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Sample records for mcs 1a patients

  1. PET in patients with clear-cut multiple chemical sensitivity (MCS); PET bei Patienten mit klar definierter multipler chemischer Sensibilitaet (MCS)

    Energy Technology Data Exchange (ETDEWEB)

    Bornschein, S. [Toxikologische Abt. der II. Medizinischen Klinik und Poliklinik der Technischen Univ. Muenchen, Klinikum rechts der Isar, Muenchen (Germany); Klinik und Poliklinik fuer Psychiatrie und Psychotherapie der Technischen Univ. Muenchen, Klinikum rechts der Isar, Muenchen (Germany); Hausteiner, C.; Foerstl, H. [Klinik und Poliklinik fuer Psychiatrie und Psychotherapie der Technischen Univ. Muenchen, Klinikum rechts der Isar, Muenchen (Germany); Drzezga, A.; Schwaiger, M. [Nuklearmedizinische Klinik und Poliklinik der Technischen Univ. Muenchen, Klinikum rechts der Isar, Muenchen (Germany); Bartenstein, P. [Klinik und Poliklinik fuer Nuklearmedizin, Universitaetsklinikum Mainz (Germany); Zilker, Th. [Toxikologische Abt. der II. Medizinischen Klinik und Poliklinik der Technischen Univ. Muenchen, Klinikum rechts der Isar, Muenchen (Germany)

    2002-12-01

    Aim: Multiple chemical sensitivity (MCS) is a controversially discussed symptom complex. Patients afflicted by MCS react to very low and generally non-toxic concentrations of environmental chemicals. It has been suggested that MCS leads to neurotoxic damage or neuroimmunological alteration in the brain detectable by positron emission tomography (PET) and single photon emission computer tomography (SPECT). These methods are often applied to MCS patients for diagnosis, although they never proved appropriate. Method: We scanned 12 MCS patients with PET, hypothesizing that it would reveal abnormal findings. Results: Mild glucose hypometabolism was present in one patient. In comparison with normal controls, the patient group showed no significant functional brain changes. Conclusion: This first systematic PET study in MCS patients revealed no hint of neurotoxic or neuroimmunological brain changes of functional significance. (orig.) [German] Ziel: Multiple chemische sensibilitaet (MCS) ist ein umstrittenes Krankheitsbild, das durch Reaktionen auf geringe, fueer Normalpersonen unschaedliche Mengen an Umweltchemikalien gekennzeichnet ist. Es wurde postuliert, dass MCS zu neurotoxischer Schaedigung bzw. neuroimmunologischer Veraenderung im Gehirn fuehrt, die mittels funktioneller bildgebender Verfahren, z. B. positronenemissionstomographie (PET), single-photon-emissions-computer-tomographie (SPECT) dargestellt werden koennte. Obwohl hierfuer kein wissenschaftlicher Beleg erbracht wurde, werden diese Methoden vielfach diagnostisch bei MCS-Patienten eingesetzt. Methode: Wir untersuchten 12 MCS-Patienten mit PET, um etwaige funktionelle Hirnveraenderungen nachzuweisen. Ergebnisse: Im Einzelvergleich war bei einem Patienten ein diskreter Glukose-Hypometabolismus in einzelnen Hirnregionen vorhanden. Im Gruppenvergleich konnte keine signifikante Abweichung von der Norm gefunden werden. Schlussfolgerung: Diese erste systematische PET-Studie bei MCS-Patienten erbrachte keinen

  2. Mcs2 and a novel CAK subunit Pmh1 associate with Skp1 in fission yeast

    International Nuclear Information System (INIS)

    Bamps, Sophie; Westerling, Thomas; Pihlak, Arno; Tafforeau, Lionel; Vandenhaute, Jean; Maekelae, Tomi P.; Hermand, Damien

    2004-01-01

    The Mcs6 CDK together with its cognate cyclin Mcs2 represents the CDK-activating kinase (CAK) of fission yeast Cdc2. We have attempted to determine complexes in which Mcs6 and Mcs2 mediate this and possible other functions. Here we characterize a novel interaction between Mcs2 and Skp1, a component of the SCF (Skp1-Cullin-F box protein) ubiquitin ligase. Furthermore, we identify a novel protein termed Pmh1 through its association with Skp1. Pmh1 associates with the Mcs6-Mcs2 complex, enhancing its kinase activity, and represents the apparent homolog of metazoan Mat1. Association of Mcs2 or Pmh1 with Skp1 does not appear to be involved in proteolytic degradation, as these complexes do not contain Pcu1, and levels of Mcs2 or Pmh1 are not sensitive to inhibition of SCF and the 26S proteasome. The identified interactions between Skp1 and two regulatory CAK subunits may reflect a novel mechanism to modulate activity and specificity of the Mcs6 kinase

  3. Plasma extraction rate and collection efficiency during therapeutic plasma exchange with Spectra Optia in comparison with Haemonetics MCS+.

    Science.gov (United States)

    Lambert, Catherine; Gericke, Marion; Smith, Richard; Hermans, Cedric

    2011-01-01

    For therapeutic plasma exchange (TPE), continuous and intermittent flow separators are known to be efficient. This study was undertaken to compare the performances of the Spectra Optia, a continuous flow centrifugal apheresis system recently developed by CaridianBCT, with the Haemonetics Multicomponents System (MCS)+ apheresis system based on intermittent flow centrifugation. The primary objective of the study was to compare the time required to exchange one total plasma volume with both separators. The secondary objectives were to determine the plasma exchange efficiency, the plasma extraction rate, the percentage of target exchange volume achieved, and the loss of cellular components. The study involved prospectively paired comparison of 16 TPE on each device performed in patients with chronic diseases treated with TPE. The time required to exchange 1 total plasma volume was 182 ± 36 minutes for MCS+ procedures and 100 ± 20 minutes for the Spectra Optia procedures (P higher plasma extraction rate was achieved (30.2 ± 4.3 vs 16.8 ± 3.4 mL/min, respectively, P exchange efficiency was slightly better with the Spectra Optia compared with the MCS+ procedures (83.4 ± 7.0 vs 80.0 ± 8.5%, P higher extraction rate and exchange efficiency than the MCS+ allowing to remove the same amount of plasma in less time, by processing less blood. It also removes significantly less platelets than the MCS+ separator. Copyright © 2010 Wiley-Liss, Inc.

  4. Designing a machinery control system (MCS) security testbed

    OpenAIRE

    Desso, Nathan H.

    2014-01-01

    Approved for public release; distribution is unlimited Industrial control systems (ICS) face daily cyber security threats, can have a significant impact to the security of our nation, and present a difficult challenge to defend. Critical infrastructures, including military systems like the machinery control systems (MCS) found onboard modern U.S. warships, are affected because of their use of commercial automation solutions. The increase of automated control systems within the U.S. Navy sa...

  5. MCS precipitation and downburst intensity response to increased aerosol concentrations

    Science.gov (United States)

    Clavner, M.; Cotton, W. R.; van den Heever, S. C.

    2015-12-01

    Mesoscale convective systems (MCSs) are important contributors to rainfall in the High Plains of the United States as well as producers of severe weather such as hail, tornados and straight-line wind events known as derechos. Past studies have shown that changes in aerosol concentrations serving as cloud condensation nuclei (CCN) alter the MCS hydrometeor characteristics which in turn modify precipitation yield, downdraft velocity, cold-pool strength, storm propagation and the potential for severe weather to occur. In this study, the sensitivity of MCS precipitation characteristics and convective downburst velocities associated with a derecho to changes in CCN concentrations were examined by simulating a case study using the Regional Atmospheric Modeling System (RAMS). The case study of the 8 May 2009 "Super-Derecho" MCS was chosen since it produced a swath of widespread wind damage in association with an embedded large-scale bow echo, over a broad region from the High Plains of western Kansas to the foothills of the Appalachians. The sensitivity of the storm to changes in CCN concentrations was examined by conducting a set of three simulations which differed in the initial aerosol concentration based on output from the 3D chemical transport model, GEOS-Chem. Results from this study indicate that while increasing CCN concentrations led to an increase in precipitation rates, the changes to the derecho strength were not linear. A moderate increase in aerosol concentration reduced the derecho strength, while the simulation with the highest aerosol concentrations increased the derecho intensity. These changes are attributed to the impact of enhanced CCN concentration on the production of convective downbursts. An analysis of aerosol loading impacts on these MCS features will be presented.

  6. Cascade filtration (CF) with the Haemonetics MCS+: a new technical adaptation.

    Science.gov (United States)

    Valbonesi, M; Bo, A; De Luigi, M C; Bruni, R; Stura, P; Sanfilippo, B; Varinelli, I

    2001-03-01

    CF was introduced in clinical medicine in 1980. Up to now, exclusively two-vein procedures have been carried out with some limitations to expansion of this technique. In this report we describe the very first application of single-needle CF carried out with Haemonetics MCS + apparatus. Twenty procedures were completed without any untoward effect in patients suffering from TTP, post-hepatitic cryoblobulinemia, familial hypercholesterolemia and acute Guillan-Barrè Syndrome. From 1 to 4 sessions were carried out per patient with the expected laboratory and clinical results. The only limit is the procedure time that averages 231 +/- 48 min., approximately 40% longer than two needle procedures.

  7. The MCS macroseismic survey of the Emilia 2012 earthquakes

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    Paolo Galli

    2012-10-01

    Full Text Available Most of the inhabitants of northern Italy were woken up during the night of May 20, 2012, by the Mw 6.1 earthquake [QRCMT 2012] that occurred in the eastern Po Plain. The mainshock was preceded a few hours before by a Mw 4.3 shock, and it was followed by a dozen Ml >4 aftershocks in May and June, amongst which 11 had Ml ≥4.5. On May 29, 2012, a second Mw 6.0 mainshock struck roughly the same area [QRCMT 2012], which resulted in further victims, most of whom were caught under the collapse of industrial warehouses. Such earthquakes are an unexpected event in this region, as testified by the lack of local epicenters in the Italian seismic catalog [Rovida et al. 2011: CPTI11 from now] and by the consequent low level of the local seismic classification (seismic zone 3 [DPC 2012]. Apart from the warehouses and hundreds of old, crumbling farmsteads, severe damage was focused on ancient, tall buildings, such as churches, bell towers, castles, towers and palaces. Residential buildings generally suffered only light and/or moderate effects, apart from some exceptional cases. Using the Mercalli–Cancani–Sieberg (MCS scale [Sieberg 1930], we began a macroseismic survey in the early morning of May 20, 2012, that ultimately included visits to almost 200 localities, 52 of which were carried out before the second mainshock. […

  8. Multi-scale evolution of a derecho-producing MCS

    Science.gov (United States)

    Bernardet, Ligia Ribeiro

    1997-12-01

    In this dissertation we address one type of severe weather: strong straight-line winds. In particular, we focus on derechos, a type of wind storm caused by a convective system and characterized by its long duration and by the large area it covers. One interesting characteristic of these storms is that they develop at night, on the cold side of a thermal boundary. This region is not characterized by large convective instability. In fact, surface parcels are generally stable with respect to vertical displacements. To gain understanding of the physical processes involved in these storms, we focused on the case of a MCS that developed in eastern Colorado on 12-13 May, 1985. The system formed in the afternoon, was active until early morning, and caused strong winds during the night. A multi-scale full physics simulation of this case was performed using a non-hydrostatic mesoscale model. Four telescopically nested grids covering from the synoptic scale down to cloud scale circulations were used. A Lagrangian model was used to follow trajectories of parcels that took part in the updraft and in the downdraft, and balance of forces were computed along the trajectories. Our results show that the synoptic and mesoscale environment of the storm largely influences convective organization and cloud-scale circulations. During the day, when the boundary layer is well mixed, the source of air for the clouds is located within the boundary layer. At night, when the boundary layer becomes stable, the source of air shifts to the top of the boundary layer. It is composed of warm, moist air that is brought by the nocturnal low-level jet. The downdraft structure also changes from day to night. During the day, parcels acquire negative buoyancy because of cooling due to evaporation and melting. As they sink, they remain colder than the environment, and end up at the surface constituting the cold pool. During the night, downdrafts are stronger, generating the strong surface winds. The most

  9. Search for all MCs in networks with unreliable nodes and arcs

    International Nuclear Information System (INIS)

    Yeh, W.-C.

    2003-01-01

    A simple method is proposed to search for all minimal cutsets (MCs ) for imperfect networks reliability subject to both arc and node failures under the condition that all of the MCs in the network with perfect nodes are given in advance. The proposed method does not require re-enumeration for all of the MCs for additional node failure consideration. All of the MC candidates found in the proposed algorithm are actual MCs without any need for further verification. This algorithm is more effective than the existing algorithm in which every MC candidate is not verified as a MC. No identical MCs are found using the proposed algorithm, which does not duplicate MCs and is more efficient than the existing methods. Only simple concepts are used to implement the proposed algorithm, which makes it easier to understand and implement. With considering unreliable nodes, the proposed method is also more realistic and valuable for reliability analysis in an existing network. The correctness of the proposed algorithm will be analyzed and proven. One example is used to illustrate how all MCs are generated in a network with arc and node failures solved using the proposed algorithm

  10. Pediatric peripheral blood progenitor cell collection: haemonetics MCS 3P versus COBE Spectra versus Fresenius AS104.

    Science.gov (United States)

    Bambi, F; Faulkner, L B; Azzari, C; Gelli, A M; Tamburini, A; Tintori, V; Lippi, A A; Tucci, F; Bernini, G; Genovese, F

    1998-01-01

    An increasing number of apheresis machines are becoming available for peripheral blood progenitor cell (PBPC) collection in children. At the Children's Hospital of Florence (Italy), three apheresis machines were evaluated: MCS 3P (Haemonetics) (10 procedures in 4 patients, aged 10-12 years, weight 23.5-64 kg), Spectra, (COBE) (8 procedures in 3 patients, aged 4-17 years, weight 19-59 kg), and AS104 (Fresenius) (24 procedures in 9 patients, aged 2-16 years, weight 13.6-60 kg). For PBPC quantitative analysis, CD34 cytofluorimetry was employed. Relevant variables analyzed included efficiency of CD34+ cell extraction and enrichment, mononuclear cell purity and red cell contamination of the apheresis components, and platelet count decreases after leukapheresis. No significant differences in CD34+ cell-extraction abilities were found. However, the AS104 provided consistently purer leukapheresis components in terms of mononuclear cell and CD34+ cell enrichment (441 +/- 59%, vs. 240 +/- 35% and 290 +/- 42% for MCS 3P and Spectra, respectively). Postapheresis platelet counts dropped the least with the AS104. The smallest patient who underwent apheresis with MCS 3P (the only machine working on discontinuous flow and hence with greater volume shifts) weighed 23.5 kg and tolerated the procedure well, with no signs of hemodynamic instability. No significant complications were observed. All machines seem to have comparable PBPC extraction efficiency, but the AS104 seems to give the component with the greatest PBPC enrichment. This feature might be relevant for further ex vivo cell processing (CD34+ cell selection, expansion, and so on).

  11. MCS and sub-band selection for downlink interference coordination in LTE-A Femtocells

    OpenAIRE

    Muñoz Medina, Olga; Agustín de Dios, Adrián; Vidal Manzano, José

    2012-01-01

    This paper proposes a decentralized algorithm for interference coordination in LTE-A networks, based on the exchange of information (pricing) at control plane level. In our approach, every user equipment (UE) report the maximum modulation and coding scheme (MCS) that can be used within several sets (sub-bands) of available resource blocks, along with a parameter (cost) that measures the MCS degradation due to the transmission from an interfering neighbor. Through the e...

  12. Motor cortex stimulation(MCS) for intractable complex regional pain syndrome (CRPS) type II: PSM analysis of Tc-99m ECD brain perfusion SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Y. A.; Son, B. C.; Yoo, I. R.; Kim, S. H.; Kim, E. N.; Park, Y. H.; Lee, S. Y.; Sohn, H. S.; Chung, S. K. [College of Medicine, The Catholic Univ. of Korea, Seoul (Korea, Republic of)

    2001-07-01

    We had experienced a patient with intractable CRPS in whom statistical parametric mapping (SPM) analysis of cerebral perfusion explained the mechanism of pain control by MCS. A 43-year-old man presented spontaneous severe burning pain in his left hand and forearm and allodynia over the left arm and left hemibody. After the electrodes for neuromodulation therapy were inserted in the central sulcus, the baseline and stimulation brain perfusion SPECT using Tc-99m ECD were obtained within two days. The differences between the baseline and stimulation SPECT images, estimated at every voxel using t-statistics using SPM-99 software, were considered significant at a threshold of uncorrected P values less than 0.01. Among several areas significantly activated following pain relief with MCS, ipsilateral pyramidal tract in the cerebral peduncle might be related to the mechanism of pain control with MCS through efferent motor pathway. The result suggested that corticospinal neurons themselves or motor cortex efferent pathway maintained by the presence of intact corticospinal neurons could play an important role in producing pain control after MCS. This study would helpful in understanding of neurophysiology.

  13. Motor cortex stimulation(MCS) for intractable complex regional pain syndrome (CRPS) type II: PSM analysis of Tc-99m ECD brain perfusion SPECT

    International Nuclear Information System (INIS)

    Chung, Y. A.; Son, B. C.; Yoo, I. R.; Kim, S. H.; Kim, E. N.; Park, Y. H.; Lee, S. Y.; Sohn, H. S.; Chung, S. K.

    2001-01-01

    We had experienced a patient with intractable CRPS in whom statistical parametric mapping (SPM) analysis of cerebral perfusion explained the mechanism of pain control by MCS. A 43-year-old man presented spontaneous severe burning pain in his left hand and forearm and allodynia over the left arm and left hemibody. After the electrodes for neuromodulation therapy were inserted in the central sulcus, the baseline and stimulation brain perfusion SPECT using Tc-99m ECD were obtained within two days. The differences between the baseline and stimulation SPECT images, estimated at every voxel using t-statistics using SPM-99 software, were considered significant at a threshold of uncorrected P values less than 0.01. Among several areas significantly activated following pain relief with MCS, ipsilateral pyramidal tract in the cerebral peduncle might be related to the mechanism of pain control with MCS through efferent motor pathway. The result suggested that corticospinal neurons themselves or motor cortex efferent pathway maintained by the presence of intact corticospinal neurons could play an important role in producing pain control after MCS. This study would helpful in understanding of neurophysiology

  14. SOBER-MCS: Sociability-Oriented and Battery Efficient Recruitment for Mobile Crowd-Sensing

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    Fazel Anjomshoa

    2018-05-01

    Full Text Available The Internet of Things (IoT concept is aiming at being an integral part of the next generation networking services by introducing pervasiveness and ubiquitous interconnectivity of uniquely-identifiable objects. The massive availability of personalized smart devices such as smartphones and wearables enable their penetration into the IoT ecosystem with their built-in sensors, particularly in Mobile Crowd-Sensing (MCS campaigns. The MCS systems achieve the objectives of the large-scale non-dedicated sensing concept in the IoT if a sufficient number of participants are engaged to the collaborative data acquisition process. Therefore, user recruitment is a key challenge in MCS, which requires effective incentivization of cooperative, truthful and trustworthy users. A grand concern for the participants is the battery drain on the mobile devices. It is a known fact that battery drain in a smartphone is a function of the user activity, which can be modeled under various contexts. With this in mind, we propose a new social activity-aware recruitment policy, namely Sociability-Oriented and Battery-Efficient Recruitment for Mobile Crowd-Sensing (SOBER-MCS. SOBER-MCS uses sociability and the residual power of the participant smartphones as two primary criteria in the selection of participating devices. The former is an indicator of the participant willingness toward sensing campaigns, whereas the latter is used to prioritize personal use over crowd-sensing under critical battery levels. We use sociability profiles that were obtained in our previous work and use those values to simulate the sociability behavior of a large pool of participants in an MCS environment. Through simulations, we show that SOBER-MCS is able to introduce battery savings up to 18.5% while improving user and platform utilities by 12% and 20%, respectively.

  15. SOBER-MCS: Sociability-Oriented and Battery Efficient Recruitment for Mobile Crowd-Sensing.

    Science.gov (United States)

    Anjomshoa, Fazel; Kantarci, Burak

    2018-05-17

    The Internet of Things (IoT) concept is aiming at being an integral part of the next generation networking services by introducing pervasiveness and ubiquitous interconnectivity of uniquely-identifiable objects. The massive availability of personalized smart devices such as smartphones and wearables enable their penetration into the IoT ecosystem with their built-in sensors, particularly in Mobile Crowd-Sensing (MCS) campaigns. The MCS systems achieve the objectives of the large-scale non-dedicated sensing concept in the IoT if a sufficient number of participants are engaged to the collaborative data acquisition process. Therefore, user recruitment is a key challenge in MCS, which requires effective incentivization of cooperative, truthful and trustworthy users. A grand concern for the participants is the battery drain on the mobile devices. It is a known fact that battery drain in a smartphone is a function of the user activity, which can be modeled under various contexts. With this in mind, we propose a new social activity-aware recruitment policy, namely Sociability-Oriented and Battery-Efficient Recruitment for Mobile Crowd-Sensing (SOBER-MCS). SOBER-MCS uses sociability and the residual power of the participant smartphones as two primary criteria in the selection of participating devices. The former is an indicator of the participant willingness toward sensing campaigns, whereas the latter is used to prioritize personal use over crowd-sensing under critical battery levels. We use sociability profiles that were obtained in our previous work and use those values to simulate the sociability behavior of a large pool of participants in an MCS environment. Through simulations, we show that SOBER-MCS is able to introduce battery savings up to 18.5% while improving user and platform utilities by 12% and 20%, respectively.

  16. SU-E-T-325: The New Evaluation Method of the VMAT Plan Delivery Using Varian DynaLog Files and Modulation Complexity Score (MCS)

    Energy Technology Data Exchange (ETDEWEB)

    Tateoka, K [Proton Treatment Center, Radiation Therapy Research Institute, Social Medical Corporation Teishinkai, Sapporo (Japan); Graduate School of Medicine, Sapporo Medical University, Sapporo, JP (Japan); Fujimomo, K; Hareyama, M [Proton Treatment Center, Radiation Therapy Research Institute, Social Medical Corporation Teishinkai, Sapporo (Japan); Saitou, Y; Nakazawa, T; Abe, T; Nakata, A; Yano, M [Graduate School of Medicine, Sapporo Medical University, Sapporo, JP (Japan)

    2014-06-01

    Purpose: The aim of the study is to evaluate the use of Varian DynaLog files to verify VMAT plans delivery and modulation complexity score (MCS) of VMAT. Methods: Delivery accuracy of machine performance was quantified by multileaf collimator (MLC) position errors, gantry angle errors and fluence delivery accuracy for volumetric modulated arc therapy (VMAT). The relationship between machine performance and plan complexity were also investigated using the modulation complexity score (MCS). Plan and Actual MLC positions, gantry angles and delivered fraction of monitor units were extracted from Varian DynaLog files. These factors were taken from the record and verify system of MLC control file. Planned and delivered beam data were compared to determine leaf position errors and gantry angle errors. Analysis was also performed on planned and actual fluence maps reconstructed from those of the DynaLog files. This analysis was performed for all treatment fractions of 5 prostate VMAT plans. The analysis of DynaLog files have been carried out by in-house programming in Visual C++. Results: The root mean square of leaf position and gantry angle errors were about 0.12 and 0.15, respectively. The Gamma of planned and actual fluence maps at 3%/3 mm criterion was about 99.21. The gamma of the leaf position errors were not directly related to plan complexity as determined by the MCS. Therefore, the gamma of the gantry angle errors were directly related to plan complexity as determined by the MCS. Conclusion: This study shows Varian dynalog files for VMAT plan can be diagnosed delivery errors not possible with phantom based quality assurance. Furthermore, the MCS of VMAT plan can evaluate delivery accuracy for patients receiving of VMAT. Machine performance was found to be directly related to plan complexity but this is not the dominant determinant of delivery accuracy.

  17. Mapping of Mcs30, a new mammary carcinoma susceptibility quantitative trait locus (QTL30 on rat chromosome 12: identification of fry as a candidate Mcs gene.

    Directory of Open Access Journals (Sweden)

    Xuefeng Ren

    Full Text Available Rat strains differ dramatically in their susceptibility to mammary carcinogenesis. On the assumption that susceptibility genes are conserved across mammalian species and hence inform human carcinogenesis, numerous investigators have used genetic linkage studies in rats to identify genes responsible for differential susceptibility to carcinogenesis. Using a genetic backcross between the resistant Copenhagen (Cop and susceptible Fischer 344 (F344 strains, we mapped a novel mammary carcinoma susceptibility (Mcs30 locus to the centromeric region on chromosome 12 (LOD score of ∼8.6 at the D12Rat59 marker. The Mcs30 locus comprises approximately 12 Mbp on the long arm of rat RNO12 whose synteny is conserved on human chromosome 13q12 to 13q13. After analyzing numerous genes comprising this locus, we identified Fry, the rat ortholog of the furry gene of Drosophila melanogaster, as a candidate Mcs gene. We cloned and determined the complete nucleotide sequence of the 13 kbp Fry mRNA. Sequence analysis indicated that the Fry gene was highly conserved across evolution, with 90% similarity of the predicted amino acid sequence among eutherian mammals. Comparison of the Fry sequence in the Cop and F344 strains identified two non-synonymous single nucleotide polymorphisms (SNPs, one of which creates a putative, de novo phosphorylation site. Further analysis showed that the expression of the Fry gene is reduced in a majority of rat mammary tumors. Our results also suggested that FRY activity was reduced in human breast carcinoma cell lines as a result of reduced levels or mutation. This study is the first to identify the Fry gene as a candidate Mcs gene. Our data suggest that the SNPs within the Fry gene contribute to the genetic susceptibility of the F344 rat strain to mammary carcinogenesis. These results provide the foundation for analyzing the role of the human FRY gene in cancer susceptibility and progression.

  18. Mutation analysis of the COL1A1 and COL1A2 genes in Vietnamese patients with osteogenesis imperfecta.

    Science.gov (United States)

    Ho Duy, Binh; Zhytnik, Lidiia; Maasalu, Katre; Kändla, Ivo; Prans, Ele; Reimann, Ene; Märtson, Aare; Kõks, Sulev

    2016-08-12

    The genetics of osteogenesis imperfecta (OI) have not been studied in a Vietnamese population before. We performed mutational analysis of the COL1A1 and COL1A2 genes in 91 unrelated OI patients of Vietnamese origin. We then systematically characterized the mutation profiles of these two genes which are most commonly related to OI. Genomic DNA was extracted from EDTA-preserved blood according to standard high-salt extraction methods. Sequence analysis and pathogenic variant identification was performed with Mutation Surveyor DNA variant analysis software. Prediction of the pathogenicity of mutations was conducted using Alamut Visual software. The presence of variants was checked against Dalgleish's osteogenesis imperfecta mutation database. The sample consisted of 91 unrelated osteogenesis imperfecta patients. We identified 54 patients with COL1A1/2 pathogenic variants; 33 with COL1A1 and 21 with COL1A2. Two patients had multiple pathogenic variants. Seventeen novel COL1A1 and 10 novel COL1A2 variants were identified. The majority of identified COL1A1/2 pathogenic variants occurred in a glycine substitution (36/56, 64.3 %), usually serine (23/36, 63.9 %). We found two pathogenic variants of the COL1A1 gene c.2461G > A (p.Gly821Ser) in four unrelated patients and one, c.2005G > A (p.Ala669Thr), in two unrelated patients. Our data showed a lower number of collagen OI pathogenic variants in Vietnamese patients compared to reported rates for Asian populations. The OI mutational profile of the Vietnamese population is unique and related to the presence of a high number of recessive mutations in non-collagenous OI genes. Further analysis of OI patients negative for collagen mutations, is required.

  19. Sequence and batch language programs and alarm related C Programs for the 242-A MCS

    International Nuclear Information System (INIS)

    Berger, J.F.

    1996-01-01

    A Distributive Process Control system was purchased by Project B-534, 242-A Evaporator/Crystallizer Upgrades. This control system, called the Monitor and Control system (MCS), was installed in the 242-A evaporator located in the 200 East Area. The purpose of the MCS is to monitor and control the Evaporator and monitor a number of alarms and other signals from various Tank Farm facilities. Applications software for the MCS was developed by the Waste Treatment Systems Engineering (WTSE) group of Westinghouse. The standard displays and alarm scheme provide for control and monitoring, but do not directly indicate the signal location or depict the overall process. To do this, WTSE developed a second alarm scheme

  20. CytoMCS: A Multiple Maximum Common Subgraph Detection Tool for Cytoscape

    DEFF Research Database (Denmark)

    Larsen, Simon; Baumbach, Jan

    2017-01-01

    such analyses we have developed CytoMCS, a Cytoscape app for computing inexact solutions to the maximum common edge subgraph problem for two or more graphs. Our algorithm uses an iterative local search heuristic for computing conserved subgraphs, optimizing a squared edge conservation score that is able...... to detect not only fully conserved edges but also partially conserved edges. It can be applied to any set of directed or undirected, simple graphs loaded as networks into Cytoscape, e.g. protein-protein interaction networks or gene regulatory networks. CytoMCS is available as a Cytoscape app at http://apps.cytoscape.org/apps/cytomcs....

  1. Mutational analysis of COL1A1 and COL1A2 genes among Estonian osteogenesis imperfecta patients.

    Science.gov (United States)

    Zhytnik, Lidiia; Maasalu, Katre; Reimann, Ene; Prans, Ele; Kõks, Sulev; Märtson, Aare

    2017-08-15

    Osteogenesis imperfecta (OI) is a rare bone disorder. In 90% of cases, OI is caused by mutations in the COL1A1/2 genes, which code procollagen α1 and α2 chains. The main aim of the current research was to identify the mutational spectrum of COL1A1/2 genes in Estonian patients. The small population size of Estonia provides a unique chance to explore the collagen I mutational profile of 100% of OI families in the country. We performed mutational analysis of peripheral blood gDNA of 30 unrelated Estonian OI patients using Sanger sequencing of COL1A1 and COL1A2 genes, including all intron-exon junctions and 5'UTR and 3'UTR regions, to identify causative OI mutations. We identified COL1A1/2 mutations in 86.67% of patients (26/30). 76.92% of discovered mutations were located in the COL1A1 (n = 20) and 23.08% in the COL1A2 (n = 6) gene. Half of the COL1A1/2 mutations appeared to be novel. The percentage of quantitative COL1A1/2 mutations was 69.23%. Glycine substitution with serine was the most prevalent among missense mutations. All qualitative mutations were situated in the chain domain of pro-α1/2 chains. Our study shows that among the Estonian OI population, the range of collagen I mutations is quite high, which agrees with other described OI cohorts of Northern Europe. The Estonian OI cohort differs due to the high number of quantitative variants and simple missense variants, which are mostly Gly to Ser substitutions and do not extend the chain domain of COL1A1/2 products.

  2. Comparison of plateletpheresis on the Fresenius AS.TEC 204 and Haemonetics MCS 3p.

    Science.gov (United States)

    Ranganathan, Sudha

    2007-02-01

    This is an attempt at comparing two cell separators for plateletpheresis, namely the Fresenius AS.TEC 204 and Haemonetics MCS 3p, at a tertiary care center in India. Donors who weighed between 55-75 kg, who had a hematocrit of 41-43%, and platelet counts of 250x10(3)-400x10(3)/microl were selected for the study. The comparability of the donors who donated on the two cell separators were analysed by t-test independent samples and no significant differences were found (P>0.05). The features compared were time taken for the procedure, volume processed on the separators, adverse reactions of the donors, quality control of the product, separation efficiency of the separators, platelet loss in the donors after the procedure, and the predictor versus the actual yield of platelets given by the cell separator. The volume processed to get a target yield of >3x10(11) was equal to 2.8-3.2 l and equal in both the cell separators. Symptoms of citrate toxicity were seen in 4 and 2.5% of donors who donated on the MCS 3p and the AS.TEC 204, respectively, and 3 and 1% of donors, respectively, had vasovagal reactions. All the platelet products collected had a platelet count of >3x10(11); 90% of the platelet products collected on the AS.TEC 204 attained the predicted yield that was set on the cell separator where as 75% of the platelet products collected on the MCS 3p attained the target yield. Quality control of the platelets collected on both the cell separators complied with the standards except that 3% of the platelets collected on the MCS 3p had a visible red cell contamination. The separation efficiency of the MCS 3p was higher, 50-52% as compared to the 40-45% on the AS.TEC 204. A provision of double venous access, less adverse reactions, negligible RBC contamination with a better predictor yield of platelets makes the AS.TEC 204 a safer and more reliable alternative than the widely used Haemonetics MCS 3p. Copyright (c) 2006 Wiley-Liss, Inc.

  3. DisoMCS: Accurately Predicting Protein Intrinsically Disordered Regions Using a Multi-Class Conservative Score Approach.

    Directory of Open Access Journals (Sweden)

    Zhiheng Wang

    Full Text Available The precise prediction of protein intrinsically disordered regions, which play a crucial role in biological procedures, is a necessary prerequisite to further the understanding of the principles and mechanisms of protein function. Here, we propose a novel predictor, DisoMCS, which is a more accurate predictor of protein intrinsically disordered regions. The DisoMCS bases on an original multi-class conservative score (MCS obtained by sequence-order/disorder alignment. Initially, near-disorder regions are defined on fragments located at both the terminus of an ordered region connecting a disordered region. Then the multi-class conservative score is generated by sequence alignment against a known structure database and represented as order, near-disorder and disorder conservative scores. The MCS of each amino acid has three elements: order, near-disorder and disorder profiles. Finally, the MCS is exploited as features to identify disordered regions in sequences. DisoMCS utilizes a non-redundant data set as the training set, MCS and predicted secondary structure as features, and a conditional random field as the classification algorithm. In predicted near-disorder regions a residue is determined as an order or a disorder according to the optimized decision threshold. DisoMCS was evaluated by cross-validation, large-scale prediction, independent tests and CASP (Critical Assessment of Techniques for Protein Structure Prediction tests. All results confirmed that DisoMCS was very competitive in terms of accuracy of prediction when compared with well-established publicly available disordered region predictors. It also indicated our approach was more accurate when a query has higher homologous with the knowledge database.The DisoMCS is available at http://cal.tongji.edu.cn/disorder/.

  4. Application of Modbus communication protocol and float-point display in MCS51 system

    International Nuclear Information System (INIS)

    Kong Xiangcheng; Liu Shaozhen

    2010-01-01

    As its widely opening and easy performance, Modbus communication protocol has a great advantage in field bus using. Details are given on a method to implement Modbus communication protocol based on MCS51 system, and the advantage of uVision integrated environment. The design realizes Modbus RTU mode communication, meanwhile the problem of synchronization in communication is solved. And float-point operation and display are achieved by format print. All of this are carried out under uVision integrated environment. The result approves that the response ratio of Modbus communication is 100%. The design shows the advantage of uVision integrated environment and MCS51 system. And also gives solution to the occasion where communication interface and low cost are required. (authors)

  5. PENGEMBANGAN SISTEM EKSPERIMEN VISKOSITAS BERBASIS PERSONAL KOMPUTER DAN MIKROKONTROLER MCS-51

    OpenAIRE

    Yohandri Yohandri

    2010-01-01

    In this work, viscosity experiment system based on personal computer and microcontroller MCS-51 has been developed. The new model of viscosity experiment system is purposed to perfom the time and viscosity calculation automatically on the personal computer. The graph and statical analysis are used to determine characteristics of LDR sensor and experiment system such as sensitivity, accuracy, and precision. There were four main results of this research as follow : 1). LDR sensor resistance dec...

  6. Debating the legitimacy of a contested environmental illness: a case study of multiple chemical sensitivities (MCS).

    Science.gov (United States)

    Phillips, Tarryn

    2010-11-01

    More than 20years after it was first identified, the anomalous condition, multiple chemical sensitivities (MCS), remains immersed in controversy, with a continuing debate over its causation being played out in the medico-scientific community and in the courts. This article examines why sceptical and supportive experts disagree over the condition's legitimacy as an organic condition. Drawing on ethnographic research conducted in Perth, Western Australia, the author scrutinises the decision-making practices of 16 experts (eight sceptical and eight supportive of a chemical explanation). Both groups were found to use evidence-based, inductive reasoning. However, sceptical experts tended to use a different set of evidence requirements, exhibited more faith in the efficiency of the current biomedical paradigm regarding toxicity and were less likely to acknowledge uncertainty in their field. All the experts recognised a spectrum of beliefs about the causal mechanisms of MCS. However, when they were engaged in litigation as expert witnesses due to their supportive or sceptical tendency, the oppositional legal system polarised their opinions and exacerbated the perceived divide between them. Ultimately, the adversarial medico-legal process inhibits genuine dialogue between some of the key players in the MCS debate, thus impeding understanding and consensus about the condition. © 2010 The Author. Sociology of Health & Illness © 2010 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

  7. AK-SYS: An adaptation of the AK-MCS method for system reliability

    International Nuclear Information System (INIS)

    Fauriat, W.; Gayton, N.

    2014-01-01

    A lot of research work has been proposed over the last two decades to evaluate the probability of failure of a structure involving a very time-consuming mechanical model. Surrogate model approaches based on Kriging, such as the Efficient Global Reliability Analysis (EGRA) or the Active learning and Kriging-based Monte-Carlo Simulation (AK-MCS) methods, are very efficient and each has advantages of its own. EGRA is well suited to evaluating small probabilities, as the surrogate can be used to classify any population. AK-MCS is built in relation to a given population and requires no optimization program for the active learning procedure to be performed. It is therefore easier to implement and more likely to spend computational effort on areas with a significant probability content. When assessing system reliability, analytical approaches and first-order approximation are widely used in the literature. However, in the present paper we rather focus on sampling techniques and, considering the recent adaptation of the EGRA method for systems, a strategy is presented to adapt the AK-MCS method for system reliability. The AK-SYS method, “Active learning and Kriging-based SYStem reliability method”, is presented. Its high efficiency and accuracy are illustrated via various examples

  8. SISTEM PENGEMBANGAN KENDALI FUZZY LOGIC BERBASIS MIKROKONTROLER KELUARGA MCS51 (PetraFuz

    Directory of Open Access Journals (Sweden)

    Thiang Thiang

    1999-01-01

    Full Text Available This paper presents a Fuzzy Logic Development Tool called PetraFuz which has been developed at Control System Laboratory, Electrical Engineering Department, Petra Christian University. The system consists of a hardware target based on MCS51 microcontroller and a software support running under PC Windows. The system is targeted for developing fuzzy logic based systems. It supports fuzzy logic design, evaluation, assembly language generator and downloading process to the target hardware to perform on-line fuzzy process. Process action and fuzzy parameters could be transferred to PC monitor via RS-232 serial communication, this on-line process parameters is used for fuzzy tuning, i.e. fuzzy if-then rules and fuzzy membership functions. The PetraFuz tool helps very much for Fuzzy system developments, it could reduce development time significantly. The tool could spur the development of fuzzy systems based on microcontroller systems such as fuzzy control systems, fuzzy information processing, etc. Abstract in Bahasa Indonesia : Makalah ini menyajikan sebuah sistem pengembangan kendali fuzzy logic (PetraFuz, Petra Fuzzy Development System yang dikembangkan oleh laboratorium Sistem Kontrol, Jurusan Teknik Elektro, Universitas Kristen Petra Surabaya. Sistem ini terdiri dari perangkat keras sistem mikrokontroler MCS51 dan perangkat lunak pendukung yang berjalan pada PC. Sistem PetraFuz digunakan untuk mengembangkan sistem berbasis fuzzy logic utamanya pada bidang kendali. Kemampuan sistem meliputi pengembangan pada fase perancangan kendali, evaluasi kendali, pembentukan program bahasa assembly MCS51 dan proses downloading program menuju target sistem mikrokontroler MCS51 untuk dieksekusi melakukan kendali pada plant yang nyata. Aksi kendali dapat diakuisi oleh program PC melalui komunikasi serial RS232 sehingga respon kendali dapat digambarkan pada layar monitor untuk dilakukan analisis lebih lanjut yang diperlukan pada proses tuning if-then fuzzy rules

  9. Evaluation of central nervous system in patients with glycogen storage disease type 1a.

    Science.gov (United States)

    Aydemir, Yusuf; Gürakan, Figen; Saltık Temizel, İnci Nur; Demir, Hülya; Oğuz, Kader Karlı; Yalnızoğlu, Dilek; Topçu, Meral; Özen, Hasan; Yüce, Aysel

    2016-01-01

    We aimed to evaluate structure and functions of central nervous system (CNS) in children with glycogen storage disease (GSD) type 1a. Neurological examination, psychometric tests, electroencephalography (EEG), magnetic resonance imaging (MRI), visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) were performed. The results were compared between patients with good and poor metabolic control and healthy children. Twenty-three patients with GSD type 1a were studied. Twelve patients were in poor metabolic control group and 11 patients in good metabolic control group. Five patients had intellectual disability, 10 had EEG abnormalities, seven had abnormal VEP and two had abnormal BAEP results. MRI was abnormal in five patients. There was significant correlation between the number of hypoglycemic attacks and MRI abnormalities. Central nervous system may be affected in GSD type 1a even in patients with normal neurologic examination. Accumulation of abnormal results in patients with poor metabolic control supports the importance of metabolic control in GSD type 1a.

  10. Alpha-defensin DEFA1A3 gene copy number elevation in Danish Crohn's disease patients

    DEFF Research Database (Denmark)

    Jespersgaard, Cathrine; Fode, Peder; Dybdahl, Marianne

    2011-01-01

    BACKGROUND AND PURPOSE OF STUDY: Extensive copy number variation is observed for the DEFA1A3 gene encoding alpha-defensins 1-3. The objective of this study was to determine the involvement of alpha-defensins in colonic tissue from Crohn's disease (CD) patients and the possible genetic association...... of DEFA1A3 with CD. METHODS: Two-hundred and forty ethnic Danish CD patients were included in the study. Reverse transcriptase PCR assays determined DEFA1A3 expression in colonic tissue from a subset of patients. Immunohistochemical analysis identified alpha-defensin peptides in colonic tissue. Copy...

  11. Improved quantitative analysis of Cu(In,Ga)Se{sub 2} thin films using MCs{sup +}-SIMS depth profiling

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jihye; Kim, Seon Hee; Lee, Kang-Bong; Lee, Yeonhee [Korea Institute of Science and Technology, Advanced Analysis Center, Seoul (Korea, Republic of); Min, Byoung Koun [Korea Institute of Science and Technology, Clean Energy Research Center, Seoul (Korea, Republic of)

    2014-06-15

    The chalcopyrite semiconductor, Cu(InGa)Se{sub 2} (CIGS), is popular as an absorber material for incorporation in high-efficiency photovoltaic devices because it has an appropriate band gap and a high absorption coefficient. To improve the efficiency of solar cells, many research groups have studied the quantitative characterization of the CIGS absorber layers. In this study, a compositional analysis of a CIGS thin film was performed by depth profiling in secondary ion mass spectrometry (SIMS) with MCs{sup +} (where M denotes an element from the CIGS sample) cluster ion detection, and the relative sensitivity factor of the cluster ion was calculated. The emission of MCs{sup +} ions from CIGS absorber elements, such as Cu, In, Ga, and Se, under Cs{sup +} ion bombardment was investigated using time-of-flight SIMS (TOF-SIMS) and magnetic sector SIMS. The detection of MCs{sup +} ions suppressed the matrix effects of varying concentrations of constituent elements of the CIGS thin films. The atomic concentrations of the CIGS absorber layers from the MCs{sup +}-SIMS exhibited more accurate quantification compared to those of elemental SIMS and agreed with those of inductively coupled plasma atomic emission spectrometry. Both TOF-SIMS and magnetic sector SIMS depth profiles showed a similar MCs{sup +} distribution for the CIGS thin films. (orig.)

  12. Regression analysis of MCS Intensity and peak ground motion data in Italy

    Science.gov (United States)

    Faenza, L.; Michelini, A.

    2009-04-01

    Intensity scales are historically important because no instrumentation is necessary, and useful measurements of earthquake shaking can be made by an unequipped observer. The use of macroseismics data are essential for the revision of historical seismicity and of great importance for seismic hazard assessment of vulnerable areas. The procedure ShakeMap (Wald et al., Earthquake Spectra., 15, 1999) provides instrumentally based estimates of intensity maps. In Italy, intensities have been hitherto reported through the use of the MCS (Mercalli, Cancani Sieberg) intensity scale. The DBMI2004 (and the most recent DBMI08) report intensities for earthquakes in Italy that date back to Roman age. In order to exploit fully the potential of such a long intensity catalogue for past large events and with the aim of presenting ShakeMaps using an intensity scale consistent with that of the past, we have ri-calibrated the relationships between MCS intensity and observed peak ground motion (PGM) values in terms of both peak-ground acceleration and peak-ground velocities. To this end, we have used the two most updataed and complete dataset available for Italy - the strong motion Itaca database and the DBMI08 macroseismic database. In this work we have first assembled a data set consisting of PGM-intensity pairs and we have then determined the most suitable regressions parameters. Many tests have been made to quantify the accuracy and robustness of the results. The new instrumental intensity scale is going to be adopted for mapping the level of shaking resulting from earthquakes in Italy replacing the instrumental Modified Mercalli scale currently in use (Michelini et al., SRL, 79, 2008) and to determine shakemaps for historical events.

  13. Genetic Alterations within the DENND1A Gene in Patients with Polycystic Ovary Syndrome (PCOS)

    DEFF Research Database (Denmark)

    Eriksen, Mette B; Nielsen, Michael F B; Brusgaard, Klaus

    2013-01-01

    sequencing. SNP genotyping was tested by allelic discrimination in real-time PCR in the additional patients and controls. Sequencing of the DENND1A gene identified eight SNPs; seven were not known to be associated with any diseases. One missense SNP was detected (rs189947178, A/C), potentially altering......Polycystic ovary syndrome (PCOS), the most common endocrine disease among premenopausal women, is caused by both genes and environment. We and others previously reported association between single nucleotide polymorphisms (SNPs) in the DENND1A gene and PCOS. We therefore sequenced the DENND1A gene...... and FG-score or PCOS diagnosis, this could be a false positive finding. In conclusion, sequence analysis of the DENND1A gene of patients with PCOS did not identify alterations that alone could be responsible for the PCOS pathogenesis, but a missense SNP (rs189947178) was identified in one patient...

