In former studies, a ratio between branched-chain and aromatic amino acids (Fischer’s ratio) revealed associations with hepatic encephalopathy. Furthermore, low concentrations of branched-chain amino acids were linked to sarcopenia in literature. Encephalopathy and sarcopenia are known to dramatically worsen the prognosis. Aim of this study was to investigate a complex panel of plasma amino acids in the context of mortality in patients with end-stage liver disease. Methods 166 patients evaluated for orthotopic liver transplant