  14. Genetic alterations within the DENND1A gene in patients with polycystic ovary syndrome (PCOS.

    Directory of Open Access Journals (Sweden)

    Mette B Eriksen

    Full Text Available Polycystic ovary syndrome (PCOS, the most common endocrine disease among premenopausal women, is caused by both genes and environment. We and others previously reported association between single nucleotide polymorphisms (SNPs in the DENND1A gene and PCOS. We therefore sequenced the DENND1A gene in white patients with PCOS to identify possible alterations that may be implicated in the PCOS pathogenesis. Patients were referred with PCOS and/or hirsutism between 1998 and 2011 (n = 261. PCOS was diagnosed according to the Rotterdam criteria (n = 165. Sequence analysis was performed in 10 patients with PCOS. Additional patients (n = 251 and healthy female controls (n = 248 were included for SNP genotyping. Patients underwent clinical examination including Ferriman-Gallwey score (FG-score, biochemical analyses and transvaginal ultrasound. Mutation analysis was carried out by bidirectional sequencing. SNP genotyping was tested by allelic discrimination in real-time PCR in the additional patients and controls. Sequencing of the DENND1A gene identified eight SNPs; seven were not known to be associated with any diseases. One missense SNP was detected (rs189947178, A/C, potentially altering the structural conformation of the DENND1A protein. SNP genotyping of rs189947178 showed significantly more carriers among patients with PCOS and moderate hirsutism compared to controls. However, due to small sample size and lack of multiple regression analysis supporting an association between rs189947178 and FG-score or PCOS diagnosis, this could be a false positive finding. In conclusion, sequence analysis of the DENND1A gene of patients with PCOS did not identify alterations that alone could be responsible for the PCOS pathogenesis, but a missense SNP (rs189947178 was identified in one patient and significantly more carriers of rs189947178 were found among patients with PCOS and moderate hirsutism vs. controls. Additional studies with independent cohort are needed

  15. Methylation status and protein expression of RASSF1A in breast cancer patients.

    Science.gov (United States)

    Hagrass, Hoda A; Pasha, Heba F; Shaheen, Mohamed A; Abdel Bary, Eman H; Kassem, Rasha

    2014-01-01

    Recently genetics and epigenetics alterations have been found to be characteristic of malignancy and hence can be used as targets for detection of neoplasia. RAS association domain family protein 1A (RASSF1A) gene hypermethylation has been a subject of interest in recent researches on cancer breast patients. The aim of the present study was to evaluate whether RASSF1A methylation status and RASSF1A protein expression are associated with the major clinico-pathological parameters. One hundred and twenty breast cancer Egyptian patients and 100-control subjects diagnosed with benign lesions of the breast were enrolled in this study. We evaluated RASSF1A methylation status in tissue and serum samples using Methyl specific PCR together with RASSF1A protein expression in tissues by immunohistochemistry. Results were studied in relation to known prognostic clinicopathological features in breast cancer. Frequency of RASSF1A methylation in tissues and serum were 70 and 63.3 % respectively and RASSF1A protein expression showed frequency of 46.7 %. There was an association between RASSF1A methylation in tissues, serum and loss of protein expression in tissues with invasive carcinoma, advanced stage breast cancer, L.N. metastasis, ER/PR and HER2 negativity. RASSF1A methylation in serum showed high degree of concordance with methylation in tissues (Kappa = 0.851, P < 0.001). RASSF1A hypermethylation in tissues and serum and its protein expression may be a valid, reliable and sensitive tool for detection and follow up of breast cancer patients.

  16. Genetic evaluation for TOR1-A (DYT1 in Brazilian patients with dystonia

    Directory of Open Access Journals (Sweden)

    Carlos Henrique F. Camargo

    2014-10-01

    Full Text Available Several genes have been mapped in families or in sporadic cases of dystonia. TOR1-A (DYT1 gene was linked to isolated dystonia. Objective To associate clinical information of patients with dystonia with the TOR1-A gene mutations. Method Eighty-eight patients with dystonia in cervical area (focal, segmental, multifocal and generalized were recruited at Movement Disorders Clinic of Hospital de Clínicas of the Federal University of Paraná between June of 2008 and June of 2009. They were submitted to the clinical evaluation. DNA was extract from blood and submitted at analysis to TOR1-A mutations by PCR according standard protocols. Results Two patients had c.907GAGdel mutation on TOR1-A gene. These patients, with familial history of dystonia, started his symptoms by legs and had secondary generalization. Conclusion We can suggest that analysis for TOR1-A mutations should be performed only in patients with early onset, generalized and familial dystonia.

  17. [Alternating hemiplegia of childhood: ATP1A3 gene analysis in 16 patients].

    Science.gov (United States)

    Ulate-Campos, Adriana; Fons, Carmen; Campistol, Jaume; Martorell, Loreto; Cancho-Candela, Ramón; Eiris, Jesús; López-Laso, Eduardo; Pineda, Mercedes; Sans, Anna; Velázquez, Ramón

    2014-07-07

    Alternating hemiplegia in childhood (AHC) is a disease characterized by recurrent episodes of hemiplegia, tonic or dystonic crisis and abnormal ocular movements. Recently, mutations in the ATP1A3 gene have been identified as the causal mechanism of AHC. The objective is to describe a series of 16 patients with clinical and genetic diagnosis of AHC. It is a descriptive, retrospective, multicenter study of 16 patients with clinical diagnosis of AHC in whom mutations in ATP1A3 were identified. Six heterozygous, de novo mutations were found in the ATP1A3 gene. The most frequent mutation was G2401A in 8 patients (50%) followed by G2443A in 3 patients (18.75%), G2893A in 2 patients (12.50%) and C2781G, G2893C and C2411T in one patient, respectively (6.25% each). In the studied population with AHC, de novo mutations were detected in 100% of patients. The most frequent mutations were D801N y la E815K, as reported in other series. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  18. SNPs in Multi-Species Conserved Sequences (MCS as useful markers in association studies: a practical approach

    Directory of Open Access Journals (Sweden)

    Pericak-Vance Margaret A

    2007-08-01

    Full Text Available Abstract Background Although genes play a key role in many complex diseases, the specific genes involved in most complex diseases remain largely unidentified. Their discovery will hinge on the identification of key sequence variants that are conclusively associated with disease. While much attention has been focused on variants in protein-coding DNA, variants in noncoding regions may also play many important roles in complex disease by altering gene regulation. Since the vast majority of noncoding genomic sequence is of unknown function, this increases the challenge of identifying "functional" variants that cause disease. However, evolutionary conservation can be used as a guide to indicate regions of noncoding or coding DNA that are likely to have biological function, and thus may be more likely to harbor SNP variants with functional consequences. To help bias marker selection in favor of such variants, we devised a process that prioritizes annotated SNPs for genotyping studies based on their location within Multi-species Conserved Sequences (MCSs and used this process to select SNPs in a region of linkage to a complex disease. This allowed us to evaluate the utility of the chosen SNPs for further association studies. Previously, a region of chromosome 1q43 was linked to Multiple Sclerosis (MS in a genome-wide screen. We chose annotated SNPs in the region based on location within MCSs (termed MCS-SNPs. We then obtained genotypes for 478 MCS-SNPs in 989 individuals from MS families. Results Analysis of our MCS-SNP genotypes from the 1q43 region and comparison to HapMap data confirmed that annotated SNPs in MCS regions are frequently polymorphic and show subtle signatures of selective pressure, consistent with previous reports of genome-wide variation in conserved regions. We also present an online tool that allows MCS data to be directly exported to the UCSC genome browser so that MCS-SNPs can be easily identified within genomic regions of

  19. PENGEMBANGAN SISTEM EKSPERIMEN VISKOSITAS BERBASIS PERSONAL KOMPUTER DAN MIKROKONTROLER MCS-51

    Directory of Open Access Journals (Sweden)

    Yohandri Yohandri

    2010-06-01

    Full Text Available In this work, viscosity experiment system based on personal computer and microcontroller MCS-51 has been developed. The new model of viscosity experiment system is purposed to perfom the time and viscosity calculation automatically on the personal computer. The graph and statical analysis are used to determine characteristics of LDR sensor and experiment system such as sensitivity, accuracy, and precision. There were four main results of this research as follow : 1. LDR sensor resistance decreased with increasing light intensity and sensitivity of sensor was  -11,55.(I-1,56, 2. The comparator output voltage are two condition depend on light intensity, below 400 lux the output voltage is 4.54 Volt and for above is 0.59 Volt, 3. The accuracy and precision average of system timer was high, each of it was 99.9% and 0.97, 4. Ability of system to determine the value of the liquids viscosity has been tested and obtained three results for glycerin, SAE40 Oil, and cooking oil which the value of each sequence are 1121.99 mPas, 795.08 mPas and 79.78 mPas. Based on repeated measurement in viscosity, the precision of system have been obtained which average 0.994.     Key words: viscosity, personal computer, microcontroller, sensitivity, accuracy, precesion

  20. The impact of MCS models and EFAC values on the dose simulation for a proton pencil beam

    International Nuclear Information System (INIS)

    Chen, Shih-Kuan; Chiang, Bing-Hao; Lee, Chung-Chi; Tung, Chuan-Jong; Hong, Ji-Hong; Chao, Tsi-Chian

    2017-01-01

    The Multiple Coulomb Scattering (MCS) model plays an important role in accurate MC simulation, especially for small field applications. The Rossi model is used in MCNPX 2.7.0, and the Lewis model in Geant4.9.6.p02. These two models may generate very different angular and spatial distributions in small field proton dosimetry. Beside angular and spatial distributions, step size is also an important issue that causes path length effects. The Energy Fraction (EFAC) value can be used in MCNPX 2.7.0 to control step sizes of MCS. In this study, we use MCNPX 2.7.0, Geant4.9.6.p02, and one pencil beam algorithm to evaluate the effect of dose deposition because of different MCS models and different EFAC values in proton disequilibrium situation. Different MCS models agree well with each other under a proton equilibrium situation. Under proton disequilibrium situations, the MCNPX and Geant4 results, however, show a significant deviation (up to 43%). In addition, the path length effects are more significant when EFAC is equal to 0.917 and 0.94 in small field proton dosimetry, and using a 0.97 EFAC value is the best for both accuracy and efficiency - Highlights: • MCS and EFAC are important in accurate MC simulation for proton pencil beams. • Bragg curves of MCNPX and Geant4 have a dose deviation up to 43%. • Lateral profiles from MCNPX is wider than those from Geant4. • Large EFAC caused path length effect, but no effects on lateral profiles. • 0.97 EFAC value is the best for both accuracy and efficiency.

  1. Intima-media thickness and endothelial dysfunction in GCK and HNF1A-MODY patients.

    Science.gov (United States)

    Szopa, Magdalena; Osmenda, Grzegorz; Wilk, Grzegorz; Matejko, Bartłomiej; Skupien, Jan; Zapala, Barbara; Młynarski, Wojciech; Guzik, Tomasz; Malecki, Maciej T

    2015-03-01

    Mutations in the glucokinase (GCK) gene, along with hepatocyte nuclear factor 1A (HNF1A) gene mutations, are the most frequent cause of maturity-onset diabetes of the young (MODY). GCK-MODY patients are typically characterized by a moderate fasting hyperglycemia; however, little is known about atherosclerosis and intermediate-related phenotypes in these subjects. To examine carotid artery intima-media thickness (IMT) and endothelial function assessed by brachial artery flow-mediated dilatation (FMD) in GCK gene mutations carriers and HNF1A-MODY. A total of 64 subjects with GCK gene mutations, and 52 HNF1A gene mutation carriers as well as 53 nondiabetic controls were examined. IMT and FMD were assessed by ultrasonography. Appropriate statistical tests were performed to assess differences between the groups, and multivariate linear regression was done for the association with IMT and FMD. The clinical characteristics of all groups were similar with the mean age at examination of 35.1, 41.1, and 39.5 years for GCK, HNF1A and the control group respectively. The highest mean IMT value was in the HNF1A-MODY group: 7.0±1.4 mm, whereas it reached 6.3±1.4 mm in GCK mutation carriers and 6.3±1.3 mm in controls (P=0.008). After adjustment for possible clinical and biochemical cofounders, IMT remained higher in HNF1A-MODY patients as compared with GCK-MODY patients (P=0.02) and controls (P=0.0003). FMD was significantly lower in HNF1A (9.9±4.6%) and GCK-MODY (11.1±4.6%) patients in comparison with controls (13.9±4.7%; P=0.0001). After adjustment, FMD remained lower in HNF1A-MODY (P=0.0005) and GCK-MODY patients (P=0.01) as compared with controls. Both examined MODY groups demonstrated evidence of endothelial dysfunction. In addition, HNF1-MODY patients seem to be more prone to an early atherosclerotic phenotype. © 2015 European Society of Endocrinology.

  2. Circulating microRNA-1a is a biomarker of Graves' disease patients with atrial fibrillation.

    Science.gov (United States)

    Wang, Fang; Zhang, Sheng-Jie; Yao, Xuan; Tian, Dong-Mei; Zhang, Ke-Qin; She, Dun-Min; Guo, Fei-Fan; Zhai, Qi-Wei; Ying, Hao; Xue, Ying

    2017-07-01

    It has been increasingly suggested that specific microRNAs expression profiles in the circulation and atrial tissue are associated with the susceptibility to atrial fibrillation. Nonetheless, the role of circulating microRNAs in Graves' disease patients with atrial fibrillation has not yet been well described. The objective of the study was to identify the role of circulating microRNAs as specific biomarkers for the diagnosis of Graves' disease with atrial fibrillation. The expression profiles of eight serum microRNAs, which are found to be critical in the pathogenesis of atrial fibrillation, were determined in patients with Graves' disease with or without atrial fibrillation. MicroRNA expression analysis was performed by real-time PCR in normal control subjects (NC; n = 17), patients with Graves' disease without atrial fibrillation (GD; n = 29), patients with Graves' disease with atrial fibrillation (GD + AF; n = 14), and euthyroid patients with atrial fibrillation (AF; n = 22). Three of the eight serum microRNAs,i.e., miR-1a, miR-26a, and miR-133, had significantly different expression profiles among the four groups. Spearman's correlation analysis showed that the relative expression level of miR-1a was positively correlated with free triiodothyronine (FT3) and free thyroxine (FT4), and negatively related to thyroid stimulating hormone. Spearman's correlations analysis also revealed that the level of miR-1a was negatively correlated with a critical echocardiographic parameter (left atrial diameter), which was dramatically increased in GD + AF group compared to GD group. Furthermore, the receiver-operating characteristic curve analysis indicated that, among the eight microRNAs, miR-1a had the largest area under the receiver-operating characteristic curves not only for discriminating between individuals with and without Graves' disease, but also for predicting the presence of atrial fibrillation in patients with Graves' disease. Our findings

  3. From individual coping strategies to illness codification: the reflection of gender in social science research on multiple chemical sensitivities (MCS).

    Science.gov (United States)

    Nadeau, Geneviève; Lippel, Katherine

    2014-09-10

    Emerging fields such as environmental health have been challenged, in recent years, to answer the growing methodological calls for a finer integration of sex and gender in health-related research and policy-making. Through a descriptive examination of 25 peer-reviewed social science papers published between 1996 and 2011, we explore, by examining methodological designs and theoretical standpoints, how the social sciences have integrated gender sensitivity in empirical work on Multiple Chemical Sensitivities (MCS). MCS is a "diagnosis" associated with sensitivities to chronic and low-dose chemical exposures, which remains contested in both the medical and institutional arenas, and is reported to disproportionately affect women. We highlighted important differences between papers that did integrate a gender lens and those that did not. These included characteristics of the authorship, purposes, theoretical frameworks and methodological designs of the studies. Reviewed papers that integrated gender tended to focus on the gender roles and identity of women suffering from MCS, emphasizing personal strategies of adaptation. More generally, terminological confusions in the use of sex and gender language and concepts, such as a conflation of women and gender, were observed. Although some men were included in most of the study samples reviewed, specific data relating to men was undereported in results and only one paper discussed issues specifically experienced by men suffering from MCS. Papers that overlooked gender dimensions generally addressed more systemic social issues such as the dynamics of expertise and the medical codification of MCS, from more consistently outlined theoretical frameworks. Results highlight the place for a critical, systematic and reflexive problematization of gender and for the development of methodological and theoretical tools on how to integrate gender in research designs when looking at both micro and macro social dimensions of environmental

  4. Prevalence of Retinopathy in Adult Patients with GCK-MODY and HNF1A-MODY.

    Science.gov (United States)

    Szopa, M; Wolkow, J; Matejko, B; Skupien, J; Klupa, T; Wybrańska, I; Trznadel-Morawska, I; Kiec-Wilk, B; Borowiec, M; Malecki, M T

    2015-10-01

    We aimed to assess the prevalence of diabetic retinopathy (DR) in adult patients with GCK-MODY and HNF1A-MODY in Poland and to identify biochemical and clinical risk factors associated with its occurrence.We examined 74 GCK mutation carriers, 51 with diabetes and 23 with prediabetes, respectively, and 63 patients with HNF1A-MODY. Retinal photographs, 12 for each patient, were done by a fundus camera. Signs of DR were graded according to the DR disease severity scale. Statistical tests were performed to assess differences between the groups and logistic regression was done for the association with DR.The mean age at examination was 34.5±14.8 and 39.9±15.2 in the GCK-MODY and HNF1A-MODY groups, respectively. Mild nonproliferative DR (NPDR) was found in one patient with the GCK mutation and likely concomitant type 1 diabetes, whereas DR was diagnosed in 15 HNF1A-MODY patients: 9 with proliferative, 3 with moderate NPDR and 2 with mild NPDR. In univariate logistic regression analysis in the HNF1A-MODY group, significant results were found for diabetes duration, fasting glycemia, HbA1c, arterial hypertension, age at the examination, and eGFR. The strongest independent predictors of DR in HNF1A-MODY were markers of glucose control: HbA1c (OR: 2.05, CL%95: 1.2-3.83, p=0.01) and glucose (p=0.006, OR: 1.40, CL%95: 1.12-1.83) analyzed in 2 separated models. Additionally, arterial hypertension independently predicted DR (OR: 9.06, CL%95: 1.19-98.99, p=0.04) in the model with HbA1c as glycaemic control marker.In conclusion, DR of any degree was not present in our GCK-MODY group, while in spite of young age almost every fourth subject with HNF1A-MODY showed signs of this complication. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Detection and monitoring of hypermethylated RASSF1A in serum from patients with metastatic breast cancer

    DEFF Research Database (Denmark)

    Kristiansen, Søren; Nielsen, Dorte Lisbet; Søletormos, Gyorgy Tamas Pal

    2016-01-01

    BACKGROUND: Circulating hypermethylated RASSF1A could be a novel and potential useful marker for monitoring patients with metastatic breast cancer. Technical obstacles include fragmentation of the circulating DNA, fluctuations in the concentration, low concentrations of circulating tumor DNA...... in circulating non-tumor DNA. As a proof of principle, there was concordance in the kinetics of the RASSF1A and the serological cancer biomarkers CA 15-3, CEA, and TPA. CONCLUSIONS: Methylation-sensitive restriction enzymes may be a useful methodological approach for monitoring circulating hypermethylated RASSF1...... of the rare circulating tumor DNA was initially optimized. By analysis of production of PCR amplicons from HpaII- or BstUI-treated DNA isolated from 24 patients with metastatic breast cancer, we located four regions resulting in sensitivities from 63 to 83 %. When examining samples from 24 control subjects...

  6. PRKAR1A mutation causing pituitary-dependent Cushing disease in a patient with Carney complex.

    Science.gov (United States)

    Kiefer, Florian W; Winhofer, Yvonne; Iacovazzo, Donato; Korbonits, Márta; Wolfsberger, Stefan; Knosp, Engelbert; Trautinger, Franz; Höftberger, Romana; Krebs, Michael; Luger, Anton; Gessl, Alois

    2017-08-01

    Carney complex (CNC) is an autosomal dominant condition caused, in most cases, by an inactivating mutation of the PRKAR1A gene, which encodes for the type 1 alpha regulatory subunit of protein kinase A. CNC is characterized by the occurrence of endocrine overactivity, myxomas and typical skin manifestations. Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine disease observed in CNC. Here, we describe the first case of a patient with CNC and adrenocorticotropic hormone (ACTH)-dependent Cushing disease due to a pituitary corticotroph adenoma. Loss-of-heterozygosity analysis of the pituitary tumour revealed loss of the wild-type copy of PRKAR1A , suggesting a role of this gene in the pituitary adenoma development. PRKAR1A loss-of-function mutations can rarely lead to ACTH-secreting pituitary adenomas in CNC patients. Pituitary-dependent disease should be considered in the differential diagnosis of Cushing syndrome in CNC patients. © 2017 European Society of Endocrinology.

  7. Sequence and batch language programs and alarm-related ``C`` programs for the 242-A MCS. Revision 2

    Energy Technology Data Exchange (ETDEWEB)

    Berger, J.F.

    1995-03-01

    A Distributive Process Control system was purchased by Project B-534, ``242-A Evaporator/Crystallizer Upgrades``. This control system, called the Monitor and Control System (MCS), was installed in the 242-A Evaporator located in the 200 East Area. The purpose of the MCS is to monitor and control the Evaporator and monitor a number of alarms and other signals from various Tank Farm facilities. Applications software for the MCS was developed by the Waste Treatment Systems Engineering (WTSE) group of Westinghouse. The standard displays and alarm scheme provide for control and monitoring, but do not directly indicate the signal location or depict the overall process. To do this, WTSE developed a second alarm scheme which uses special programs, annunciator keys, and process graphics. The special programs are written in two languages; Sequence and Batch Language (SABL), and ``C`` language. The WTSE-developed alarm scheme works as described below: SABL relates signals and alarms to the annunciator keys, called SKID keys. When an alarm occurs, a SABL program causes a SKID key to flash, and if the alarm is of yellow or white priority then a ``C`` program turns on an audible horn (the D/3 system uses a different audible horn for the red priority alarms). The horn and flashing key draws the attention of the operator.

  8. Molecular detection of interleukin-1A +4845 G→T gene in aggresive periodontitis patients

    Directory of Open Access Journals (Sweden)

    Chiquita Prahasanti

    2012-12-01

    Full Text Available Background: Abundant researches had been conducted based on the clinical and histopathological pathogenesis of aggresive periodontitis. Nevertheless, there were still few researches which based on molecular biology, and especially related to gene polymorphism. This study was done based on IL-1A +4845G→T gene polymorphism in aggressive periodontitis patients. Purpose: The purpose of this tudy was to characterized the generic variation of IL-1A +4845G→T as a risk factor aggressive periodontitis and chronic periodontitis. Methods: DNA from patients with aggressive periodontitis and chronic periodontitis was taken determination of IL-1A +4845 G→T polimorphism was conducted with PCR-RFLP technique. Results: Homozygous allele TT polymorphism was not found in all samples, only allele GG (wild type and allele GT (heterozygous mutant were not affect aggressive periodontitis and chronic periodontitis. Conclusion: The study showed there was no significant association between IL-1A +4845G→T gene polymorphism and aggressive periodontitis and chronic periodontitis. Latar belakang: Penelitian tentang patogenesa periodontitis agresif berdasar klinis dan histopatologi telah banyak dilakukan, akan tetapi penelitian berdasar biologimolekuler terutama polimorfisme gen masih sangat jarang dilakukan. Penelitian ini dilakukan berdasarkan pada polimorfisme gen IL-1A +4845G→T pada penderita periodontitis agresif. Tujuan: Tujuan dari penelitian ini adalah untuk mengetahui variasi genetik dari IL-1A +4845G→T yang merupakan faktor risiko periodontitis agresif dan periodontitis kronis. Metode: DNA dari penderita periodontitis agresif dan periodontitis kronis diisolasi, selanjutnya dilakukan determinasi dari polimorfisme gen IL-1A +4845G→T dengan menggunakan teknik PCR-RFLP. Hasil: Pada seluruh sampel penelitian ini tidak dijumpai polimorfisme allel TT (homosigot mutan, yang didapat adalah jenis allel GG (wild type dan allel GT (heterosigot mutan yang tidak

  9. Sporadic Carney complex without PRKAR1A mutation in a young patient with ischemic stroke.

    Science.gov (United States)

    Aguiar de Sousa, Diana; Gouveia, Ana Isabel; Wessling, Ana; Geraldes, Ruth; Canhão, Patrícia

    2015-03-01

    We describe a 29-year-old male, with a previous history of testicular tumor, who presented with a posterior circulation ischemic stroke associated to an atrial myxoma. Dermatologic observation disclosed spotty skin and mucosal pigmentation (lentigines), and a cutaneous myxoma was histopathologically confirmed. Although there was no family history of any of the Carney complex (CNC) features and no mutations in the PRKAR1A gene were found, these findings lead to the diagnosis of CNC. We emphasize the importance of recognizing this entity in young patients with stroke. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  10. Removal of MCs by Bi2O2CO3: adsorption and the potential of photocatalytic degradation.

    Science.gov (United States)

    Wang, Yujiao; Cao, Yanqiu; Li, Hongmei; Gong, Aijun; Han, Jintao; Qian, Zhen; Chao, Wenran

    2018-04-01

    Microcystins (MCs) is a kind of hepatotoxin, which is the secondary metabolite of cyanobacteria. Bi 2 O 2 CO 3 (BOC) is a kind of cheap and nontoxic semiconductor material. BOC was synthetized by solvothermal method and then microcystin-LR (MC-LR) and microcystin-RR (MC-RR) were removed by BOC, through adsorption and photocatalytic degradation. When the dosage of BOC is 6 g/L, the MC-LR and MC-RR in the natural water sample can be completely adsorbed in 30 min and then after 12 h irradiation, MC-LR and MC-RR were photocatalytically degraded by BOC.

  11. Inertial Microfluidic Cell Stretcher (iMCS): Fully Automated, High-Throughput, and Near Real-Time Cell Mechanotyping.

    Science.gov (United States)

    Deng, Yanxiang; Davis, Steven P; Yang, Fan; Paulsen, Kevin S; Kumar, Maneesh; Sinnott DeVaux, Rebecca; Wang, Xianhui; Conklin, Douglas S; Oberai, Assad; Herschkowitz, Jason I; Chung, Aram J

    2017-07-01

    Mechanical biomarkers associated with cytoskeletal structures have been reported as powerful label-free cell state identifiers. In order to measure cell mechanical properties, traditional biophysical (e.g., atomic force microscopy, micropipette aspiration, optical stretchers) and microfluidic approaches were mainly employed; however, they critically suffer from low-throughput, low-sensitivity, and/or time-consuming and labor-intensive processes, not allowing techniques to be practically used for cell biology research applications. Here, a novel inertial microfluidic cell stretcher (iMCS) capable of characterizing large populations of single-cell deformability near real-time is presented. The platform inertially controls cell positions in microchannels and deforms cells upon collision at a T-junction with large strain. The cell elongation motions are recorded, and thousands of cell deformability information is visualized near real-time similar to traditional flow cytometry. With a full automation, the entire cell mechanotyping process runs without any human intervention, realizing a user friendly and robust operation. Through iMCS, distinct cell stiffness changes in breast cancer progression and epithelial mesenchymal transition are reported, and the use of the platform for rapid cancer drug discovery is shown as well. The platform returns large populations of single-cell quantitative mechanical properties (e.g., shear modulus) on-the-fly with high statistical significances, enabling actual usages in clinical and biophysical studies. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    Energy Technology Data Exchange (ETDEWEB)

    Khatami, Mahin [Inflammation and Cancer Biology, National Cancer Institute (Ret), the National Institutes of Health, Bethesda, MD 20817 (United States)

    2014-01-27

    Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates) is heavy investment on numerous genetic mutations (molecular false-flags) in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance). Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs) demonstrated at least three stages of interactions between resident (host) and recruited immune cells: (a), acute phase; activation of mast cells (MCs), IgE Abs, histamine and prostaglandin synthesis; (b), intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos) infiltrations into epithelia and goblet cells (GCs), tissue hypertrophy and neovascularization; and (c), chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mϕs), increased (irregular size) B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth) and/or thinning (necrosis) and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune

  13. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs and Eosinophils (Eos with Host Mast Cells (MCs and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    Directory of Open Access Journals (Sweden)

    Mahin Khatami

    2014-01-01

    Full Text Available Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates is heavy investment on numerous genetic mutations (molecular false-flags in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance. Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs demonstrated at least three stages of interactions between resident (host and recruited immune cells: (a, acute phase; activation of mast cells (MCs, IgE Abs, histamine and prostaglandin synthesis; (b, intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos infiltrations into epithelia and goblet cells (GCs, tissue hypertrophy and neovascularization; and (c, chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mfs, increased (irregular size B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth and/or thinning (necrosis and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune

  14. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    International Nuclear Information System (INIS)

    Khatami, Mahin

    2014-01-01

    Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates) is heavy investment on numerous genetic mutations (molecular false-flags) in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance). Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs) demonstrated at least three stages of interactions between resident (host) and recruited immune cells: (a), acute phase; activation of mast cells (MCs), IgE Abs, histamine and prostaglandin synthesis; (b), intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos) infiltrations into epithelia and goblet cells (GCs), tissue hypertrophy and neovascularization; and (c), chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mϕs), increased (irregular size) B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth) and/or thinning (necrosis) and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune

  15. Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome.

    Science.gov (United States)

    Zheng, Qing-Qing; Zhao, You-Shan; Guo, Juan; Zhao, Si-da; Song, Lu-Xi; Fei, Cheng-Ming; Zhang, Zheng; Li, Xiao; Chang, Chun-Kang

    2017-07-01

    Erythroid apoptosis increases significantly in myelodysplastic syndrome (MDS) patients with iron overload, but the underlying mechanism is not fully clear. In this study, we aim to explore the effect of HIF-1a/ROS on erythroid apoptosis in MDS patients with iron overload. We found that iron overload injured cellular functions through up-regulating ROS levels in MDS/AML cells, including inhibited cell viability, increased cell apoptosis and blocked cell cycle at G0/G1 phase. Interestingly, overexpression of hypoxia inducible factor-1a (HIF-1a), which was under-expressed in iron overload models, reduced ROS levels and attenuated cell damage caused by iron overload in MDS/AML cells. And gene knockdown of HIF-1a got the similar results as iron overload in MDS/AML cells. Furthermore, iron overload caused high erythroid apoptosis was closely related with ROS in MDS patients. Importantly, the HIF-1a protein levels of erythrocytes elevated obviously after incubation with desferrioxamine (DFO) from MDS patients with iron overload, accompanied by ROS levels inhibited and erythroid apoptosis reduced. Taken together, our findings determine that the HIF-1a/ROS signaling pathway plays a key role in promoting erythroid apoptosis in MDS patients with iron overload. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Modeling the Pathogenesis of Charcot-Marie-Tooth Disease Type 1A Using Patient-Specific iPSCs

    Directory of Open Access Journals (Sweden)

    Lei Shi

    2018-01-01

    Full Text Available Charcot-Marie-Tooth disease type 1A (CMT1A, one of the most frequent inherited peripheral neuropathies, is associated with PMP22 gene duplication. Previous studies of CMT1A mainly relied on rodent models, and it is not yet clear how PMP22 overexpression leads to the phenotype in patients. Here, we generated the human induced pluripotent stem cell (hiPSC lines from two CMT1A patients as an in vitro cell model. We found that, unlike the normal control cells, CMT1A hiPSCs rarely generated Schwann cells through neural crest stem cells (NCSCs. Instead, CMT1A NCSCs produced numerous endoneurial fibroblast-like cells in the Schwann cell differentiation system, and similar results were obtained in a PMP22-overexpressing iPSC model. Therefore, despite the demyelination-remyelination and/or dysmyelination theory for CMT1A pathogenesis, developmental disabilities of Schwann cells may be considered as an underlying cause of CMT1A. Our results may have important implications for the uncovering of the underlying mechanism and the development of a promising therapeutic strategy for CMT1A neuropathy.

  17. Association of diminished expression of RASSF1A with promoter methylation in primary gastric cancer from patients of central China

    Directory of Open Access Journals (Sweden)

    Zhou Feng

    2007-07-01

    Full Text Available Abstract Background Although methylation-mediated inactivation of expression of RASSF1A, a candidate tumor suppressor gene, has been observed in several human cancers, the data concerning alteration of RASSF1A expression and methylation in Chinese primary gastric cancer are scarce. Moreover, direct evidence showing the association between protein expression of RASSF1A and primary human cancers is lacking. The aim of this study was to investigate RASSF1A expression in tissue of primary gastric cancer (GC at mRNA and protein levels, and to establish the possible relationship between DNA methylation status and protein expression of RASSF1A in Chinese. Methods Fifty-four patients with primary gastric cancers were included in the study of RASSF1A mRNA expression and methylation status between the cancer tissue and the corresponding adjacent normal tissue. 20 out of 54 patients were included for study of RASSF1A protein expression. The expression of RASSF1A at mRNA and protein levels was determined by RT-PCR and Western-blotting, respectively. The RASSF1A promoter methylation was detected by methylation-specific PCR. Results RASSF1A mRNA and protein expressions in GC were reduced significantly with comparison to the corresponding normal tissues (OD value: 0.2589 ± 0.2407 vs 0.5448 ± 0.2971, P P P P Conclusion Expression of RASSF1A was reduced in tissue of GC at mRNA and protein levels. Diminished expression of RASSF1A was associated with the promoter methylation.

  18. Complete loss of insulin secretion capacity in type 1A diabetes patients during long-term follow up.

    Science.gov (United States)

    Uno, Sae; Imagawa, Akihisa; Kozawa, Junji; Fukui, Kenji; Iwahashi, Hiromi; Shimomura, Iichiro

    2017-10-16

    Patients with type 1 diabetes are classified into three subtypes in Japan: acute onset, fulminant and slowly progressive. Acute-onset type 1 diabetes would be equivalent to type 1A diabetes, the typical type 1 diabetes in Western countries. The insulin secretion capacity in Japanese patients with long-standing type 1A diabetes is unclear. The aim of the present study was to clarify the course of endogenous insulin secretion during long-term follow up and the factors associated with residual insulin secretion in patients with acute-onset type 1 diabetes (autoimmune). We retrospectively investigated endogenous insulin secretion capacity in 71 patients who fulfilled the diagnostic criteria for acute-onset type 1 diabetes (autoimmune) in Japan. To assess the residual insulin secretion capacity, we evaluated randomly measured C-peptide levels and the results of glucagon stimulation test in 71 patients. In the first year of disease, the child- and adolescent-onset patients had significantly more in residual insulin secretion than the adult-onset patients (34 patients in total). C-peptide levels declined more rapidly in patients whose age of onset was ≤18 years than in patients whose age of onset was ≥19 years. Endogenous insulin secretion capacity stimulated by glucagon was completely lost in almost all patients at >15 years after onset (61 patients in total). Most patients with acute-onset type 1 diabetes (autoimmune) completely lose their endogenous insulin secretion capacity during the disease duration in Japan. Age of onset might affect the course of insulin secretion. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  19. [11C]WAY-100635 PET imaging of 5-HT1A receptor binding in patients with temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Sasai, Taeko; Matsuura, Masato; Itou, Shigeo; Suhara, Tetsuya; Yahata, Noriaki; Okubo, Yoshiro

    2006-01-01

    To understand the role of 5-HT in human temporal lobe epilepsy, here we measured 5-HT 1A receptor binding potential by positron emission tomography (PET) with [carbonyl- 11 C]WAY100635, a selective 5-HT 1A receptor antagonist, in patients with temporal lobe epilepsy and normal controls. Twelve patients with temporal lobe epilepsy and seventeen healthy controls participated in the study. For each subject, we conducted PET and magnetic resonance imaging (MRI), by which we measured the 5-HT 1A receptor binding potential, the R1-value, a relative indicator of cerebral blood flow in regions of interest, and the volume of gray matter. Patients with temporal lobe epilepsy showed significantly reduced 5-HT 1A receptor binding potential in the temporal lobe. The laterality of the reduction was coincided with the epileptogenic foci estimated by a scalp electroencephalography (EEG). In contrast, the R1-value and gray matter volume showed no difference between the patient and control groups. Our study revealed that 5-HT 1A receptor binding was reduced significantly at the epileptogenic foci. We suggest that PET imaging with [carbonyl- 11 C]WAY100635 is potentially a useful non-invasive method for determining the epileptogenic foci. (author)

  20. Sleep-Related Breathing Disorders in Chiari Malformation Type 1: A Prospective Study of 90 Patients.

    Science.gov (United States)

    Ferré, Álex; Poca, Maria A; de la Calzada, Maria D; Moncho, Dulce; Romero, Odile; Sampol, Gabriel; Sahuquillo, Juan

    2017-06-01

    The aim of the present study is to describe the prevalence of sleep disorders in a large group of patients with Chiari malformation type 1 (CM-1) and determine the presence of risk factors associated with these abnormalities. Prospective study with consecutive patient selection. We included 90 adult patients with CM-1, defined by the presence of a cerebellar tonsillar descent (TD) ≥3 mm. Clinical, neuroradiological studies, and nocturnal polysomnography (PSG) was carried out. In addition, patients were also subclassified into 2 CM subtypes: CM-1, with the obex above the foramen magnum (FM) and CM-1.5, in which along with a TD ≥3 mm, the obex was located below the FM. We observed a high prevalence (50%) of sleep-related breathing disorders (SRBDs) with predominant hypopnea. Only six patients showed a central apnea index of ≥5. Hypoventilation was observed in only three patients. SRBD severity was associated with male sex, older age, excess weight, and the presence of hydrocephalus. No differences in clinical or PSG parameters were found when comparing CM subtypes (CM-1 and CM-1.5). Sleep architecture study showed decreased sleep efficiency with an increase in arousal and waking after sleep onset. The presence of SRBDs was found to be associated with poorer sleep architecture parameters. This study confirms a high prevalence of SRBDs in patients with CM-1 and CM-1.5, with a predominant obstructive component. Nocturnal PSG recordings should be systematically conducted in these patients, especially those who are male, older, or overweight or those who present hydrocephalus. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  1. Application of rain scanner SANTANU and transportable weather radar in analyze of Mesoscale Convective System (MCS) events over Bandung, West Java

    Science.gov (United States)

    Nugroho, G. A.; Sinatra, T.; Trismidianto; Fathrio, I.

    2018-05-01

    Simultaneous observation of transportable weather radar LAPAN-GMR25SP and rain-scanner SANTANU were conducted in Bandung and vicinity. The objective is to observe and analyse the weather condition in this area during rainy and transition season from March until April 2017. From the observation result reported some heavy rainfall with hail and strong winds occurred on March 17th and April 19th 2017. This events were lasted within 1 to 2 hours damaged some properties and trees in Bandung. Mesoscale convective system (MCS) are assumed to be the cause of this heavy rainfall. From two radar data analysis showed a more local convective activity in around 11.00 until 13.00 LT. This local convective activity are showed from the SANTANU observation supported by the VSECT and CMAX of the Transportable radar data that signify the convective activity within those area. MCS activity were observed one hour after that. This event are confirm by the classification of convective-stratiform echoes from radar data and also from the high convective index from Tbb Himawari 8 satellite data. The different MCS activity from this two case study is that April 19 have much more MCS activity than in March 17, 2017.

  2. Mindfulness-based cognitive therapy (MBCT) for multiple chemical sensitivity (MCS): Results from a randomized controlled trial with 1-year follow-up

    DEFF Research Database (Denmark)

    Hauge, Christian Riise; Rasmussen, Alice; Piet, Jacob

    2015-01-01

    the effects of mindfulness-based cognitive therapy (MBCT) for individuals with MCS. Methods The intention-to-treat sample (ITT) included 69 individuals who had been randomized to either MBCT or treatment as usual (TAU). The primary outcome measure was the Quick Environmental Exposure and Sensitivity Inventory...

  3. Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat

    International Nuclear Information System (INIS)

    Kamath, Ravi S.; Lukina, Elena; Watman, Nora; Dragosky, Marta; Pastores, Gregory M.; Arreguin, Elsa Avila; Rosenbaum, Hanna; Zimran, Ari; Aguzzi, Rasha; Puga, Ana Cristina; Norfleet, Andrea M.; Peterschmitt, M.J.; Rosenthal, Daniel I.

    2014-01-01

    Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1). Its skeletal effects were evaluated by prospective monitoring of bone mineral density (BMD), fractures, marrow infiltration by Gaucher cells, focal bone lesions, and infarcts during an open-label, multi-site, single-arm phase 2 trial (NCT00358150). Institutional review board approval and patient informed consent were obtained. Eliglustat (50 or 100 mg) was self-administered by mouth twice daily; 19 patients completed 4 years of treatment. All were skeletally mature (age range, 18-55 years). DXA and MRI assessments were conducted at baseline and annually thereafter. X-rays were obtained annually until month 24, and then every other year. Lumbar spine BMD increased significantly (p = 0.02; n = 15) by a mean (SD) of 9.9 % (14.2 %) from baseline to year 4; corresponding T-scores increased significantly (p = 0.01) from a mean (SD) of -1.6 (1.1) to -0.9 (1.3). Mean femur T-score remained normal through 4 years. Femur MRI showed that 10/18 (56 %) patients had decreased Gaucher cell infiltration compared to baseline; one patient with early improvement had transient worsening at year 4. There were no lumbar spine or femoral fractures and no reported bone crises during the study. At baseline, 8/19 (42 %) patients had focal bone lesions, which remained stable, and 7/19 (37 %) patients had bone infarctions, which improved in one patient by year 2. At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved. Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1. (orig.)

  4. Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat

    Energy Technology Data Exchange (ETDEWEB)

    Kamath, Ravi S. [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Fairfax Radiological Consultants, Fairfax, VA (United States); Lukina, Elena [Russian Academy of Medical Sciences, Moscow (Russian Federation); Watman, Nora [Hospital Ramos Mejia, Buenos Aires (Argentina); Dragosky, Marta [Instituto Mexicano del Seguro Social Hospital de Especialidades, Col. La Raza (Mexico); Pastores, Gregory M. [New York University, New York (United States); Yale University School of Medicine, New Haven, CT (United States); Arreguin, Elsa Avila [Instituto Argentino de Diagnostico y Tratamiento, Buenos Aires (Argentina); Rosenbaum, Hanna [Rambam Medical Center, Haifa (Israel); Zimran, Ari [Sha' are Zedek Hebrew University and Hadassah Medical School, Jerusalem (Israel); Aguzzi, Rasha [Genzyme, a Sanofi company, Cambridge, MA (United States); Alexion Pharmaceuticals, Cambridge, MA (United States); Puga, Ana Cristina; Norfleet, Andrea M.; Peterschmitt, M.J. [Genzyme, a Sanofi company, Cambridge, MA (United States); Rosenthal, Daniel I. [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Massachusetts General Hospital, Department of Radiology, Boston, MA (United States)

    2014-10-15

    Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1). Its skeletal effects were evaluated by prospective monitoring of bone mineral density (BMD), fractures, marrow infiltration by Gaucher cells, focal bone lesions, and infarcts during an open-label, multi-site, single-arm phase 2 trial (NCT00358150). Institutional review board approval and patient informed consent were obtained. Eliglustat (50 or 100 mg) was self-administered by mouth twice daily; 19 patients completed 4 years of treatment. All were skeletally mature (age range, 18-55 years). DXA and MRI assessments were conducted at baseline and annually thereafter. X-rays were obtained annually until month 24, and then every other year. Lumbar spine BMD increased significantly (p = 0.02; n = 15) by a mean (SD) of 9.9 % (14.2 %) from baseline to year 4; corresponding T-scores increased significantly (p = 0.01) from a mean (SD) of -1.6 (1.1) to -0.9 (1.3). Mean femur T-score remained normal through 4 years. Femur MRI showed that 10/18 (56 %) patients had decreased Gaucher cell infiltration compared to baseline; one patient with early improvement had transient worsening at year 4. There were no lumbar spine or femoral fractures and no reported bone crises during the study. At baseline, 8/19 (42 %) patients had focal bone lesions, which remained stable, and 7/19 (37 %) patients had bone infarctions, which improved in one patient by year 2. At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved. Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1. (orig.)

  5. Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients.

    Science.gov (United States)

    Stender, Johan; Kupers, Ron; Rodell, Anders; Thibaut, Aurore; Chatelle, Camille; Bruno, Marie-Aurélie; Gejl, Michael; Bernard, Claire; Hustinx, Roland; Laureys, Steven; Gjedde, Albert

    2015-01-01

    The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.

  6. MR imaging of abdominopelvic involvement in neurofibromatosis type 1: a review of 43 patients

    Energy Technology Data Exchange (ETDEWEB)

    Zacharia, T. Thomas [Massachusetts General Hospital, Department of Radiology, Boston, MA (United States); Jaramillo, Diego [Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Poussaint, Tina Young [Children' s Hospital Boston, Department of Radiology, Boston, MA (United States); Korf, Bruce [University of Alabama at Birmingham Hospital, Department of Genetics, Birmingham, AL (United States)

    2005-03-01

    Plexiform neurofibromas are a frequent complication of neurofibromatosis type 1. This article discusses MR imaging findings and distribution of plexiform neurofibromas in the abdomen and pelvis. To define the most prevalent patterns of involvement and MR imaging findings in abdominopelvic neurofibromatosis type 1. We reviewed the MR appearance of abdominopelvic lesions in 23 male and 20 female patients (median age: 16 years) with type 1 neurofibromatosis. The patients were part of a multi-institutional study of 300 patients. Imaging included coronal or sagittal, and axial short tau inversion recovery images. The most common abdominopelvic involvement was in the abdominopelvic wall (n=28, 65%) and lumbosacral plexus (n=27, 63%). Retroperitoneal involvement was frequent (n=15, 35%). Lesions were less often intraperitoneal (21%) (P=0.001). Pelvic disease (n=27, 63%), neural canal involvement (n=18, 42%), and hydronephrosis (n=4, 9%) were also noted. Target-like appearance of plexiform lesions was noted in more than half the patients. Abdominopelvic involvement in neurofibromatosis type 1 is primarily extraperitoneal. Although lesions are most prevalent in the abdominopelvic wall and lumbosacral plexus, retroperitoneal and pelvic involvement is common and usually affects important organs. MR imaging added information in the initial and follow-up clinical evaluation of these patients. (orig.)

  7. Aerobic anti-gravity exercise in patients with Charcot-Marie-Tooth disease types 1A and X

    DEFF Research Database (Denmark)

    Knak, Kirsten L; Andersen, Linda K; Vissing, John

    2017-01-01

    Background: Charcot-Marie-Tooth (CMT) disease is a hereditary neuropathy associated with impaired walking capacity. Some patients are too weak in the lower extremity muscles to walk at gravity with sufficient intensity or duration to gain benefit. Aim: The aim was to investigate the effect...... of aerobic anti-gravity exercise in weak patients with CMT 1A and X. Methods: Five adult patients performed moderate-intensity aerobic anti-gravity exercise 3/week for 10 weeks. Results: There was a significant positive difference in Berg balance scale and postural stability test between test occasions...

  8. CpG methylation of APC promoter 1A in sporadic and familial breast cancer patients.

    Science.gov (United States)

    Debouki-Joudi, Saoussen; Trifa, Fatma; Khabir, Abdelmajid; Sellami-Boudawara, Tahia; Frikha, Mounir; Daoud, Jamel; Mokdad-Gargouri, Raja

    2017-01-01

    Tumour suppressor gene (TSG) silencing through promoter hypermethylation plays an important role in cancer initiation. The aim of this study was to assess the extent of methylation of APC gene promoter in 91 sporadic and 44 familial cases of Tunisian patients with breast cancer (BC) in. The frequency of APC promoter methylation is somewhat similar for sporadic and familial breast cancer cases, (52.1%, and 54.5% respectively). For sporadic breast cancer patients, there was a significant correlation of APC promoter hypermethylation with TNM stage (p = 0.024) and 3-year survival (p = 0.025). Regarding the hormonal status (HR), we found significant association between negativity to PR and unmethylated APC (p= 0.005) while ER and Her2/neu are not correlated. Moreover, unmethylated APC promoter is more frequent in tumours expressing at least one out the 3 proteins compared to triple negative cases (p= 0.053). On the other hand, aberrant methylation of APC was associated with tumour size (p = 0.036), lymph node (p = 0.028), distant metastasis (p = 0.031), and 3-year survival (p = 0.046) in the group of patients with familial breast cancer. Moreover, patients with sporadic breast cancer displaying the unmethylated profile have a significant prolonged overall survival compared to those with the methylated pattern of APC promoter (p log rank = 0.008). Epigenetic change at the CpG islands in the APC promoter was associated with the silence of its transcript and the loss of protein expression suggesting that this event is the main mechanism regulating the APC expression in breast cancer. In conclusion, our data showed that the loss of APC through aberrant methylation is associated with the aggressive behavior of both sporadic and familial breast cancer in Tunisian patients.

  9. Craniofacial and dental characteristics of patients with vitamin-D-dependent rickets type 1A compared to controls and patients with X-linked hypophosphatemia

    DEFF Research Database (Denmark)

    Gjørup, Hans; Beck-Nielsen, Signe Sparre; Haubek, Dorte

    2017-01-01

    ᅟOBJECTIVES: Vitamin-D-dependent rickets type 1A (VDDR1A) is a rare inherited disease caused by defective activation of vitamin D. The aim of the study was to describe the craniofacial characteristics and the dental phenotype of patients with genetically confirmed VDDR1A. The VDDR1A findings were...... of dental findings was 30 adults with XLH. Clinical examination, clinical photos, and radiographs were obtained. Cephalometric analysis was performed. Photos and radiographs were visually evaluated. RESULTS: The depth of the posterior cranial fossa (d-p and d-s-iop) in VDDR1A adults was reduced compared...... of both calcium and phosphate to be critical in periods of enamel formation. CLINICAL RELEVANCE: Knowledge on craniofacial and dental aberration in patients with rare diseases, e.g., inherited rickets, is of importance to the dental practitioner, especially during diagnostics and treatment in special care...

  10. Does DNA Methylation of PPARGC1A Influence Insulin Action in First Degree Relatives of Patients with Type 2 Diabetes?

    DEFF Research Database (Denmark)

    Gillberg, Linn; Jacobsen, Stine; Ribel-Madsen, Rasmus

    2013-01-01

    and in muscle from individuals at risk of T2D. This study aimed to investigate DNA promoter methylation and gene expression of PPARGC1A in skeletal muscle from first degree relatives (FDR) of T2D patients, and to determine the association with insulin action as well as the influence of family relation. We...... genetic regulation to play a role. No significant effect of familiality on DNA methylation was found. Taken together, increased DNA methylation of the PPARGC1A promoter is unlikely to play a major causal role for the development of insulin resistance in FDR of patients with T2D....... included 124 Danish FDR of T2D patients from 46 different families. Skeletal muscle biopsies were excised from vastus lateralis and insulin action was assessed by oral glucose tolerance tests. DNA methylation and mRNA expression levels were measured using bisulfite sequencing and quantitative real-time PCR...

  11. Lifestyle of patients with diabetes mellitus type 1: a systematic review.

    Science.gov (United States)

    Sales-Peres, Silvia Helena de Carvalho; Guedes, Maria de Fatima Santos; Sá, Letícia Marques; Negrato, Carlos Antonio; Lauris, José Roberto Pereira

    2016-04-01

    The aim of this review was to verify data concerning the relationship between the existent lifestyle and glycemic control in patients with Diabetes Mellitus Type 1 (DM1). The methods applied included the literature search strategy, selection of studies by means of inclusion and exclusion strategies, according to the characteristics of the studies. The search was conducted in the Lilacs, Medline, PubMed, Cochrame, SciELO and IBECS databases between in the period between 2005 and 2014. The articles selected were studies in humans, investing lifestyle, physical activities and glycemic levels. Of the 1798 studies initially identified, 11 met the eligibility criteria. Among the studies analyzed, 1 cohort; 1 longitudinal prospective, 1 case control and 8 transversal studies that approached the proposed theme were related. Regular physical activity was the variable that presented greatest relationship with the improvement in glycemic levels. Healthy active life, balanced diet, physical activities and education in diabetes improved the glycemic control of the DM1 patient. The results allowed the authors to conclude that a lifestyle based on physical activities interfered directly in the health of patients with DM1, in addition to contributing the glycemic control.

  12. NDN and CD1A are novel prognostic methylation markers in patients with head and neck squamous carcinomas

    International Nuclear Information System (INIS)

    Virani, Shama; Bellile, Emily; Bradford, Carol R.; Carey, Thomas E.; Chepeha, Douglas B.; Colacino, Justin A.; Helman, Joseph I.; McHugh, Jonathan B.; Peterson, Lisa A.; Sartor, Maureen A.; Taylor, Jeremy MG; Walline, Heather M.; Wolf, Greg T.; Rozek, Laura S.

    2015-01-01

    HPV-associated HNSCCs have a distinct etiologic mechanism and better prognosis than those with non-HPV associated HNSCCs. However, even within the each group, there is heterogeneity in survival time. Here, we test the hypothesis that specific candidate gene methylation markers (CCNA1, NDN, CD1A, DCC, p16, GADD45A) are associated with tumor recurrence and survival, in a well-characterized, prospective, cohort of 346 HNSCC patients. Kaplan-Meier curves were used to estimate survival time distributions. Multivariable Cox Proportional Hazards models were used to test associations between each methylation marker and OST/RPFT after adjusting for known or identified prognostic factors. Stratified Cox models included an interaction term between HPV and methylation marker to test for differences in the associations of the biomarker with OST or RPFT across HPV status. Methylation markers were differentially associated with patient characteristics. DNA hypermethylation of NDN and CD1A was found to be significantly associated with overall survival time (OST) in all HNSCC patients (NDN hazard ratio (HR): 2.35, 95 % CI: 1.40-3.94; CD1A HR: 1.31, 95 % CI: 1.01-1.71). Stratification by HPV status revealed hypermethylation of CD1A was associated with better OST and recurrence/persistence-free time (RPFT) (OST HR: 3.34, 95 % CI: 1.88-5.93; RPFT HR: 2.06, 95 % CI: 1.21-3.49), while hypomethylation of CCNA1 was associated with increased RPFT in HPV (+) patients only (HR: 0.31, 95 % CI: 0.13-0.74). This study is the first to describe novel epigenetic alterations associated with survival in an unselected, prospectively collected, consecutive cohort of patients with HNSCC. DNA hypermethylation of NDN and CD1A was found to be significantly associated with increased overall survival time in all HNSCC patients. However, stratification by the important prognostic factor of HPV status revealed the immune marker, CD1A, and the cell cycle regulator, CCNA1 to be associated with prognosis in HPV

  13. Clinical Utility of promoter methylation of the tumor suppressor genes DKK3, and RASSF1A in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Marwa H. Saied

    2018-04-01

    Full Text Available Background: DNA methylation is the commonest known epigenetic change that results in silencing of tumor suppressor genes. Promoter methylation of tumor suppressor genes has the potential for early detection of breast cancer. Aim: Aim is to examine the potential usefulness of blood based methylation specific polymerase chain reaction (MSP of methylated DKK3 and RASSF1A genes in early detection of breast cancer. Method: Methylation status of DKK3 and RASSF1 was investigated in forty breast cancer patients, twenty fibroadenoma patients and twenty healthy ladies as control group using MSP. Results: Methylation of DKK3 promoter was found in 22.5% of breast cancer patients, while DKK3 methylation was absent in both fibroadenoma patients and control group. Similarly, methylation of RASSF1 promoter was found in 17.5% of breast cancer patients and in none of fibroadenoma and control group. Conclusion: Promoter methylation of DKK3 and RASSF1 was found in breast cancer patients while absent in control group suggesting that tumorspecific methylation of the two genes (DKK3 and RASSF1A might be a valuable biomarker for the early detection of breast cancer. Keywords: DNA methylation, Breast cancer, DKK3, RASSF1

  14. Pilot Study on Genetic Polymorphisms CYP1A2*1F on Asthma Patients and Nonasthma in Indonesia

    Directory of Open Access Journals (Sweden)

    Doddy de Queljoe

    2015-03-01

    Full Text Available Genetic polymorphisms of CYP1A2 is related to the theophylline metabolism that may affect drug levels in the blood, which can also affect incidence of adverse drug reaction (ADR and clinical outcomes of asthma therapy. The frequency of CYP1A2 polymorphism is known to vary among ethnic. Allegedly the Indonesian population has high frequency of gene variants of CYP1A2*1F. This study aims to determine the profile of CYP1A2*1F gene polymorphism in a sample of nonasthma and asthma in Indonesia with other populations based on the literature. Data were taken on January–June 2014. Blood samples were obtained from 29 nonasthma samples and 16 patients with asthma. After extraction of genomic DNA, CYP1A2*1F gene polymorphisms determined by PCR-RFLP. The results of this study indicate that the CYP1A2*1F gene polymorphism in nonasthma samples was 10.35% (3/29 for C/C, 37.93% (11/29 for the C/A, and 51.72% (15/29 for A/A. The asthmatics genotype have a frequency distribution of C/A genotype of 81.25% (13/16 and A/A of 18.75% (3/16. There was no significant difference (p=0.276 allele frequencies between samples of nonasthma and asthma patients. The frequency of CYP1A2*1F gene in Indonesian population is higher than the population of Egypt, Japan, and UK, but lower compared to Malaysia. It can be concluded that there is no difference in frequency.

  15.  Resistance-associated polymorphisms in Dutch hepatitis C genotype 1a patients with and without HIV infection.

    Science.gov (United States)

    Lieveld, Faydra I; Swaans, Niels; Newsum, Astrid M; Ho, Cynthia K Y; Schinkel, Janke; Molenkamp, Richard; van der Meer, Jan T M; Arends, Joop E; Hoepelman, Andy I M; Wensing, Anne M J; Siersema, Peter D; van Erpecum, Karel J; Boland, Greet J

    2016-01-01

     Background and aim. Resistance-associated variants (RAVs) on the NS3 region of the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed frequencies of NS3 RAVs in patients infected with HCV genotype 1a with or without HIV coinfection. HCV NS3 amino acids 1-181 were sequenced by the Sanger method and analyzed for RAVs. RAVs and their distribution between HCV genotype 1a clade I and II viruses were compared between HIV-infected versus HIV-uninfected patients. 148 samples were available (n = 68 HIV and n = 80 non-HIV). Relative frequency of clade I and clade II was significantly different between HIV (85% and 15%) and non-HIV groups (49% and 51%). Overall, HIV infected patients exhibited significantly lower prevalence of RAVs than HIV-uninfected patients (62% vs. 79%, p = 0.03). However, Q80K prevalence was significantly higher in HIV-infected subjects (50% vs. 24%, p = 0.001), whereas prevalence of S122D/G/N/S (2% vs. 16%, p = 0.002) and N174G/N/S (10% vs. 55%, p < 0.0001) polymorphisms were significantly lower. Q80K was found exclusively in clade I viruses. S122 (3% vs. 22%, p=0.001) and N174 (13% vs. 75%, p<0.0001) polymorphisms had significantly lower prevalence in clade I than clade II viruses. In the Netherlands, prevalence of clade I viruses and Q80K was significantly higher in HCV genotype 1a infected patients with HIV coinfection than in those without HIV coinfection. Prevalence of N174 and S122 polymorphisms was significantly higher in clade II than clade I viruses.

  16. Corneal endothelial cell changes after cataract surgery in patients on systemic sympathetic α-1a antagonist medication (tamsulosin).

    Science.gov (United States)

    Storr-Paulsen, Allan; Jørgensen, Jesper Skovlund; Norregaard, Jens Christian; Thulesen, Jesper

    2014-06-01

      The purpose of this study was to assess the incidence of intraoperative floppy iris syndrome (IFIS) and the morphology of the corneal endothelium after cataract extraction in Caucasian male patients exposed to the α-1a adrenergic receptor antagonist tamsulosin.   In a clinical prospective study, 23 male patients (23 eyes) treated with tamsulosin due to benign prostatic hyperplasia and 25 male patients (25 eyes) with no tamsulosin treatment had cataract surgery. The divide-and-conquer technique was used with the Infinity OZil(®) machine. A combination of Healon and Healon5 was used in all patients, but the use of additional Vision Blue, iris retractors or intracameral phenylephrine in the tamsulosin group was at the discretion of the surgeon. The endothelial cell density, variation in endothelial cell size (CV), percentage of hexagonal cells and central corneal thickness (CCT) were recorded at baseline and at 3 months postoperatively.   In the tamsulosin-treated group, 19 of 23 eyes (83%) developed IFIS, compared with no IFIS in the control group. Compared with the control group, the tamsulosin group showed significantly less dilatation at the start of the operation, significant miosis during surgery and significantly greater corneal endothelial cell loss 3 months postoperatively (12% versus 3%; ptamsulosin-treated male patients. Patients on tamsulosin showed less preoperative dilatation, significant miosis during surgery, and had significantly greater postoperative endothelial cell loss compared with nontreated patients despite recommended precautions. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by Blackwell Publishing Ltd.

  17. Dynamics of Large-Scale Solar-Wind Streams Obtained by the Double Superposed Epoch Analysis: 2. Comparisons of CIRs vs. Sheaths and MCs vs. Ejecta

    Science.gov (United States)

    Yermolaev, Y. I.; Lodkina, I. G.; Nikolaeva, N. S.; Yermolaev, M. Y.

    2017-12-01

    This work is a continuation of our previous article (Yermolaev et al. in J. Geophys. Res. 120, 7094, 2015), which describes the average temporal profiles of interplanetary plasma and field parameters in large-scale solar-wind (SW) streams: corotating interaction regions (CIRs), interplanetary coronal mass ejections (ICMEs including both magnetic clouds (MCs) and ejecta), and sheaths as well as interplanetary shocks (ISs). As in the previous article, we use the data of the OMNI database, our catalog of large-scale solar-wind phenomena during 1976 - 2000 (Yermolaev et al. in Cosmic Res., 47, 2, 81, 2009) and the method of double superposed epoch analysis (Yermolaev et al. in Ann. Geophys., 28, 2177, 2010a). We rescale the duration of all types of structures in such a way that the beginnings and endings for all of them coincide. We present new detailed results comparing pair phenomena: 1) both types of compression regions ( i.e. CIRs vs. sheaths) and 2) both types of ICMEs (MCs vs. ejecta). The obtained data allow us to suggest that the formation of the two types of compression regions responds to the same physical mechanism, regardless of the type of piston (high-speed stream (HSS) or ICME); the differences are connected to the geometry ( i.e. the angle between the speed gradient in front of the piston and the satellite trajectory) and the jumps in speed at the edges of the compression regions. In our opinion, one of the possible reasons behind the observed differences in the parameters in MCs and ejecta is that when ejecta are observed, the satellite passes farther from the nose of the area of ICME than when MCs are observed.

  18. The 2015 Middle Childhood Survey (MCS) of mental health and well-being at age 11 years in an Australian population cohort

    Science.gov (United States)

    Laurens, Kristin R; Tzoumakis, Stacy; Dean, Kimberlie; Brinkman, Sally A; Bore, Miles; Lenroot, Rhoshel K; Smith, Maxwell; Holbrook, Allyson; Robinson, Kim M; Stevens, Robert; Harris, Felicity; Carr, Vaughan J; Green, Melissa J

    2017-01-01

    Purpose The Middle Childhood Survey (MCS) was designed as a computerised self-report assessment of children’s mental health and well-being at approximately 11 years of age, conducted with a population cohort of 87 026 children being studied longitudinally within the New South Wales (NSW) Child Development Study. Participants School Principals provided written consent for teachers to administer the MCS in class to year 6 students at 829 NSW schools (35.0% of eligible schools). Parent or child opt-outs from participation were received for 4.3% of children, and MCS data obtained from 27 808 children (mean age 11.5 years, SD 0.5; 49.5% female), representing 85.9% of students at participating schools. Findings to date Demographic characteristics of participating schools and children are representative of the NSW population. Children completed items measuring Social Integration, Prosocial Behaviour, Peer Relationship Problems, Supportive Relationships (at Home, School and in the Community), Empathy, Emotional Symptoms, Conduct Problems, Aggression, Attention, Inhibitory Control, Hyperactivity-Inattention, Total Difficulties (internalising and externalising psychopathology), Perceptual Sensitivity, Psychotic-Like Experiences, Personality, Self-esteem, Daytime Sleepiness and Connection to Nature. Distributions of responses on each item and construct demarcate competencies and vulnerabilities within the population: most children report mental health and well-being, but the population distribution spanned the full range of possible scores on every construct. Future plans Multiagency, intergenerational linkage of the MCS data with health, education, child protection, justice and early childhood development records took place late in 2016. Linked data were used to elucidate patterns of risk and protection across early and middle child development, and these data will provide a foundation for future record linkages in the cohort that will track mental and physical health

  19. The 2015 Middle Childhood Survey (MCS) of mental health and well-being at age 11 years in an Australian population cohort.

    Science.gov (United States)

    Laurens, Kristin R; Tzoumakis, Stacy; Dean, Kimberlie; Brinkman, Sally A; Bore, Miles; Lenroot, Rhoshel K; Smith, Maxwell; Holbrook, Allyson; Robinson, Kim M; Stevens, Robert; Harris, Felicity; Carr, Vaughan J; Green, Melissa J

    2017-06-23

    The Middle Childhood Survey (MCS) was designed as a computerised self-report assessment of children's mental health and well-being at approximately 11 years of age, conducted with a population cohort of 87 026 children being studied longitudinally within the New South Wales (NSW) Child Development Study. School Principals provided written consent for teachers to administer the MCS in class to year 6 students at 829 NSW schools (35.0% of eligible schools). Parent or child opt-outs from participation were received for 4.3% of children, and MCS data obtained from 27 808 children (mean age 11.5 years, SD 0.5; 49.5% female), representing 85.9% of students at participating schools. Demographic characteristics of participating schools and children are representative of the NSW population. Children completed items measuring Social Integration, Prosocial Behaviour, Peer Relationship Problems, Supportive Relationships (at Home, School and in the Community), Empathy, Emotional Symptoms, Conduct Problems, Aggression, Attention, Inhibitory Control, Hyperactivity-Inattention, Total Difficulties (internalising and externalising psychopathology), Perceptual Sensitivity, Psychotic-Like Experiences, Personality, Self-esteem, Daytime Sleepiness and Connection to Nature. Distributions of responses on each item and construct demarcate competencies and vulnerabilities within the population: most children report mental health and well-being, but the population distribution spanned the full range of possible scores on every construct. Multiagency, intergenerational linkage of the MCS data with health, education, child protection, justice and early childhood development records took place late in 2016. Linked data were used to elucidate patterns of risk and protection across early and middle child development, and these data will provide a foundation for future record linkages in the cohort that will track mental and physical health, social and educational/occupational outcomes into

  20. The implications of non-linear biological oscillations on human electrophysiology for electrohypersensitivity (EHS) and multiple chemical sensitivity (MCS).

    Science.gov (United States)

    Sage, Cindy

    2015-01-01

    maintenance; and resilience can be compromised. Electrohypersensitivity can be caused by successive assaults on human bioelectrochemical dynamics from exogenous electromagnetic fields (EMF) and RFR or a single acute exposure. Once sensitized, further exposures are widely reported to cause reactivity to lower and lower intensities of EMF/RFR, at which point thousand-fold lower levels can cause adverse health impacts to the electrosensitive person. Electrohypersensitivity (EHS) can be a precursor to, or linked with, multiple chemical sensitivity (MCS) based on reports of individuals who first develop one condition, then rapidly develop the other. Similarity of chemical biomarkers is seen in both conditions [histamines, markers of oxidative stress, auto-antibodies, heat shock protein (HSP), melatonin markers and leakage of the blood-brain barrier]. Low intensity pulsed microwave activation of voltage-gated calcium channels (VGCCs) is postulated as a mechanism of action for non-thermal health effects.

  1. Numerical and Observational Investigations of Long-Lived Mcs-Induced Severe Surface Wind Events: the Derecho

    Science.gov (United States)

    Schmidt, Jerome Michael

    This study addresses the production of sustained, straight-line, severe surface winds associated with mesoscale convective systems (MCSs) of extratropical origin otherwise known as derechos. The physical processes which govern the observed derecho characteristics are identified and their possible forcing mechanisms are determined. Detailed observations of two derechos are presented along with simulations using the Colorado State University Regional Atmospheric Modeling System (CSU-RAMS). The observations revealed a derecho environment characterized by strong vertical wind shear through the depth of the troposphere and large values of convective available potential energy (CAPE). The thermodynamic environment of the troposphere in each case had a distinct three-layer structure consisting of: (i) a surface-based stable layer of 1-to-2 km in depth, (ii) an elevated well -mixed layer of 2-4 km in depth, and (iii) an upper tropospheric layer of intermediate stability that extended to the tropopause. Two primary sets of simulations were performed to assess the impact of the observed environmental profiles on the derecho structure, propagation, and longevity. The first set consisted of nested-grid regional-scale simulations initialized from the standard NMC analyses on a domain having relatively coarse horizontal resolution (75 km). The second set of simulations consisted of two and three-dimensional experiments initialized in a horizontally homogeneous environment having a relatively fine horizontal resolution (2 km) and explicit microphysics. The results from these experiments indicate the importance of convectively -induced gravity waves on the MCS structure, propagation, longevity, and severe surface wind development. The sensitivity of the simulated convection and gravity waves to variations in the vertical wind shear and moisture profiles are described. Detailed Doppler radar analyses and 3-D simulations of a severe, bow echo squall line are presented which reveal

  2. Half-Life of Sulfonylureas in HNF1A and HNF4A Human MODY Patients is not Prolonged as Suggested by the Mouse Hnf1a(-/-) Model.

    Science.gov (United States)

    Urbanova, Jana; Andel, Michal; Potockova, Jana; Klima, Josef; Macek, Jan; Ptacek, Pavel; Mat'oska, Vaclav; Kumstyrova, Tereza; Heneberg, Petr

    2015-01-01

    Sulfonylurea derivatives are widely used for clinical treatment of human subjects with Maturity Onset Diabetes of the Young (MODY) caused by mutations in HNF-1α or HNF-4α despite the mechanism leading to their hypersensitivity is incompletely understood. In Hnf1a(-/-) mice, serum concentrations and half-life of sulfonylurea derivatives are strongly increased. We thus hypothesized that reduced sulfonylurea derivatives clearance stands behind their therapeutic potential in human HNF1A/HNF4A MODY subjects. Single doses of 3 mg glipizide and 5 mg glibenclamide/glyburide were administered sequentially to seven HNF1A/HNF4A MODY subjects and six control individuals matched for their age, BMI and CYP2C9 genotype. Pharmacokinetic (plasma concentration levels, Cmax, tmax, t1/2, AUC) and pharmacodynamic parameters (glycemia, C-peptide and insulin plasma levels) were followed for 24 hours after drug administration. We provide the first evidence on the pharmacokinetics and pharmacodynamics of sulfonylurea derivatives in human MODY subjects. The half-life of glipizide did not change, and reached 3.8±0.7 and 3.7±1.8 h in the MODY and control subjects, respectively. The half-life of glibenclamide was increased only in some MODY subjects (t1/2 9.5±6.7 and 5.0±1.4 h, respectively). Importantly, the intra- individual responses of MODY (but control) subjects to glipizide and glibenclamide treatment were highly correlated. With regards to pharmacodynamics, we observed a differential response of control but not MODY subjects to the doses of glipizide and glibenclamide applied. We rejected the hypothesis that all human MODY-associated mutations in HNF1A / HNF4A induce changes in the pharmacokinetics of sulfonylureas in humans analogically to the Hnf1a(-/-) mouse model.

  3. Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection.

    Science.gov (United States)

    Ekholm, E; Shaat, N; Holst, J J

    2012-10-01

    The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. BMI-matched T2D and healthy subjects were used as two separate control groups. The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. T2D: 26.6 ± 14.3). Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. The AUC insulin during the test meal was strongly correlated with the GIP secretion (Correlation coefficient 1.0, P MODY showed an attenuated early phase of insulin secretion similar to T2Ds. AUC insulin during the test meal was strongly correlated with GIP secretion, whereas no such correlation was seen for insulin and GLP-1. Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients.

  4. Skeletal phenotypes in adult patients with osteogenesis imperfecta-correlations with COL1A1/COL1A2 genotype and collagen structure

    DEFF Research Database (Denmark)

    Hald, J D; Folkestad, L; Harsløf, T

    2016-01-01

    Osteogenesis imperfecta (OI) is characterized by a high fracture rate and great heterogeneity. This cross-sectional study presents skeletal investigations and protein analyses in 85 adult OI patients. We find significant differences in bone mass, architecture, and fracture rate that correlate well...

  5. Differentiation between microcystin contaminated and uncontaminated fish by determination of unconjugated MCs using an ELISA anti-Adda test based on receiver-operating characteristic curves threshold values: application to Tinca tinca from natural ponds.

    Science.gov (United States)

    Moreno, Isabel María; Herrador, M Ángeles; Atencio, Loyda; Puerto, María; González, A Gustavo; Cameán, Ana María

    2011-02-01

    The aim of this study was to evaluate whether the enzyme-linked immunosorbent assay (ELISA) anti-Adda technique could be used to monitor free microcystins (MCs) in biological samples from fish naturally exposed to toxic cyanobacteria by using receiver operating characteristic (ROC) curve software to establish an optimal cut-off value for MCs. The cut-off value determined by ROC curve analysis in tench (Tinca tinca) exposed to MCs under laboratory conditions by ROC curve analysis was 5.90-μg MCs/kg tissue dry weight (d.w.) with a sensitivity of 93.3%. This value was applied in fish samples from natural ponds (Extremadura, Spain) in order to asses its potential MCs bioaccumulation by classifying samples as either true positive (TP), false positive (FP), true negative (TN), or false negative (FN). In this work, it has been demonstrated that toxic cyanobacteria, mainly Microcystis aeruginosa, Aphanizomenon issatchenkoi, and Anabaena spiroides, were present in two of these ponds, Barruecos de Abajo (BDown) and Barruecos de Arriba (BUp). The MCs levels were detected in waters from both ponds with an anti-MC-LR ELISA immunoassay and were of similar values (between 3.8-6.5-μg MC-LR equivalent/L in BDown pond and 4.8-6.0-μg MC-LR equivalent/L in BUp). The MCs cut-off values were applied in livers from fish collected from these two ponds using the ELISA anti-Adda technique. A total of 83% of samples from BDown pond and only 42% from BUp were TP with values of free MCs higher than 8.8-μg MCs/kg tissue (d.w.). Copyright © 2009 Wiley Periodicals, Inc.

  6. Immunophenotypic and Ultrastructural Analysis of Mast Cells in Hermansky-Pudlak Syndrome Type-1: A Possible Connection to Pulmonary Fibrosis.

    Directory of Open Access Journals (Sweden)

    Arnold S Kirshenbaum

    Full Text Available Hermansky-Pudlak Syndrome type-1 (HPS-1 is an autosomal recessive disorder caused by mutations in HPS1 which result in reduced expression of the HPS-1 protein, defective lysosome-related organelle (LRO transport and absence of platelet delta granules. Patients with HPS-1 exhibit oculocutaneous albinism, colitis, bleeding and pulmonary fibrosis postulated to result from a dysregulated immune response. The effect of the HPS1 mutation on human mast cells (HuMCs is unknown. Since HuMC granules classify as LROs along with platelet granules and melanosomes, we set out to determine if HPS-1 cutaneous and CD34+ culture-derived HuMCs have distinct granular and cellular characteristics. Cutaneous and cultured CD34+-derived HuMCs from HPS-1 patients were compared with normal cutaneous and control HuMCs, respectively, for any morphological and functional differences. One cytokine-independent HPS-1 culture was expanded, cloned, designated the HP proMastocyte (HPM cell line and characterized. HPS-1 and idiopathic pulmonary fibrosis (IPF alveolar interstitium showed numerous HuMCs; HPS-1 dermal mast cells exhibited abnormal granules when compared to healthy controls. HPS-1 HuMCs showed increased CD63, CD203c and reduced mediator release following FcɛRI aggregation when compared with normal HuMCs. HPM cells also had the duplication defect, expressed FcɛRI and intracytoplasmic proteases and exhibited less mediator release following FcɛRI aggregation. HPM cells constitutively released IL-6, which was elevated in patients' serum, in addition to IL-8, fibronectin-1 (FN-1 and galectin-3 (LGALS3. Transduction with HPS1 rescued the abnormal HPM morphology, cytokine and matrix secretion. Microarray analysis of HPS-1 HuMCs and non-transduced HPM cells confirmed upregulation of differentially expressed genes involved in fibrogenesis and degranulation. Cultured HPS-1 HuMCs appear activated as evidenced by surface activation marker expression, a decrease in mediator

  7. A part of patients with autism spectrum disorder has haploidy of HPC-1/syntaxin1A gene that possibly causes behavioral disturbance as in experimentally gene ablated mice.

    Science.gov (United States)

    Kofuji, Takefumi; Hayashi, Yuko; Fujiwara, Tomonori; Sanada, Masumi; Tamaru, Masao; Akagawa, Kimio

    2017-03-22

    Autism spectrum disorder (ASD) is highly heritable and encompasses a various set of neuropsychiatric disorders with a wide-ranging presentation. HPC-1/syntaxin1A (STX1A) encodes a neuronal plasma membrane protein that regulates the secretion of neurotransmitters and neuromodulators. STX1A gene ablated mice (null and heterozygote mutant) exhibit abnormal behavioral profiles similar to human autistic symptoms, accompanied by reduction of monoamine secretion. To determine whether copy number variation of STX1A gene and the change of its expression correlate with ASD as in STX1A gene ablated mice, we performed copy number assay and real-time quantitative RT-PCR using blood or saliva samples from ASD patients. We found that some ASD patients were haploid for the STX1A gene similar to STX1A heterozygote mutant mice. However, copy number of STX1A gene was normal in the parents and siblings of ASD patients with STX1A gene haploidy. In ASD patients with gene haploidy, STX1A mRNA expression was reduced to about half of their parents. Thus, a part of ASD patients had haploidy of STX1A gene and lower STX1A gene expression. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection

    DEFF Research Database (Denmark)

    Ekholm, E; Shaat, N; Holst, Jens Juul

    2012-01-01

    eight different families. BMI-matched T2D and healthy subjects were used as two separate control groups. The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P ....01). Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. T2D: 26.6 ± 14.3). Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.......8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. The AUC insulin during the test meal was strongly correlated with the GIP secretion (Correlation coefficient 1.0, P

  9. Antimony (Sb) sorption studies on zircaloy, carbon steel (CS) and magnetite coated CS (MCS) surfaces in aqueous medium at pH 10.2 and 280℃

    International Nuclear Information System (INIS)

    Keny, S.J.; Kumbhar, A.G.; Achary, S.N.; Basu, Saibal

    2014-01-01

    Antimony sorption studies on zircaloy, CS and magnetite coated carbon steel (MCS) at primary heat transport temperature (290℃) of pressurised heavy water reactor (PHWR) are of direct relevance in investigating Sb activity problem faced in Indian PHWRs. Sb impregnated PHT pump carbon bearing releases Sb to reactor core. This Sb activates, and redeposit on out-of-core surfaces and results in exposure and apparent high decontamination factors. This Sb is not amenable to normal decantation. The form and state of deposited Sb is not yet fully known. This works attempts for this

  10. Scoring Mental Health Quality of Life With the SF-36 in Patients With and Without Diabetes Foot Complications.

    Science.gov (United States)

    Ahn, Junho; Del Core, Michael A; Wukich, Dane K; Liu, George T; Lalli, Trapper; VanPelt, Michael D; La Fontaine, Javier; Lavery, Lawrence A; Raspovic, Katherine M

    2018-03-01

    The aim of this study was to examine if using orthogonal and oblique factor analysis detect changes in health-related quality of life differently in diabetic patients on the Short Form-36 (SF-36) survey. A total of 155 patients had diabetic foot complications (DFC), and 145 patients had no DFCs. The SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were calculated using scoring coefficients determined by orthogonal and oblique rotation principle component analyses of the subscales. The DFC group had lower orthogonal ( P < .00001) and oblique PCS scores ( P < .00001). However, despite lower Mental Health subscale scores in the patients with DFCs, orthogonal MCS scores ( P = .156) did not differ. In contrast, the oblique MCS scores reflected the difference in the Mental Health subscale ( P = .0005). Orthogonal and oblique PCS scores did not differ significantly. However, orthogonal MCS scores were significantly higher than oblique MCS scores in those with DFCs ( P = .0004) and without DFCs ( P = .005). The shorter, 12-item SF-12 survey demonstrated similar results. Poorer physical function leads to higher orthogonal MCS scores than if determined by oblique scoring coefficients since Physical Function, Bodily Pain, and General Health are weighted more negatively in orthogonal coefficients when calculating the MCS score. Oblique scoring coefficients may address this issue, but further study is necessary to confirm whether oblique MCS scores accurately represent the mental health of patients with diabetic foot disease.

  11. COL1A2 gene analysis in a Czech osteogenesis imperfecta patient: a candidate novel mutation in a patient affected by osteogenesis imperfecta type 3

    Directory of Open Access Journals (Sweden)

    Hrušková L

    2015-08-01

    Full Text Available Lucie Hrušková,1 Ivo Mařík,2,3 Stella Mazurová,1 Pavel Martásek,1 Ivan Mazura1 1Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 2Ambulant Centre for Defects of Locomotor Apparatus 1.1.c., Prague, Czech Republic; 3Faculty of Medical Studies, West Bohemia University, Pilsen, Czech RepublicAbstract: Osteogenesis imperfecta is a heritable bone fragility disease with a heterogenic genetic origin. Most cases result from mutations of either the COL1A1 gene or the COL1A2 gene. We identified a novel COL1A2 gene mutation in a Czech patient, born to unaffected parents, who was diagnosed according to clinical and anthropometric findings and radiographic features as having type 3 osteogenesis imperfecta, which is a severe form of this disease. The identified Gly814Trp mutation was predicted by a number of complementary bioinformatic programs to result in functional alteration of the protein. This case report provides both evidence of a novel COL1A2 mutation resulting in type 3 osteogenesis imperfecta and a genotype:phenotype correlation in this affected individual. Keywords: osteogenesis imperfecta type 3, collagen, alpha-2 (I chain, substitution, sequencing 

  12. Adaptive MCS selection and resource planning for energy-efficient communication in LTE-M based IoT sensing platform.

    Science.gov (United States)

    Dao, Nhu-Ngoc; Park, Minho; Kim, Joongheon; Cho, Sungrae

    2017-01-01

    As an important part of IoTization trends, wireless sensing technologies have been involved in many fields of human life. In cellular network evolution, the long term evolution advanced (LTE-A) networks including machine-type communication (MTC) features (named LTE-M) provide a promising infrastructure for a proliferation of Internet of things (IoT) sensing platform. However, LTE-M may not be optimally exploited for directly supporting such low-data-rate devices in terms of energy efficiency since it depends on core technologies of LTE that are originally designed for high-data-rate services. Focusing on this circumstance, we propose a novel adaptive modulation and coding selection (AMCS) algorithm to address the energy consumption problem in the LTE-M based IoT-sensing platform. The proposed algorithm determines the optimal pair of MCS and the number of primary resource blocks (#PRBs), at which the transport block size is sufficient to packetize the sensing data within the minimum transmit power. In addition, a quantity-oriented resource planning (QORP) technique that utilizes these optimal MCS levels as main criteria for spectrum allocation has been proposed for better adapting to the sensing node requirements. The simulation results reveal that the proposed approach significantly reduces the energy consumption of IoT sensing nodes and #PRBs up to 23.09% and 25.98%, respectively.

  13. Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with prostate cancer

    International Nuclear Information System (INIS)

    Sáenz-López, Pablo; Carretero, Rafael; Cózar, José Manuel; Romero, José Maria; Canton, Julia; Vilchez, José Ramón; Tallada, Miguel; Garrido, Federico; Ruiz-Cabello, Francisco

    2008-01-01

    Inflammation has been implicated as an etiological factor in several human cancers, including prostate cancer. Allelic variants of the genes involved in inflammatory pathways are logical candidates as genetic determinants of prostate cancer risk. The purpose of this study was to investigate whether single nucleotide polymorphisms of genes that lead to increased levels of pro-inflammatory cytokines and chemokines are associated with an increased prostate cancer risk. A case-control study design was used to test the association between prostate cancer risk and the polymorphisms TNF-A-308 A/G (rs 1800629), RANTES-403 G/A (rs 2107538), IL1-A-889 C/T (rs 1800587) and MCP-1 2518 G/A (rs 1024611) in 296 patients diagnosed with prostate cancer and in 311 healthy controls from the same area. Diagnosis of prostate cancer was significantly associated with TNF-A GA + AA genotype (OR, 1.61; 95% CI, 1.09–2.64) and RANTES GA + AA genotype (OR, 1.44; 95% CI, 1.09–2.38). A alleles in TNF-A and RANTES influenced prostate cancer susceptibility and acted independently of each other in these subjects. No epistatic effect was found for the combination of different polymorphisms studied. Finally, no overall association was found between prostate cancer risk and IL1-A or MCP-1 polymorphisms. Our results and previously published findings on genes associated with innate immunity support the hypothesis that polymorphisms in proinflammatory genes may be important in prostate cancer development

  14. ANTIBODIES TO BENZO[A]PYRENE AND POLYMORPHISMS OF CYP1A1*2A, CYP1A2*1F, GSTT1, AND GSTM1 GENES IN HEALTHY MEN AND LUNG CANCER PATIENTS

    Directory of Open Access Journals (Sweden)

    A. N. Glushkov

    2016-01-01

    Full Text Available Some genetic polymorphisms of CYP and GST enzymes metabolizing low-molecular weight xenobiotics may represent endogenous risk factors for carcinogenesis. However, possible relationships between the enzyme activities, amounts of carcinogen adducts and synthesis of anticarcinogen antibodies in humans (including cancer patients are still poorly studied. The purpose of this study was to identify possible associations between occurrence of antibodies against benzo[a]pyrene, and frequency of genetic polymorphisms of CYP1A1*2A, CYP1A2*1F, GSTT1, GSTM1 in healthy men and in lung cancer patients. Materials and methods. We have examined 203 men with non-small cell lung cancer and 267 apparently healthy donors without respiratory diseases. A non-competitive solid phase immunoassay of antibodies to benzo[a]pyrene was performed. Analysis of polymorphic loci within CYP1A1 (rs4646903, CYP1A2 (rs762551, GSTP1 (rs1695, rs1138272 was performed by means of real-time PCR using TaqMan technology. Null-alleles of GSTM1 (del, GSTT1 (del genes were detected by multiplex PCR with real-time fluorescent assay. Results. Among the lung cancer patients, the proportion of cases with a high level of IgG antibodies to benzo[a]pyrene in carriers of GSTT1+ and GSTM1+ in conjunction with the CYP1A2*1F C allele was significantly greater than in AA homozygotes CYP1A2*1F. The risk of lung cancer was increased to 5.5 in carriers of CYP1A2*1F C allele combined with GSTT1+ and GSTM1+ at high levels of IgG antibodies to benzo [a] pyrene. In healthy male donors, we have not found differences between the incidence of low and high levels of IgG anti-benzo[a]pyrene antibodies in the carriers of certain CYP1A1*2A, CYP1A2*1F, GSTT1 and GSTM1 genotypes. Conclusions. We have first reported a relationship between CYP1 and GST gene polymorphisms and specific immune response to chemical carcinogens in lung cancer patients. Immunoassays of IgG antibodies to benzo[a]pyrene combined with molecular

  15. The non-protein coding breast cancer susceptibility locus Mcs5a acts in a non-mammary cell-autonomous fashion through the immune system and modulates T-cell homeostasis and functions.

    Science.gov (United States)

    Smits, Bart M G; Sharma, Deepak; Samuelson, David J; Woditschka, Stephan; Mau, Bob; Haag, Jill D; Gould, Michael N

    2011-08-16

    Mechanisms underlying low-penetrance, common, non-protein coding variants in breast cancer risk loci are largely undefined. We showed previously that the non-protein coding mammary carcinoma susceptibility locus Mcs5a/MCS5A modulates breast cancer risk in rats and women. The Mcs5a allele from the Wistar-Kyoto (WKy) rat strain consists of two genetically interacting elements that have to be present on the same chromosome to confer mammary carcinoma resistance. We also found that the two interacting elements of the resistant allele are required for the downregulation of transcript levels of the Fbxo10 gene specifically in T-cells. Here we describe mechanisms through which Mcs5a may reduce mammary carcinoma susceptibility. We performed mammary carcinoma multiplicity studies with three mammary carcinoma-inducing treatments, namely 7,12-dimethylbenz(a)anthracene (DMBA) and N-nitroso-N-methylurea (NMU) carcinogenesis, and mammary ductal infusion of retrovirus expressing the activated HER2/neu oncogene. We used mammary gland and bone marrow transplantation assays to assess the target tissue of Mcs5a activity. We used immunophenotyping assays on well-defined congenic rat lines carrying susceptible and resistant Mcs5a alleles to identify changes in T-cell homeostasis and function associated with resistance. We show that Mcs5a acts beyond the initial step of mammary epithelial cell transformation, during early cancer progression. We show that Mcs5a controls susceptibility in a non-mammary cell-autonomous manner through the immune system. The resistant Mcs5a allele was found to be associated with an overabundance of gd T-cell receptor (TCR)+ T-cells as well as a CD62L (L-selectin)-high population of all T-cell classes. In contrast to in mammary carcinoma, gdTCR+ T-cells are the predominant T-cell type in the mammary gland and were found to be overabundant in the mammary epithelium of Mcs5a resistant congenic rats. Most of them simultaneously expressed the CD4, CD8, and CD161

  16. Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients

    DEFF Research Database (Denmark)

    Russell, James A; Vincent, Jean-Louis; Kjølbye, Anne Louise

    2017-01-01

    BACKGROUND: Vasopressin is widely used for vasopressor support in septic shock patients, but experimental evidence suggests that selective V1A agonists are superior. The initial pharmacodynamic effects, pharmacokinetics, and safety of selepressin, a novel V1A-selective vasopressin analogue, was e...

  17. Methylation status of the APC and RASSF1A promoter in cell-free circulating DNA and its prognostic role in patients with colorectal cancer.

    Science.gov (United States)

    Matthaios, Dimitrios; Balgkouranidou, Ioanna; Karayiannakis, Anastasios; Bolanaki, Helen; Xenidis, Nikolaos; Amarantidis, Kyriakos; Chelis, Leonidas; Romanidis, Konstantinos; Chatzaki, Aikaterini; Lianidou, Evi; Trypsianis, Grigorios; Kakolyris, Stylianos

    2016-07-01

    DNA methylation is the most frequent epigenetic alteration. Using methylation-specific polymerase chain reaction (MSP), the methylation status of the adenomatous polyposis coli ( APC ) and Ras association domain family 1 isoform A ( RASSF1A ) genes was examined in cell-free circulating DNA from 155 plasma samples obtained from patients with early and advanced colorectal cancer (CRC). APC and RASSF1A hypermethylation was frequently observed in both early and advanced disease, and was significantly associated with a poorer disease outcome. The methylation status of the APC and RASSF1A promoters was investigated in cell-free DNA of patients with CRC. Using MSP, the promoter methylation status of APC and RASSF1A was examined in 155 blood samples obtained from patients with CRC, 88 of whom had operable CRC (oCRC) and 67 had metastatic CRC (mCRC). The frequency of APC methylation in patients with oCRC was 33%. Methylated APC promoter was significantly associated with older age (P=0.012), higher stage (P=0.014) and methylated RASSF1A status (P=0.050). The frequency of APC methylation in patients with mCRC was 53.7%. In these patients, APC methylation was significantly associated with methylated RASSF1A status (P=0.016). The frequency of RASSF1A methylation in patients with oCRC was 25%. Methylated RASSF1A in oCRC was significantly associated with higher stage (P=0.021). The frequency of RASSF1A methylation in mCRC was 44.8%. Methylated RASSF1A in mCRC was associated with moderate differentiation (P=0.012), high levels of carcinoembryonic antigen (P=0.023) and methylated APC status (P=0.016). Patients with an unmethylated APC gene had better survival in both early (81±5 vs. 27±4 months, PAPC . Patients with an unmethylated RASSF1A gene had better survival in both early (71±6 vs. 46±8 months, PAPC and RASSF1A promoter methylation status and survival may be indicative of a prognostic role for these genes in CRC, which requires additional testing in larger studies.

  18. Development of a method for determining the location of heterogeneous activity present in 200 litre waste drum using USB based MCS system

    International Nuclear Information System (INIS)

    Singh, Sarbjit; Mhatre, Amol; Sagar, Veena; Gupta, Nidhi

    2014-01-01

    A method was developed for determining the location of activity present in 200 litre waste drum using USB based MCS system coupled to a segmented gamma ray scanner. 137 Cs source was kept at various distances from centre of the drum along the axis of the detector. Drum was rotated and the activity profiles were determined as a function of angle of rotation. The plot of the count rate as a function of angle of rotation was found to have two peaks. The experimental and calculated data were found to match well at all angles. Present studies have shown that the ratio of height and width of the profile at angles of 0 ° and 180° can be used to determine the location of the activity in the drum. (author)

  19. Women with multiple chemical sensitivity have increased harm avoidance and reduced 5-HT(1A receptor binding potential in the anterior cingulate and amygdala.

    Directory of Open Access Journals (Sweden)

    Lena Hillert

    Full Text Available Multiple chemical sensitivity (MCS is a common condition, characterized by somatic distress upon exposure to odors. As in other idiopathic environmental intolerances, the underlying mechanisms are unknown. Contrary to the expectations it was recently found that persons with MCS activate the odor-processing brain regions less than controls, while their activation of the anterior cingulate cortex (ACC is increased. The present follow-up study was designed to test the hypotheses that MCS subjects have increased harm avoidance and deviations in the serotonin system, which could render them intolerant to environmental odors. Twelve MCS and 11 control subjects, age 22-44, all working or studying females, were included in a PET study where 5-HT(1A receptor binding potential (BP was assessed after bolus injection of [(11C]WAY100635. Psychological profiles were assessed by the Temperament and Character Inventory and the Swedish universities Scales of Personality. All MCS and 12 control subjects were also tested for emotional startle modulation in an acoustic startle test. MCS subjects exhibited significantly increased harm avoidance, and anxiety compared to controls. They also had a reduced 5-HT(1A receptor BP in amygdala (p = 0.029, ACC (p = 0.005 (planned comparisons, significance level 0.05, and insular cortex (p = 0.003; significance level p<0.005 with Bonferroni correction, and showed an inverse correlation between degree of anxiety and the BP in the amygdala (planned comparison. No group by emotional category difference was found in the startle test. Increased harm avoidance and the observed changes in the 5-HT(1A receptor BP in the regions processing harm avoidance provides a plausible pathophysiological ground for the symptoms described in MCS, and yields valuable information for our general understanding of idiopathic environmental intolerances.

  20. Urinary calcium to creatinine ratio: a potential marker of secondary hyperparathyroidism in patients with vitamin D-dependent rickets type 1A.

    Science.gov (United States)

    Miyai, Kentaro; Onishi, Toshikazu; Kashimada, Kenichi; Hasegawa, Yukihiro

    2015-01-01

    Patients with vitamin D-dependent rickets type 1A (VDDR1A) are usually treated with alfacalcidol, an analog of vitamin D. Around puberty, an increased dose of alfacalcidol is recommended for these patients to avoid hypocalcemia and secondary hyperparathyroidism. However, no indicators of secondary hyperparathyroidism except for PTH are presently known. The aim of this study is to evaluate whether urinary calcium to creatinine ratio (U-Ca/Cr) is useful as a biomarker of secondary hyperparathyroidism in VDDR1A patients in order to determine the proper dose of alfacalcidol. Two brothers with VDDR1A were recruited who had null mutations of CYP27B1 which encodes 1-alpha-hydroxylase of vitamin D. We investigated the relationship between U-Ca/Cr and intact-PTH around puberty when the brothers showed hypocalcemia with secondary hyperparathyroidism. The results were compared to those of five patients with vitamin D deficiency (VDD). As a result, high intact-PTH levels were observed when U-Ca/Cr decreased to less than 0.1 (mg/mg) in both VDDR1A brothers. This relationship was also observed in the VDD patients. However, it is necessary to take into account body calcium status, either in depletion or in excess, to accurately evaluate the relationship between U-Ca/Cr and secondary hyperparathyroidism. First, low U-Ca/Cr was detected in situations with calcium depletion without hyperparathyroidism in the VDDR1A patients. Second, high U-Ca/Cr with hyperparathyroidism could be detected theoretically in a condition of excess calcium supply. In conclusion, a U-Ca/Cr ratio of less than 0.1 (mg/mg) in VDDR1A patients is useful to accurately evaluate calcium depletion and secondary hyperparathyroidism.

  1. The SLCO1A2 -189_-188InsA polymorphism reduces clearance of rocuronium in patients submitted to elective surgeries.

    Science.gov (United States)

    Costa, A C C; Coelho, E B; Lanchote, V L; Correia, B V; Abumansur, J T; Lauretti, G R; de Moraes, N V

    2017-08-01

    Rocuronium (ROC) is a neuromuscular blocker mainly eliminated by biliary excretion dependent on organic anion transporting polypeptide 1A2 (OATP1A2) hepatocellular uptake. However, the influence of SLCO1A2 (gene encoding OATP1A2) genetic polymorphism on ROC pharmacokinetics was never described before. The objective of this work was to evaluate the influence of genetic polymorphisms of SLCO1A2 on the pharmacokinetics of rocuronium (ROC). Patients undergoing elective surgeries under general anesthesia using rocuronium as a neuromuscular blocker were genotyped for SLCO1A2 polymorphisms in the coding region (41A>G, 382A>T, 404A>T, 502C>T, 516A>C, 559G>A, 830C>A, and 833delA) and in the promoter region (-1105G>A, -1032G>A, -715T>C, -361G>A, and -189_-188insA). Rocuronium pharmacokinetic parameters were estimated by non-compartmental analysis. None of the patients had heterozygous or homozygous variant of 404A>T, 382A>T, 502C>T, 833delA, 830C>A, 41A>G, and -715T>C. A linkage disequilibrium was found between -1105G>A and -1032G>A genotypes. Patients genotyped as -A or AA (n = 17) for SLCO1A2 -189_-188InsA showed reduced total clearance of ROC compared to patients genotyped as -/- (n = 13) (151.6 vs 207.1 mL/min, p ≤ 0.05). The pharmacokinetics parameters of ROC were not significantly different between other SLCO1A2 genotypes. SLCO1A2 -189_-188InsA polymorphism is related to the reduced clearance of rocuronium in patients submitted to elective surgeries under general anesthesia. NCT 02399397 ( ClinicalTrials.gov ).

  2. Can aerobic exercise alleviate flu-like symptoms following interferon beta-1a injections in patients with multiple sclerosis?

    DEFF Research Database (Denmark)

    Langeskov-Christensen, Martin; Kjølhede, Tue; Stenager, Egon

    2016-01-01

    IFNß-1a injections in persons with multiple sclerosis (PwMS). OBJECTIVE: To test the hypothesis that aerobic exercise can alleviate FLS following IFNß-1a injections in PwMS, and secondarily to examine whether or not fluctuations in circulating cytokines provide a mechanism that can explain a potential...

  3. Age and associated fibrocystic changes are prognostically significant in patients with small node-negative (T1a,bN0) invasive breast cancer.

    Science.gov (United States)

    Durak, Merih Guray; Gonzalez-Angulo, Ana M; Hanrahan, Emer O; Broglio, Kristine R; Valero, Vicente; Hortobagyi, Gabriel N; Hunt, Kelly K; Sahin, Aysegul A

    2011-01-01

    Some patients with small (≤1.0 cm) node-negative (T1a,bN0) invasive breast cancer (IBC) who undergo only local therapy experience recurrences. There is limited information on prognostic factors in these patients. We sought to identify prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in patients with T1a,bN0 IBC. Histologic sections from 273 T1a,bN0 IBC patients treated at M. D. Anderson Cancer Center (MDACC) between 1980 and 1999 were reviewed. Microscopic tumor size; multifocality; histologic type, grade of tumor; presence, type, grade of associated ductal carcinoma in situ (DCIS); presence of fibrocystic changes (FCC) with/without atypia; and lymphovascular invasion were identified. The Kaplan-Meier method was used to evaluate DFS and OS. Median patient age was 58 years, median follow-up period was 10.8 years, and median tumor size was 0.8 cm. Multifocal disease was identified in 26% of cases. At 10 years, the DFS and OS rates were 91% and 88%, respectively. Twenty-one percent of patients had extensive (>50%), and 30% had grade 3 DCIS. Nonproliferative FCC and proliferative FCC with/without atypia were present in 80%, 36%, and 38% of patients, respectively. In univariate analysis, age at diagnosis (p < 0.0001), grade (p = 0.015), and percent (p = 0.046) of DCIS were significantly associated with DFS; presence of FCC was associated with longer DFS and OS. In multivariable models, age and presence of FCC remained significantly associated with survival. Age at diagnosis and associated FCC are significant factors in predicting recurrence in patients with T1a,bN0 IBC. Adjuvant systemic therapy should be discussed with and considered for young patients with T1a,bN0 IBC. © 2011 Wiley Periodicals, Inc.

  4. 5-HT(1A) receptor binding in euthymic bipolar patients using positron emission tomography with [carbonyl-(11)C]WAY-100635.

    Science.gov (United States)

    Sargent, Peter A; Rabiner, Eugenii A; Bhagwagar, Zubin; Clark, Luke; Cowen, Philip; Goodwin, Guy M; Grasby, Paul M

    2010-06-01

    This study was undertaken to examine whether brain 5-HT(1A) receptor binding is reduced in euthymic bipolar patients. Eight medicated euthymic bipolar patients and 8 healthy volunteers underwent positron emission tomography scanning using the selective 5-HT(1A) receptor radioligand [carbonyl-(11)C]WAY-100635. No significant difference in global postsynaptic parametric binding potential (BP(ND)) was found between euthymic bipolar patients (mean + or - SD, 4.24 + or - 0.76) and healthy volunteers (mean + or - SD, 4.34 + or - 0.86). Ninety five percent Confidence Intervals for the difference in group mean global postsynaptic BP(ND) were -0.77 to 0.97. Analysis of regional BP(ND) did not reveal regional differences between patients and healthy controls. The number of subjects studied was limited and all subjects were on medication. In contrast to previous findings of reduced 5-HT(1A) receptor binding in untreated unipolar and bipolar depressed patients [Sargent, P.A., Kjaer, K.H., Bench, C.J., Rabiner, E.A., Messa, C., Meyer, J., Gunn, R.N., Grasby, P.M., Cowen, P.J., 2000. Brain serotonin1A receptor binding measured by positron emission tomography with [(11)C]WAY-100635: effects of depression and antidepressant treatment. Arch. Gen. Psychiatry 57, 174-180]; [Drevets, W.C., Frank, E., Price, J.C., Kupfer, D.J., Holt, D., Greer, P.J., Huang, Y., Gautier, C., Mathis, C., 1999. PET imaging of serotonin1A receptor binding in depression. Biol. Psychiatry 46, 1375-1387] and in recovered unipolar depressed patients [Bhagwagar, Z., Rabiner, E.A., Sargent, P.A., Grasby, P.M., Cowen, P.J., 2004. Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [(11)C]WAY-100635. Mol. Psychiatry 9, 386-92], this study found no difference in 5-HT(1A) receptor BP(ND) between medicated euthymic bipolar patients and healthy controls. Normal 5-HT(1A) receptor BP(ND) in these patients may be a result of drug treatment or

  5. Prognostic role of APC and RASSF1A promoter methylation status in cell free circulating DNA of operable gastric cancer patients.

    Science.gov (United States)

    Balgkouranidou, I; Matthaios, D; Karayiannakis, A; Bolanaki, H; Michailidis, P; Xenidis, N; Amarantidis, K; Chelis, L; Trypsianis, G; Chatzaki, E; Lianidou, E S; Kakolyris, S

    2015-08-01

    Gastric carcinogenesis is a multistep process including not only genetic mutations but also epigenetic alterations. The best known and more frequent epigenetic alteration is DNA methylation affecting tumor suppressor genes that may be involved in various carcinogenetic pathways. The aim of the present study was to investigate the methylation status of APC promoter 1A and RASSF1A promoter in cell free DNA of operable gastric cancer patients. Using methylation specific PCR, we examined the methylation status of APC promoter 1A and RASSF1A promoter in 73 blood samples obtained from patients with gastric cancer. APC and RASSF1A promoters were found to be methylated in 61 (83.6%) and 50 (68.5%) of the 73 gastric cancer samples examined, but in none of the healthy control samples (p APC promoter and elevated CEA (p = 0.033) as well as CA-19.9 (p = 0.032) levels, was noticed. The Kaplan-Meier estimates of survival, significantly favored patients with a non-methylated APC promoter status (p = 0.008). No other significant correlations between APC and RASSF1A methylation status and different tumor variables examined was observed. Serum RASSF1A and APC promoter hypermethylation is a frequent epigenetic event in patients with early operable gastric cancer. The observed correlations between APC promoter methylation status and survival as well as between a hypermethylated RASSF1A promoter and nodal positivity may be indicative of a prognostic role for those genes in early operable gastric cancer. Additional studies, in a larger cohort of patients are required to further explore whether these findings could serve as potential molecular biomarkers of survival and/or response to specific treatments. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Role of UDP-Glucuronosyltransferase 1A1 in the Metabolism and Pharmacokinetics of Silymarin Flavonolignans in Patients with HCV and NAFLD

    Directory of Open Access Journals (Sweden)

    Ying Xie

    2017-01-01

    Full Text Available Silymarin is the most commonly used herbal medicine by patients with chronic liver disease. Silymarin flavonolignans undergo rapid first-pass metabolism primarily by glucuronidation. The aims of this investigation were: (1 to determine the association of UGT1A1*28 polymorphism with the area under the plasma concentration-time curves (AUCs for silybin A (SA and silybin B (SB; (2 to evaluate the effect of UGT1A1*28 polymorphism on the profile of flavonolignan glucuronide conjugates found in the plasma; and (3 to investigate the role of UGT1A1 enzyme kinetics on the pharmacokinetics of SA and SB. AUCs and metabolic ratios for thirty-three patients with chronic liver disease administered oral doses of silymarin were compared between different UGT1A1*28 genotypes. The AUCs, metabolic ratios, and the profiles of major SA and SB glucuronides did not differ significantly among the three UGT1A1 genotypes. In contrast, an increase in the proportion of sulfated flavonolignan conjugates in plasma was observed in subjects with UGT1A1*28/*28 genotype compared to subjects carrying wild type alleles. Differences in SA and SB in vitro intrinsic clearance estimates for UGTIA1 correlated inversely with SA and SB exposures observed in vivo indicating a major role for UGT1A1 in silymarin metabolism. In addition, a significant difference in the metabolic ratio observed between patients with NAFLD and HCV suggests that any effect of UGT1A1 polymorphism may be obscured by a greater effect of liver disease on the pharmacokinetics of silymarin. Taken together, these results suggest the presence of the UGT1A1*28 allele does not contribute significantly to a large inter-subject variability in the pharmacokinetics of silybin A and silybin B which may obscure the ability to detect beneficial effects of silymarin in patients with liver disease.

  7. Resistance-associated polymorphisms in Dutch hepatitis C genotype 1a patients with and without HIV infection

    NARCIS (Netherlands)

    Lieveld, Faydra I.; Swaans, Niels; Newsum, Astrid M.; Ho, Cynthia K. Y.; Schinkel, Janke; Molenkamp, Richard; van der Meer, Jan T. M.; Arends, Joop E.; Hoepelman, Andy I. M.; Wensing, Anne M. J.; Siersema, Peter D.; van Erpecum, Karel J.; Boland, Greet J.

    2016-01-01

    Background and aim. Resistance-associated variants (RAVs) on the NS3 region of the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed frequencies of NS3 RAVs in patients infected with HCV genotype

  8. Intensive strength and balance training with the Kinect console (Xbox 360) in a patient with CMT1A.

    Science.gov (United States)

    Pagliano, Emanuela; Foscan, Maria; Marchi, Alessia; Corlatti, Alice; Aprile, Giorgia; Riva, Daria

    2017-08-01

    Effective drugs for type 1A Charcot-Marie-Tooth (CMT1A) disease are not available. Various forms of moderate exercise are beneficial, but few data are available on the effectiveness of exercise in CMT1A children. To investigate the feasibility and effectiveness of exercises to improve ankle strength and limb function in a child with CMT1A. Outpatient clinic. Nine-year-old boy with CMT1A. The rehabilitation program consisted of ankle exercises and Kinect videogame-directed physical activities (using an Xbox 360 console/movement sensor) that aimed to improve balance and limb strength. The program was given 3 times a week for 5 weeks. The child was assessed at baseline, after 5 weeks, and 3 and 6 months after. By the end of follow-up, child balance and endurance had improved, but ankle strength did not. The encouraging results for balance and endurance justify further studies on videogame-directed activities in CMT1A children/adolescents.

  9. THE COLLABORATIVE OCULAR TUBERCULOSIS STUDY (COTS)-1: A Multinational Review of 251 Patients With Tubercular Retinal Vasculitis.

    Science.gov (United States)

    Gunasekeran, Dinesh V; Agrawal, Rupesh; Agarwal, Aniruddha; Carreño, Ester; Raje, Dhananjay; Aggarwal, Kanika; Kon, Onn M; Nguyen, Quan Dong; Pavesio, Carlos; Gupta, Vishali

    2018-04-24

    Tubercular retinal vasculitis (TRV) is a heterogeneous disease that can be difficult to manage because of nonspecific presentation and limitations of confirmatory tests for tuberculosis. This is a big data analysis on phenotypes and treatment outcomes for TRV. Multicentre retrospective study of patients with TRV between January 2004 and December 2014 and a minimum follow-up of 1 year. Two hundred and fifty-one patients with TRV with a mean age of 38.9 ± 14.4 years (range, 9-86 years) were included. The patients were predominantly males (n = 167/251; 66.5%) of Asian ethnicity (n = 174/246; 70.7%), and geographical origin (n = 137/251; 54.6%). Most patients had features of occlusive type of RV (n = 113/185; 61.1%) except Caucasians (n = 11; 28.2%). There was no significant difference in treatment failure whether patients received antitubercular therapy (ATT) (P = 0.29), although treatment failure was less frequent in patients who received ATT (13.6%; n = 31/228) compared with those who did not (21.7%, n = 5/23). Less treatment failures were observed in patients with occlusive type RV who received ATT; however, this was not significant on survival analysis (P = 0.09). Treatment with ATT was associated with higher failure rates in patients of Hispanic and African American race and those with TRV associated with panuveitis (compared with posterior uveitis). In this multinational study of TRV, there was no significant therapeutic effect of ATT. However, a definitive conclusion about the role of ATT could not be made because of a few patients who did not receive ATT. Because this is a retrospective study with a limited 1-year follow-up, the effect of ATT may have been overestimated (or underestimated) in the duration of follow-up.

  10. The spectrum of HNF1A gene mutations in Greek patients with MODY3: relative frequency and identification of seven novel germline mutations.

    Science.gov (United States)

    Tatsi, Christina; Kanaka-Gantenbein, Christina; Vazeou-Gerassimidi, Adriani; Chrysis, Dionysios; Delis, Dimitrios; Tentolouris, Nikolaos; Dacou-Voutetakis, Catherine; Chrousos, George P; Sertedaki, Amalia

    2013-11-01

    Maturity-Onset Diabetes of the Young (MODY) is the most common type of monogenic diabetes accounting for 1-2% of the population with diabetes. The relative incidence of HNF1A-MODY (MODY3) is high in European countries; however, data are not available for the Greek population. The aims of this study were to determine the relative frequency of MODY3 in Greece, the type of the mutations observed, and their relation to the phenotype of the patients. Three hundred ninety-five patients were referred to our center because of suspected MODY during a period of 15 yr. The use of Denaturing Gradient Gel Electrophoresis of polymerase chain reaction amplified DNA revealed 72 patients carrying Glucokinase gene mutations (MODY2) and 8 patients carrying HNF1A gene mutations (MODY3). After using strict criteria, 54 patients were selected to be further evaluated by direct sequencing or by multiplex ligation probe amplification (MLPA) for the presence of HNF1A gene mutations. In 16 unrelated patients and 13 of their relatives, 15 mutations were identified in the HNF1A gene. Eight of these mutations were previously reported, whereas seven were novel. Clinical features, such as age of diabetes at diagnosis or severity of hyperglycemia, were not related to the mutation type or location. In our cohort of patients fulfilling strict clinical criteria for MODY, 12% carried an HNF1A gene mutation, suggesting that defects of this gene are responsible for a significant proportion of monogenic diabetes in the Greek population. No clear phenotype-genotype correlations were identified. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Expression of HERV-Fc1, a human endogenous retrovirus, is increased in patients with active Multiple Sclerosis

    DEFF Research Database (Denmark)

    Laska, Magdalena Janina; Brudek, Tomasz; Nissen, Kari Konstantin

    2012-01-01

    of a capsid (Gag) protein of HERV-H/F origin by flow cytometry in peripheral blood mononuclear cells (PBMCs) from healthy controls and from MS patients with nonactive or active disease. There was a significant increase in HERV-H/F Gag expression in CD4(+) (P ...-fold increase in extracellular HERV-Fc1 RNA titers in patients with active MS compared with healthy controls (P

  12. Usefulness of Whole-Body Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in Patients with Neurofibromatosis Type 1: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Giorgio Treglia

    2012-01-01

    Full Text Available Aim. To systematically review the role of positron emission tomography (PET with fluorine-18-fluorodeoxyglucose (FDG in patients with neurofibromatosis type 1 (NF1. Methods. A comprehensive literature search of published studies regarding FDG-PET and PET/CT in patients with NF1 was performed. No beginning date limit and language restriction were used; the search was updated until December 2011. Only those studies or subsets in studies including whole-body FDG-PET or PET/CT scans performed in patients with NF1 were included. Results. We identified 12 studies including 352 NF1 patients. Qualitative evaluation was performed in about half of the studies and semiquantitative analysis, mainly based on different values of SUV cutoff, in the others. Most of the studies evaluated the role of FDG-PET for differentiating benign from malignant peripheral nerve sheath tumors (MPNSTs. Malignant lesions were detected with a sensitivity ranging between 100% and 89%, but with lower specificity, ranging between 100% and 72%. Moreover, FDG-PET seems to be an important imaging modality for predicting the progression to MPNST and the outcome in patients with MPNST. Two studies evaluated the role of FDG-PET in pediatric patients with NF1. Conclusions. FDG-PET and PET/CT are useful methods to identify malignant change in neurogenic tumors in NF1 and to discriminate malignant from benign neurogenic lesions.

  13. Aneurysmal rupture of the costo-cervical trunk in a patient with neurofibromatosis type 1: A case report.

    Science.gov (United States)

    Hoonjan, Bhupinder; Thayur, Nagendra; Abu-Own, Abdusalam

    2014-01-01

    Rupture of blood vessels associated with neurofibromatosis type 1 (NF-1) is a rare but life threatening complication. We report the first case of an aneurysmal rupture from the costocervical trunk in a NF-1 patient treated by endovascular embolisation. A 43 year-old gentleman with a past medical history of NF-1 presented with sudden onset left sided neck swelling. A computed tomography (CT) revealed a large cervical haematoma, which was causing airway compromise, requiring the patient to be intubated. Percutaneous embolisation of the bleeding vessel from the costo-cervical trunk was performed with successful haemostasis and no immediate complications. A repeat CT scan showed a reduction in the original cervical haematoma. However, six days post embolisation, the patient arrested with complete whiteout of the left hemithorax. CT angiography is the gold standard for diagnosis of an aneurysmal rupture in NF-1 patients, and percutaneous embolisation is the preferred modality in patients who are haemodynamically stable due to arterial fragility and high intra operative mortality rates. The increasing haemothorax could be explained by the original cervical haematoma draining down into the pleural space, or the possibility of a new second bleed. This is the first reported episode of bleeding from the costocervical trunk in NF-1 patients. Ruptured aneurysms require urgent CT angiography, if haemodynamically stable, and further input from the vascular surgeons and vascular radiologists. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Aneurysmal rupture of the costo-cervical trunk in a patient with neurofibromatosis type 1: A case report☆

    Science.gov (United States)

    Hoonjan, Bhupinder; Thayur, Nagendra; Abu-Own, Abdusalam

    2013-01-01

    INTRODUCTION Rupture of blood vessels associated with neurofibromatosis type 1 (NF-1) is a rare but life threatening complication. We report the first case of an aneurysmal rupture from the costocervical trunk in a NF-1 patient treated by endovascular embolisation. PRESENTATION OF CASE A 43 year-old gentleman with a past medical history of NF-1 presented with sudden onset left sided neck swelling. A computed tomography (CT) revealed a large cervical haematoma, which was causing airway compromise, requiring the patient to be intubated. Percutaneous embolisation of the bleeding vessel from the costo-cervical trunk was performed with successful haemostasis and no immediate complications. A repeat CT scan showed a reduction in the original cervical haematoma. However, six days post embolisation, the patient arrested with complete whiteout of the left hemithorax. DISCUSSION CT angiography is the gold standard for diagnosis of an aneurysmal rupture in NF-1 patients, and percutaneous embolisation is the preferred modality in patients who are haemodynamically stable due to arterial fragility and high intra operative mortality rates. The increasing haemothorax could be explained by the original cervical haematoma draining down into the pleural space, or the possibility of a new second bleed. CONCLUSION This is the first reported episode of bleeding from the costocervical trunk in NF-1 patients. Ruptured aneurysms require urgent CT angiography, if haemodynamically stable, and further input from the vascular surgeons and vascular radiologists. PMID:24463561

  15. Usefulness of Whole-Body Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in Patients with Neurofibromatosis Type 1: A Systematic Review

    International Nuclear Information System (INIS)

    Treglia, G.; Taralli, S.; Giordano, A.; Bertagna, F.; Salsano, M.; Maggi, F.; Muoio, B.; Novellis, P.; Vita, M.L.

    2012-01-01

    To systematically review the role of positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG) in patients with neurofibromatosis type 1 (NF1). Methods. A comprehensive literature search of published studies regarding FDG-PET and PET/CT in patients with NF1 was performed. No beginning date limit and language restriction were used; the search was updated until December 2011. Only those studies or subsets in studies including whole-body FDG-PET or PET/CT scans performed in patients with NF1 were included. Results. We identified 12 studies including 352 NF1 patients. Qualitative evaluation was performed in about half of the studies and semiquantitative analysis, mainly based on different values of SUV cutoff, in the others. Most of the studies evaluated the role of FDG-PET for differentiating benign from malignant peripheral nerve sheath tumors (MPNSTs). Malignant lesions were detected with a sensitivity ranging between 100% and 89%, but with lower specificity, ranging between 100% and 72%. Moreover, FDG-PET seems to be an important imaging modality for predicting the progression to MPNST and the outcome in patients with MPNST. Two studies evaluated the role of FDG-PET in pediatric patients with NF1. Conclusions. FDG-PET and PET/CT are useful methods to identify malignant change in neurogenic tumors in NF1 and to discriminate malignant from benign neurogenic lesions

  16. Web-based stress management for newly diagnosed cancer patients (STREAM-1): a randomized, wait-list controlled intervention study.

    Science.gov (United States)

    Grossert, Astrid; Urech, Corinne; Alder, Judith; Gaab, Jens; Berger, Thomas; Hess, Viviane

    2016-11-03

    Being diagnosed with cancer causes major psychological distress, yet the majority of newly diagnosed cancer patients lack psychological support. Internet interventions overcome many barriers for seeking face-to-face support and allow for independence in time and place. We assess efficacy and feasibility of the first web-based stress management intervention (STREAM: STREss-Aktiv-Mindern) for newly diagnosed, German-speaking cancer patients. In a prospective, wait-list controlled trial 120 newly diagnosed cancer patients will be included within 12 weeks of starting anti-cancer treatment and randomized between an immediate (intervention group) or delayed (control group) 8-week, web-based intervention. The intervention consists of eight modules with weekly written feedback by a psychologist ("minimal-contact") based on well-established stress management manuals including downloadable audio-files and exercises. The aim of this study is to evaluate efficacy in terms of improvement in quality of life (FACT-F), as well as decrease in anxiety and depression (HADS), as compared to patients in the wait-list control group. A sample size of 120 patients allows demonstrating a clinically relevant difference of nine points in the FACT score after the intervention (T2) with a two-sided alpha of 0.05 and 80 % power. As this is the first online stress management intervention for German-speaking cancer patients, more descriptive outcomes are equally important to further refine the group of patients with the largest potential for benefit who then will be targeted more specifically in future trials. These descriptive endpoints include: patients' characteristics (type of cancer, type of treatment, socio-demographic factors), dropout rate and dropout reasons, adherence and satisfaction with the program. New technologies open new opportunities: minimal-contact psychological interventions are becoming standard of care in several psychological disorders, where their efficacy is often

  17. Expansive hematoma in delayed cerebral radiation necrosis in patients treated with T-DM1: a report of two cases

    International Nuclear Information System (INIS)

    Mitsuya, Koichi; Watanabe, Junichiro; Nakasu, Yoko; Hayashi, Nakamasa; Harada, Hideyuki; Ito, Ichiro

    2016-01-01

    Multiple new targeted agents have been developed for patients with human epidermal growth factor receptor type 2 (HER2) – positive breast cancer. Patients with HER2– positive breast cancer will develop brain metastases with greater incidence than patients with non-HER2 cancers, and many of them will undergo stereotactic radiosurgery (SRS) or other CNS radiotherapy. The interaction between radiation effects and new targeted agents is not well understood. We report two cases suggesting a novel adverse effect of T-DM1 (trastuzumab emtansine) on symptomatic enlargement of radiation necrosis (RN) after SRS. Two patients with HER2-positive breast cancer had received SRS for single brain metastasis more than 5-years ago. They had been heavily treated for HER2-positive metastatic breast cancer (trastuzumab and pacritaxel, lapatinib and capecitabine). They initiated T-DM1 therapy for progressive systematic disease 5.5 years after stereotactic irradiation, when a small RN was recognized on brain MR images of each patient. The RN lesions increased in size and became symptomatic during 13 or 14 months of T-DM1 treatment. The patients underwent surgical resection of the lesion. Pathological examination revealed necrosis, hematoma, granulation tissue and telangiectasia without neoplastic cells. A potential enhancement of RN by T-DM1 in the brain may be one of important adverse events associated with the use of T-DM1 for patients after SRS. These cases highlight the need of careful follow-up when combining new systemic targeted therapies and SRS for brain metastases

  18. Increased lipogenesis and resistance of lipoproteins to oxidative modification in two patients with glycogen storage disease type 1a

    NARCIS (Netherlands)

    Bandsma, RHJ; Rake, JP; Visser, G; Neese, RA; Hellerstein, MK; van Duyvenvoorde, W; Princen, HMG; Stellaard, F; Smit, GPA; Kuipers, F

    We describe 2 patients with glycogen storage disease type la and severe hyperlipidemia without premature atherosclerosis. Susceptibility of low-density lipoproteins to oxidation was decreased, possibly related to the similar to40-fold increase in palmitate synthesis altering lipoprotein saturated

  19. Assessment of Newly Proposed Clinical Criteria to Identify HNF1A MODY in Patients with an Initial Diagnosis of Type 1 or Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Malgorzata Grzanka

    2016-01-01

    Full Text Available The most common form of maturity-onset diabetes of the young (MODY is caused by mutations in the hepatocyte nuclear factor 1A (HNF1A gene. However, most HNF1A mutation-carriers are initially misdiagnosed with type 1 (T1DM or type 2 (T2DM diabetes mellitus; hence, they often receive nonoptimal treatment. The aim of our study was to test newly proposed clinical criteria for the identification of HNF1A MODY in patients with a diagnosis of T1DM or T2DM. To achieve this, the following criteria to preselect patients for screening were used: for T1DM: TDIR (total daily insulin requirement > 0.3 IU of insulin/kg and the percentage of basal insulin > 30% of TDIR; for T2DM: sulphonylurea- (SU- based oral treatment (monotherapy or combined with Metformin > 15 years and BMI < 30 kg/m2. We reviewed the clinical data of 140 patients with T1DM and 524 clinically diagnosed with T2DM. On the basis of these criteria, we found a HNF1A mutation in 1 out of 2 individuals with a diagnosis of T1DM and 1 out of 11 selected individuals with a diagnosis of T2DM. We believe that the simplicity of the proposed criteria might prove useful in clinical practice, as an alternative to more time-consuming classical diagnostic techniques.

  20. Assessment of Newly Proposed Clinical Criteria to Identify HNF1A MODY in Patients with an Initial Diagnosis of Type 1 or Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Grzanka, Malgorzata; Matejko, Bartlomiej; Szopa, Magdalena; Kiec-Wilk, Beata; Malecki, Maciej T; Klupa, Tomasz

    2016-01-01

    The most common form of maturity-onset diabetes of the young (MODY) is caused by mutations in the hepatocyte nuclear factor 1A (HNF1A) gene. However, most HNF1A mutation-carriers are initially misdiagnosed with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus; hence, they often receive nonoptimal treatment. The aim of our study was to test newly proposed clinical criteria for the identification of HNF1A MODY in patients with a diagnosis of T1DM or T2DM. To achieve this, the following criteria to preselect patients for screening were used: for T1DM: TDIR (total daily insulin requirement) > 0.3 IU of insulin/kg and the percentage of basal insulin > 30% of TDIR; for T2DM: sulphonylurea- (SU-) based oral treatment (monotherapy or combined with Metformin) > 15 years and BMI < 30 kg/m(2). We reviewed the clinical data of 140 patients with T1DM and 524 clinically diagnosed with T2DM. On the basis of these criteria, we found a HNF1A mutation in 1 out of 2 individuals with a diagnosis of T1DM and 1 out of 11 selected individuals with a diagnosis of T2DM. We believe that the simplicity of the proposed criteria might prove useful in clinical practice, as an alternative to more time-consuming classical diagnostic techniques.

  1. Prevalence of Hepatitis C Virus Subgenotypes 1a and 1b in Japanese Patients: Ultra-Deep Sequencing Analysis of HCV NS5B Genotype-Specific Region

    Science.gov (United States)

    Wu, Shuang; Kanda, Tatsuo; Nakamoto, Shingo; Jiang, Xia; Miyamura, Tatsuo; Nakatani, Sueli M.; Ono, Suzane Kioko; Takahashi-Nakaguchi, Azusa; Gonoi, Tohru; Yokosuka, Osamu

    2013-01-01

    Background Hepatitis C virus (HCV) subgenotypes 1a and 1b have different impacts on the treatment response to peginterferon plus ribavirin with direct-acting antivirals (DAAs) against patients infected with HCV genotype 1, as the emergence rates of resistance mutations are different between these two subgenotypes. In Japan, almost all of HCV genotype 1 belongs to subgenotype 1b. Methods and Findings To determine HCV subgenotype 1a or 1b in Japanese patients infected with HCV genotype 1, real-time PCR-based method and Sanger method were used for the HCV NS5B region. HCV subgenotypes were determined in 90% by real-time PCR-based method. We also analyzed the specific probe regions for HCV subgenotypes 1a and 1b using ultra-deep sequencing, and uncovered mutations that could not be revealed using direct-sequencing by Sanger method. We estimated the prevalence of HCV subgenotype 1a as 1.2-2.5% of HCV genotype 1 patients in Japan. Conclusions Although real-time PCR-based HCV subgenotyping method seems fair for differentiating HCV subgenotypes 1a and 1b, it may not be sufficient for clinical practice. Ultra-deep sequencing is useful for revealing the resistant strain(s) of HCV before DAA treatment as well as mixed infection with different genotypes or subgenotypes of HCV. PMID:24069214

  2. A Novel PRKAR1A Mutation Identified in a Patient with Isolated Primary Pigmented Nodular Adrenocortical Disease

    Directory of Open Access Journals (Sweden)

    Sira Korpaisarn

    2017-08-01

    Full Text Available Primary pigmented nodular adrenocortical disease (PPNAD is a rare cause of Cushing syndrome, especially the isolated form without Carney complex, associated with germline mutations in PRKAR1A, the protein kinase A regulatory subunit type 1 alpha gene. We report a 31-year-old female who presented with secondary amenorrhea, cushingoid appearance, and hypertension without Carney complex. Biochemical laboratory examinations confirmed the ACTH-independent adrenal Cushing syndrome with negative Liddle test. A small right adrenal adenoma of 0.8 cm was shown on computed tomography while magnetic resonance imaging revealed nodularity of both adrenal glands. The histological report confirmed PPNAD using laparoscopic right adrenalectomy, and subsequent left adrenalectomy was performed 6 months later. She had inherited heterozygosity of a novel germline mutation of the PRKAR1A gene (g.114213T>G or c.709-5T>G. This splice site mutation results in exon 8 skipping. Her father carrying the same mutation had no clinical features of either PPNAD or Carney complex. This novel PRKAR1A gene mutation, c.709-5T>G, is reported here for the first time manifesting as an incomplete clinical expression of the isolated form of PPNAD and being inherited with low penetrance unlike other inherited mutations of the Carney complex which have a penetrance of almost 100%.

  3. Patient subgroup analyses of the treatment effect of subcutaneous interferon beta-1a on development of multiple sclerosis in the randomized controlled REFLEX study

    NARCIS (Netherlands)

    Freedman, M.S.; De Stefano, N.; Barkhof, F.; Polman, C.H.; Comi, G.; Uitdehaag, B.M.J.; Casset-Semanaz, F.; Hennessy, B.; Lehr, L.; Stubinski, B.; Jack, D.L.; Kappos, L.

    2014-01-01

    The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to

  4. Treatment of patients with severe sepsis using Ulinastatin and Thymosin α1: a prospective, randomized, controlled pilot study

    Institute of Scientific and Technical Information of China (English)

    CHEN Hao; HE Ming-yan; LI Yu-min

    2009-01-01

    Background Tradition treatment of sepsis and new therapies, including high dose corticosteroids and non-steroidal anti-inflammatory drugs, have proven unsuccessful in improving survival. This study aimed to evaluate the potential efficacy of immunomodulating therapy using Ulinastatin (UTI) plus Thymosin α1 (Tα1) for improving organ function and reducing mortality in patients with severe sepsis.Methods A prospective study was carried out with randomized and controlled clinical analysis of 114 patients conforming to the enrollment standard. All patients had severe sepsis and received standard supportive care and antimicrobial therapy. Fifty-nine patients were also administered UTI plus Tα1 (defined as Group A), 55 patients were given a placebo (defined as Group B). Clinical parameters were determined by evaluation with the Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ), multiple organ failure (MOF) and the Glasgow Coma Scores (GCS) on entry and after therapy on the 3rd, 8th, and 28th day. By flow cytometery and ELISA lymphocyte subsets and cytokines were analyzed. Survival analysis was determined by the Kaplan-Meier method at 28, 60, and 90 days. Results Based on comparison of the two groups, patients in Group A exhibited a better performance in organ failure scores which was noticeable soon after initiation of treatment. Patients in Group A also demonstrated a better resolution of pre-existing organ failures during the observation period. After initiation of treatment, significant improvements in the CD4+/CD8+ ratio, a quicker balance between proinflammatory mediators such as tumor necrosis factor a, interleukin 6 and anti-inflammatory cytokines including interleukin 4 and interleukin 10 were found. This was followed by cumulative survival increases of 17.3% at 28 days, 28.9% at 60 days, and 31.4% at 90 days in Group A. The reduction in mortality was accompanied by a considerably shorter stay in the ICU and a shorter length of supportive

  5. Effects of UGT1A9 genetic polymorphisms on monohydroxylated derivative of oxcarbazepine concentrations and oxcarbazepine monotherapeutic efficacy in Chinese patients with epilepsy.

    Science.gov (United States)

    Lu, Yao; Fang, Youxin; Wu, Xunyi; Ma, Chunlai; Wang, Yue; Xu, Lan

    2017-03-01

    The human UDP-glucuronosyltransferase which is genetically polymorphic catalyzes glucuronidations of various drugs. The interactions among UGT1A4, UGT1A6, UGT1A9, and UGT2B15 genetic polymorphisms, monohydroxylated derivative (MHD) of oxcarbazepine (OXC) plasma concentrations, and OXC monotherapeutic efficacy were explored in 124 Chinese patients with epilepsy receiving OXC monotherapy. MHD is the major active metabolite of OXC, and its plasma concentration was measured using high-performance liquid chromatography when patients reached their maintenance dose of OXC. Genomic DNA was extracted from whole blood and SNP genotyping performed using PCR followed by dideoxy chain termination sequencing. We followed the patients for at least 1 year to evaluate the OXC monotherapy efficacy. Patients were divided into two groups according to their therapeutic outcome: group 1, seizure free; group 2, not seizure free. The data were analyzed using T test, one-way analysis of variance (ANOVA), Kruskal-Wallis test, chi-square test, Fisher's exact test, correlation analysis, and multivariate regression analysis. T test analysis showed that MHD plasma concentrations were significantly different between the two groups (p = 0.002). One-way ANOVA followed by Bonferroni post hoc testing of four candidate SNPs revealed that carriers of the UGT1A9 variant allele I399 C > T (TT 13.28 ± 7.44 mg/L, TC 16.41 ± 6.53 mg/L) had significantly lower MHD plasma concentrations and poorer seizure control than noncarriers (CC 22.24 ± 8.49 mg/L, p effects of UGT1A9 genetic polymorphisms on MHD plasma concentrations and OXC therapeutic efficacy. Through MHD monitoring, we can predict OXC therapeutic efficacy, which may be useful for the personalization of OXC therapy in epileptic patients.

  6. Phenotype of CNTNAP1: a study of patients demonstrating a specific severe congenital hypomyelinating neuropathy with survival beyond infancy.

    Science.gov (United States)

    Low, K J; Stals, K; Caswell, R; Wakeling, M; Clayton-Smith, J; Donaldson, A; Foulds, N; Norman, A; Splitt, M; Urankar, K; Vijayakumar, K; Majumdar, A; Study, Ddd; Ellard, S; Smithson, S F

    2018-06-01

    CHN is genetically heterogeneous and its genetic basis is difficult to determine on features alone. CNTNAP1 encodes CASPR, integral in the paranodal junction high molecular mass complex. Nineteen individuals with biallelic variants have been described in association with severe congenital hypomyelinating neuropathy, respiratory compromise, profound intellectual disability and death within the first year. We report 7 additional patients ascertained through exome sequencing. We identified 9 novel CNTNAP1 variants in 6 families: three missense variants, four nonsense variants, one frameshift variant and one splice site variant. Significant polyhydramnios occurred in 6/7 pregnancies. Severe respiratory compromise was seen in 6/7 (tracheostomy in 5). A complex neurological phenotype was seen in all patients who had marked brain hypomyelination/demyelination and profound developmental delay. Additional neurological findings included cranial nerve compromise: orobulbar dysfunction in 5/7, facial nerve weakness in 4/7 and vocal cord paresis in 5/7. Dystonia occurred in 2/7 patients and limb contractures in 5/7. All had severe gastroesophageal reflux, and a gastrostomy was required in 5/7. In contrast to most previous reports, only one patient died in the first year of life. Protein modelling was performed for all detected CNTNAP1 variants. We propose a genotype-phenotype correlation, whereby hypomorphic missense variants partially ameliorate the phenotype, prolonging survival. This study suggests that biallelic variants in CNTNAP1 cause a distinct recognisable syndrome, which is not caused by other genes associated with CHN. Neonates presenting with this phenotype will benefit from early genetic definition to inform clinical management and enable essential genetic counselling for their families.

  7. An observational, retrospective, UK and Ireland audit of patient adherence to subcutaneous interferon beta-1a injections using the RebiSmart® injection device

    Directory of Open Access Journals (Sweden)

    Willis H

    2014-06-01

    Full Text Available Helen Willis,1 Julie Webster,1 Anne Marie Larkin,2 Laura Parkes,31Broomfield Hospital, Chelmsford, Essex, United Kingdom; 2MySupport Nurse, Quintiles Ireland Ltd, Dublin, Ireland; 3Medical Affairs, Merck Serono Ltd, Feltham, United KingdomBackground: Poor adherence to disease-modifying drugs is associated with an increased risk of relapse in patients with multiple sclerosis. However, adherence is difficult to assess objectively. RebiSmart® (Merck Serono SA, Geneva, Switzerland, a device for subcutaneous (sc injection of interferon (IFN β-1a, features an electronic injection log that can assist in objective monitoring of adherence.Objective: To assess adherence to sc IFN β-1a injections using data from RebiSmart®.Methods: This was a single-group, observational, retrospective audit. Adherence data were collected from patients with relapsing multiple sclerosis in the United Kingdom and Ireland who had been prescribed sc IFN β-1a and had been using RebiSmart® for a minimum of 24 months.Results: In total, 225 patients were included in the full analysis set; 72% were in the United Kingdom, and 28% were in Ireland. Overall, the mean age was 44.1 years, and 73% were women. Patients received sc IFN β-1a 44 µg (68% or 22 µg (32% three times per week. Mean adherence over the course of 24 months was 95.0% (median, 99.4%, and similar values were observed across all periods. The proportion of patients with 80% or higher adherence was 92.0% at 12 months and 91.1% at 24 months.Conclusion: High adherence to sc IFN β-1a was observed across all patient groups using RebiSmart®, according to 2-year treatment adherence data. This may be partly attributed to the expert support patients received, supplemented by routine and regular contact from the MySupport patient-support program, as well as the self-motivation of patients who persisted with treatment for 2 or more years.Keywords: multiple sclerosis, support program, persistence, objective

  8. The effect of UGT1A1 promoter polymorphism in the development of hyperbilirubinemia and cholelithiasis in hemoglobinopathy patients.

    Directory of Open Access Journals (Sweden)

    Suad AlFadhli

    Full Text Available Present study was aimed to explore the effect of (TAn UGT1A1 gene promoter polymorphism on bilirubin metabolism, bilirubinaemia, predisposition to cholelithiasis and subsequent cholecystectomy, in Sickle-Cell Anemia (SCA and beta-Thalasemia major (bTH in Kuwaiti subjects compared to other population. This polymorphism was analyzed and correlated to total bilirubin and cholelithiasis in 270 age, gender, ethnically matched subjects (92 bTH, 116 SCA and 62 Controls using PCR, dHPLC, fragment analysis and direct sequencing. Four genotypes of UGT1A1 were detected in this study (TA6/6, TA6/7, TA6/8 and TA7/7. (TA6/8 was found only in four individuals; hence it was not included in the analysis. There was a statistically significant association of genotypes with serum total bilirubin levels in both bTH and SCA groups (p<0.001. Subjects with (TA7/7 had the highest total serum bilirubin level (178.7 ± 3.5 µmole/l. A significant association was observed between allele (TA7 and cholelithiasis development (p = 0.0001. The 40%, 67.5% and 100% of SCA with (TA6/6, (TA6/7 and (TA7/7 respectively developed cholelithiasis and were subsequently cholecystectomized. Our results confirm UGT1A1 (TA7 allele as one of the factors accounting for the hyperbilirubinemia and cholelithiasis observed in SCA and bTH.

  9. Quantitative Rates of Brain Glucose Metabolism Distinguish Minimally Conscious from Vegetative State Patients

    DEFF Research Database (Denmark)

    Stender, Johan; Kupers, Ron; Rodell, Anders

    2015-01-01

    of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global......The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function...... these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.Journal of Cerebral Blood Flow & Metabolism advance online publication, 8 October 2014; doi:10...

  10. Prevalence of relevant NS5A resistance-associated substitutions to elbasvir in genotype 1a hepatitis C virus patients in Spain.

    Science.gov (United States)

    Palladino, Claudia; Esteban-Cartelle, Beatriz; Mate-Cano, Irene; Sánchez-Carrillo, Marta; Resino, Salvador; Briz, Verónica

    2018-05-01

    Resistance-associated substitutions (RASs) to the new HCV NS5A inhibitor elbasvir may limit its efficacy and lead to virological failure in HCV-GT1a-infected patients. There are no data outside clinical trials evaluating their prevalence and impact in grazoprevir/elbasvir in GT1a-infected patients in Spain. A multicentre cross-sectional study of 632 initial patients was conducted. In 13 of these patients, the sample could not be amplified or a consensus sequence by Sanger sequencing could not be performed. Ultimately, 617 HCV-G1a-infected individuals treated at 84 Spanish hospitals from the 17 autonomous communities plus the 2 autonomous cities of Spain were analysed. HCV population sequencing was used to identify RAS to elbasvir and the mutational pattern and drug sensitivity were confirmed by geno2pheno[HCV]. Viruses bearing RASs to elbasvir were present in 6.2% of HCV-G1a infected patients. The most common RASs were the Y93C/H/N and Q30E/H/R (2.4% and 2.3%, respectively). Only 3.4% of the identified RASs to elbasvir conferred reduced susceptibility to elbasvir by geno2pheno[HCV], which exclusively identified the positions Q30H/R (n=7) and Y93C/H/N (n=8) as single mutations and Q30H+Y93H (n=4) and Q30R+Y93H (n=2) as double mutations as the major RASs to elbasvir. A lower prevalence of RASs to elbasvir was observed in our HCV-G1a Spanish cohort than reported previously in clinical trials evaluating patients from the USA. This information may be essential to guide the implementation of grazoprevir/elbasvir in Spain and to manage G1a-infected patients. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  11. Infiltrating Mast Cells Correlate with Angiogenesis in Bone Metastases from Gastric Cancer Patients

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    Michele Ammendola

    2015-02-01

    Full Text Available While gastric cancer is a well established angiogenesis driven tumor, no data has been published regarding angiogenesis stimulated by mast cells (MCs positive for tryptase in bone metastases from gastric cancer patients (BMGCP. It is well established that MCs play a role in immune responses and more recently it was demonstrated that MCs have been involved in tumor angiogenesis. We analyzed infiltrating MCs and neovascularization in BMGCP diagnosed by histology. A series of 15 stage T3-4N2-3M1 (by AJCC for Gastric Cancer Staging 7th Edition BMGCP from bone biopsies were selected. Tumour tissue samples were evaluated by mean of immunohistochemistry and image analysis methods in terms of MCs density positive to tryptase (MCDPT, MCs area positive to tryptase (MCAPT, microvascular density (MVD and endothelial area (EA. A significant correlation between MCDPT, MCAPT, MVD and EA groups to each other was found by Pearson and t-test analysis (r ranged from 0.68 to 0.82; p-value ranged from 0.00 to 0.02. Our very preliminary data suggest that infiltrating MCs positive for tryptase may play a role in BMGCP angiogenesis, and could be further evaluated as a novel target of anti-angiogenic therapy.

  12. Prevalence of pre-treatment hepatitis C virus NS5A resistance associated amino-acid substitutions in genotype 1A infected patients in Scotland.

    Science.gov (United States)

    Bradley-Stewart, Amanda; Goldstein, Emily; MacLean, Alasdair; Gunson, Rory

    2018-04-01

    Hepatitis C (HCV) NS5A resistance associated amino-acid substitutions (RAS) can exist at baseline in treatment naïve individuals and have been shown to be associated with lower rates of sustained virological response (SVR) for patients infected with HCV genotype 1A (G1A) following treatment with NS5A inhibitors. The aim of this study was to measure the prevalence of baseline NS5A resistance in Scotland. The study population consisted of 531 treatment naïve, G1A infected patients. The patient samples were collected between March and September 2017. The NS5A region was amplified and sequenced. Baseline NS5A resistance in Scotland is high (16.8%) and is comparable to rates reported by a number of previously published studies. The high rate of baseline RAS, together with the high cost of direct-acting antivirals (DAAs), supports resistance testing to guide current patient treatment. However, given the rate at which new DAAs are currently being licensed with ever broader genotype efficacy and higher SVR rates, baseline resistance testing may not be required in the near future. Baseline NS5A inhibitor resistance is high. The results of the present study support performing resistance testing at baseline for current regimens. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  13. The importance of pheochromocytoma case detection in patients with neurofibromatosis type 1: A case report and review of literature.

    Science.gov (United States)

    Tate, Joshua M; Gyorffy, Janelle B; Colburn, Jeffrey A

    2017-01-01

    Neurofibromatosis type 1 is a complex, multi-system genetic disorder that is associated with an increased prevalence of pheochromocytoma and paraganglioma compared to the general population, 1.0%-5.7% versus 0.2%-0.6%, respectively. A delay in pheochromocytoma and paraganglioma diagnosis or undiagnosed pheochromocytoma and paraganglioma, as seen in normotensive and asymptomatic patients, may portend a significant morbidity and mortality risk due to excess catecholamine secretion. Currently, there are no generally accepted guidelines of screening for pheochromocytoma and paragangliomas in asymptomatic individuals of this population with approaches and practices varying considerably between physicians. Emerging data suggest benefit in routine pheochromocytoma and paraganglioma screening of all individuals with neurofibromatosis type 1. Herein, we present a case to highlight how routine case detection screening would have identified pheochromocytoma earlier in an active duty military member.

  14. Prevalence of polymorphisms with significant resistance to NS5A inhibitors in treatment-naive patients with hepatitis C virus genotypes 1a and 3a in Sweden.

    Science.gov (United States)

    Lindström, Ida; Kjellin, Midori; Palanisamy, Navaneethan; Bondeson, Kåre; Wesslén, Lars; Lannergard, Anders; Lennerstrand, Johan

    2015-08-01

    The future treatment of hepatitis C virus (HCV) infection will be combinations of direct-acting antivirals (DAAs) that not only target multiple viral targets, but are also effective against different HCV genotypes. Of the many drug targets in HCV, one promising target is the non-structural 5A protein (NS5A), against which inhibitors, namely daclatasvir, ledipasvir and ombitasvir, have shown potent efficacy. However, since HCV is known to have very high sequence diversity, development of resistance is a problem against but not limited to NS5A inhibitors (i.e. resistance also found against NS3-protease and NS5B non-nucleoside inhibitors), when used in suboptimal combinations. Furthermore, it has been shown that natural resistance against DAAs is present in treatment-naïve patients and such baseline resistance will potentially complicate future treatment strategies. A pan-genotypic population-sequencing method with degenerated primers targeting the NS5A region was developed. We have investigated the prevalence of baseline resistant variants in 127 treatment-naïve patients of HCV genotypes 1a, 1b, 2b and 3a. The method could successfully sequence more than 95% of genotype 1a, 1b and 3a samples. Interpretation of fold resistance data against the NS5A inhibitors was done with the help of earlier published phenotypic data. Baseline resistance variants associated with high resistance (1000-50,000-fold) was found in three patients: Q30H or Y93N in genotype 1a patients and further Y93H in a genotype 3a patient. Using this method, baseline resistance can be examined and the data could have a potential role in selecting the optimal and cost-efficient treatment for the patient.

  15. Soluble Receptor for Advanced Glycation End Products (sRAGE is Up-Regulated in Multiple Sclerosis Patients Treated with Interferon β-1a

    Directory of Open Access Journals (Sweden)

    Mahnoosh Rahimi

    2018-03-01

    Full Text Available Background/Aims: Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system. Considering the role of immune system in its pathogenesis, researchers have focused on evaluation of the expression of immune-related genes or proteins in MS patients. Among proteins whose participation in inflammatory process has been documented is the receptor for advanced glycation end products (RAGE. Methods: In the present study, we compared RAGE transcript levels by means of quantitative real-time PCR as well as the serum level of soluble RAGE (sRAGE by means of enzyme- linked immunosorbent assay (ELISA in 50 IFNβ-1a responsive relapsing-remitting MS patients when compared with age and sex-matched healthy subjects. Results: Elevated expression of RAGE as well as higher levels of sRAGE were detected in IFN-β responsive MS patients compared with the controls. A significant inverse correlation between sRAGE plasma concentrations and the expanded disability status scale (EDSS was also detected in which each unit of increase in sRAGE level resulted in a 0.308 unit decrease in EDSS. Conclusion: Considering the stable clinical state of the MS patients in this study and their response to IFNβ-1a, the elevated levels of sRAGE in patients compared with healthy subjects could be related to the effects of this kind of treatment.

  16. Subcutaneous interferon β-1a in pediatric patients with multiple sclerosis: Regional differences in clinical features, disease management, and treatment outcomes in an international retrospective study.

    Science.gov (United States)

    Krupp, Lauren B; Pohl, Daniela; Ghezzi, Angelo; Boyko, Alexey; Tenembaum, Silvia; Chen, Liang; Aycardi, Ernesto; Banwell, Brenda

    2016-04-15

    To further understand management of pediatric patients with multiple sclerosis (MS), we examined disease features, clinical practice patterns, and response to treatment in the United States (US) and seven other countries ('rest of World'; ROW). Anonymized data, recorded as part of routine clinical practice, were obtained from medical records (1997-2009) of study participants (who received subcutaneous interferon β-1a before age 18 years) from the US and ROW. Samples were stratified by age (preadolescents [managed differently, compared with ROW patients. Future prospective studies are needed to confirm these observations and ascertain their clinical significance. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Patient assessment of an electronic device for subcutaneous self-injection of interferon ß-1a for multiple sclerosis: an observational study in the UK and Ireland

    Directory of Open Access Journals (Sweden)

    D'Arcy C

    2012-01-01

    Full Text Available Caroline D’Arcy1, Del Thomas2, Dee Stoneman3, Laura Parkes31West London Neuroscience Centre, Charing Cross Hospital, London, UK; 2Wye Valley NHS Trust, Hereford, UK; 3Merck Serono Ltd, Feltham, Middlesex, UKBackground: Injectable disease-modifying drugs (DMDs reduce the number of relapses and delay disability progression in patients with relapsing–remitting multiple sclerosis (RRMS. Regular self-injection can be stressful and impeded by MS symptoms. Auto-injection devices can simplify self-injection, overcome injection-related issues, and increase treatment satisfaction. This study investigated patient responses to an electronic auto-injection device.Methods: Patients with RRMS (n = 63, aged 18–65 years, naïve to subcutaneous (sc interferon (IFN ß-1a therapy, were recruited to a Phase IV, observational, open-label, multicenter study (NCT01195870. Patients self-injected sc IFN ß-1a using the RebiSmart™ (Merck Serono S.A. – Geneva, Switzerland electronic auto-injector for 12 weeks, including an initial titration period if recommended by the prescribing physician. In week 12, patients completed a questionnaire comprising of a visual analog scale (VAS to rate how much they liked using the device, a four-point response question on ease of use (‘very difficult’, ‘difficult’, ‘easy’, or ‘very easy’, and a list of ten device functions to rank, based upon their experiences.Results: Six patients (9.5% discontinued the study: one switched to manual injection; two discontinued all treatment; three changed therapy. In total, 59 out of 63 patients (93.7% completed the VAS; 54 out of 59 (91.5%; 95% confidence interval: 81.3%–97.2% ‘liked’ using the electronic auto-injector (score ≥6, whereas 57 out of 59 (96.6% rated the device overall as ‘easy’ or ‘very easy’ to use. Device features rated as most useful were the hidden needle (mean [standard deviation] score: 3.3 [3.01]; n = 56, confirmation sound (3.9 [2.45], and

  18. Urine Kidney Injury Molecule-1: A Potential Non-invasive Biomarker for Patients with Renal Cell Carcinoma

    Science.gov (United States)

    Zhang, Ping L.; Mashni, Joseph W.; Sabbisetti, Venkata S.; Schworer, Charles M.; Wilson, George D.; Wolforth, Stacy C.; Kernen, Kenneth M.; Seifman, Brian D.; Amin, Mitual B.; Geddes, Timothy J.; Lin, Fan; Bonventre, Joseph V.; Hafron, Jason M.

    2014-01-01

    Objective To evaluate the use of urine KIM-1 as a biomarker for supporting a diagnosis of kidney cancers before operation. Methods A total of 19 patients were enrolled in the study based on preoperative imaging studies. Pre-operative and follow-up (1 month) uKIM-1 levels were measured and normalized with uCr levels and renal tumors were stained for KIM-1 using immunohistochemical techniques. Results The percentage of KIM-1 positive staining RCC cells ranged from 10 to 100% and the staining intensity ranged from 1+ to 3+. Based on the KIM-1 staining, 19 cases were divided into the KIM-1-negative staining group (n =7) and the KIM-1-positive group (n = 12). Serum creatinine (sCR) levels were significantly elevated after nephrectomy in both groups. In the KIM-1 negative group, uKIM-1/uCr remained at a similar level before (0.37 ± 0.1 ng/mg Cr) and after nephrectomy (0.32 ± 0.01 ng/mg Cr). However, in the KIM-1 positive group, elevated uKIM-1/uCr at 1.20 ± 0.31 ng/mg Cr was significantly reduced to 0.36± 0.1 ng/mg Cr, which was similar to the pre-operative uKIM-1/uCr (0.37 ± 0.1 ng/mg Cr) in the KIM-1 negative group. Conclusion Our study showed significant reduction in uKIM-1/uCr after nephrectomy, suggesting that urine KIM-1 may serve as a surrogate biomarker for kidney cancer and a non-invasive pre-operative measure to evaluate the malignant potential of renal masses. PMID:23979814

  19. Qualitative Parameters of the Colonic Flora in Patients with HNF1A-MODY Are Different from Those Observed in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Mrozinska, Sandra; Radkowski, Piotr; Gosiewski, Tomasz; Szopa, Magdalena; Bulanda, Malgorzata; Ludwig-Galezowska, Agnieszka H; Morawska, Iwona; Sroka-Oleksiak, Agnieszka; Matejko, Bartlomiej; Kapusta, Przemyslaw; Salamon, Dominika; Malecki, Maciej T; Wolkow, Pawel; Klupa, Tomasz

    2016-01-01

    Background . Type 2 diabetes mellitus (T2DM) is determined by genetic and environmental factors. There have been many studies on the relationship between the composition of the gastrointestinal bacterial flora, T2DM, and obesity. There are no data, however, on the gut microbiome structure in monogenic forms of the disease including Maturity Onset Diabetes of the Young (MODY). Methods . The aim of the investigation was to compare the qualitative parameters of the colonic flora in patients with HNF1A - MODY and T2DM and healthy individuals. 16S sequencing of bacterial DNA isolated from the collected fecal samples using the MiSeq platform was performed. Results . There were significant between-group differences in the bacterial profile. At the phylum level, the amount of Proteobacteria was higher ( p = 0.0006) and the amount of Bacteroidetes was lower ( p = 0.0005) in T2DM group in comparison to the control group. In HNF1A-MODY group, the frequency of Bacteroidetes was lower than in the control group ( p = 0.0143). At the order level, Turicibacterales was more abundant in HNF1A-MODY group than in T2DM group. Conclusions . It appears that there are differences in the gut microbiome composition between patients with HNF1A-MODY and type 2 diabetes. Further investigation on this matter should be conducted.

  20. Qualitative Parameters of the Colonic Flora in Patients with HNF1A-MODY Are Different from Those Observed in Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Sandra Mrozinska

    2016-01-01

    Full Text Available Background. Type 2 diabetes mellitus (T2DM is determined by genetic and environmental factors. There have been many studies on the relationship between the composition of the gastrointestinal bacterial flora, T2DM, and obesity. There are no data, however, on the gut microbiome structure in monogenic forms of the disease including Maturity Onset Diabetes of the Young (MODY. Methods. The aim of the investigation was to compare the qualitative parameters of the colonic flora in patients with HNF1A-MODY and T2DM and healthy individuals. 16S sequencing of bacterial DNA isolated from the collected fecal samples using the MiSeq platform was performed. Results. There were significant between-group differences in the bacterial profile. At the phylum level, the amount of Proteobacteria was higher (p=0.0006 and the amount of Bacteroidetes was lower (p=0.0005 in T2DM group in comparison to the control group. In HNF1A-MODY group, the frequency of Bacteroidetes was lower than in the control group (p=0.0143. At the order level, Turicibacterales was more abundant in HNF1A-MODY group than in T2DM group. Conclusions. It appears that there are differences in the gut microbiome composition between patients with HNF1A-MODY and type 2 diabetes. Further investigation on this matter should be conducted.

  1. A novel needle for subcutaneous injection of interferon beta-1a: effect on pain in volunteers and satisfaction in patients with multiple sclerosis

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    Prais Wes A

    2008-10-01

    Full Text Available Abstract Background To reduce injection pain and improve satisfaction, a thinner (29-gauge [29G], sharper (5-bevel needle than the 27G/3-bevel needle used previously to inject interferon (IFN beta-1a, 44 or 22 mcg subcutaneously (sc three times weekly (tiw, was developed for use in multiple sclerosis (MS. Methods Two clinical trials in healthy volunteers and five surveys of patients with MS were conducted to assess whether the 29G/5-bevel needle with a Thermo Plastic Elastomer (TPE needle shield (a sleeve that houses the tip of the needle in a secure location is an improvement over the 27G/3-bevel needle with a rubber shield for injection of IFN beta-1a, 44 or 22 mcg sc tiw. Parameters assessed were: pain and ease of insertion (healthy volunteer and nurse responses on subjective pain measurement scales; and patient satisfaction (surveys of patients with MS. Results In healthy volunteers, the 29G/5-bevel needle with TPE shield was associated with the least perceived pain on the Visual Analog Scale (VAS and Verbal VAS (VB-VAS; mean VAS pain scores decreased by 40% and skin penetration improved by 69% compared with the 27G/3-bevel needle with standard rubber shield (p Conclusion Together these studies indicate that the 29G/5-bevel needle with the TPE shield is an improvement over the 27G/3-bevel needle with standard rubber shield in terms of pain, ease of insertion and patient satisfaction. These improvements are expected to result in improved compliance in patients with MS treated with IFN beta-1a, 44 or 22 mcg sc tiw.

  2. Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patients

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    Chen Z

    2017-08-01

    Full Text Available Zhi-wei Chen,* Xi-chen Pang,* Zhao Li, Hong Ren, Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China *These authors contributed equally to this work Background: Direct-acting antiviral (DAA resistance-associated substitutions (RASs can jeopardize the effectiveness of DAAs in patients with hepatitis C virus (HCV. The selection pressure by pegylated-interferon (Peg-IFN plus ribavirin (P/R treatment may enhance HCV genome variation. However, whether P/R treatment alters the rate of change of RASs is still unclear. Materials and methods: We retrieved the genomic sequences of HCV genotype (GT 1a patients from GenBank, which included patients naïve to P/R (pre-IFN group and those previously treated with P/R (post-IFN group. The sequences were aligned and analyzed by using MEGA 6.0 software. Clinically relevant RASs were summarized from the current medical literature. Results: In the cross-sectional study, the total prevalence of clinically relevant RASs was high, independent of the treatment group (pre-IFN: 219/403 [54.34%] vs post-IFN: 67/131 [51.15%]. The high prevalence was mainly detected in the NS3 region RAS at Q80 (40.69% vs 36.64%. The RASs in the NS5A region, such as M28, Q30, L31 and Y93, were uncommon (0%–5%. Similarly, all RASs showed no difference between the two groups. One exception was the RAS at I170 in the NS3 region, which was significantly higher in the post-IFN group than in the pre-IFN group. In the longitudinal study, similar results were observed. However, no difference in RAS at I170 was observed between the two groups. Finally, no clinically relevant RASs were detected in response to the DAA regimens approved for GT 1a patients treated with P/R. Conclusion: Our results suggest that previous P/R treatment failure was not

  3. Athletic groin pain (part 1): a prospective anatomical diagnosis of 382 patients--clinical findings, MRI findings and patient-reported outcome measures at baseline.

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    Falvey, É C; King, E; Kinsella, S; Franklyn-Miller, A

    2016-04-01

    Athletic groin pain remains a common field-based team sports time-loss injury. There are few reports of non-surgically managed cohorts with athletic groin pain. To describe clinical presentation/examination, MRI findings and patient-reported outcome (PRO) scores for an athletic groin pain cohort. All patients had a history including demographics, injury duration, sport played and standardised clinical examination. All patients underwent MRI and PRO score to assess recovery. A clinical diagnosis of the injured anatomical structure was made based on these findings. Statistical assessment of the reliability of accepted standard investigations undertaken in making an anatomical diagnosis was performed. 382 consecutive athletic groin pain patients, all male, enrolled. Median time in pain at presentation was (IQR) 36 (16-75) weeks. Most (91%) played field-based ball-sports. Injury to the pubic aponeurosis (PA) 240 (62.8%) was the most common diagnosis. This was followed by injuries to the hip in 81 (21.2%) and adductors in 56 (14.7%) cases. The adductor squeeze test (90° hip flexion) was sensitive (85.4%) but not specific for the pubic aponeurosis and adductor pathology (negative likelihood ratio 1.95). Analysed in series, positive MRI findings and tenderness of the pubic aponeurosis had a 92.8% post-test probability. In this largest cohort of patients with athletic groin pain combining clinical and MRI diagnostics there was a 63% prevalence of PA injury. The adductor squeeze test was sensitive for athletic groin pain, but not specific individual pathologies. MRI improved diagnostic post-test probability. No hernia or incipient hernia was diagnosed. NCT02437942. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. The influence of the rs6295 gene polymorphism on serotonin-1A receptor distribution investigated with PET in patients with major depression applying machine learning.

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    Kautzky, A; James, G M; Philippe, C; Baldinger-Melich, P; Kraus, C; Kranz, G S; Vanicek, T; Gryglewski, G; Wadsak, W; Mitterhauser, M; Rujescu, D; Kasper, S; Lanzenberger, R

    2017-06-13

    Major depressive disorder (MDD) is the most common neuropsychiatric disease and despite extensive research, its genetic substrate is still not sufficiently understood. The common polymorphism rs6295 of the serotonin-1A receptor gene (HTR1A) is affecting the transcriptional regulation of the 5-HT 1A receptor and has been closely linked to MDD. Here, we used positron emission tomography (PET) exploiting advances in data mining and statistics by using machine learning in 62 healthy subjects and 19 patients with MDD, which were scanned with PET using the radioligand [carbonyl- 11 C]WAY-100635. All the subjects were genotyped for rs6295 and genotype was grouped in GG vs C allele carriers. Mixed model was applied in a ROI-based (region of interest) approach. ROI binding potential (BP ND ) was divided by dorsal raphe BP ND as a specific measure to highlight rs6295 effects (BP Div ). Mixed model produced an interaction effect of ROI and genotype in the patients' group but no effects in healthy controls. Differences of BP Div was demonstrated in seven ROIs; parahippocampus, hippocampus, fusiform gyrus, gyrus rectus, supplementary motor area, inferior frontal occipital gyrus and lingual gyrus. For classification of genotype, 'RandomForest' and Support Vector Machines were used, however, no model with sufficient predictive capability could be computed. Our results are in line with preclinical data, mouse model knockout studies as well as previous clinical analyses, demonstrating the two-pronged effect of the G allele on 5-HT 1A BP ND for, we believe, the first time. Future endeavors should address epigenetic effects and allosteric heteroreceptor complexes. Replication in larger samples of MDD patients is necessary to substantiate our findings.

  5. Sea Level History in 3D: Early results of an ultra-high resolution MCS survey across IODP Expedition 313 drillsites

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    Mountain, G. S.; Kucuk, H. M.; Nedimovic, M. R.; Austin, J. A., Jr.; Fulthorpe, C.; Newton, A.; Baldwin, K.; Johnson, C.; Stanley, J. N.; Bhatnagar, T.

    2015-12-01

    Although globally averaged sea level is rising at roughly 3 mm/yr (and is accelerating), rates of local sea-level change measured at coastlines may differ from this number by a factor of two or more; at some locations, sea level may even be falling. This is due to local processes that can match or even reverse the global trend, making it clear that reliable predictions of future impacts of sea-level rise require a firm understanding of processes at the local level. The history of local sea-level change and shoreline response is contained in the geologic record of shallow-water sediments. We report on a continuing study of sea-level history in sediments at the New Jersey continental margin, where compaction and glacial isostatic adjustment are currently adding 2 mm/yr to the globally averaged rise. We collected 570 sq km of ultra-high resolution 3D MCS data aboard the R/V Langseth in June-July 2015; innovative recording and preliminary results are described by Nedimovic et al. in this same session. The goal was to provide regional context to coring and logging at IODP Exp 313 sites 27-29 that were drilled 750 m into the New Jersey shelf in 2009. These sites recovered a nearly continuous record of post-Eocene sediments from non-marine soils, estuaries, shoreface, delta front, pro-delta and open marine settings. Existing seismic data are good but are 2D high-resolution profiles at line spacings too wide to enable mapping of key nearshore features. The Langseth 3D survey used shallow towing of a tuned air gun array to preserve high frequencies, and twenty-four 50-m PCables each 12.5 apart provided 6.25 x 3.125 m common-midpoint bins along seventy-seven 50-km sail lines. With this especially dense spatial resolution of a pre-stack time migrated volume we expect to map rivers, incised valleys, barrier islands, inlets and bays, pro-delta clinoforms, tidal deltas, sequence boundaries, debris flow aprons, and more. Seismic attributes linked to sedimentary facies and

  6. Phylogenetic Diversity in Core Region of Hepatitis C Virus Genotype 1a as a Factor Associated with Fibrosis Severity in HIV-1-Coinfected Patients

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    Micaela Parra

    2017-01-01

    Full Text Available High hepatitis C virus (HCV genetic diversity impacts infectivity/pathogenicity, influencing chronic liver disease progression associated with fibrosis degrees and hepatocellular carcinoma. HCV core protein is crucial in cell-growth regulation and host-gene expression. Liver fibrosis is accelerated by unknown mechanisms in human immunodeficiency virus-1- (HIV-1- coinfected individuals. We aimed to study whether well-defined HCV-1a core polymorphisms and genetic heterogeneity are related to fibrosis in a highly homogeneous group of interferon-treated HIV-HCV-coinfected patients. Genetic heterogeneity was weighed by Faith’s phylogenetic diversity (PD, which has been little studied in HCV. Eighteen HCV/HIV-coinfected patients presenting different liver fibrosis stages before anti-HCV treatment-initiation were recruited. Sampling at baseline and during and after treatment was performed up to 72 weeks. At inter/intrahost level, HCV-1a populations were studied using molecular cloning and Sanger sequencing. Over 400 complete HCV-1a core sequences encompassing 573 positions of C were obtained. Amino acid substitutions found previously at positions 70 and 91 of HCV-1b core region were not observed. However, HCV genetic heterogeneity was higher in mild than in severe fibrosis cases. These results suggest a potential utility of PD as a virus-related factor associated with chronic hepatitis C progression. These observations should be reassessed in larger cohorts to corroborate our findings and assess other potential covariates.

  7. Promoter Variation and Expression Levels of Inflammatory Genes IL1A, IL1B, IL6 and TNF in Blood of Spinocerebellar Ataxia Type 3 (SCA3) Patients.

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    Raposo, Mafalda; Bettencourt, Conceição; Ramos, Amanda; Kazachkova, Nadiya; Vasconcelos, João; Kay, Teresa; Bruges-Armas, Jácome; Lima, Manuela

    2017-03-01

    Age at onset in spinocerebellar ataxia type 3 (SCA3/MJD) is incompletely explained by the size of the CAG tract at the ATXN3 gene, implying the existence of genetic modifiers. A role of inflammation in SCA3 has been postulated, involving altered cytokines levels; promoter variants leading to alterations in cytokines expression could influence onset. Using blood from 86 SCA3 patients and 106 controls, this work aimed to analyse promoter variation of four cytokines (IL1A, IL1B, IL6 and TNF) and to investigate the association between variants detected and their transcript levels, evaluated by quantitative PCR. Moreover, the effect of APOE isoforms, known to modulate cytokines, was investigated. Correlations between cytokine variants and onset were tested; the cumulative modifier effects of cytokines and APOE were analysed. Patients carrying the IL6*C allele had a significant earlier onset (4 years in average) than patients carrying the G allele, in agreement with lower mRNA levels produced by IL6*C carriers. The presence of APOE*ɛ2 allele seems to anticipate onset in average 10 years in patients carrying the IL6*C allele; a larger number of patients will be needed to confirm this result. These results highlight the pertinence of conducting further research on the role of cytokines as SCA3 modulators, pointing to the presence of shared mechanisms involving IL6 and APOE.

  8. NS3 protease resistance-associated substitutions in liver tissue and plasma samples from patients infected by hepatitis C virus genotype 1A or 1B.

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    Morsica, Giulia; Andolina, Andrea; Merli, Marco; Messina, Emanuela; Hasson, Hamid; Lazzarin, Adriano; Uberti-Foppa, Caterina; Bagaglio, Sabrina

    2017-08-01

    The presence of naturally occurring resistance-associated substitutions (RASs) in the HCV-protease domain has been poorly investigated in the liver, the main site of HCV replication. We evaluated the natural resistance of the virus to NS3 protease inhibitors in liver tissue and plasma samples taken from HCV-infected patients. RASs were investigated by means of viral population sequencing in liver tissue samples from 18 HCV-infected patients harbouring genotype 1a or genotype 1b; plasma samples from 12 of these patients were also available for virological investigation. A discordant genotype was found in two of the 12 patients (16.6%) who provided samples from both compartments. Sequence analysis of the NS3 protease domain showed the presence of RASs in four of the 18 liver tissue samples (22.2%), two of which showed cross-resistance to protease inhibitors in clinical use or phase 2-3 trials. The analysis of the 12 paired tissues and plasma samples excluded the presence of RASs in the plasma compartment. The dominance of discordant genotypes in the paired liver and plasma samples of some HCV-infected patients suggests mixed infection possibly leading to the selective advantage of different genotype in the two compartments. The presence of RASs at intra-hepatic level is not uncommon and may lead to the early emergence of cross-resistant strains.

  9. A Randomized Study of Peginterferon Lambda-1a Compared to Peginterferon Alfa-2a in Combination with Ribavirin and Telaprevir in Patients with Genotype-1 Chronic Hepatitis C.

    Science.gov (United States)

    Flisiak, Robert; Shiffman, Mitchell; Arenas, Juan; Cheinquer, Hugo; Nikitin, Igor; Dong, Yuping; Rana, Khurram; Srinivasan, Subasree

    2016-01-01

    A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a (Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection. Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post treatment week 12 (SVR12), which was tested for noninferiority of Lambda/RBV/TVR. A total of 838 patients were enrolled, and 617 were treated; 411 and 206 patients received Lambda/RBV/TVR and Alfa/RBV/TVR, respectively. The majority of patients were treatment-naïve, with HCV GT-1b and a high baseline viral load (≥800,000 IU/mL). Less than 10% of patients had cirrhosis (Lambda, 7.5%; Alfa, 6.8%). Lambda/RBV/TVR did not meet the criterion for noninferiority (lower bound of the treatment difference interval was -12.3%); the SVR12 in all patients (modified intent-to-treat) was 76.2% in the Lambda arm and 82.0% in the Alfa arm. Overall, the frequency of adverse events in each arm was comparable (Lambda, 91.7%; Alfa, 97.1%). As expected based on the safety profile of the 2 interferons, there were more hepatobiliary events observed in the Lambda arm and more hematologic events in the Alfa arm. In this comparison of Lambda/RBV/TVR and Alfa/RBV/TVR in patients who were treatment-naïve or had relapsed on prior Alfa/RBV treatment, Lambda failed to demonstrate noninferiority based on SVR12 results. Treatment with Lambda/RBV/TVR was associated with a higher incidence of relapse. More patients discontinued Lambda/RBV/TVR treatment during the first 4 weeks of study treatment, mainly due to hepatobiliary

  10. Methylation of the RASSF1A, RARβ2, and SEMA3B genes in epithelial breast and ovarian tumors, and in patients with polyneoplasia

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    T. P. Kazubskaya

    2012-01-01

    Full Text Available The methylation status of the tumor suppressor genes RASSF1A, RARβ2, and SEMA3B was studied in the samples of cancer and its histologically normal tissue of the breast and ovaries. The high rate of abnormal methylation of the CpG islet in the RASSF1A, RARβ2, and SEMA3B genes was found in the tumors of the breast (78% (32/41, 46% (26/56, and 35% (22/65, respectively and ovaries 73% (33/45, 30% (15/50, and 50% (25/51. Hypermethylation in the CpG islets belonging to the RASSF1A and RARβ2 genes was first ascertained in 90% of the patients with polyneoplasms involving the breast and ovaries. Abnormal methylation of the promotor region of the RASSF1A gene was shown to be detectable in preclinical-stage and anaplasia-degree breast and ovarian cancer. There was a correlation of the rate of methylation in the promoter regions of the RARβ2 and SEMA3B genes with clinical-stage and anaplasia-degree breast and ovarian cancer. Analysis of gene methylation in biological fluids provides considerable opportunity to use methylation of DNA as a marker in clinical practice.

  11. CYP1A2 – a novel genetic marker for early aromatase inhibitor response in the treatment of breast cancer patients

    International Nuclear Information System (INIS)

    Simonsson, Maria; Veerla, Srinivas; Markkula, Andrea; Rose, Carsten; Ingvar, Christian; Jernström, Helena

    2016-01-01

    Endocrine resistance is a major obstacle to optimal treatment effect in breast cancer. Some genetic markers have been proposed to predict response to aromatase inhibitors (AIs) but the data is insufficient. The aim of the study was to find new genetic treatment predictive markers of AIs. The ongoing population-based BC-blood study in Lund, Sweden includes women with primary breast cancer. This paper is based on AI-treated patients with estrogen receptor positive tumors who underwent breast cancer surgery in 2002–2008. First, an exploratory analysis of 1931 SNPs in 227 genes involved in absorption, distribution, metabolism, and elimination of multiple medications, using DMET™ chips, was conducted in a subset of the cohort with last follow-up in December 31 st 2011 (13 cases, 11 controls). Second, selected SNPs from the first analysis were re-analyzed concerning risk for early breast cancer events in the extended cohort of 201 AI-treated with last follow-up in June 30 th 2014. Clinical data were obtained from medical records and population registries. Only CYP1A2 rs762551 C-allele was significantly associated with increased risk for early events in the 24 patients (P = 0.0007) and in the extended cohort, adjusted Hazard ratio (HR) 2.22 (95 % CI 1.03–4.80). However, the main prognostic impact was found within five years, adjusted HR 7.88 (95 % CI 2.13–29.19). The impact of the CYP1A2 rs762551 C-allele was modified by a functional polymorphism in the regulator gene AhR Arg554Lys (G > A). Compared to patients who were homozygous for the major allele in both genes (CYP1A2 A/A and AhR G/G), a 9-fold risk for early events was found in patients who had at least one minor allele in both genes, adjusted HR 8.95 (95 % CI 2.55–31.35), whereas patients with at least one minor allele in either but not both genes had a 3-fold risk for early events, adjusted HR 2.81 (95 % CI 1.07–7.33). The impact of CYP1A2 rs762551 C-allele was also modified by the CYP19A1 rs4646 C

  12. Involvement of mast cells by the malignant process in patients with Philadelphia chromosome negative myeloproliferative neoplasms.

    Science.gov (United States)

    Wang, J; Ishii, T; Zhang, W; Sozer, S; Dai, Y; Mascarenhas, J; Najfeld, V; Zhao, Z J; Hoffman, R; Wisch, N; Xu, M

    2009-09-01

    The Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) are clonal hematologic malignancies frequently characterized by a mutation in JAK2 (JAK2V617F). Peripheral blood (PB) CD34(+) cells from patients with polycythemia vera (PV) and primary myelofibrosis (PMF) generated in vitro significantly fewer mast cells (MCs) than normal PB CD34(+) cells. The numbers of MC progenitors assayed from MPN CD34(+) cells were, however, similar to that assayed from normal CD34(+) cells. A higher percentage of the cultured MPN MCs expressed FcvarepsilonRIalpha, CD63 and CD69 than normal MCs, suggesting that cultured MPN MCs are associated with an increased state of MC activation. Further analysis showed that a higher proportion of cultured PV and PMF MCs underwent apoptosis in vitro. By using JAK2V617F, MplW515L and chromosomal abnormalities as clonality markers, we showed that the malignant process involved MPN MCs. JAK2V617F-positive MC colonies were assayable from the PB CD34(+) cells of each of the 17 JAK2V617F positive MPN patients studied. Furthermore, erlotinib, a JAK2 inhibitor, was able to inhibit JAK2V617F-positive PV MC progenitor cells, indicating that malignant MC progenitor cells are a potential cellular target for such JAK2 inhibitor-directed therapy.

  13. Peginterferon beta-1a reduces the evolution of MRI lesions to black holes in patients with RRMS: a post hoc analysis from the ADVANCE study.

    Science.gov (United States)

    Arnold, Douglas L; You, Xiaojun; Castrillo-Viguera, Carmen

    2017-08-01

    The presence of chronic black holes, i.e., chronic lesions that are hypointense on T1-weighted images and are indicative of more severe tissue injury, has been increasingly utilized as a surrogate marker of therapeutic outcome in multiple sclerosis. The ADVANCE study was a 2-year, double-blind, pivotal trial evaluating the safety and efficacy of subcutaneous peginterferon beta-1a 125 mcg in 1512 patients with relapsing-remitting multiple sclerosis (RRMS). This report describes the correlation of clinical outcomes with the evolution of acute lesions into chronic black holes in ADVANCE, and the efficacy of peginterferon beta-1a in reducing this evolution. Treatment with peginterferon beta-1a significantly reduced the mean number of new/enlarging T2-weighted (NET2) lesions (0.76 vs. 1.03 from week 24, p = 0.0037; 0.44 vs. 0.99 from week 48, p < 0.0001) and new gadolinium-enhancing (Gd+) lesions (0.15 vs. 0.32 from week 24, p < 0.0001; 0.09 vs. 0.19 from week 48) that evolved into chronic black holes by 2 years. Patients with NET2 or Gd+ lesions at 24 weeks that evolved into chronic black holes showed significantly worse clinical outcomes, including a greater proportion with 12-week (14.9 vs. 8.4%; p = 0.0167) and 24-week (12.3 vs. 7.0%; p = 0.0333) confirmed disability worsening and higher mean annualized relapse rate (0.62 vs. 0.43; p = 0.0118), compared with patients with lesions that did not evolve into black holes. The correlation was independent of treatment. Reduced risk of evolution of new lesions into chronic black holes with peginterferon beta-1a treatment suggests potential to reduce long-term disability in RRMS by preventing irreversible tissue damage.

  14. Complex aberrant splicing in the induced pluripotent stem cell-derived cardiomyocytes from a patient with long-QT syndrome carrying KCNQ1-A344Aspl mutation.

    Science.gov (United States)

    Wuriyanghai, Yimin; Makiyama, Takeru; Sasaki, Kenichi; Kamakura, Tsukasa; Yamamoto, Yuta; Hayano, Mamoru; Harita, Takeshi; Nishiuchi, Suguru; Chen, Jiarong; Kohjitani, Hirohiko; Hirose, Sayako; Yokoi, Fumika; Gao, Jingshan; Chonabayashi, Kazuhisa; Watanabe, Ken; Ohno, Seiko; Yoshida, Yoshinori; Kimura, Takeshi; Horie, Minoru

    2018-05-29

    Long-QT syndrome type 1 (LQT1) is caused by mutations in KCNQ1, which encodes the α-subunit of the slow delayed rectifier potassium current (I Ks ) channel. We previously reported that a synonymous mutation, c.1032G>A, p.A344Aspl in KCNQ1 is most commonly identified in the genotyped LQT1 Japanese patients, and the aberrant splicing was analyzed in the lymphocytes isolated from patients' blood samples. However, the mechanisms underlying the observed processes in human cardiomyocytes remains unclear. To establish and analyze patient-specific human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) model carrying KCNQ1-A344Aspl. We generated hiPSCs from the peripheral blood mononuclear cells obtained from an LQT1 patient carrying KCNQ1-A344Aspl. Using the differentiated cardiomyocytes, we analyzed splicing variants and performed electrophysiological studies. We identified seven aberrant RNA variants in A344Aspl-hiPSC-CMs, more complex compared with those in the peripheral lymphocytes. Multi-electrode array analysis revealed that 1 μM isoproterenol significantly prolonged the duration of corrected field potential in A344Aspl-hiPSC-CMs, compared with that in the controls. Additionally, 100 nM E-4031, I Kr blocker, was shown to induce early afterdepolarization-like waveforms in A344Aspl-hiPSC-CMs. Action potential durations (APDs) did not significantly differ between the hiPSC-CM groups. After administrating 500 nM isoproterenol, APDs of A344Aspl-hiPSC-CMs were significantly longer than those of the controls. ML277 and phenylboronic acid, I Ks activators, ameliorated the APDs of hiPSC-CMs. We identified complex aberrant mRNA variants in the A344Aspl-hiPSC-CM model, and successfully recapitulated the clinical phenotypes of the patient with concealed LQT1. This model allows the investigation of the underlying mechanisms and development of novel therapies. Copyright © 2018. Published by Elsevier Inc.

  15. Pegvisomant-Induced Cholestatic Hepatitis in an Acromegalic Patient with UGT1A1 ​⁎ 28 Mutation

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    Maria Susana Mallea-Gil

    2016-01-01

    Full Text Available Pegvisomant (PEGv is a growth hormone receptor antagonist approved for the treatment of acromegaly; one of its documented adverse effects is reversible elevation of hepatic enzymes. We report a 39-year-old male acromegalic patient with a pituitary macroadenoma who underwent transsphenoidal surgery. The patient’s condition improved but GH and IGF-I levels did not normalize; as a consequence, we first administered dopamine agonists and then somatostatin receptor ligands (SRLs with poor response. PEGv 15 mg every other day was added to lanreotide 120 mg monthly. The patient developed a severe hepatitis five months after starting the combination therapy. Elevated ferritin, iron, and transferrin saturation suggested probable hepatitis due to haemochromatosis. We performed a liver biopsy which showed an acute cholestatic hepatitis consistent with toxic etiology. A heterozygous genotype UGT1A1​⁎28 polymorphism associated with Gilbert’s syndrome was also found in this Argentine patient. The predominant clinical presentation resembled an acute cholestatic hepatitis associated with severe hemosiderosis, a different and new pattern of PEGv hepatotoxicity.

  16. CD1a, HAM56, CD68 and S-100 are present in lesional skin biopsies from patients affected by autoimmune blistering diseases

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    Ana Maria Abreu Velez

    2014-04-01

    Full Text Available Introduction: Previous research on autoimmune skin blistering diseases (ABD has primarily focused on the humoral immune response; moreover, little attention has been given to the potential role of the antigen presenting cells (APCs in lesional skin. Aim: The purpose of our study was to immunophenotype selected APC in the lesional skin of ABDs, utilizing immunohistochemistry (IHC stains. Materials and Methods: We utilized IHC to stain for dendritic cells (DC, staining with CD1a, CD68, HAM56, and S-100 in lesional skin from 30 patients with endemic pemphigus foliaceus (EPF, 15 controls from the EPF endemic area, and 15 healthy controls from the USA. We also tested archival biopsies from patients with selected ABD, including 30 patients with bullous pemphigoid (BP, 20 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus (PF and 14 with dermatitis herpetiformis (DH and 2 with epidermolysis bullosa acquisita (EBA. Results: Cells stained by CD68, HAM56 and S-100 were present in the majority of the ABD skin biopsies; these cells were located primarily in perivascular infiltrates surrounding dermal vessels subjacent to the blisters. However, these cells were also noted within the blisters, in vessels supplying dermal eccrine glands and ducts, and in areas of dermal endothelial-mesenchymal cell junction-like structures, especially in BP cases. In our CD1a staining, the number and location of positive staining cells varied with each disease, being abundant in most ABD in the epidermis suprajacent to the blisters, or in the epidermis surrounding the blister site if the blister site epidermis was missing. In the control biopsies, most did not display positive IHC staining, with the exception of a few CD1a positive cells in the epidermis Conclusion: Our findings confirm positive IHC staining for APCs in areas of the skin besides the disease blisters. Our findings suggest that the antigen presentation in ABD proceeds in areas distant from the blister site

  17. Epidemiological assessment of influenza (H1N1- A in patients hospitalized in Tohid hospital in Sanandaj, Iran during 2013-2014

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    Houshiyar Ghafouri

    2016-12-01

    Full Text Available Background: Influenza is an acute respiratory infection caused by influenza virus which is highly contagious and spread easily. Objectives: The aim of this study was to evaluate the epidemiology of influenza (H1N1 type A in patients admitted to Tohid hospital, Sanandaj, Iran during 2013-2014. Material and Methods: This study was descriptive. Data were collected using a questionnaire which was designed based on study goals. The questionnaires were completed via interview, observation and performing clinical tests. After clinical confirmation of influenza by a specialist, genotype was determined by PCR. Results: Of the total 76 cases, 36 cases (48.6% were male, mean age was 42.7 ± 16.3 and 13.5% were rural and 86.5 were urban dwellers. 52 patient (70.3% were hospitalized and 22 (29.7% were outpatients. Travel history was including, abroad 9.5%, domestic 16.2% and without traveling 75.3%. The average time between referring to the doctor and sampling for H1N1 was 2.7 days. The prevalence of influenza (H1N1 A was 1.4%. Conclusion: The low incidence of H1N1 influenza type A in this study was probably due to travel to infected areas. Considering virus mutation, the readiness of health services to prevent an epidemic of this disease is essential and recommended.

  18. Genetic Variants in CD44 and MAT1A Confer Susceptibility to Acute Skin Reaction in Breast Cancer Patients Undergoing Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mumbrekar, Kamalesh Dattaram; Bola Sadashiva, Satish Rao [Department of Radiation Biology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka (India); Kabekkodu, Shama Prasada [Department of Biotechnology, School of Life Sciences, Manipal University, Manipal, Karnataka (India); Fernandes, Donald Jerard [Department of Radiotherapy and Oncology, Shirdi Saibaba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka (India); Vadhiraja, Bejadi Manjunath [Department of Radiation Oncology, Manipal Hospital, Bengaluru, Karnataka (India); Suga, Tomo; Shoji, Yoshimi; Nakayama, Fumiaki; Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Satyamoorthy, Kapaettu, E-mail: ksatyamoorthy@yahoo.com [Department of Biotechnology, School of Life Sciences, Manipal University, Manipal, Karnataka (India)

    2017-01-01

    Purpose: Heterogeneity in radiation therapy (RT)-induced normal tissue toxicity is observed in 10% of cancer patients, limiting the therapeutic outcomes. In addition to treatment-related factors, normal tissue adverse reactions also manifest from genetic alterations in distinct pathways majorly involving DNA damage–repair genes, inflammatory cytokine genes, cell cycle regulation, and antioxidant response. Therefore, the common sequence variants in these radioresponsive genes might modify the severity of normal tissue toxicity, and the identification of the same could have clinical relevance as a predictive biomarker. Methods and Materials: The present study was conducted in a cohort of patients with breast cancer to evaluate the possible associations between genetic variants in radioresponsive genes described previously and the risk of developing RT-induced acute skin adverse reactions. We tested 22 genetic variants reported in 18 genes (ie, NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A, TGFβR3, MAD2L2, MAP3K7, MAT1A, RPS6KB2, ZNF830, SH3GL1, BAX, and XRCC1) using TaqMan assay-based real-time polymerase chain reaction. At the end of RT, the severity of skin damage was scored, and the subjects were dichotomized as nonoverresponders (Radiation Therapy Oncology Group grade <2) and overresponders (Radiation Therapy Oncology Group grade ≥2) for analysis. Results: Of the 22 single nucleotide polymorphisms studied, the rs8193 polymorphism lying in the micro-RNA binding site of 3′-UTR of CD44 was significantly (P=.0270) associated with RT-induced adverse skin reactions. Generalized multifactor dimensionality reduction analysis showed significant (P=.0107) gene–gene interactions between MAT1A and CD44. Furthermore, an increase in the total number of risk alleles was associated with increasing occurrence of overresponses (P=.0302). Conclusions: The genetic polymorphisms in radioresponsive genes act as genetic modifiers of acute normal tissue toxicity

  19. FOLFIRI and regorafenib combination therapy with dose escalation of irinotecan as fourth-line treatment for patients with metastatic colon cancer according to UGT1A1 genotyping

    Directory of Open Access Journals (Sweden)

    Lu CY

    2014-11-01

    classified as stable disease and partial response, respectively. Moreover, the progression-free survival was over 6 months. FOLFIRI, with dose escalation of irinotecan according to UGT1A1 genotyping plus regorafenib appears to be a promising salvage therapy for patients with refractory metastatic colorectal cancer. Keywords: UGT1A1, irinotecan, dose escalation, metastatic colon cancer, regorafenib

  20. Clinical flow cytometric screening of SAP and XIAP expression accurately identifies patients with SH2D1A and XIAP/BIRC4 mutations.

    Science.gov (United States)

    Gifford, Carrie E; Weingartner, Elizabeth; Villanueva, Joyce; Johnson, Judith; Zhang, Kejian; Filipovich, Alexandra H; Bleesing, Jack J; Marsh, Rebecca A

    2014-07-01

    X-linked lymphoproliferative disease is caused by mutations in two genes, SH2D1A and XIAP/BIRC4. Flow cytometric methods have been developed to detect the gene products, SAP and XIAP. However, there is no literature describing the accuracy of flow cytometric screening performed in a clinical lab setting. We reviewed the clinical flow cytometric testing results for 656 SAP and 586 XIAP samples tested during a 3-year period. Genetic testing was clinically performed as directed by the managing physician in 137 SAP (21%) and 115 XIAP (20%) samples. We included these samples for analyses of flow cytometric test accuracy. SH2D1A mutations were detected in 15/137 samples. SAP expression was low in 13/15 (sensitivity 87%, CI 61-97%). Of the 122 samples with normal sequencing, SAP was normal in 109 (specificity 89%, CI 82-94%). The positive predictive values (PPVs) and the negative predictive values (NPVs) were 50% and 98%, respectively. XIAP/BIRC4 mutations were detected in 19/115 samples. XIAP expression was low in 18/19 (sensitivity 95%, CI 73-100%). Of the 96 samples with normal sequencing, 59 had normal XIAP expression (specificity 61%, CI 51-71%). The PPVs and NPVs were 33% and 98%, respectively. Receiver-operating characteristic analysis was able to improve the specificity to 75%. Clinical flow cytometric screening tests for SAP and XIAP deficiencies offer good sensitivity and specificity for detecting genetic mutations, and are characterized by high NPVs. We recommend these tests for patients suspected of having X-linked lymphoproliferative disease type 1 (XLP1) or XLP2. © 2014 Clinical Cytometry Society.

  1. Deep brain stimulation for the early treatment of the minimally conscious state and vegetative state: experience in 14 patients.

    Science.gov (United States)

    Chudy, Darko; Deletis, Vedran; Almahariq, Fadi; Marčinković, Petar; Škrlin, Jasenka; Paradžik, Veronika

    2018-04-01

    OBJECTIVE An effective treatment of patients in a minimally conscious state (MCS) or vegetative state (VS) caused by hypoxic encephalopathy or traumatic brain injury (TBI) is not yet available. Deep brain stimulation (DBS) of the thalamic reticular nuclei has been attempted as a therapeutic procedure mainly in patients with TBI. The purpose of this study was to investigate the therapeutic use of DBS for patients in VS or MCS. METHODS Fourteen of 49 patients in VS or MCS qualified for inclusion in this study and underwent DBS. Of these 14 patients, 4 were in MCS and 10 were in VS. The etiology of VS or MCS was TBI in 4 cases and hypoxic encephalopathy due to cardiac arrest in 10. The selection criteria for DBS, evaluating the status of the cerebral cortex and thalamocortical reticular formation, included: neurological evaluation, electrophysiological evaluation, and the results of positron emission tomography (PET) and MRI examinations. The target for DBS was the centromedian-parafascicular (CM-pf) complex. The duration of follow-up ranged from 38 to 60 months. RESULTS Two MCS patients regained consciousness and regained their ability to walk, speak fluently, and live independently. One MCS patient reached the level of consciousness, but was still in a wheelchair at the time the article was written. One VS patient (who had suffered a cerebral ischemic lesion) improved to the level of consciousness and currently responds to simple commands. Three VS patients died of respiratory infection, sepsis, or cerebrovascular insult (1 of each). The other 7 patients remained without substantial improvement of consciousness. CONCLUSIONS Spontaneous recovery from MCS/VS to the level of consciousness with no or minimal need for assistance in everyday life is very rare. Therefore, if a patient in VS or MCS fulfills the selection criteria (presence of somatosensory evoked potentials from upper extremities, motor and brainstem auditory evoked potentials, with cerebral glucose

  2. Functional connectivity substrates for tDCS response in Minimally Conscious State patients

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    Carlo Cavaliere

    2016-11-01

    Full Text Available Transcranial direct current stimulation (tDCS is a non-invasive technique recently employed in disorders of consciousness, and determining a transitory recovery of signs of consciousness in almost half of minimally conscious state (MCS patients. Although the rising evidences about its possible role in the treatment of many neurological and psychiatric conditions, no evidences exist about brain functional connectivity substrates underlying tDCS response. We retrospectively evaluated resting state functional Magnetic Resonance Imaging (fMRI of 16 sub-acute and chronic MCS patients (6 tDCS responders who successively received a single left dorsolateral prefrontal cortex (DLPFC tDCS in a double-blind randomized cross-over trial. A seed-based approach for regions of left extrinsic control network and default-mode network was performed.TDCS responders showed an increased left intra-network connectivity for regions co-activated with left DLPFC, and significantly with left inferior frontal gyrus. Non-responders MCS patients showed an increased connectivity between left DLPFC and midline cortical structures, including anterior cingulate cortex and precuneus.Our findings suggest that a prior high connectivity with regions belonging to extrinsic control network can facilitate transitory recovery of consciousness in a subgroup of MCS patients that underwent tDCS treatment. Therefore, resting state-fMRI could be very valuable in detecting the neuronal conditions necessary for tDCS to improve behavior in MCS.

  3. Generation of an induced pluripotent stem cell (iPSC line from a patient with maturity-onset diabetes of the young type 3 (MODY3 carrying a hepatocyte nuclear factor 1-alpha (HNF1A mutation

    Directory of Open Access Journals (Sweden)

    Frank Griscelli

    2018-05-01

    Full Text Available Heterozygous non-synonymous (p.S142F mutation in HNF1A leads to maturity-onset diabetes of the young (MODY type 3, which is a subtype of dominant inherited young-onset non-autoimmune diabetes due to the defect of insulin secretion from pancreatic beta cells. We generated induced pluripotent stem cells (iPSCs from a patient with HNF1A p.S142F mutation. Cells from this patient, which were reprogrammed by non-integrative viral transduction had normal karyotype, harboured the HNF1A p.S142F mutation, expressed pluripotency hallmarks.

  4. Changes in cerebral blood flow during olfactory stimulation in patients with multiple chemical sensitivity: a multi-channel near-infrared spectroscopic study.

    Directory of Open Access Journals (Sweden)

    Kenichi Azuma

    Full Text Available Multiple chemical sensitivity (MCS is characterized by somatic distress upon exposure to odors. Patients with MCS process odors differently from controls. This odor-processing may be associated with activation in the prefrontal area connecting to the anterior cingulate cortex, which has been suggested as an area of odorant-related activation in MCS patients. In this study, activation was defined as a significant increase in regional cerebral blood flow (rCBF because of odorant stimulation. Using the well-designed card-type olfactory test kit, changes in rCBF in the prefrontal cortex (PFC were investigated after olfactory stimulation with several different odorants. Near-infrared spectroscopic (NIRS imaging was performed in 12 MCS patients and 11 controls. The olfactory stimulation test was continuously repeated 10 times. The study also included subjective assessment of physical and psychological status and the perception of irritating and hedonic odors. Significant changes in rCBF were observed in the PFC of MCS patients on both the right and left sides, as distinct from the center of the PFC, compared with controls. MCS patients adequately distinguished the non-odorant in 10 odor repetitions during the early stage of the olfactory stimulation test, but not in the late stage. In comparison to controls, autonomic perception and negative affectivity were poorer in MCS patients. These results suggest that prefrontal information processing associated with odor-processing neuronal circuits and memory and cognition processes from past experience of chemical exposure play significant roles in the pathology of this disorder.

  5. Relapse outcomes, safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon β-1a or dimethyl fumarate: a real-world study.

    Science.gov (United States)

    Ernst, Frank R; Barr, Peri; Elmor, Riad; Wong, Schiffon L

    2017-12-01

    To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif) vs dimethyl fumarate (DMF; Tecfidera), to treat relapsing-remitting multiple sclerosis (RRMS). A US retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF. Two years' follow-up data were captured. Patient characteristics, persistence, and adverse events between treatment groups were compared using t-tests or Chi-square tests. Kaplan-Meier curves with log-rank tests and Cox proportional hazards models were used to compare time to, and risk of non-persistence. Annualized Relapse Rates (ARR) were calculated using a robust variance Poisson model adjusting for covariates. Propensity scores were used to address possible selection bias. One hundred and twelve patients became non-persistent, most commonly due to an adverse event (n = 37). No difference was observed in time to overall non-persistence between sc IFN β-1a and DMF patients. Among treatment-naïve patients, those receiving DMF had 2.4-times the risk (HR = 2.439, 95% CI = 1.007-5.917, p = .0483) of experiencing a discontinuation than patients receiving sc IFN β-1a. Non-persistent patients receiving DMF had 2.3-times the risk (HR = 2.311, 95% CI = 1.350-3.958, p = .0023) of experiencing an adverse event at a given time point than patients prescribed sc IFN β-1a. No differences in relapse risk or ARR between sc IFN β-1a- and DMF-treated patients were observed. sc IFN β-1a-treated patients had comparable persistence and relapse outcomes, and better safety outcomes vs DMF-treated patients across 2 years.

  6. The growth hormone-insulin-like growth factor axis in glycogen storage disease type 1: evidence of different growth patterns and insulin-like growth factor levels in patients with glycogen storage disease type 1a and 1b.

    Science.gov (United States)

    Melis, Daniela; Pivonello, Rosario; Parenti, Giancarlo; Della Casa, Roberto; Salerno, Mariacarolina; Balivo, Francesca; Piccolo, Pasquale; Di Somma, Carolina; Colao, Annamaria; Andria, Generoso

    2010-04-01

    To investigate the growth hormone (GH)-insulin-like growth factor (IGF) system in patients with glycogen storage disease type 1 (GSD1). This was a prospective, case-control study. Ten patients with GSD1a and 7 patients with GSD1b who were given dietary treatment and 34 sex-, age-, body mass index-, and pubertal stage-matched control subjects entered the study. Auxological parameters were correlated with circulating GH, either at basal or after growth hormone releasing hormone plus arginine test, insulin-like growth factors (IGF-I and IGF-II), and anti-pituitary antibodies (APA). Short stature was detected in 10.0% of patients with GSD1a, 42.9% of patients with GSD1b (P = .02), and none of the control subjects. Serum IGF-I levels were lower in patients with GSD1b (P = .0001). An impaired GH secretion was found in 40% of patients with GSD1a (P = .008), 57.1% of patients with GSD1b (P = .006), and none of the control subjects. Short stature was demonstrated in 3 of 4 patients with GSD1b and GH deficiency. The prevalence of APA was significantly higher in patients with GSD1b than in patients with GSD1a (P = .02) and control subjects (P = .03). The GH response to the provocative test inversely correlated with the presence of APA (P = .003). Compared with levels in control subjects, serum IGF-II and insulin levels were higher in both groups of patients, in whom IGF-II levels directly correlated with height SD scores (P = .003). Patients with GSD1a have an impaired GH secretion associated with reference range serum IGF-I levels and normal stature, whereas in patients with GSD1b, the impaired GH secretion, probably because of the presence of APA, was associated with reduced IGF-I levels and increased prevalence of short stature. The increased IGF-II levels, probably caused by increased insulin levels, in patients with GSD1 are presumably responsible for the improved growth pattern observed in patients receiving strict dietary treatment. Copyright 2010 Mosby, Inc. All

  7. Association of Odor Thresholds and Responses in Cerebral Blood Flow of the Prefrontal Area during Olfactory Stimulation in Patients with Multiple Chemical Sensitivity.

    Directory of Open Access Journals (Sweden)

    Kenichi Azuma

    Full Text Available Multiple chemical sensitivity (MCS is a disorder characterized by nonspecific and recurrent symptoms from various organ systems associated with exposure to low levels of chemicals. Patients with MCS process odors differently than controls do. Previously, we suggested that this odor processing was associated with increased regional cerebral blood flow (rCBF in the prefrontal area during olfactory stimulation using near-infrared spectroscopic (NIRS imaging. The aim of this study was to investigate the association of odor thresholds and changes in rCBF during olfactory stimulation at odor threshold levels in patients with MCS. We investigated changes in the prefrontal area using NIRS imaging and a T&T olfactometer during olfactory stimulation with two different odorants (sweet and fecal at three concentrations (zero, odor recognition threshold, and normal perceived odor level in 10 patients with MCS and six controls. The T&T olfactometer threshold test and subjective assessment of irritating and hedonic odors were also performed. The results indicated that the scores for both unpleasant and pungent odors were significantly higher for those for sweet odors at the normal perceived level in patients with MCS than in controls. The brain responses at the recognition threshold (fecal odor and normal perceived levels (sweet and fecal odors were stronger in patients with MCS than in controls. However, significant differences in the odor detection and recognition thresholds and odor intensity score between the two groups were not observed. These brain responses may involve cognitive and memory processing systems during past exposure to chemicals. Further research regarding the cognitive features of sensory perception and memory due to past exposure to chemicals and their associations with MCS symptoms is needed.

  8. The actin regulator coronin-1A is mutated in a thymic egress deficient mouse strain and in a T?B+NK+ SCID patient

    OpenAIRE

    Shiow, Lawrence R.; Roadcap, David W.; Paris, Kenneth; Watson, Susan R.; Grigorova, Irina L.; Lebet, Tonya; An, Jinping; Xu, Ying; Jenne, Craig N.; F?ger, Niko; Sorensen, Ricardo U.; Goodnow, Christopher C.; Bear, James E.; Puck, Jennifer M.; Cyster, Jason G.

    2008-01-01

    Mice carrying the recessive peripheral T cell deficiency (Ptcd) locus have a block in thymic egress but the mechanism responsible is undefined. Here we found that Ptcd T cells have an intrinsic migration defect, impaired lymphoid tissue trafficking and irregularly shaped protrusions. Characterization of the Ptcd locus revealed an E26K point mutation within the actin regulator coronin-1A (Coro1a) that enhanced its inhibition of the actin regulator Arp2/3 and resulted in its mislocalization fro...

  9. Evaluation of treatment results in patients with early glottic cancer (stage T 1a N 0, T 1b N 0) treated with Manchester irradiation modality

    International Nuclear Information System (INIS)

    Przeorek, W.; Skladowski, K.; Przeorek, C.

    2007-01-01

    Data charts of 64 patients with stage I glottic cancer treated with Manchester irradiation modality in the 1 st Radiotherapy Clinic of Msc Memorial Institute in Gliwice has been retrospectively analyzed. There were 55 males and 9 females at median age 63 years (range from 37 to 83 years). In 40 (62%) patients pathological subtype of squamous cell cancer has not been established. In 19 (30%) patients microscopic examination revealed keratinizing and in 5 (8%) nonkeratinizing type of neoplasm. In 49 (77%) patients the tumour involved only one vocal cord, in 11 (17%) both, in 3 (5%) vocal cord and commissure and 1 (1%) patient both cords and commissure. All patients were treated with 60C o machines (36 patients - 56%) or high energy photons (28 patients - 44%). Radiotherapy was conducted with so called Manchester modality with one daily fraction of 3 Gy to a total dose of 51-54 Gy. Overall treatment time varied between 21 and 23 days. Acute mucosal reaction was evaluated with the morphological-functional Dische scale as well as with the EORTC/RTOG scoring system. The criteria of treatment efficacy were: 5-year local control, 5-year survival without serious complications (3 and 4 EORTC) and 5-year survival after salvage surgery in relapsed patients. In 63 patients complete regression of the tumour was observed up to 6 months of follow-up. One patient failed at the time of radiotherapy ending. In one case distant metastases to lungs were noticed. In 6 patients local relapses were discovered of which 3 were successfully salvaged with the surgery. In one patient, 18 months after radiotherapy massive oedema of laryngeal mucosa occurred. In this case tracheostomy was needed. 5-year local control, local control after salvage surgery and survival without serious complication rates are 89%, 97% and 95% respectively. 1. Radiotherapy with Manchester modality is a safe and effective treatment of stage I glottic cancer. 2. Despite hypofractionation the risk of severe complication

  10. CYP1A1 genetic polymorphism is a promising predictor to improve chemotherapy effects in patients with metastatic breast cancer treated with docetaxel plus thiotepa vs. docetaxel plus capecitabine.

    Science.gov (United States)

    Zhou, Xinna; Qiao, Guoliang; Wang, Xiaoli; Song, Qingkun; Morse, Michael A; Hobeika, Amy; Gwin, William R; Ren, Jun; Lyerly, H Kim

    2018-02-01

    A prospective study was performed to compare the outcome for metastatic breast cancer (MBC) patients treated with docetaxel plus thiotepa (DT) or docetaxel plus capecitabine (DC), and to explore the value of CYP1A1*2C polymorphisms in predicting clinical efficacy of these chemotherapies. MBC patients (n = 130) were randomized to treatment with DT (n = 65) or DC (n = 65). Response rate, disease control rate, progression-free and overall survival were monitored. Genotyping of CYP1A1*2C was performed in all patients. DT and DC produced similar overall disease control rates (76.9 vs 69.2%), median PFS (6.7 vs. 7.5 months) and OS (20.1 vs. 21.0 months) (P > 0.05 for all comparisons); however, DT exhibited a higher rate of control of localized liver metastases (78.6 vs 41.2%, P = 0.023). Among patients homozygous for wild-type CYP1A1*1 genotype (AA), DT treatment was associated with a significantly longer PFS (8.4 vs. 6.4 months, P = 0.019) and OS (33.4 vs. 15.8 months, P = 0.018). Conversely, among patients carrying the variant CYP1A1*2C genotype (AG/GG), DC treatment was associated with a significantly longer PFS (8.4 vs. 5.5 month, P = 0.005), and OS (28.5 vs. 19.6 months, P = 0.010). After adjusting for competing risk factors, CYP1A1*2C genotype was confirmed to be an independent predictor of PFS and OS for each chemotherapy combination. Overall, DT and DC result in similar clinical efficacy for MBC patients; however, efficacy for each therapy differs depending on CYP1A1*2C genotype.

  11. Prevalence of autoantibodies in the course of Gaucher disease type 1: A multicenter study comparing Gaucher disease patients to healthy subjects.

    Science.gov (United States)

    Serratrice, Christine; Bensalah, Nesma; Penaranda, Guillaume; Bardin, Nathalie; Belmatoug, Nadia; Masseau, Agathe; Rose, Christian; Lidove, Olivier; Camou, Fabrice; Maillot, François; Leguy, Vanessa; Magy-Bertrand, Nadine; Marie, Isabelle; Cherin, Patrick; Bengherbia, Monia; Carballo, Sebastian; Boucraut, José; Serratrice, Jacques; Berger, Marc; Verrot, Denis

    2018-01-01

    Type 1 Gaucher disease may be related to the presence of autoantibodies. Their clinical significance is questioned. Primary endpoint was to compare the prevalence of autoantibodies in type 1 Gaucher disease patients with healthy subjects, seeking correlations with autoimmune characteristics. Secondary endpoints were to determine whether patients with autoantibodies reported autoimmunity-related symptoms and if genotype, splenectomy or treatment influenced autoantibodies presence. Type 1 Gaucher disease patients and healthy volunteers were included in this national multicenter exploratory study. Autoantibodies presence was compared in both groups and assessed regarding to genotype, splenectomy, Gaucher disease treatment and autoimmunity-related symptoms. Twenty healthy subjects and 40 type 1 Gaucher disease patients were included. Of the studied group: 15 patients undergone splenectomy, 37 were treated either with enzyme replacement therapy (34) or with substrate reduction therapy (3), 25 were homozygous/heterozygous for the N370S mutation. In type 1 Gaucher disease group (studied group), 52% had positive autoantibodies versus 26% in control group. Antiphospholipid antibodies were more frequent in the studied group (30% vs. 5%), but without correlation to thrombosis, osteonecrosis or bone infarcts. In the studied group, antinuclear antibodies were more frequent (25% vs. 16%). None of the patients with autoantibodies had clinical manifestations of autoimmune diseases. Autoantibodies were not correlated with treatment, genotype, or splenectomy, except for anticardiolipid, more frequent in splenectomized patients. In type 1 Gaucher disease, autoantibodies were more frequent compared to a healthy population. However, they were not associated with an increased prevalence of clinical active autoimmune diseases. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  12. The C(-1019G 5-HT1A promoter polymorphism and personality traits: no evidence for significant association in alcoholic patients

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    Zill P

    2006-02-01

    Full Text Available Abstract The 5HT1A receptor is one of at least 14 different receptors for serotonin which has a role in moderating several brain functions and may be involved in the aetiology of several psychiatric disorders. The C(-1019G 5-HT1A promoter polymorphism was reported to be associated with major depression, depression-related personality traits and suicidal behavior in various samples. The G(-1019 allele carriers are prone to depressive personality traits and suicidal behavior, because serotonergic neurotransmission is reduced. The aim of this study is to replicate previous findings in a sample of 185 Alcohol-dependent individuals. Personality traits were evaluated using the NEO FFI and TCI. History of suicidal behavior was assessed by a standardized semistructured interview (SSAGA. No significant differences across C(-1019G 5-HT1A genotype groups were found for TCI temperament and character traits and for NEO FFI personality scales. No association was detected between this genetic variant and history of suicide attempts. These results neither support a role of C(-1019G 5-HT1A promoter polymorphism in the disposition of personality traits like harm avoidance or neuroticism, nor confirm previous research reporting an involvement of the G allele in suicidal behavior in alcoholics. Significant associations, however, were detected between Babor's Type B with number of suicide attempts in history, high neuroticism and harm avoidance scores in alcoholics.

  13. A genetic variant in Rassf1a predicts outcome in mCRC patients treated with cetuximab plus chemotherapy: results from FIRE-3 and JACCRO 05 and 06 trials.

    Science.gov (United States)

    Sebio, A; Stintzing, S; Heinemann, V; Sunakawa, Y; Zhang, W; Ichikawa, W; Tsuji, A; Takahashi, T; Parek, A; Yang, D; Cao, S; Ning, Y; Stremitzer, S; Matsusaka, S; Okazaki, S; Barzi, A; Berger, M D; Lenz, H-J

    2018-01-01

    The Hippo pathway is involved in colorectal cancer (CRC) development and progression. The Hippo regulator Rassf1a is also involved in the Ras signaling cascade. In this work, we tested single nucleotide polymorphisms within Hippo components and their association with outcome in CRC patients treated with cetuximab. Two cohorts treated with cetuximab plus chemotherapy were evaluated (198 RAS wild-type (WT) patients treated with first-line FOLFIRI plus Cetuximab within the FIRE-3 trial and 67 Ras WT patients treated either with first-line mFOLFOX6 or SOX plus Cetuximab). In these two populations, Rassf1a rs2236947 was associated with overall survival (OS), as patients with a CC genotype had significantly longer OS compared with those with CA or AA genotypes. This association was stronger in patients with left-side CRC (hazard ratio (HR): 1.79 (1.01-3.14); P=0.044 and HR: 2.83 (1.14-7.03); P=0.025, for Fire 3 and JACCRO cohorts, respectively). Rassf1a rs2236947 is a promising biomarker for patients treated with cetuximab plus chemotherapy.

  14. Frequent phosphodiesterase 11A gene (PDE11A) defects in patients with Carney complex (CNC) caused by PRKAR1A mutations: PDE11A may contribute to adrenal and testicular tumors in CNC as a modifier of the phenotype.

    Science.gov (United States)

    Libé, Rossella; Horvath, Anelia; Vezzosi, Delphine; Fratticci, Amato; Coste, Joel; Perlemoine, Karine; Ragazzon, Bruno; Guillaud-Bataille, Marine; Groussin, Lionel; Clauser, Eric; Raffin-Sanson, Marie-Laure; Siegel, Jennifer; Moran, Jason; Drori-Herishanu, Limor; Faucz, Fabio Rueda; Lodish, Maya; Nesterova, Maria; Bertagna, Xavier; Bertherat, Jerome; Stratakis, Constantine A

    2011-01-01

    Carney complex (CNC) is an autosomal dominant multiple neoplasia, caused mostly by inactivating mutations of the regulatory subunit 1A of the protein kinase A (PRKAR1A). Primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine manifestation of CNC with a great inter-individual variability. Germline, protein-truncating mutations of phosphodiesterase type 11A (PDE11A) have been described to predispose to a variety of endocrine tumors, including adrenal and testicular tumors. Our objective was to investigate the role of PDE11A as a possible gene modifier of the phenotype in a series of 150 patients with CNC. A higher frequency of PDE11A variants in patients with CNC compared with healthy controls was found (25.3 vs. 6.8%, P CNC patients, those with PPNAD were significantly more frequently carriers of PDE11A variants compared with patients without PPNAD (30.8 vs. 13%, P = 0.025). Furthermore, men with PPNAD were significantly more frequently carriers of PDE11A sequence variants (40.7%) than women with PPNAD (27.3%) (P CNC patients, a high frequency of PDE11A variants, suggesting that PDE11A is a genetic modifying factor for the development of testicular and adrenal tumors in patients with germline PRKAR1A mutation.

  15. Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial.

    Science.gov (United States)

    Okkersen, Kees; Jimenez-Moreno, Cecilia; Wenninger, Stephan; Daidj, Ferroudja; Glennon, Jeffrey; Cumming, Sarah; Littleford, Roberta; Monckton, Darren G; Lochmüller, Hanns; Catt, Michael; Faber, Catharina G; Hapca, Adrian; Donnan, Peter T; Gorman, Gráinne; Bassez, Guillaume; Schoser, Benedikt; Knoop, Hans; Treweek, Shaun; van Engelen, Baziel G M

    2018-06-18

    Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1. We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK). Eligible participants were patients aged 18 years and older with a confirmed genetic diagnosis of myotonic dystrophy type 1, who were severely fatigued (ie, a score of ≥35 on the checklist-individual strength, subscale fatigue). We randomly assigned participants (1:1) to either cognitive behavioural therapy plus standard care and optional graded exercise or standard care alone. Randomisation was done via a central web-based system, stratified by study site. Cognitive behavioural therapy focused on addressing reduced patient initiative, increasing physical activity, optimising social interaction, regulating sleep-wake patterns, coping with pain, and addressing beliefs about fatigue and myotonic dystrophy type 1. Cognitive behavioural therapy was delivered over a 10-month period in 10-14 sessions. A graded exercise module could be added to cognitive behavioural therapy in Nijmegen and Newcastle. The primary outcome was the 10-month change from baseline in scores on the DM1-Activ-c scale, a measure of capacity for activity and social participation (score range 0-100). Statistical analysis of the primary outcome included all participants for whom data were available, using mixed-effects linear regression models with baseline scores as a covariate. Safety data were presented as descriptives. This trial is registered

  16. Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial

    NARCIS (Netherlands)

    Eron, Joseph J.; Rockstroh, Jürgen K.; Reynes, Jacques; Andrade-Villanueva, Jaime; Ramalho-Madruga, Jose Valdez; Bekker, Linda-Gail; Young, Benjamin; Katlama, Christine; Gatell-Artigas, Jose Maria; Arribas, Jose R.; Nelson, Mark; Campbell, Havilland; Zhao, Jing; Rodgers, Anthony J.; Rizk, Matthew L.; Wenning, Larissa; Miller, Michael D.; Hazuda, Daria; DiNubile, Mark J.; Leavitt, Randi; Isaacs, Robin; Robertson, Michael N.; Sklar, Peter; Nguyen, Bach-Yen; Bloch, M. T.; Hoy, J.; Workman, C.; Madruga, J. V.; Souza, T.; Telles, F. Q.; Zajdenverg, R.; Angel, J.; Montaner, J. S.; Smith, G. H. R.; Trottier, B.; Tamara, J. R.; Velez, J. D.; Gerstoft, J.; Laursen, A. L.; Mathiesen, L.; Katlama, C.; Molina, J. M.; Raffi, F.; Reynes, J.; Yazdanpanah, Y.; Bogner, J. R.; Fatkenheuer, G.; Hartl, H.; Jaeger, H.; Geerlings, S. E.

    2011-01-01

    Twice-daily raltegravir with once-daily tenofovir-emtricitabine is an effective initial antiretroviral regimen for patients with HIV-1. On the basis of pharmacokinetic data suggesting efficacy of once-daily raltegravir and because adherence is often improved with once-daily dosing, we aimed to

  17. A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors

    NARCIS (Netherlands)

    de Weger, Vincent A; Goel, Sanjay; von Moos, Roger; Schellens, Jan H M; Mach, Nicholas; Tan, Eugene; Anand, Suraj; Scott, Jeffrey W; Lassen, Ulrik N

    PURPOSE: Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. This study was performed to investigate the potential drug-drug interaction of dovitinib with the CYP1A2 inhibitor fluvoxamine in patients with advanced solid tumors. METHODS:

  18. A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors

    DEFF Research Database (Denmark)

    de Weger, Vincent A; Goel, Sanjay; von Moos, Roger

    2018-01-01

    PURPOSE: Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. This study was performed to investigate the potential drug-drug interaction of dovitinib with the CYP1A2 inhibitor fluvoxamine in patients with advanced solid tumors. METHODS: ...

  19. Positive effects on hematological and biochemical imbalances in patients with metastatic breast cancer stage IV, of BP-C1, a new anticancer substance

    Directory of Open Access Journals (Sweden)

    Lindkær-Jensen S

    2015-03-01

    Full Text Available Steen Lindkær-Jensen,1 Stig Larsen,2 Nina Habib-Lindkær-Jensen,1 Hans E Fagertun3 1Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College, London, UK; 2Center of Epidemiology and Biostatistics, Faculty of Veterinary Medicine, University of Life Science, Oslo, Norway; 3Meddoc Research AS, Skjetten, Norway Abstract: A benzene-poly-carboxylic acid complex with cis-diammineplatinum(II dihydrocholride, BP-C1 is currently used in clinical trials in treating metastatic breast cancer. BP-C1 controls tumor growth with a few mild side-effects, improving quality of life.Methods: The data consisted of prospectively collected laboratory results from 47 patients in two controlled clinical trials of daily intramuscular injections of BP-C1 for 32 days. Study I was performed as an open, nonrandomized, Phase I dose–response, multicenter study with a three-level, between-patient, response surface pathway design. The second study was a randomized, double-blind, and placebo-controlled, multicenter study with a stratified semi-crossover design.Results: Hemoglobin (Hb and hematocrit (Hct increased significantly (P<0.01 during BP-C1 treatment, while red blood cell (RBC count increased but not significantly. The most pronounced increase in Hb, RBC, Hct, and white blood cell (WBC was in anemic patients (P≤0.01. WBC count and neutrophils increased significantly (P=0.01 in the overall data. WBCs and neutrophils (P<0.01, eosinophils (P=0.05 and monocytes (P<0.01 increased significantly and markedly in patients with lowest baseline levels. Additionally, low levels of thrombocytes significantly increased. No changes in liver parameters, amylase, glucose, creatinine, or albumin, were detected except for albumin in the subgroup with low baseline levels, where levels increased significantly (P=0.04. An increase in K+, Ca2+, and PO43- was most pronounced in patients with low baseline levels (P≤0.02. A similar pattern detected for Mg2+, prothrombin

  20. CYP1A2*1C, CYP2E1*5B, and GSTM1 polymorphisms are predictors of risk and poor outcome in head and neck squamous cell carcinoma patients

    DEFF Research Database (Denmark)

    Olivieri, Eloisa Helena Ribeiro; da Silva, Sabrina Daniela; Mendonça, Fernando Fernandes

    2009-01-01

    is performed by glutathione S-transferases (GSTs). It has been suggested that genetic alterations, such as polymorphisms, play an important role in tumorigenesis and HNSCC progression. The aim of this study was to investigate CYP1A1, CYP1A2, CYP2E1, GSTM1, and GSTT1 polymorphisms as risk factors in HNSCC...... and their association with clinicopathologic data. The patients comprised 153 individuals with HNSCC (cases) and 145 with no current or previous diagnosis of cancer (controls). Genotyping of the single nucleotide polymorphisms (SNPs) of the CYP1A1, CYP1A2, and CYP2E1 genes was performed by PCR-RFLP and the GSTM1...... for determining the parameters associated with tumor progression and poor outcomes in HNSCC....

  1. An audit about music therapy assessments and recommendations for adult patients suspected to be in a low awareness state.

    Science.gov (United States)

    Daveson, Barbara

    2010-01-01

    In neuro-rehabilitation, the role of music therapy is expanding to include assessment of patients with severely-altered states of consciousness. Diagnosis of these conditions is a complex task for all, and cases of misdiagnosis have been reported. Aggregated findings from 33 music therapy assessments of patients suspected of being in a low awareness state are described and discussed here. The Music Therapy Assessment Tool for Low Awareness States (MATLAS) was used during these assessments. All assessments were offered as part of a specialist multidisciplinary assessment package. A brief description of the patient group is supplied, along with details regarding the assessment tool and the recommendations that followed. In summary, a difference in the time it took to assess patients in vegetative state (VS) as compared to those in minimally conscious state (MCS) was found and, on average, the assessment of those in VS took less time to complete than for those in MCS. A greater range in session length was found for patients in VS, as compared to those in MCS. Generally after the assessments, patients in VS were likely to be admitted to a sensory regulation group administered by a music therapy assistant, supervised by a qualified music therapist, to enable the continued collection of behavioral responses to stimuli. Patients in MCS were admitted to a music therapy treatment program offered by a qualified music therapist. Ongoing work is recommended to advance the assessment and treatment of this patient population, and to consolidate the role of music therapy with this population.

  2. Prevalence of naturally occurring NS5A resistance-associated substitutions in patients infected with hepatitis C virus subtype 1a, 1b, and 3a, co-infected or not with HIV in Brazil.

    Science.gov (United States)

    Malta, Fernanda; Gaspareto, Karine Vieira; Lisboa-Neto, Gaspar; Carrilho, Flair José; Mendes-Correa, Maria Cássia; Pinho, João Renato Rebello

    2017-11-13

    Non-structural 5A protein (NS5A) resistance-associated substitutions (RASs) have been identified in patients infected with hepatitis C virus (HCV), even prior to exposure to direct-acting antiviral agents (DAAs). Selection for these variants occurs rapidly during treatment and, in some cases, leads to antiviral treatment failure. DAAs are currently the standard of care for hepatitis C treatment in many parts of the world. Nevertheless, in Brazil, the prevalence of pre-existing NS5A RASs is largely unknown. In this study, we evaluated the frequency of naturally occurring NS5A RASs in Brazilian patients infected with HCV as either a monoinfection or coinfection with human immunodeficiency virus (HIV). Direct Sanger sequencing of the NS5A region was performed in 257 DAA-naïve patients chronically infected with HCV (156 monoinfected with HCV and 101 coinfected with HIV/HCV). The frequencies of specific RASs in monoinfected patients were 14.6% for HCV GT-1a (M28 V and Q30H/R), 6.0% for GT-1b (L31F/V and Y93H), and 22.6% for GT-3a (A30K and Y93H). For HIV/HCV-coinfected patients, the frequencies of RAS were 3.9% for GT-1a (M28 T and Q30H/R), and 11.1% for GT-1b (Y93H); no RASs were found in GT-3a sequences. Substitutions that may confer resistance to NS5A inhibitors exist at baseline in Brazilian DAA-naïve patients infected with HCV GT-1a, -1b, and -3a. Standardization of RAS definitions is needed to improve resistance analyses and to facilitate comparisons of substitutions reported across studies worldwide. Therapeutic strategies should be optimized to efficiently prevent DAA treatment failure due to selection for RASs, especially in difficult-to-cure patients.

  3. Fetal antigen 1, a member of the epidermal growth factor superfamily, in neurofibromas and serum from patients with neurofibromatosis type 1

    DEFF Research Database (Denmark)

    Jensen, Charlotte Harken; Schroder, H D; Teisner, B

    1999-01-01

    Fetal antigen 1 (FA1) is a 26-32 kDa glycoprotein containing six epidermal growth factor-like repeats closely related to the delta/notch/serrate proteins in Drosophila. FA1 has been shown to be involved in cell differentiation in a juxtacrine/paracrine manner. As neurofibromatosis type 1 (NF-1......), also called von Recklinghausen disease, involves aberrant growth of tissues derived from the neural crest, the expression of FA1 was examined in neurofibroma skin biopsies and serum from patients with NF-1. FA1 was found in the spindle cells of all (n = 10) skin tumour specimens from adult NF-1...

  4. Biodistribution of adult derived human liver stem cells following intraportal infusion in a 17-year-old patient with glycogenosis type 1A

    International Nuclear Information System (INIS)

    Defresne, Florence; Tondreau, Tatiana; Stéphenne, Xavier; Smets, Françoise; Bourgois, Annick; Najimi, Mustapha; Jamar, François; Sokal, Etienne M.

    2014-01-01

    Introduction: Current treatment of inherited liver inborn errors of metabolism in children consists in appropriate diet and drugs and, for unstable patients, final orthotopic liver transplantation. Unfortunately, liver transplantation remains not easily available because of organ shortage and imposes inherent risks and lifelong immunosuppressive therapy. Therefore alternative treatments are required. Hepatocytes transplantation and its limitations led to consider innovative alternative such as transplantation of adult derived human liver stem cells (ADLHSC). These cells present high proliferative capacity, good resistance to cryopreservation and ability to differentiate into hepatocyte-like cells displaying mature hepatocyte functions. Aim: Biodistribution of ADHLSC had never been assessed after infusion through the portal vein in patients. This information is required to determine the safety of the method. Methods: ADHLSC were efficiently labelled with 111-Indium DTPA radiotracer and SPECT imaging was used for the acquisition of whole body imaging to document short term biodistribution of ADHLSC. Results: Following infusion through the portal vein, ADHLSC diffused homogenously throughout the liver and remained strictly within the targeted organ. Images were acquired until 5 days after infusion. At that time, no signal was observed in any other organs except the liver. Urinary excretion of 111-Indium DTPA was also monitored. Conclusion: For the first time, we documented the short term biodistribution of ADHLSC within the liver after infusion through the portal vein

  5. Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial

    Directory of Open Access Journals (Sweden)

    Harrington KJ

    2016-11-01

    Full Text Available Kevin J Harrington,1 Robert HI Andtbacka,2 Frances Collichio,3 Gerald Downey,4 Lisa Chen,5 Zsolt Szabo,6 Howard L Kaufman7 1The Institute of Cancer Research/The Royal Marsden Hospital NIHR Biomedical Research Centre, London, UK; 2Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; 3Division of Hematology and Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 4Amgen Ltd, Cambridge, UK; 5Amgen Inc, Thousand Oaks, CA, USA; 6Amgen GmbH, Zug, Switzerland; 7Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA Objectives: Talimogene laherparepvec is the first oncolytic immunotherapy to receive approval in Europe, the USA and Australia. In the randomized, open-label Phase III OPTiM trial (NCT00769704, talimogene laherparepvec significantly improved durable response rate (DRR versus granulocyte-macrophage colony-stimulating factor (GM-CSF in 436 patients with unresectable stage IIIB–IVM1c melanoma. The median overall survival (OS was longer versus GM-CSF in patients with earlier-stage melanoma (IIIB–IVM1a. Here, we report a detailed subgroup analysis of the OPTiM study in patients with IIIB–IVM1a disease. Patients and methods: The patients were randomized (2:1 ratio to intralesional talimogene laherparepvec or subcutaneous GM-CSF and were evaluated for DRR, overall response rate (ORR, OS, safety, benefit–risk and numbers needed to treat. Descriptive statistics were used for subgroup comparisons. Results: Among 249 evaluated patients with stage IIIB–IVM1a melanoma, DRR was higher with talimogene laherparepvec compared with GM-CSF (25.2% versus 1.2%; P<0.0001. ORR was also higher in the talimogene laherparepvec arm (40.5% versus 2.3%; P<0.0001, and 27 patients in the talimogene laherparepvec arm had a complete response, compared with none in GM-CSF-treated patients. The incidence rates of exposure-adjusted adverse events (AE and serious AEs were similar with both treatments. Conclusion

  6. For or against adjuvant trastuzumab for pT1a-bN0M0 breast cancer patients with HER2-positive tumors: a meta-analysis of published literatures.

    Directory of Open Access Journals (Sweden)

    Qiong Zhou

    Full Text Available BACKGROUND: Although the prognosis of patients with small (≤1cm tumors is generally favorable, emerging data suggests that biological behavior varies between intrinsic subtypes in such patients. Furthermore, it still remains unclear whether HER2-positive pT1a-bN0M0 patients could benefit from adjuvant trastuzumab. For further evaluation, we sought to conduct a meta-analysis so as to get a better understanding of the prognosis for HER2-positive pT1a-bN0M0 patients and their survival benefit from adjuvant trastuzumab, accordingly, offering the implications for current practice. METHODS: The PubMed database, the online proceedings of the American Society of Clinical Oncology (ASCO Annual Meetings, the online proceedings of the San Antonio Breast Cancer Symposium, and the CD proceedings of the International St. Gallen Breast Cancer Conference were searched for all relevant studies published before September 2012. Relative risks (RRs were used to compare the prognosis of different intrinsic subtypes for pT1a-bN0M0 breast cancer. Analyses were also performed to estimate the association between adjuvant trastuzumab and various survival outcomes. RESULTS: With eight eligible studies identified, this meta-analysis demonstrated a deleterious effect of HER2+ phenotype on disease-free survival (DFS; RR = 3.677, 95% CI 2.606-5.189, p <0.001 and distant disease-free survival (DDFS; RR = 3.824, 95% CI 2.249-6.501, p<0.001 as compared to HR+/HER2- subgroup. However, significant difference failed to be achieved in terms of any endpoint between HER2+ and triple negative breast cancer (TNBC. Besides, a marked improvement in DFS was observed with the addition of trastuzumab for HER2-positive pT1a-bN0M0 patients (RR = 0.323, 95% CI 0.191-0.547, p<0.001. CONCLUSION: This meta-analysis clarifies that intrinsic subtypes might be a reliable marker to predict the prognosis in pT1a-bN0M0 breast cancer. Besides, even for such early stage HER2-positive

  7. NS5A resistance leading to failure of 24-week therapy with sofosbuvir/ledipasvir and ribavirin for the treatment of hepatitis C genotype 1a infection in a HIV-1 co-infected patient.

    Science.gov (United States)

    Sevastianova, Ksenia; Dean, Jonathan; Bannan, Ciaran; Coghlan, Miriam; Farrell, Gillian; Murray, Catherine; De Gascun, Cillian F; Bergin, Colm

    2016-09-01

    Herein we report a previously undescribed case of treatment-emergent non-structural protein 5A (NS5A) resistance mutations, Q30H and Y93C, leading to a failure of 24-week course of sofosbuvir/ledipasvir+ribavirin therapy for the treatment of hepatitis C virus (HCV) genotype 1a in interferon-experienced, human immunodeficiency virus type 1 (HIV-1) co-infected patient with cirrhosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Randomized, double-blind, placebo-controlled trial of the 5-HT1A receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate) in patients with irritable bowel syndrome.

    Science.gov (United States)

    Drossman, Douglas A; Danilewitz, Mervyn; Naesdal, Jørgen; Hwang, Clara; Adler, John; Silberg, Debra G

    2008-10-01

    To investigate the efficacy and safety of the 5-hydroxytrypamine 1A (5-HT(1A)) receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate), termed AZD7371 here, in patients with irritable bowel syndrome (IBS). Patients meeting the Rome II criteria for IBS (N = 402) were randomized to treatment with AZD7371 20 mg or 5 mg or matching placebo tablets twice daily for 12 wk. The patients completed daily and weekly diary assessments, reporting abdominal discomfort or pain and description of bowel movements. They also completed validated symptom and quality-of-life questionnaires. Neither AZD7371 regimen was significantly more effective than placebo in providing adequate relief from IBS symptoms in at least 2 out of 4 wk per month over the 12 wk of treatment. There was also no significant difference between the treatment groups and placebo in the change in score in the validated symptom and quality-of-life questionnaires. Overall, 22.1% of patients experienced adverse events (AEs) attributed to the study medication: 44 of 133 (33.1%) in the 20 mg AZD7371 group, 27 of 131 (20.6%) in the 5 mg AZD7371 group, and 17 of 134 (12.7%) in the placebo group. Also, 31 of 57 (54%) of AEs leading to discontinuation were central nervous system-related. Hallucinations or hallucination-like AEs were reported by eight patients taking AZD7371, and by none of the patients in the placebo group. After these events led to discontinuation in six patients, the study was prematurely terminated. In view of the AE profile and lack of efficacy in IBS, the clinical development of AZD7371 has been stopped.

  9. Association of serotonin transporter (SLC6A4 & receptor (5HTR1A, 5HTR2A polymorphisms with response to treatment with escitalopram in patients with major depressive disorder : A preliminary study

    Directory of Open Access Journals (Sweden)

    Aniruddha Basu

    2015-01-01

    Full Text Available Background & objectives: Genetic factors have potential of predicting response to antidepressants in patients with major depressive disorder (MDD. In this study, an attempt was made to find an association between response to escitalopram in patients with MDD, and serotonin transporter (SLC6A4 and receptor (5HTR1A, 5HTR2A polymorphisms. Methods: Fifty five patients diagnosed as suffering from MDD, were selected for the study. The patients were treated with escitalopram over a period of 6-8 wk. Severity of depression, response to treatment and side effects were assessed using standardised instruments. Genetic variations from HTR1A (rs6295, HTR2A (rs6311 and rs6313 and SLC6A4 (44 base-pair insertion/deletion at 5-HTTLPR were genotyped. The genetic data of the responders and non-responders were compared to assess the role of genetic variants in therapeutic outcome. Results: Thirty six (65.5% patients responded to treatment, and 19 (34.5% had complete remission. No association was observed for genotype and allelic frequencies of single nucleotide polymorphisms (SNPs among remitter/non-remitter and responder/non-responder groups, and six most common side-effects, except memory loss which was significantly associated with rs6311 ( p0 =0.03. Interpretation & conclusions: No significant association was found between the SNPs analysed and response to escitalopram in patients with MDD though a significant association was seen between the side effect of memory loss and rs6311. Studies with larger sample are required to find out genetic basis of antidepressant response in Indian patients.

  10. Transcranial Direct Current Stimulation in Patients with Prolonged Disorders of Consciousness: Combined Behavioral and Event-Related Potential Evidence

    Directory of Open Access Journals (Sweden)

    Ye Zhang

    2017-11-01

    Full Text Available BackgroundThe electrophysiological evidence supporting the therapeutic efficacy of multiple transcranial direct current stimulation (tDCS sessions on consciousness improvement in patients with prolonged disorders of consciousness (DOCs has not been firmly established.ObjectivesTo assess the effects of repeated tDCS in patients with prolonged DOCs by Coma Recovery Scale-Revised (CRS-R score and event-related potential (ERP.MethodUsing a sham-controlled randomized double-blind design, 26 patients were randomly assigned to either a real [five vegetative state (VS and eight minimally conscious state (MCS patients] or sham (six VS and seven MCS patients stimulation group. The patients in the real stimulation group underwent 20 anodal tDCS sessions of the left dorsolateral prefrontal cortex (DLPFC over 10 consecutive working days. The CRS-R score and P300 amplitude and latency in a hierarchical cognitive assessment were recorded to evaluate the consciousness level before tDCS and immediately after the 20 sessions.ResultsThe intra-group CRS-R analysis revealed a clinically significant improvement in the MCS patients in the real stimulation group. The inter-group CRS-R analysis showed a significant difference in CRS-R between VS and MCS patients at baseline in both the real and sham stimulation groups. The intra-group ERP analysis revealed a significant increase in P300 amplitude after tDCS in the MCS patients in the real stimulation group, but no significant differences in P300 latency. For the inter-group ERP analysis, we observed significant differences regarding the presence of P300 at baseline between the VS and MCS patients in both groups.ConclusionThe repeated anodal tDCS of the left DLPFC could produce clinically significant improvements in MCS patients. The observed tDCS-related consciousness improvements might be related to improvements in attention resource allocation (reflected by the P300 amplitude. The findings support the use of tDCS in

  11. RECQ1 A159C Polymorphism Is Associated With Overall Survival of Patients With Resected Pancreatic Cancer: A Replication Study in NRG Oncology Radiation Therapy Oncology Group 9704

    Energy Technology Data Exchange (ETDEWEB)

    Li, Donghui, E-mail: dli@mdanderson.org [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Moughan, Jennifer [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Crane, Christopher [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hoffman, John P. [Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland, Baltimore, Maryland (United States); Abrams, Ross A. [Rush University Medical Center, Chicago, Illinois (United States); Safran, Howard [Brown University Oncology Group, Providence, Rhode Island (United States); Liu, Chang; Chang, Ping [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Freedman, Gary M. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Winter, Kathryn A. [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Guha, Chandan [Department of Radiation Oncology, Montefiore Medical Center, Bronx, New York (United States); Abbruzzese, James L. [Duke University Medical Center, Durham, North Carolina (United States)

    2016-03-01

    Purpose: To confirm whether a previously observed association between RECQ1 A159C variant and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population prospectively treated with postoperative chemoradiation. Methods and Materials: Patients were selected, according to tissue availability, from eligible patients with resected pancreatic cancer who were enrolled on the NRG Oncology Radiation Therapy Oncology Group 9704 trial of 5-fluorouacil (5-FU)-based chemoradiation preceded and followed by 5-FU or gemcitabine. Deoxyribonucleic acid was extracted from paraffin-embedded tissue sections, and genotype was determined using the Taqman method. The correlation between genotype and overall survival was analyzed using a Kaplan-Meier plot, log-rank test, and multivariate Cox proportional hazards models. Results: In the 154 of the study's 451 eligible patients with evaluable tissue, genotype distribution followed Hardy-Weinberg equilibrium (ie, 37% had genotype AA, 43% AC, and 20% CC). The RECQ1 variant AC/CC genotype carriers were associated with being node positive compared with the AA carrier (P=.03). The median survival times (95% confidence interval [CI]) for AA, AC, and CC carriers were 20.6 (16.3-26.1), 18.8 (14.2-21.6), and 14.2 (10.3-21.0) months, respectively. On multivariate analysis, patients with the AC/CC genotypes were associated with worse survival than patients with the AA genotype (hazard ratio [HR] 1.54, 95% CI 1.07-2.23, P=.022). This result seemed slightly stronger for patients on the 5-FU arm (n=82) (HR 1.64, 95% CI 0.99-2.70, P=.055) than for patients on the gemcitabine arm (n=72, HR 1.46, 95% CI 0.81-2.63, P=.21). Conclusions: Results of this study suggest that the RECQ1 A159C genotype may be a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant 5-FU before and after 5-FU-based chemoradiation. Further study is

  12. Predictive factors associated with neck pain in patients with cervical disc degeneration: A cross-sectional study focusing on Modic changes.

    Science.gov (United States)

    Kong, Lingde; Tian, Weifeng; Cao, Peng; Wang, Haonan; Zhang, Bing; Shen, Yong

    2017-10-01

    The predictive factors associated with neck pain remain unclear. We conducted a cross-sectional study to assess predictive factors, especially Modic changes (MCs), associated with the intensity and duration of neck pain in patients with cervical disc degenerative disease.We retrospectively reviewed patients in our hospital from January 2013 to December 2016. Severe neck pain (SNP) and persistent neck pain (PNP) were the 2 main outcomes, and were assessed based on the numerical rating scale (NRS). Basic data, and also imaging data, were collected and analyzed as potential predictive factors. Univariate analysis and multiple logistic regression analysis were performed to assess the predictive factors for neck pain.In all, 381 patients (193 males and 188 females) with cervical degenerative disease were included in our study. The number of patients with SNP and PNP were 94 (24.67%) and 109 (28.61%), respectively. The NRS of neck pain in patients with type 1 MCs was significantly higher than type 2 MCs (4.8 ± 0.9 vs 3.9 ± 1.1; P = .004). The multivariate logistic analysis showed that kyphosis curvature (odds ratio [OR] 1.082, 95% confidence interval [CI] 1.044-1.112), spondylolisthesis (OR 1.339, 95% CI 1.226-1.462), and annular tear (OR 1.188, 95% CI 1.021-1.382) were factors associated with SNP, whereas kyphosis curvature (OR 1.568, 95% CI 1.022-2.394), spondylolisthesis (OR 1.486, 95% CI 1.082-2.041), and MCs (OR 1.152, 95% CI 1.074-1.234) were associated with PNP.We concluded that kyphosis curvature, spondylolisthesis, and annular tear are associated with SNP, whereas kyphosis curvature, spondylolisthesis, and MCs are associated with PNP. This study supports the view that MCs can lead to a long duration of neck pain.

  13. TDCS modulates cortical excitability in patients with disorders of consciousness

    Directory of Open Access Journals (Sweden)

    Yang Bai

    2017-01-01

    Full Text Available Transcranial direct current stimulation (tDCS has been reported to be a promising technique for consciousness improvement for patients with disorders of consciousness (DOC. However, there has been no direct electrophysiological evidence to demonstrate the efficacy of tDCS on patients with DOC. Therefore, we aim to measure the cortical excitability changes induced by tDCS in patients with DOC, to find electrophysiological evidence supporting the therapeutic efficacy of tDCS on patients with DOC. In this study, we enrolled sixteen patients with DOC, including nine vegetative state (VS and seven minimally conscious state (MCS (six females and ten males. TMS-EEG was applied to assess cortical excitability changes after twenty minutes of anodal tDCS of the left dorsolateral prefrontal cortex. Global cerebral excitability were calculated to quantify cortical excitability in the temporal domain: four time intervals (0–100, 100–200, 200–300, 300-400 ms. Then local cerebral excitability in the significantly altered time windows were investigated (frontal, left/right hemispheres, central, and posterior. Compared to baseline and sham stimulation, we found that global cerebral excitability increased in early time windows (0–100 and 100-200 ms for patients with MCS; for the patients with VS, global cerebral excitability increased in the 0-100 ms interval but decreased in the 300-400 ms interval. The local cerebral excitability was significantly different between MCS and VS. The results indicated that tDCS can effectively modulate the cortical excitability of patients with DOC; and the changes in excitability in temporal and spatial domains are different between patients with MCS and those with VS.

  14. A Comparison of SF-36 and SF-12 Composite Scores and Subsequent Hospitalization and Mortality Risks in Long-Term Dialysis Patients

    Science.gov (United States)

    Xu, Jianglin; Lin, Shu-Fang; Dean, Sandie Guerra; Lazarus, J. Michael; Hakim, Raymond M.

    2010-01-01

    Background and objectives: The Short Form 12 (SF-12) has not been validated for long-term dialysis patients. The study compared physical and mental component summary (PCS/MCS) scores from the SF-36 with those from the embedded SF-12 in a national cohort of dialysis patients. Design, setting, participants, & measurements: All 44,395 patients who had scorable SF-36 and SF-12 from January 1, 2006, to December 31, 2006, and were treated at Fresenius Medical Care, North America facilities were included. Death and first hospitalization were followed for up to 1 year from the date of survey. Correlation and agreement were obtained between PCS-36 and PCS-12 and MCS-36 and MCS-12; then Cox models were constructed to compare associated hazard ratios (HRs) between them. Results: Physical and mental dimensions both exhibited excellent intraclass correlation coefficients of 0.94. Each incremental point for both PCS-12 and PCS-36 was associated with a 2.4% lower adjusted HR of death and 0.4% decline in HR for first hospitalization (both P < 0.0001). Corresponding improvement in HR of death for each MCS point was 1.2% for MCS-12 and 1.3% for MCS-36, whereas both had similar 0.6% lower HR for hospitalization per point (all P < 0.0001). Conclusions: The use of the SF-12 alone or as part of a larger survey is valid in dialysis patients. Composite scores from the SF-12 and SF-36 have similar prognostic association with death and hospitalization risk. Prospective longitudinal studies of SF-12 surveys that consider responsiveness to specific clinical, situational, and interventional changes are needed in this population. PMID:20019120

  15. Causes of death and prognostic factors in multiple endocrine neoplasia type 1: a prospective study: comparison of 106 MEN1/Zollinger-Ellison syndrome patients with 1613 literature MEN1 patients with or without pancreatic endocrine tumors.

    Science.gov (United States)

    Ito, Tetsuhide; Igarashi, Hisato; Uehara, Hirotsugu; Berna, Marc J; Jensen, Robert T

    2013-05-01

    Multiple endocrine neoplasia type 1 (MEN1) is classically characterized by the development of functional or nonfunctional hyperplasia or tumors in endocrine tissues (parathyroid, pancreas, pituitary, adrenal). Because effective treatments have been developed for the hormone excess state, which was a major cause of death in these patients in the past, coupled with the recognition that nonendocrine tumors increasingly develop late in the disease course, the natural history of the disease has changed. An understanding of the current causes of death is important to tailor treatment for these patients and to help identify prognostic factors; however, it is generally lacking.To add to our understanding, we conducted a detailed analysis of the causes of death and prognostic factors from a prospective long-term National Institutes of Health (NIH) study of 106 MEN1 patients with pancreatic endocrine tumors with Zollinger-Ellison syndrome (MEN1/ZES patients) and compared our results to those from the pooled literature data of 227 patients with MEN1 with pancreatic endocrine tumors (MEN1/PET patients) reported in case reports or small series, and to 1386 patients reported in large MEN1 literature series. In the NIH series over a mean follow-up of 24.5 years, 24 (23%) patients died (14 MEN1-related and 10 non-MEN1-related deaths). Comparing the causes of death with the results from the 227 patients in the pooled literature series, we found that no patients died of acute complications due to acid hypersecretion, and 8%-14% died of other hormone excess causes, which is similar to the results in 10 large MEN1 literature series published since 1995. In the 2 series (the NIH and pooled literature series), two-thirds of patients died from an MEN1-related cause and one-third from a non-MEN1-related cause, which agrees with the mean values reported in 10 large MEN1 series in the literature, although in the literature the causes of death varied widely. In the NIH and pooled literature

  16. Nontraditional factors influencing the quality of life of hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Diana-Cristina Varela

    2014-06-01

    Full Text Available Introduction: The prevalence of CKD patients in advanced stages with dialysis requirement continues to grow. A goal for the medical team, the patient and their caregivers is to provide a treatment that offers an impact on the prognosis and quality of life (QOL. Methods: In 100 patients with CKD on hemodialysis, randomized assigned, the quality of life by SF-36 was assessed, it was evaluated the functional capacity using the Karnofsky, ability to perform basic tasks of daily life through the index Barthel, presence of depression using the Beck test, family functioning through family APGAR, cognitive state through Minimental and presence of comorbidities using the Charlson index correlated with the sum of physical components (PCS and mental components (MCS of the SF-36 in patients in two renal units in Medellín and Bogotá, Colombia. Results: A decrease in QOL in the physical components (PCS Mental components (MCS regarding the general population. A significant correlation between low PCS and diabetes mellitus (-16 p=0.008 95% CI 2.49 was found. Low MCS showed relation with PTH (p=0.046 95% CI 0.000-0.014, Karnofsky index (p=0.034 95% CI 0.244 to 5.984 and Beck depression test (p=0.000 95% CI -13.606 to 6.253. Conclusions: The QOL of hemodialysis patients is affected with more impact on PCS, there is significant relationship between MCS with functional status and depression. To improve QOL in hemodialysis patients, non traditionally-measured variables should be measured and monitored and the therapeutic focus should be optimized addressed to physical rehabilitation, nutritional, functional and psychological state.

  17. RPL13A and EEF1A1 Are Suitable Reference Genes for qPCR during Adipocyte Differentiation of Vascular Stromal Cells from Patients with Different BMI and HOMA-IR.

    Science.gov (United States)

    Gentile, Adriana-Mariel; Lhamyani, Said; Coín-Aragüez, Leticia; Oliva-Olivera, Wilfredo; Zayed, Hatem; Vega-Rioja, Antonio; Monteseirin, Javier; Romero-Zerbo, Silvana-Yanina; Tinahones, Francisco-José; Bermúdez-Silva, Francisco-Javier; El Bekay, Rajaa

    2016-01-01

    Real-time or quantitative PCR (qPCR) is a useful technique that requires reliable reference genes for data normalization in gene expression analysis. Adipogenesis is among the biological processes suitable for this technique. The selection of adequate reference genes is essential for qPCR gene expression analysis of human Vascular Stromal Cells (hVSCs) during their differentiation into adipocytes. To the best of our knowledge, there are no studies validating reference genes for the analyses of visceral and subcutaneous adipose tissue hVSCs from subjects with different Body Mass Index (BMI) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. The present study was undertaken to analyze this question. We first analyzed the stability of expression of five potential reference genes: CYC, GAPDH, RPL13A, EEF1A1, and 18S ribosomal RNA, during in vitro adipogenic differentiation, in samples from these types of patients. The expression of RPL13A and EEF1A1 was not affected by differentiation, thus being these genes the most stable candidates, while CYC, GAPDH, and 18S were not suitable for this sort of analysis. This work highlights that RPL13A and EEF1A1 are good candidates as reference genes for qPCR analysis of hVSCs differentiation into adipocytes from subjects with different BMI and HOMA-IR.

  18. Characterization CYP1A2, CYP2C9, CYP2C19 and CYP2D6 polymorphisms using HRMA in Psychiatry patients with schizophrenia and bipolar disease for personalized medicine.

    Science.gov (United States)

    Yenilmez, Ebru Dundar; Tamam, Lut; Karaytug, Onur; Tuli, Abdullah

    2018-06-19

    The interindividual genetic variations in drug metabolizing enzymes effects the impact and toxicity in plenty of drugs. The CYP1A2, CYP2C9, CYP2C19 and CYP2D6 gene polymorphisms characterized using high resolution melting analysis (HRMA) in follow-up patients in psychiatry clinic as a preliminary preparation for personalized medicine. Genotyping of CYP1A2*1F, CYP2C9 *2, *3, CYP2C19 *2, *3 and *17 and CYP2D6 *3, *4 was conducted in 101 patients using HRMA. Genotype and allele frequencies of the CYP variants were found to be in equilibrium with the Hardy-Weinberg equation. The frequency of the CYP1A2*1F allele in schizophrenia and bipolar disease was 0.694 and 0.255, respectively. The CYP2C9 allele frequencies were 0.087 (CYP2C9*2), and 0.549 (CYP2C9*3) for bipolar; 0.278 (CYP2C9*2) and 0.648 (CYP2C9*3) in schizophrenias. The CYP2C19*2 and *17 allele frequencies was 0.111 and 0.185 in schizophrenia and variant *2 was 0.117 and variant *17 was 0.255 in bipolar group. The frequency of the CYP2D6*3 allele was 0.027 in schizophrenias. The frequencies for the CYP2D6*4 variant was 0.092 and 0.096 in schizophrenia and bipolar groups, respectively. The knowledge in pharmacogenomics and also the developments in molecular genetics are growing rapidly. In the future this can be expected to provide new methodologies in the prediction of the activity in drug metabolizing enzymes. The HRMA is a rapid and useful technique to identify the genotypes for drug dosage adjustment before therapy in psychiatry patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Comparing the measured basal metabolic rates in patients with chronic disorders of consciousness to the estimated basal metabolic rate calculated from common predictive equations.

    Science.gov (United States)

    Xiao, Guizhen; Xie, Qiuyou; He, Yanbin; Wang, Ziwen; Chen, Yan; Jiang, Mengliu; Ni, Xiaoxiao; Wang, Qinxian; Murong, Min; Guo, Yequn; Qiu, Xiaowen; Yu, Ronghao

    2017-10-01

    Accurately predicting the basal metabolic rate (BMR) of patients in a vegetative state (VS) or minimally conscious state (MCS) is critical to proper nutritional therapy, but commonly used equations have not been shown to be accurate. Therefore, we compared the BMR measured by indirect calorimetry (IC) to BMR values estimated using common predictive equations in VS and MCS patients. Body composition variables were measured using the bioelectric impedance analysis (BIA) technique. BMR was measured by IC in 82 patients (64 men and 18 women) with VS or MCS. Patients were classified by body mass index as underweight (BMR was estimated for each group using the Harris-Benedict (H-B), Schofield, or Cunningham equations and compared to the measured BMR using Bland-Altman analyses. For the underweight group, there was a significant difference between the measured BMR values and the estimated BMR values calculated using the H-B, Schofield, and Cunningham equations (p BMR values estimated using the H-B and Cunningham equations were different significantly from the measured BMR (p BMR in the normal-weight group. The Schofield equation showed the best concordance (only 41.5%) with the BMR values measured by IC. None of the commonly used equations to estimate BMR were suitable for the VS or MCS populations. Indirect calorimetry is the preferred way to avoid either over or underestimate of BMR values. Copyright © 2016. Published by Elsevier Ltd.

  20. Motor Cortex Stimulation in Patients Suffering from Chronic Neuropathic Pain : Summary of Expert Meeting and Premeeting Questionnaire, Combined with Literature Review

    NARCIS (Netherlands)

    Kurt, Erkan; Henssen, Dylan J. H. A.; Steegers, Monique; Staal, Michiel; Beese, Ulrich; Maarrawi, Joseph; Pirotte, Benoit; Garcia-Larrea, Luis; Rasche, Dirk; Vesper, Jan; Holsheimer, Jan; Duyvendak, Wim; Herregodts, Patrick; van Dongen, Robert; Moens, Maarten

    2017-01-01

    BACKGROUND: Motor cortex stimulation (MCS) was introduced in the early 1990s by Tsubokawa and his group for patients diagnosed with drug-resistant, central neuropathic pain. Inconsistencies concerning the details of this therapy and its outcomes and poor methodology of most clinical essays divide

  1. Hospitalization and other risk factors for depressive and anxious symptoms in oncological and non-oncological patients.

    Science.gov (United States)

    De Fazio, Pasquale; Cerminara, Gregorio; Ruberto, Stefania; Caroleo, Mariarita; Puca, Maurizio; Rania, Ornella; Suffredini, Elina; Procopio, Leonardo; Segura-Garcìa, Cristina

    2017-04-01

    Depression and anxiety are common in hospitalized patients. In particular, oncological patients might be vulnerable to depression and anxiety. The aim of this study is to assess and compare different variables and the prevalence of anxiety and depression symptoms between oncological and medically ill inpatients and to identify variables that can influence depressive and anxious symptoms during hospitalization of patients. A total of 360 consecutive hospitalized patients completed the following questionnaires: Hospital Anxiety and Depression Scale (HADS), Patients Health Questionnaire-9, General Health Questionnaire (GHQ-12), 12-Item Short-Form Survey: physical component summary (PCS), and mental component summary (MCS). Patients were divided into oncological patients and non-oncological patients: groups 1 and 2. Only two significant differences were evident between the groups: the PCS of 12-item Short-form Survey was higher in non-oncological patient (p < 0.000), and the GHQ total score was higher in oncological patients. Variables significantly associated with HADS-D ≥ 8 were lower MCS, higher GHQ-12 score, lower PCS, more numerous previous hospitalizations, longer duration of hospitalization, and positive psychiatric family history. Variables significantly associated with HADS-A ≥ 8 were lower MCS, higher GHQ-12 score, positive psychiatric family history, longer duration of hospitalization, and younger age. Anxiety and depression symptoms in concurrent general medical conditions were associated with a specific sociodemographic profile, and this association has implications for clinical care. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Analysis of UGT1A1*28 genotype and SN-38 pharmacokinetics for irinotecan-based chemotherapy in patients with advanced colorectal cancer: results from a multicenter, retrospective study in Shanghai.

    Science.gov (United States)

    Cai, Xun; Cao, Weiguo; Ding, Honghua; Liu, Tianshu; Zhou, Xinli; Wang, Mei; Zhong, Ming; Zhao, Ziyi; Xu, Qing; Wang, Liwei

    2013-09-01

    The UGT1A1*28 polymorphism, although closely linked with CPT-11-related adverse effects, cannot be used alone to guide individualized treatment decisions. However, CPT-11 dosage can be adjusted according to measured SN-38 pharmacokinetics. Our study is designed to investigate whether there is a relationship between SN-38 peak or valley concentrations and efficacy or adverse effects of CPT-11-based chemotherapy. We retrospectively studied 98 patients treated with advanced colorectal cancer in various UGT1A1*28 genotype groups (mainly (TA)6/(TA)6 and (TA)6/(TA)7 genotypes) treated with CPT-11 as first-line chemotherapy in Shanghai. One hundred and sixty-four advanced colorectal cancer patients were enrolled. To understand differences in genotype expression, the frequency of UGT1A1*28 thymine-adenine (TA) repeats in TATA box arrangement was assessed by PCR with genomic DNA extracted from peripheral blood. For ninety-eight cases with the (TA)6/(TA)6 and (TA)6/(TA)7 genotypes treated with CPT-11 as first-line chemotherapy, the plasma concentration of SN-38 was detected by HPLC 1.5 and 49 h after CPT-11 infusion. Efficacy and adverse effects were observed subsequently, and the relationship between SN-38 plasma concentration and efficacy or adverse effects within genotype groups, as well as differences in efficacy and adverse effects between (TA)6/(TA)6 and (TA)6/(TA)7 genotypes were analyzed statistically. One hundred and fourteen patients (69.51 %) were identified with the (TA)6/(TA)6 genotype, forty-eight patients (29.27 %) with the (TA)6/(TA)7 genotype, and two patients (1.22 %) with the (TA)7/(TA)7 genotype. The average peak and valley concentrations of SN-38 after CPT-11 infusion and plasma bilirubin average levels before and after CPT-11 treatment in the (TA)6/(TA)7 genotype group were all higher than those in (TA)6/(TA)6 group, and the difference was statistically significant (p = 0.00). Stepwise regression analysis showed that SN-38 peak and valley

  3. Enhancing clinical communication assessments using an audiovisual BCI for patients with disorders of consciousness

    Science.gov (United States)

    Wang, Fei; He, Yanbin; Qu, Jun; Xie, Qiuyou; Lin, Qing; Ni, Xiaoxiao; Chen, Yan; Pan, Jiahui; Laureys, Steven; Yu, Ronghao; Li, Yuanqing

    2017-08-01

    Objective. The JFK coma recovery scale-revised (JFK CRS-R), a behavioral observation scale, is widely used in the clinical diagnosis/assessment of patients with disorders of consciousness (DOC). However, the JFK CRS-R is associated with a high rate of misdiagnosis (approximately 40%) because DOC patients cannot provide sufficient behavioral responses. A brain-computer interface (BCI) that detects command/intention-specific changes in electroencephalography (EEG) signals without the need for behavioral expression may provide an alternative method. Approach. In this paper, we proposed an audiovisual BCI communication system based on audiovisual ‘yes’ and ‘no’ stimuli to supplement the JFK CRS-R for assessing the communication ability of DOC patients. Specifically, patients were given situation-orientation questions as in the JFK CRS-R and instructed to select the answers using the BCI. Main results. Thirteen patients (eight vegetative state (VS) and five minimally conscious state (MCS)) participated in our experiments involving both the BCI- and JFK CRS-R-based assessments. One MCS patient who received a score of 1 in the JFK CRS-R achieved an accuracy of 86.5% in the BCI-based assessment. Seven patients (four VS and three MCS) obtained unresponsive results in the JFK CRS-R-based assessment but responsive results in the BCI-based assessment, and 4 of those later improved scores in the JFK CRS-R-based assessment. Five patients (four VS and one MCS) obtained usresponsive results in both assessments. Significance. The experimental results indicated that the audiovisual BCI could provide more sensitive results than the JFK CRS-R and therefore supplement the JFK CRS-R.

  4. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial.

    Science.gov (United States)

    Bourke, Stephen C; Tomlinson, Mark; Williams, Tim L; Bullock, Robert E; Shaw, Pamela J; Gibson, G John

    2006-02-01

    Few patients with amyotrophic lateral sclerosis currently receive non-invasive ventilation (NIV), reflecting clinical uncertainty about the role of this intervention. We aimed to assess the effect of NIV on quality of life and survival in amyotrophic lateral sclerosis in a randomised controlled trial. 92 of 102 eligible patients participated. They were assessed every 2 months and randomly assigned to NIV (n=22) or standard care (n=19) when they developed either orthopnoea with maximum inspiratory pressure less than 60% of that predicted or symptomatic hypercapnia. Primary validated quality-of-life outcome measures were the short form 36 mental component summary (MCS) and the sleep apnoea quality-of-life index symptoms domain (sym). Both time maintained above 75% of baseline (T(i)MCS and T(i)sym) and mean improvement (microMCS and microsym) were measured. NIV improved T(i)MCS, T(i)sym, microMCS, microsym, and survival in all patients and in the subgroup with better bulbar function (n=20). This subgroup showed improvement in several measures of quality of life and a median survival benefit of 205 days (p=0.006) with maintained quality of life for most of this period. NIV improved some quality-of-life indices in those with poor bulbar function, including microsym (p=0.018), but conferred no survival benefit. In patients with amyotrophic lateral sclerosis without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy. In patients with severe bulbar impairment, NIV improves sleep-related symptoms, but is unlikely to confer a large survival advantage.

  5. [Beneficial effect of preferred music on cognitive functions in minimally conscious state patients].

    Science.gov (United States)

    Verger, J; Ruiz, S; Tillmann, B; Ben Romdhane, M; De Quelen, M; Castro, M; Tell, L; Luauté, J; Perrin, F

    2014-11-01

    Several studies have shown that music can boost cognitive functions in normal and brain-damaged subjects. A few studies have suggested a beneficial effect of music in patients with a disorder of consciousness but it is difficult to conclude since they did not use quantified measures and a control condition/group. The aim of the present study was to compare the effect of music to that of a continuous sound on the relational behavior of patients in a minimally conscious state (MCS). Behavioral responses of six MCS patients were evaluated using items from the Coma Recovery Scale-Revised. Weekly evaluation sessions were carried out, over four weeks, under two conditions: following the presentation of either the patient's preferred music, or following a continuous sound (control condition). Qualitative and quantitative analyses showed that twelve of the eighteen sessions (66.6%) showed a better result for the music condition than for the control condition. This new protocol suggests that preferred music has a beneficial effect on the cognitive abilities of MCS patients. The results further suggest that cerebral plasticity may be enhanced in autobiographical (emotional and familiar) contexts. These findings should now be further extended with an increased number of patients to further validate the hypothesis of the beneficial effect of music on cognitive recovery. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. NUTRITION-RELATED PREDICTORS OF SLEEP DURATION IN HEMODIALYSIS PATIENTS

    Directory of Open Access Journals (Sweden)

    Jerrilynn Burrowes

    2012-06-01

    At baseline, mean SD was 7.8±2.4 hrs; 33%, 43% and 24% of subjects were in the short, medium and long sleep groups, respectively. In univariate analysis, dietary protein intake, serum albumin, appetite, and QOL measures (mental component score [MCS] and physical component score [PCS] were significant predictors of SD. In multivariate analysis, age (P=0.008, race (White vs. Black (P=0.001, appetite on dialysis days (DD (P=0.0001, MCS and PCS (P<0.0001, respectively were also significant predictors of SD. Younger patients and those with good appetite on DD were more likely to sleep less, whereas Blacks and those with higher MCS and PCS were more likely to sleep more. Of the nutrition variables, higher protein intake and better appetite were associated with long vs. short SD in univariate analysis. In multivariate analysis, appetite on DD was the only variable predictive of SD. The odds ratio (95% CI of having a good appetite for those in the short SD group compared to the medium and long SD groups was 0.81 (0.72, 0.92 and 0.86 (0.78, 0.95, respectively. Further research on SD and appetite and the potential effects of short sleep on inflammation needs to be done in MHD patients.

  7. Predictive factors associated with neck pain in patients with cervical disc degeneration

    Science.gov (United States)

    Kong, Lingde; Tian, Weifeng; Cao, Peng; Wang, Haonan; Zhang, Bing; Shen, Yong

    2017-01-01

    Abstract The predictive factors associated with neck pain remain unclear. We conducted a cross-sectional study to assess predictive factors, especially Modic changes (MCs), associated with the intensity and duration of neck pain in patients with cervical disc degenerative disease. We retrospectively reviewed patients in our hospital from January 2013 to December 2016. Severe neck pain (SNP) and persistent neck pain (PNP) were the 2 main outcomes, and were assessed based on the numerical rating scale (NRS). Basic data, and also imaging data, were collected and analyzed as potential predictive factors. Univariate analysis and multiple logistic regression analysis were performed to assess the predictive factors for neck pain. In all, 381 patients (193 males and 188 females) with cervical degenerative disease were included in our study. The number of patients with SNP and PNP were 94 (24.67%) and 109 (28.61%), respectively. The NRS of neck pain in patients with type 1 MCs was significantly higher than type 2 MCs (4.8 ± 0.9 vs 3.9 ± 1.1; P = .004). The multivariate logistic analysis showed that kyphosis curvature (odds ratio [OR] 1.082, 95% confidence interval [CI] 1.044–1.112), spondylolisthesis (OR 1.339, 95% CI 1.226–1.462), and annular tear (OR 1.188, 95% CI 1.021–1.382) were factors associated with SNP, whereas kyphosis curvature (OR 1.568, 95% CI 1.022–2.394), spondylolisthesis (OR 1.486, 95% CI 1.082–2.041), and MCs (OR 1.152, 95% CI 1.074–1.234) were associated with PNP. We concluded that kyphosis curvature, spondylolisthesis, and annular tear are associated with SNP, whereas kyphosis curvature, spondylolisthesis, and MCs are associated with PNP. This study supports the view that MCs can lead to a long duration of neck pain. PMID:29069048

  8. Relationship between symptom clusters and quality of life in patients at stages 2 to 4 chronic kidney disease in Korea.

    Science.gov (United States)

    Lee, Suk Jeong; Jeon, JaeHee

    2015-11-01

    This study was conducted to identify the relationship between symptom clusters and quality of life (QOL) in patients with stages 2 to 4 chronic kidney disease (CKD) in Korea. Using self-reported questionnaires, data were collected from 143 patients who underwent treatment for CKD at one hospital in Korea. The 17-item Patient Outcome Scale was used to measure symptoms, and the 36-item Short Form Health Survey Instrument Version 2 (SF-36v2) was used to measure the QOL. Data were analyzed using factor analysis to draw symptom clusters. Among five symptom clusters, the energy insufficiency and pain cluster was found to have the highest prevalence and greatest severity. The severity of symptom clusters showed negative correlations with both physical and mental component summary (PCS and MCS) scores. Elderly patients scored low on PCS, whereas younger patients in their 30s and 40s scored low on MCS. Negative correlations were found between symptom clusters and PCS as well as MCS. The severity of symptoms and QOL had stronger relationships with subjective perception of symptoms and psychological factors than with objective clinical indicators. As the effects of physical and psychological symptoms on the QOL in patients with stages 2 to 4 CKD were identified in this study, nurses should develop strategic nursing plans focused on symptom clusters and patients' subjective perception of symptoms rather than objective clinical indicators in order to improve the QOL in patients with CKD. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Quantification of the radio-metabolites of the serotonin-1A receptor radioligand [carbonyl-11C]WAY-100635 in human plasma: An HPLC-assay which enables measurement of two patients in parallel

    International Nuclear Information System (INIS)

    Nics, L.; Hahn, A.; Zeilinger, M.; Vraka, C.; Ungersboeck, J.; Haeusler, D.; Hartmann, S.; Wagner, K-H.; Lanzenberger, R.; Wadsak, W.; Mitterhauser, M.

    2012-01-01

    [Carbonyl- 11 C]WAY-100635 is a potent and effective antagonist for the 5-HT 1A receptor subtype. We aimed to assess the status of [carbonyl- 11 C]WAY-100635 and its main radio-metabolites, [carbonyl- 11 C]desmethyl-WAY-100635 and [carbonyl- 11 C]cyclohexanecarboxylic acid, on the basis of an improved radio-HPLC method. Common methods were characterized by preparative HPLC columns with long runtimes and/or high flow rates. Considering the short half-life of C-11, we developed a more rapid and solvent saving HPLC assay, allowing a fast, efficient and reliable quantification of these major metabolites. - Highlights: ► We developed a HPLC assay which allows the measurement of two patients in parallel. ► It allows a fast and efficient quantification of WAY-100635 and its metabolites. ► Better counting statistics with late samples for modeling the input function is achieved. ► The fastest assay so far is about 40% slower in comparison to the presented method.

  10. Are affective temperaments determinants of quality of life in euthymic patients with bipolar disorder?

    Science.gov (United States)

    Costa, Julio; García-Blanco, Ana; Cañada, Yolanda; García-Portilla, María P; Safont, Gemma; Arranz, Belén; Sanchez-Autet, Mónica; Livianos, Lorenzo; Fornés-Ferrer, Victoria; Sierra, Pilar

    2018-04-01

    Bipolar disorder (BD) is a disabling illness that is associated with low quality of life (QoL). This low QoL goes further than mood episodes, which suggests that stable traits, such as affective temperaments, can cause functional impairment. Our study analyses the impact of affective temperaments on the Physical Component Summary (PCS) and Mental Component Summary (MCS) of QoL in euthymic BD patients. A multicentre study was conducted in 180 euthymic BD patients and 95 healthy controls. Firstly, statistical analyses were performed to compare QoL and affective temperaments between the two groups. Secondly, Adaptive Lasso Analysis was carried out to identify the potential confounding variables and select the affective temperaments as potential predictors on the PCS and MCS of QoL in BD patients, as well as the control group. QoL scores in terms of PCS and MCS in BD patients were significantly lower than in healthy individuals. Whereas anxious temperament, anxiety disorder comorbidity, and age were the best predictors of PCS impairment in BD patients, anxious temperament, subclinical depressive symptoms, and age were the best predictors of MCS impairment. Further longitudinal studies with unaffected high-risk relatives are needed to examine the potential interaction between affective temperament and psychopathology. Anxious temperament has an impact on QoL in BD in terms of both the physical component and the mental component. Systematic screening of temperament in BD would give clinicians better knowledge of QoL predictors. Further research should allow more individualized treatment of BD patients based on temperamental factors. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. The Effect of Socioeconomic Factors on Quality of Life After Treatment in Patients With Head and Neck Cancer

    International Nuclear Information System (INIS)

    Demiral, Ayse Nur; Sen, Mehmet; Demiral, Yuecel; Kinay, Muenir

    2008-01-01

    Purpose: To determine the effect of socioeconomic factors on quality of life (QoL) after treatment in patients with head and neck carcinoma (HNC). Patients and Methods: The study population included 50 HNC patients seen in their control examinations after radiotherapy during a 2-month interval and who were willing to complete the Short-Form 36 QoL questionnaire. Socioeconomic, demographic, and tumor- and treatment-related factors were analyzed for their effect on physical component summary score (PCS) and mental component summary score (MCS) using the Mann-Whitney U test. Results: All patients received radiotherapy, and 33 patients (66%) underwent surgery for the primary tumor and/or neck disease. Chemotherapy was given in 9 patients (18%). Mean PCS and MCS were 47.9 (range, 24.8-59.3) and 46.7 (range, 22-63.3) for the whole patient population. There was no significant factor affecting PCS. Education level of 'middle school or higher,' perceived economic status of 'medium or higher,' social security status of not being 'absent or minimally covered,' and unilateral type of neck surgery were found to increase MCS significantly. According to separate linear regression analyses performed for three socioeconomic variables, the most significant factor for MCS was social security status compared with education level and perceived economic status. It was the only parameter that retained its significance when all five parameters were combined in a linear regression model. Conclusion: This study demonstrated that educational status, perceived economic status, and social security status showed a significant effect on the QoL of HNC patients after radiotherapy. When all variables were taken into account, only 'social security status' remained significant

  12. Role of long-term mechanical circulatory support in patients with advanced heart failure.

    Science.gov (United States)

    Stokes, M B; Bergin, P; McGiffin, D

    2016-05-01

    Advanced heart failure represents a small proportion of patients with heart failure that possess high-risk features associated with high hospital readmission rates, significant functional impairment and mortality. Identification of those who have progressed to, or are near a state of advanced heart failure should prompt referral to a service that offers therapies in mechanical circulatory support (MCS) and cardiac transplantation. MCS has grown as a management strategy in the care of these patients, most commonly as a bridge to cardiac transplantation. The predominant utilisation of MCS is implantation of left ventricular assist devices (LVAD), which have evolved significantly in their technology and application over the past 15-20 years. The technology has evolved to such an extent that Destination Therapy is now being utilised as a strategy in management of advanced heart failure in appropriately selected patients. Complication rates have decreased with VAD implantation, but remain a significant consideration in the decision to implant a device, and in the follow up of these patients. © 2016 Royal Australasian College of Physicians.

  13. Evaluation of Health-Related Quality of Life among Tuberculosis Patients in Two Cities in Yemen.

    Science.gov (United States)

    Jaber, Ammar Ali Saleh; Khan, Amer Hayat; Syed Sulaiman, Syed Azhar; Ahmad, Nafees; Anaam, Mohamed Saif

    2016-01-01

    The health-related quality of life (HRQoL) of Tuberculosis (TB) patients is important because it directly influences the outcome of TB patients in several aspects. The current study aims to evaluate and to find the factors influencing the HRQoL of TB patients in two major TB-prevalent cities (Taiz and Alhodidah) in Yemen. A prospective study was conducted, and all TB patients meeting the HRQoL criteria were asked to complete the HRQoL SF-36 survey. The records of TB patients were examined for disease confirmation, and a follow-up was consequently performed for patients during treatment between March 2013 and February 2014 in Taiz and Alhodidah Cities. HRQol scores were calculated by using QM scoring software version 4.5, in which the physical component score (PCS) and mental component score (MCS) were obtained. The scores obtained between 47-53 normal based score (NBS) were considered equivalent to the US normal score. Low scores indicate the poor health situation of TB patients. A total of 243 TB patients enrolled in the study at the beginning of the treatment. A total of 235 and 197 TB patients completed the questionnaire at the end of the intensive phase (I.P.) and continuation phase (C.P.), respectively. The final dropout rate was 16.2%. The mean PCS and MCS scores at the beginning of treatment were low, thus showing the poor health situation of TB patients. The mean PCS scores at the beginning of treatment, end of I.P., and end of treatment were (36.1), (44.9), and (48), respectively. Moreover, the mean MCS score at the beginning of treatment, end of I.P., and end of treatment were (35.1), (42.2), and (44.3), respectively. The result shows that significant increases are observed at the end of I.P. for PCS and MCS because of the treatment and slight changes at the end of C.P. Despite this finding, the MCS score remains below the normal range (47), thus indicating a significant risk of depression among TB patients. Furthermore, general linear repeated measure

  14. Psychopharmacology of 5-HT1A receptors

    International Nuclear Information System (INIS)

    Cowen, Philip J.

    2000-01-01

    Serotonin 1A (5-HT 1A ) receptors are located on both 5-HT cell bodies where they act as inhibitory autoreceptors and at postsynaptic sites where they mediate the effects of 5-HT released from nerve terminals. The sensitivity of 5-HT 1A receptors in humans can be measured using the technique of pharmacological challenge. For example, acute administration of a selective 5-HT 1A receptor agonist, such as ipsapirone, decreases body temperature and increases plasma cortisol through activation of pre- and postsynaptic 5-HT 1A receptors, respectively. Use of this technique has demonstrated that unmedicated patients with major depression have decreased sensitivity of both pre- and postsynaptic 5-HT 1A receptors. Treatment with selective serotonin reuptake inhibitors further down-regulates 5-HT 1A receptor activity. Due to the hypotheses linking decreased sensitivity of 5-HT 1A autoreceptors with the onset of antidepressant activity, there is current interest in the therapeutic efficacy of combined treatment with selective serotonin reuptake inhibitors and 5-HT 1A receptor antagonists

  15. Prospectively surveying health-related quality of life and symptom relief in a lot-based sample of medical cannabis-using patients in urban Washington State reveals managed chronic illness and debility.

    Science.gov (United States)

    Aggarwal, S K; Carter, G T; Sullivan, M D; Zumbrunnen, C; Morrill, R; Mayer, J D

    2013-09-01

    To characterize health-related quality of life (HRQoL) in medical cannabis patients. Short Form 36 (SF-36) Physical Health Component Score and Mental Health Component Score (MCS) surveys as well has CDC (Centers for Disease Control) HRQoL-14 surveys were completed by 37 qualified patients. Mean SF-36 PCS and MCS, normalized at 50, were 37.4 and 44.2, respectively. Eighty percent of participants reported activity/functional limitations secondary to impairments or health problems. Patients reported using medical cannabis to treat a wide array of symptoms across multiple body systems with relief ratings consistently in the 7-10/10 range. The HRQoL results in this sample of medical cannabis-using patients are comparable with published norms in other chronically ill populations. Data presented provide insight into medical cannabis-using patients' self-rated health, HRQoL, disease incidences, and cannabis-related symptom relief.

  16. Adherence and Quality of Life of Hypertension Patients in Gunung Jati Hospital, Cirebon, Indonesia

    Directory of Open Access Journals (Sweden)

    Dyah A.Perwitasari

    2015-12-01

    Full Text Available The treatment effectiveness of hypertension could be influenced by patients’ characteristics and patients’ adherence with medication. Besides reaching the goal of blood pressure decrease after the treatment, their quality of life has become the main concern regarding effectiveness of hypertension treatment. This study aimed to explore the hypertension patients’ adherence and quality of life. In addition, it was studied which factors associated with adherence and quality of life in hypertension patients treated with antihypertensive at Gunung Jati Hospital, Cirebon. We recruited 85 adult hypertension patients who were treated with antihypertensive agents for at least 6 months. The patients’ adherence was measured by Medication Adherence Report Scale and the patients’ quality of life was measured by Indonesian version of Short Form-36 questionnaire. The patients’ adherence was found as 24.03 (SD: 1.98 and there were no significant differences of patients’ adherence using monotherapy and combination therapy. The patients’ characteristics such as, age, gender and education level could not predict patients’ adherence (p>0.05. The average of Physical Component Summary (PCS and Mental Component Summary (MCS were 43.35 (SD: 9.4 and 52.13 (SD:5.59. Age and gender may predict PCS, however, education and comorbidity may predict MCS (p<0.05. Hypertension patients’ adherence in Gunung Jati hospital is good. The PCS and MCS scores in this study are comparable to the other previous studies. The patients’ characteristic could not be the predictor of patients’ adherence.

  17. A phase IIa randomised clinical study of GNbAC1, a humanised monoclonal antibody against the envelope protein of multiple sclerosis-associated endogenous retrovirus in multiple sclerosis patients.

    Science.gov (United States)

    Derfuss, Tobias; Curtin, François; Guebelin, Claudia; Bridel, Claire; Rasenack, Maria; Matthey, Alain; Du Pasquier, Renaud; Schluep, Myriam; Desmeules, Jules; Lang, Alois B; Perron, Hervé; Faucard, Raphael; Porchet, Hervé; Hartung, Hans-Peter; Kappos, Ludwig; Lalive, Patrice H

    2015-06-01

    GNbAC1 is an immunoglobulin (IgG4) humanised monoclonal antibody against multiple sclerosis-associated retrovirus (MSRV)-Env, a protein of endogenous retroviral origin, expressed in multiple sclerosis (MS) lesions, which is pro-inflammatory and inhibits oligodendrocyte precursor cell differentiation. This is a randomised, double-blind placebo-controlled dose-escalation study followed by a six-month open-label phase to test GNbAC1 in MS patients. The primary objective was to assess GNbAC1 safety in MS patients, and the other objectives were pharmacokinetic and pharmacodynamic assessments. Ten MS patients were randomised into two cohorts to receive a single intravenous infusion of GNbAC1/placebo at doses of 2 or 6 mg/kg. Then all patients received five infusions of GNbAC1 at 2 or 6 mg/kg at four-week intervals in an open-label setting. Safety, brain magnetic resonance imaging (MRI), pharmacokinetics, immunogenicity, cytokines and MSRV RNA expression were studied. All patients completed the study. GNbAC1 was well tolerated in all patients. GNbAC1 pharmacokinetics is dose-linear with mean elimination half-life of 27-37 d. Anti-GNbAC1 antibodies were not detected. Cytokine analysis did not indicate an adverse effect. MSRV-transcripts showed a decline after the start of treatment. Nine patients had stable brain lesions at MRI. The safety, pharmacokinetic profile, and pharmacodynamic responses to GNbAC1 are favourable in MS patients over a six-month treatment period. © The Author(s) 2014.

  18. Fatigue, mood and quality of life improve in MS patients after progressive resistance training

    DEFF Research Database (Denmark)

    Dalgas, U; Stenager, E; Jakobsen, J

    2010-01-01

    Fatigue occurs in the majority of multiple sclerosis patients and therapeutic possibilities are few. Fatigue, mood and quality of life were studied in patients with multiple sclerosis following progressive resistance training leading to improvement of muscular strength and functional capacity...... disabled (Expanded Disability Status Scale, EDSS: 3-5.5) multiple sclerosis patients including a Control group (n = 15) and an Exercise group (n = 16). Fatigue (FSS > 4) was present in all patients. Scores of FSS, MDI, PCS-SF36 and MCS-SF36 were comparable at start of study in the two groups. Fatigue...

  19. Daclatasvir/peginterferon lambda-1a/ribavirin in patients with chronic HCV infection and haemophilia who are treatment naïve or prior relapsers to peginterferon alfa-2a/ribavirin.

    Science.gov (United States)

    Santagostino, E; Pol, S; Olveira, A; Reesink, H W; van Erpecum, K; Bogomolov, P; Xu, D; Critelli, L; Srinivasan, S; Cooney, E

    2016-09-01

    This study explores the potential role of a novel interferon-containing regimen for treatment of patients with chronic hepatitis C (CHC) and underlying haemophilia. This trial (NCT01741545) was an open-label, non-randomized phase 3 study, which included adult haemophiliacs with hepatitis C virus (HCV). Patients with HCV genotypes (GT)-2 or -3 were treated with Lambda-IFN/ribavirin (RBV)/daclatasvir (DCV) for 12 weeks (cohort A). Patients with HCV GT-1b or -4 were treated with Lambda-IFN/RBV/DCV for 12 weeks, followed by Lambda-IFN/RBV for an additional 12 weeks (cohort B). The primary endpoint was the proportion of patients with a sustained virologic response at post-treatment follow-up week 12 (SVR12). Clinical development of Lambda-IFN was discontinued during this trial leading to study termination before a 24-week post-treatment follow-up was obtained for all participants. Overall, 51 patients were treated (cohort A, n = 12; cohort B, n = 39). The proportion of patients achieving SVR12 was 92% in cohort A and 90% in cohort B. Therapy was generally well tolerated. The most common adverse events (AEs) were related to elevations in serum transaminases and/or bilirubin. Five serious AEs, four discontinuations due to AEs, and no deaths were reported. The rate of grade 3-4 bilirubin elevations was 17-18% across cohorts. Lambda-IFN/RBV/DCV treatment demonstrated a high SVR rate and was generally well tolerated with a safety profile consistent with expectations for this special patient population. This study supports use of DCV as part of a combination treatment regimen for haemophiliacs with CHC. © 2016 John Wiley & Sons Ltd.

  20. Assessment of health-related quality of life and its determinants in patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    M Manavalan

    2017-01-01

    Full Text Available Health-related quality of life is an important, yet neglected aspect of chronic kidney disease (CKD care. We evaluated the quality of life and its determinants across CKD 3 to 5D using a kidney disease specific tool (Kidney Disease Quality of Life-SF™ in an underprivileged, predominantly rural population with high rates of illiteracy and unemployment. The scores of individual domains were summarized to three composite scores – physical composite summary (PCS, mental composite summary (MCS, and kidney disease component summary score (KDCS. A total number of 204 participants were recruited from nephrology outpatient clinics. About 68.1% of participants were males. The mean age of the study population was 49.14 ± 13.63 years. There was a high proportion of illiteracy (36.3% and unemployment (80.9%. KDCS showed a significant decline (P = 0.01 from CKD 3 to CKD 5D whereas MCS and PCS showed a nonsignificant decrease. There was no difference in KDCS, PCS, or MCS scores between patients treated by hemodialysis and CAPD. Illiteracy and unemployment were associated with significantly lower KDCS, PCS, and MCS scores. Age ≥50 years was associated with poor PCS (29.49 ± 8.20 vs. 34.17 ± 9.99 ; P< 0.001. Hemoglobin <10 g/dL was associated with poor KDCS (58.93 ± 13.09 vs. 65.55 ± 13.38 ; P< 0.001 and PCS (29.56 ± 8.13 vs. 33.37 ± 9.82; P< 0.001. The presence of comorbidities such as diabetes and hypertension had no impact on the composite scores. KDCS, MCS, or PCS scores did not vary among patients having high serum phosphorus (≥4.5 mg/dL, low albumin (<3.5 g/dL, and elevated parathyroid hormone (≥150 pg/ml. On multiple linear regression analysis, the predictors of KDCS were unemployment (P < 0.001 and illiteracy (P = 0.03. Unemployment (P < 0.001 and age (P < 0.001 were predictors of PCS whereas literacy level (P < 0.001 was predictive of MCS.

  1. Enterovirus Exposure Uniquely Discriminates Type 1 Diabetes Patients with a Homozygous from a Heterozygous Melanoma Differentiation-Associated Protein 5/Interferon Induced with Helicase C Domain 1 A946T Genotype.

    Science.gov (United States)

    Schulte, Barbara M; Gielen, Paul R; Kers-Rebel, Esther D; Prosser, Amy C; Lind, Katharina; Flodström-Tullberg, Malin; Tack, Cees J; Elving, Lammy D; Adema, Gosse J

    2016-09-01

    In children at risk for type 1 diabetes, innate immune activity is detected before seroconversion. Enterovirus infections have been linked to diabetes development, and a polymorphism (A946T) in the innate immune sensor recognizing enterovirus RNA, interferon-induced with helicase C domain 1/melanoma differentiation-associated protein 5, predisposes to disease. We hypothesized that the strength of innate antienteroviral responses is affected in autoimmune type 1 diabetes patients and linked to the A946T polymorphism. We compared induction of interferon-stimulated genes (ISGs) in peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) in healthy individuals and diabetes patients upon stimulation with enterovirus, enterovirus-antibody complexes, or ligands mimicking infection in relation to the A946T polymorphism. Overall, PBMCs of diabetes patients and healthy donors showed comparable ISG induction upon stimulation. No differences were observed in DCs. Interestingly, the data imply that the magnitude of responses to enterovirus and enterovirus-antibody complexes in PBMCs is critically influenced by the A946T polymorphism and elevated in heterozygotes compared to TT homozygous individuals in autoimmune diabetes patients, but not healthy controls. These data imply an intrinsic difference in the responses to enterovirus and enterovirus-antibody complexes in diabetes patients carrying a TT risk genotype compared to heterozygotes that may influence control of enterovirus clearance.

  2. Denture quality has a minimal effect on health-related quality of life in patients with removable dentures.

    Science.gov (United States)

    Inoue, M; John, M T; Tsukasaki, H; Furuyama, C; Baba, K

    2011-11-01

    The present study examined the association of denture quality and health-related quality of life (HRQoL) in patients with removable dentures. In a study of 171 consecutive patients with removable partial dentures or complete dentures (mean age: 68·0 ± 9·3 years) at a university-based prosthodontic clinic, dentists rated two aspects of denture quality (stability and aesthetics) using a 100-mm visual analog scale (VAS). HRQoL was evaluated using the mental and physical component summary (MCS and PCS) scores of the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36). Oral health-related quality of life (OHRQoL) was evaluated using the Oral Health Impact Profile-Japanese version (OHIP-J). The associations among denture quality, OHRQoL, and HRQoL were examined by linear regression models. Bivariable linear regression analyses revealed that denture stability was significantly associated with the SF-36 MCS [regression coefficient = 0·52 for a 10-unit increase in denture stability on a 0-100 VAS, 95% confidence interval (CI): 0·03-1·00, P = 0·04], but not with the PCS (0·11, 95% CI: -0·49 to 0·70). Denture aesthetics was not related to the PCS or the MCS (0·22, 95% CI: -0·44 to 0·88 or 0·07, 95%CI: -0·47 to 0·62). When OHIP-J was added to the regression model, this variable was substantially and significantly associated with the MCS and PCS summary scores; in addition, the regression coefficient for denture quality decreased in magnitude and was statistically nonsignificant in all analyses. The quality of removable dentures had a minimal effect on HRQoL in patients with removable dentures, and this association was mediated by OHRQoL. © 2011 Blackwell Publishing Ltd.

  3. LETM1, a novel gene encoding a putative EF-hand Ca(2+)-binding protein, flanks the Wolf-Hirschhorn syndrome (WHS) critical region and is deleted in most WHS patients.

    Science.gov (United States)

    Endele, S; Fuhry, M; Pak, S J; Zabel, B U; Winterpacht, A

    1999-09-01

    Deletions within human chromosome 4p16.3 cause Wolf-Hirschhorn syndrome (WHS), which is characterized by severe mental and developmental defects. It is thought that haploinsufficiency of more than one gene contributes to the complex phenotype. We have cloned and characterized a novel gene (LETM1) that is deleted in nearly all WHS patients. LETM1 encodes a putative member of the EF-hand family of Ca(2+)-binding proteins. The protein contains two EF-hands, a transmembrane domain, a leucine zipper, and several coiled-coil domains. On the basis of its possible Ca(2+)-binding property and involvement in Ca(2+) signaling and/or homeostasis, we propose that haploinsufficiency of LETM1 may contribute to the neuromuscular features of WHS patients. Copyright 1999 Academic Press.

  4. Abnormal corticospinal excitability in patients with disorders of consciousness.

    Science.gov (United States)

    Lapitskaya, Natallia; Gosseries, Olivia; De Pasqua, Victor; Pedersen, Asger Roer; Nielsen, Joergen Feldbaek; de Noordhout, Alain Maertens; Laureys, Steven

    2013-07-01

    Transcranial magnetic stimulation (TMS) has been frequently used to explore changes in the human motor cortex in different conditions, while the extent of motor cortex reorganization in patients in vegetative state (VS) (now known as unresponsive wakefulness syndrome, UWS) and minimally conscious (MCS) states due to severe brain damage remains largely unknown. It was hypothesized that cortical motor excitability would be decreased and would correlate to the level of consciousness in patients with disorders of consciousness. Corticospinal excitability was assessed in 47 patients (24 VS/UWS and 23 MCS) and 14 healthy controls. The test parameters included maximal peak-to-peak M-wave (Mmax), F-wave persistence, peripheral and central motor conduction times, sensory (SEP) and motor evoked (MEP) potential latencies and amplitudes, resting motor threshold (RMT), stimulus/response curves, and short latency afferent inhibition (SAI). TMS measurements were correlated to the level of consciousness (assessed using the Coma Recovery Scale-Revised). On average, the patient group had lower Mmax, lower MEP and SEP amplitudes, higher RMTs, narrower stimulus/response curves, and reduced SAI compared to the healthy controls (P < 0.05). The SAI alterations were correlated to the level of consciousness (P < 0.05). The findings demonstrated the impairment of the cortical inhibitory circuits in patients with disorders of consciousness. Moreover, the significant relationship was found between cortical inhibition and clinical consciousness dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Alteration in the Expression of Cytochrome P450s (CYP1A1, CYP2E1, and CYP3A11 in the Liver of Mouse Induced by Microcystin-LR

    Directory of Open Access Journals (Sweden)

    Bangjun Zhang

    2015-03-01

    Full Text Available Microcystins (MCs are cyclic heptapeptide toxins and can accumulate in the liver. Cytochrome P450s (CYPs play an important role in the biotransformation of endogenous substances and xenobiotics in animals. It is unclear if the CYPs are affected by MCs exposure. The objective of this study was to evaluate the effects of microcystin-LR (MCLR on cytochrome P450 isozymes (CYP1A1, CYP2E1, and CYP3A11 at mRNA level, protein content, and enzyme activity in the liver of mice the received daily, intraperitoneally, 2, 4, and 8 µg/kg body weight of MCLR for seven days. The result showed that MCLR significantly decreased ethoxyresorufin-O-deethylase (EROD (CYP1A1 and erythromycin N-demthylase (ERND (CYP3A11 activities and increased aniline hydroxylase (ANH activity (CYP2E1 in the liver of mice during the period of exposure. Our findings suggest that MCLR exposure may disrupt the function of CYPs in liver, which may be partly attributed to the toxicity of MCLR in mice.

  6. Assessment of quality of life and functional outcome in patients sustaining moderate and major trauma: a multicentre, prospective cohort study.

    Science.gov (United States)

    Rainer, T H; Yeung, J H H; Cheung, S K C; Yuen, Y K Y; Poon, W S; Ho, H F; Kam, C W; Cattermole, G N; Chang, A; So, F L; Graham, C A

    2014-05-01

    Trauma care systems aim to reduce both death and disability, yet there is little data on post-trauma health status and functional outcome. To evaluate baseline, discharge, six month and 12 month post-trauma quality of life, functional outcome and predictors of quality of life in Hong Kong. Multicentre, prospective cohort study using data from the trauma registries of three regional trauma centres in Hong Kong. Trauma patients with an ISS≥9 and aged≥18 years were included. The main outcome measures were the physical component summary (PCS) score and mental component summary (MCS) scores of the Short-Form 36 (SF36) for health status, and the extended Glasgow Outcome Scale (GOSE) for functional outcome. Between 1 January 2010 and 31 September 2010, 400 patients (mean age 53.3 years; range 18-106; 69.5% male) were recruited to the study. There were no statistically significant differences in baseline characteristics between responders (N=177) and surviving non-responders (N=163). However, there were significant differences between these groups and the group of patients who died (N=60). Only 16/400 (4%) cases reported a GOSE≥7. 62/400 (15.5%) responders reached the HK population norm for PCS. 125/400 (31%) responders reached the HK population norm for MCS. If non-responders had similar outcomes to responders, then the percentages for GOSE≥7 would rise from 4% to 8%, for PCS from 15.5% to 30%, and for MCS from 31% to 60%. Univariate analysis showed that 12-month poor quality of life was significantly associated with age>65 years (OR 4.77), male gender (OR 0.44), pre-injury health problems (OR 2.30), admission to ICU (OR 2.15), ISS score 26-40 (OR 3.72), baseline PCS (OR 0.89), one-month PCS (OR 0.89), one-month MCS (OR 0.97), 6-month PCS (OR 0.76) and 6-month MCS (OR 0.97). For patients sustaining moderate or major trauma in Hong Kong at 12 months after injury<1 in 10 patients had an excellent recovery, ≤3 in 10 reached a physical health status score

  7. Patients in a vegetative state following traumatic brain injury display a reduced intracortical modulation.

    Science.gov (United States)

    Bagnato, Sergio; Boccagni, Cristina; Sant'Angelo, Antonino; Prestandrea, Caterina; Rizzo, Silvia; Galardi, Giuseppe

    2012-10-01

    Patients in coma who fail to wake develop a condition known as a vegetative state (VS). While we know that some cortical activities exist in patients in VS, it remains unclear whether interneuronal modulation can be abnormal in the cerebral cortex of these patients. The aim of the study was to evaluate the inhibitory and excitatory interneuronal circuits in patients in VS following a traumatic brain injury. Cortical excitability was studied in 5 VS patients and in 10 healthy subjects using paired pulses transcranial magnetic stimulation (TMS). Resting motor threshold and intracortical inhibition and facilitation at short intervals (2 and 10 ms, respectively) were evaluated. Two patients were studied again after their level of consciousness transitioned into a minimally conscious state (MCS). Both intracortical inhibition and facilitation were significantly reduced in patients compared to healthy subjects (p<0.05). In addition, these results did not significantly change in the 2 patients who evolved into a MCS. This is the first report showing an abnormal cortical excitability in patients in VS. Our findings suggest a pathophysiological base for future work aiming to restore the lack of interneuronal transmission in patients in VS. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  8. How much do cancer-related symptoms contribute to health-related quality of life in lung and colorectal cancer patients? A report from the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium.

    Science.gov (United States)

    Kenzik, Kelly M; Ganz, Patricia A; Martin, Michelle Y; Petersen, Laura; Hays, Ron D; Arora, Neeraj; Pisu, Maria

    2015-08-15

    The objective of this study was to examine associations of symptoms with physical and mental health-related quality of life (HRQOL) in patients with colorectal cancer (CRC) and in patients with lung cancer. Patients with newly diagnosed CRC (n = 3040) or lung cancer (n = 2297) who were participating in the Cancer Care Outcomes Research and Surveillance Consortium study completed surveys on general HRQOL and symptoms. HRQOL was measured by using physical component summary (PCS) and mental component summary (MCS) scores on the Medical Outcomes Study 12-item short-form heath survey. Nonspecific cancer symptoms were measured using items from the European Organization for Research and Treatment of Cancer core quality-of-life questionnaire. Cancer type-specific modules developed by the European Organization for Research and Treatment of Cancer were used to assess CRC-specific and lung cancer-specific symptoms. For both cancer types, linear regression models that were controlled for demographic and clinical information were used to examine correlations of nonspecific and cancer-specific symptoms with PCS and MCS scores. PCS scores for patients with CRC and lung cancer were below the general population norm of 50 (43 and 37, respectively), and MCS scores were at the population norm. For the CRC sample, in the model that included both symptom indices, an increase in nonspecific symptoms was more strongly associated with lower PCS and MCS scores than an increase in CRC-specific symptoms (PCS, standardized coefficient [β] = -0.41 vs -0.09; MCS, β = -0.38 vs -0.08). In a similar model for lung cancer, increases in lung cancer-specific symptoms were more strongly associated with lower PCS scores (β = -0.34 vs -0.20), whereas nonspecific symptoms were more strongly associated with lower MCS scores (β = -0.34 vs -0.14). Symptoms were associated with HRQOL impairments in recently diagnosed patients. Additional supportive care implemented early in cancer care

  9. Effectiveness of postoperative radiotherapy in patients with small oral and oropharyngeal squamous cell carcinoma and concomitant ipsilateral singular cervical lymph node metastasis (pN1). A meta-analysis

    International Nuclear Information System (INIS)

    Moergel, Maximilian; Meurer, Philipp; Al-Nawas, Bilal; Wendt, Thomas G.

    2011-01-01

    The positive effect of radiation therapy for patients with advanced oropharyngeal squamous cell carcinoma (OSCC) has been substantially verified. The present work investigated whether a meta-analysis of current data is able to evaluate the effectiveness of postoperative radiotherapy (PORT) in patients with small OSCC (pT1, pT2) and a single ipsilateral lymph node metastasis (pN1). The meta-analysis comprises randomized and non-randomized studies. High-risk tumors were excluded and defined by size ≥ pT3/pT4, lymph node involvement ≥ pN2, or presence of additional histological risk factors, e.g., involved positive resection margins, extra nodal spread of the disease, or lymphangiosis carcinomatosa. The primary outcome analyzed mortality between the different treatment arms. Only one prospective randomized clinical trial and six retrospective observational studies were adequate for evaluation. Descriptive analysis revealed a marginally higher mortality in the irradiation group (44% vs. 34%). In contrast, a forest plot presentation of two of seven studies with and without events in the control and therapy arms presented an advantage for the irradiation group with the limitation of large heterogeneity and a lack of statistical significance. Present data are poor and exhibit limited internal and external validity; thus, direct comparison was not possible with the eligible studies. Therefore, a meta-analysis of present data may not serve as the basis for a general treatment recommendation but underlines the need of prospective, randomized, controlled clinical trials. (orig.)

  10. Evaluation of functional health and well-being in patients receiving levomilnacipran ER for the treatment of major depressive disorder.

    Science.gov (United States)

    Blum, Steven I; Tourkodimitris, Stavros; Ruth, Adam

    2015-01-01

    Levomilnacipran extended-release (ER) is an FDA-approved serotonin norepinephrine reuptake inhibitor (SNRI) for treating major depressive disorder (MDD). SF-36v2 Health Survey outcomes from a Phase III, randomized, double-blind, placebo-controlled study (NCT00969709) were evaluated. Prospective and post hoc analyses of SF-36 Mental and Physical Component Summaries (MCS, PCS), and individual domains compared pooled levomilnacipran ER doses (40, 80, 120 mg/day) with placebo. Patients (18-65 years) had MDD, depressive episode ≥ 8 weeks, and Montgomery-Åsberg Depression Rating Scale total score ≥ 30. SF-36 score changes from baseline to Week 8 were analyzed using ANCOVA and the observed cases approach (Intent-to-Treat [ITT] Population). Minimally important differences (MID) evaluated clinical relevance. Baseline MCS scores reflected marked mental deficits in the ITT Population (levomilnacipran ER = 529; placebo = 175). MCS change at Week 8 was significantly greater for levomilnacipran ER than placebo (LSMD [SE] = 4.8 [1.5]; P = 0.0011); MID exceeded the 3-point threshold. Baseline PCS scores suggested minimal physical deficits; no between-group difference at Week 8 was noted. LSMD was nominally statistically significant (P Health [2.44; P = 0.0010], Vitality [2.48; P = 0.0307], Social Functioning [3.25; P = 0.0097], Role-Emotional [3.38; P = 0.0078], Mental Health [4.34; P = 0.0005]); changes in Vitality, Social Functioning, and Mental Health exceeded MID. The trial was limited by short duration; analyses were post hoc and adjustments were not made for multiplicity. Statistically significant and clinically meaningful improvement on the MCS and several individual domains suggest overall and dimensional improvement in health-related functioning for patients with MDD treated with levomilnacipran ER versus placebo. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  11. The changes of regional cerebral blood flow: successful pain relief of intractable CRPS type II patients by motor cortex stimulation

    International Nuclear Information System (INIS)

    Jung, J. A.; Son, H. S.; Kim, S. H.; Jung, S. G

    2004-01-01

    Authors report the effectiveness of MCS in extraordinarily extended pain due to intractable CRPS type II and rCBF study result for mechanism of pain control by MCS. A 43-year-old male presented severe spontaneous burning pain in his left hand and forearm and allodynia over the left arm and left hemibody. Authors planned MCS as a neuromodulation therapy for this intractable peripheral neuropathic pain patient because further neurodestructive procedure did not work anymore and have a potential risk of further aggrevation of neuopathic pain. We performed baseline and stimulation brain perfusion SPECT using 20 mCi of Tc-99m ECD. The baseline CBD studies were done with stimulator 'off' state and stimulation studies were done after stimulator 'on' with satisfactory pain relief. For the stimulation study, the radioisotope was injected immediately after pain-relief and the images were taken about 50 minutes after injection of radioisotope. In resting rCBF in the patient was compared with normal control datas, we found significant increase in rCBF in the bilateral prefrontal cortex, right dorsolateral prefrontal cortex, right superior temporal gyrus, left temporooccipital area. When rCBF datas obtained after alleviation of pain with stimulator 'on' . there were significant increase in rCBF in bilateral prefrontal cortex and left temporoocipital area. After subtraction of ECD SPECT, we found significant increase in rCBF in the right premotor and supplementary motor cortex left sensorimotor cortex, right cingulated cortex, right posterior insular cortex, right anterior limb of internal capsule. left orbitofrontal cortex and right pyramidal tract in cerebral peduncle. Authors report exellent pain control by MCS in a case of severe CRPS type II with hemibody involvement and regional cerebral blood flow changes according to successful pain control

  12. The changes of regional cerebral blood flow: successful pain relief of intractable CRPS type II patients by motor cortex stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Jung, J. A.; Son, H. S.; Kim, S. H.; Jung, S. G [The Catholic University of Korea, Seoul (Korea, Republic of)

    2004-07-01

    Authors report the effectiveness of MCS in extraordinarily extended pain due to intractable CRPS type II and rCBF study result for mechanism of pain control by MCS. A 43-year-old male presented severe spontaneous burning pain in his left hand and forearm and allodynia over the left arm and left hemibody. Authors planned MCS as a neuromodulation therapy for this intractable peripheral neuropathic pain patient because further neurodestructive procedure did not work anymore and have a potential risk of further aggrevation of neuopathic pain. We performed baseline and stimulation brain perfusion SPECT using 20 mCi of Tc-99m ECD. The baseline CBD studies were done with stimulator 'off' state and stimulation studies were done after stimulator 'on' with satisfactory pain relief. For the stimulation study, the radioisotope was injected immediately after pain-relief and the images were taken about 50 minutes after injection of radioisotope. In resting rCBF in the patient was compared with normal control datas, we found significant increase in rCBF in the bilateral prefrontal cortex, right dorsolateral prefrontal cortex, right superior temporal gyrus, left temporooccipital area. When rCBF datas obtained after alleviation of pain with stimulator 'on' . there were significant increase in rCBF in bilateral prefrontal cortex and left temporoocipital area. After subtraction of ECD SPECT, we found significant increase in rCBF in the right premotor and supplementary motor cortex left sensorimotor cortex, right cingulated cortex, right posterior insular cortex, right anterior limb of internal capsule. left orbitofrontal cortex and right pyramidal tract in cerebral peduncle. Authors report exellent pain control by MCS in a case of severe CRPS type II with hemibody involvement and regional cerebral blood flow changes according to successful pain control.

  13. A fast data acquisition system for PHA and MCS measurements

    International Nuclear Information System (INIS)

    Eijk, P.J.A. van; Keyser, C.J.; Rigterink, B.J.; Hasper, H.

    1985-01-01

    A microprocessor controlled data acquisition system for pulse height analysis and multichannel scaling is described. A 4K x 24 bit static memory is used to obtain a fast data acquisition rate. The system can store 12 bit ADC or TDC data within 150 ns. Operating commands can be entered via a small keyboard or by a RS-232-C interface. An oscilloscope is used to display a spectrum. The display of a spectrum or the transmission of spectrum data to an external computer causes only a short interruption of a measurement in progress and is accomplished by using a DMA circuit. The program is written in Modular Pascal and is divided into 15 modules. These implement 9 parallel processes which are synchronized by using semaphores. Hardware interrupts from the data acquisition, DMA, keyboard and RS-232-C circuits are used to signal these processes. (orig.)

  14. Quality of life is modestly improved in older patients with mild primary hyperparathyroidism postoperatively: results of a prospective multicenter study.

    Science.gov (United States)

    Blanchard, Claire; Mathonnet, Muriel; Sebag, Frédéric; Caillard, Cécile; Kubis, Caroline; Drui, Delphine; van Nuvel, Elise; Ansquer, Catherine; Henry, Jean-François; Masson, Damien; Kraeber-Bodéré, Françoise; Hardouin, Jean-Benoît; Zarnegar, Rasa; Hamy, Antoine; Mirallié, Eric

    2014-10-01

    The objectives of this study were to evaluate, in mild primary hyperparathyroidism (pHPT) patients, the quality of life (QoL) using the SF-36 questionnaire before and after parathyroidectomy and to detect preoperatively patients who benefit the most from surgery. Most pHPT patients present a mild pHPT defined by calcemia ≤11.4 mg/dL. For these patients, there is debate about whether they should be managed with surveillance, medical therapy, or surgery. A prospective multicenter study investigated QoL (SF-36) in patients with mild pHPT before and after parathyroidectomy in four university hospitals. Laboratory results and SF-36 scores were obtained preoperatively and postoperatively (3, 6, and 12 months). One hundred sixteen patients were included. After surgery, the biochemical cure rate was 98%. Preoperatively, the mental component summary and the physical component summary (PCS) were 38.69 of 100 and 39.53 of 100, respectively. At 1 year, the MCS and the PCS were 41.29 of 100 and 42.03 of 100. The subgroup analysis showed a more significant improvement in patients < 70 years and with calcemia ≥10.4 mg/dL. Postoperative PCS was correlated with age and preoperative PCS: variation = 32.11 - 0.21 × age - 0.4 × preoperative PCS. Men did not improve their MCS postoperatively. Only women with a preoperative MCS <43.6 of 100 showed postoperative improvement. This study showed, in patients with mild pHPT, an improvement of QoL 1 year after parathyroidectomy. Patients <70 years and with calcemia ≥10.4 mg/dL had a more significant improvement.

  15. Health-related quality of life and associated factors among patients with diabetes mellitus in Botswana

    Directory of Open Access Journals (Sweden)

    Godfrey Mutashambara Rwegerera

    2018-06-01

    Full Text Available Background: Health-related quality of life (HRQOL is an important aspect of diabetes mellitus care. The objective of the study was to determine the HRQOL of diabetes mellitus (DM patients in Botswana as little known in Africa. Materials and methods: A cross-sectional study of 380 randomly selected DM patients in a tertiary clinic in Gaborone, Botswana was conducted to obtain Data on HRQOL and structured questionnaire was used to collect information on sociodemographic and clinical characteristics. Multivariate logistic regression to determine sociodemographic and clinical characteristics associated. Results: Majority of patients were female with no formal education or primary level of education. Mean HbA1c was 7.97% (SD: 2.02 and most patients had poor glycemic control. The majority had both worse physical composite score (PCS-12 and mental composite score (MCS-12, with worse proportions of the two. Female gender, older age ≥65 years, and the presence of three or more documented diabetic complications were associated with significant worse PCS-12. Presence of two diabetic complications, three or more diabetic complications, and musculoskeletal disease were associated with significant MCS-12. Conclusions: Diabetic patients in Botswana have relatively poor HRQOL. The fact that most patients present late with complications calls for policy attention to diagnose diabetes mellitus early and prevent associated complications, ultimately improving health-related quality of life among diabetes mellitus patients. Keywords: Botswana, Diabetes mellitus, Health-related quality of life, Musculoskeletal disease

  16. Quality of life improves for pediatric patients after total pancreatectomy and islet autotransplant for chronic pancreatitis.

    Science.gov (United States)

    Bellin, Melena D; Freeman, Martin L; Schwarzenberg, Sarah Jane; Dunn, Ty B; Beilman, Gregory J; Vickers, Selwyn M; Chinnakotla, Srinath; Balamurugan, A N; Hering, Bernhard J; Radosevich, David M; Moran, Antoinette; Sutherland, David E R

    2011-09-01

    Total pancreatectomy (TP) and islet autotransplant (IAT) have been used to treat patients with painful chronic pancreatitis. Initial studies indicated that most patients experienced significant pain relief, but there were few validated measures of quality of life. We investigated whether health-related quality of life improved among pediatric patients undergoing TP/IAT. Nineteen consecutive children (aged 5-18 years) undergoing TP/IAT from December 2006 to December 2009 at the University of Minnesota completed the Medical Outcomes Study 36-item Short Form (SF-36) health questionnaire before and after surgery. Insulin requirements were recorded. Before TP/IAT, patients had below average health-related quality of life, based on data from the Medical Outcomes Study SF-36; they had a mean physical component summary (PCS) score of 30 and mental component summary (MCS) score of 34 (2 and 1.5 standard deviations, respectively, below the mean for the US population). By 1 year after surgery, PCS and MCS scores improved to 50 and 46, respectively (global effect, PCS P Puestow) had lower yields of islets (P = .01) and greater incidence of insulin dependence (P = .04). Quality of life (physical and emotional components) significantly improve after TP/IAT in subsets of pediatric patients with severe chronic pancreatitis. Minimal or no insulin was required for most patients, although islet yield was reduced in patients with previous surgical drainage operations. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  17. Polymorphisms of UGT1A1*6, UGT1A1*27 & UGT1A1*28 in three major ethnic groups from Malaysia.

    Science.gov (United States)

    Teh, L K; Hashim, H; Zakaria, Z A; Salleh, M Z

    2012-08-01

    Genetic polymorphisms of uridine diphosphate glucuronyltransferase 1A1 (UGT1A1) have been associated with a wide variation of responses among patients prescribed with irinotecan. Lack of this enzyme is known to be associated with a high incidence of severe toxicity. The objective of this study was to investigate the prevalence of three different variants of UGT1A1 (UGT1A1*6, UGT1A1*27 and UGT1A1*28), which are associated with reduced enzyme activity and increased irinotecan toxicity, in the three main ethnic groups in Malaysia (Malays, Chinese and Indians). A total of 306 healthy unrelated volunteers were screened for UGT1A1*28, UGT1A1*6 and UGT1A1*27. Blood samples (5 ml) were obtained from each subject and DNA was extracted. PCR based methods were designed and validated for detection of UGT1A1*, UUGT1A1*27 and UUGT1A1*28. Direct DNA sequencing was performed to validate the results of randomly selected samples. Malays and Indian have two-fold higher frequency of homozygous of UGT1A1*28 (7TA/7TA) which was 8 and 8.8 per cent, respectively compared to the Chinese (4.9%). However, the distribution of UGT1A1*6 and UGT1A1*27 showed no significant differences among them. UGT1A1*27 which has not been detected in Caucasian and African American population, was found in the Malaysian Malays (3.33%) and Malaysian Chinese (2.0%). There was interethnic variability in the frequency of UGT1A1*28 in the Malaysian population. Our results suggest that genotyping of UUGT1A1*6, UGT1A1*28 and UGT1A1*27 need to be performed before patients are prescribed with irinotecan due to their high prevalence of allelic variant which could lead to adverse drug reaction.

  18. Charcot-Marie-Tooth disease type 1A

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Børglum, A D; Brandt, C A

    1994-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant peripheral neuropathy associated with a DNA duplication on chromosome 17p11.2-p12 in the majority of cases. Most of the sporadic cases are due to a de novo duplication. We have screened for this duplication in 11 Danish patients...

  19. Complete COL1A1 allele deletions in osteogenesis imperfecta

    NARCIS (Netherlands)

    van Dijk, Fleur S.; Huizer, Margriet; Kariminejad, Ariana; Marcelis, Carlo L.; Plomp, Astrid S.; Terhal, Paulien A.; Meijers-Heijboer, Hanne; Weiss, Marjan M.; van Rijn, Rick R.; Cobben, Jan M.; Pals, Gerard

    Purpose: To identify a molecular genetic cause in patients with a clinical diagnosis of osteogenesis imperfecta (OI) type I/IV. Methods: The authors performed multiplex ligation-dependent probe amplification analysis of the COL1A1 gene in a group of 106 index patients. Results: In four families with

  20. Complete COL1A1 allele deletions in osteogenesis imperfecta

    NARCIS (Netherlands)

    van Dijk, Fleur S.; Huizer, Margriet; Kariminejad, Ariana; Marcelis, Carlo L.; Plomp, Astrid S.; Terhal, Paulien A.; Meijers-Heijboer, Hanne; Weiss, Marjan M.; van Rijn, Rick R.; Cobben, Jan M.; Pals, Gerard

    2010-01-01

    To identify a molecular genetic cause in patients with a clinical diagnosis of osteogenesis imperfecta (OI) type I/IV. The authors performed multiplex ligation-dependent probe amplification analysis of the COL1A1 gene in a group of 106 index patients. In four families with mild osteogenesis

  1. Evaluation of coping strategies in established rheumatoid arthritis patients: emergence of concealment in an Asian cohort.

    Science.gov (United States)

    Chew, Elizabeth; Griva, Konstadina; Cheung, Peter P

    2016-11-01

    To evaluate coping strategies of Asian RA patients and their associations with health-related quality of life (HRQoL). A cross-sectional sample of patients with established RA was evaluated using measures of coping (Coping in Rheumatoid Arthritis Questionnaire [C-RAQ]; appraisal of coping effectiveness and helplessness), HRQoL (Mental and Physical Components [MCS/PCS] of the Short Form 12v2; Rheumatoid Arthritis Impact of Disease score [RAID]) and clinical/laboratory assessments. Principal component analysis was conducted to identify coping strategies. Multiple linear regression analyses were performed to evaluate the associations between coping strategies and HRQoL outcomes. The study sample comprised 101 patients, 81% female, 72.3% Chinese, mean age 54.2 ± 12.6 years. Five coping strategies were identified: Active problem solving (E = 5.36), Distancing (E = 2.30), Concealment (E = 1.89), Cognitive reframing (E = 1.55) and Emotional expression (E = 1.26). Concealment was consistently associated with PCS (r s = -0.23, P = 0.049), MCS (r s = -0.24, P = 0.04) and RAID (r s = 0.39, P culture-specific. Interventions should tailor psychosocial support needs to address not only coping strategies, but patients' perception of their coping. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  2. Quantitative EEG analysis in minimally conscious state patients during postural changes.

    Science.gov (United States)

    Greco, A; Carboncini, M C; Virgillito, A; Lanata, A; Valenza, G; Scilingo, E P

    2013-01-01

    Mobilization and postural changes of patients with cognitive impairment are standard clinical practices useful for both psychic and physical rehabilitation process. During this process, several physiological signals, such as Electroen-cephalogram (EEG), Electrocardiogram (ECG), Photopletysmography (PPG), Respiration activity (RESP), Electrodermal activity (EDA), are monitored and processed. In this paper we investigated how quantitative EEG (qEEG) changes with postural modifications in minimally conscious state patients. This study is quite novel and no similar experimental data can be found in the current literature, therefore, although results are very encouraging, a quantitative analysis of the cortical area activated in such postural changes still needs to be deeply investigated. More specifically, this paper shows EEG power spectra and brain symmetry index modifications during a verticalization procedure, from 0 to 60 degrees, of three patients in Minimally Consciousness State (MCS) with focused region of impairment. Experimental results show a significant increase of the power in β band (12 - 30 Hz), commonly associated to human alertness process, thus suggesting that mobilization and postural changes can have beneficial effects in MCS patients.

  3. Postural instability in Charcot-Marie-Tooth 1A disease.

    Science.gov (United States)

    Tozza, Stefano; Aceto, Maria Gabriella; Pisciotta, Chiara; Bruzzese, Dario; Iodice, Rosa; Santoro, Lucio; Manganelli, Fiore

    2016-09-01

    The aim of this study was to evaluate the influence of somatosensory impairment, distal muscle weakness and foot deformities on the balance in 21 CMT1A patients using a baropodometric platform. Stabilometric analysis by measuring sway area and velocity of a centre of pressure (CoP) both at open and closed eyes were used to assess postural imbalance. Static analysis, by measuring the load and the plantar surface of forefoot, midfoot and hindfoot was used to define the footprint shape and to assess as a whole foot deformities. Stabilometric and static results were compared with those of a control group. In CMT1A patients, stabilometric findings were correlated with static parameters, Achilles' tendon retraction, distal muscle strength and CMT examination score (CMTES). CMT1A patients compared to controls had lower plantar surface and load on midfoot, and higher load on a forefoot. CMT1A patients had a greater postural instability, since they had a higher CoP velocity, both at open and closed eyes. Moreover, the CoP velocity correlated inversely with the strength of ankle dorsi-flexion muscles and directly with CMTES as whole and with the item "motor symptoms legs". Postural imbalance was not correlated with sensory impairment and foot deformities as expressed by static analysis and Achilles' tendon retraction. In this study we demonstrated an altered balance in CMT1A patients during upright standing. The imbalance in our CMT patients seems to be related to the weakness of ankle dorsi-flexor muscles rather than sensory impairment or foot deformities. These results could be due to a mildly affected CMT1A population, evaluated in an early stage of the disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Low-Pass Filtering Approach via Empirical Mode Decomposition Improves Short-Scale Entropy-Based Complexity Estimation of QT Interval Variability in Long QT Syndrome Type 1 Patients

    Directory of Open Access Journals (Sweden)

    Vlasta Bari

    2014-09-01

    Full Text Available Entropy-based complexity of cardiovascular variability at short time scales is largely dependent on the noise and/or action of neural circuits operating at high frequencies. This study proposes a technique for canceling fast variations from cardiovascular variability, thus limiting the effect of these overwhelming influences on entropy-based complexity. The low-pass filtering approach is based on the computation of the fastest intrinsic mode function via empirical mode decomposition (EMD and its subtraction from the original variability. Sample entropy was exploited to estimate complexity. The procedure was applied to heart period (HP and QT (interval from Q-wave onset to T-wave end variability derived from 24-hour Holter recordings in 14 non-mutation carriers (NMCs and 34 mutation carriers (MCs subdivided into 11 asymptomatic MCs (AMCs and 23 symptomatic MCs (SMCs. All individuals belonged to the same family developing long QT syndrome type 1 (LQT1 via KCNQ1-A341V mutation. We found that complexity indexes computed over EMD-filtered QT variability differentiated AMCs from NMCs and detected the effect of beta-blocker therapy, while complexity indexes calculated over EMD-filtered HP variability separated AMCs from SMCs. The EMD-based filtering method enhanced features of the cardiovascular control that otherwise would have remained hidden by the dominant presence of noise and/or fast physiological variations, thus improving classification in LQT1.

  5. Physical therapy in patients with disorders of consciousness: Impact on spasticity and muscle contracture.

    Science.gov (United States)

    Thibaut, A; Wannez, S; Deltombe, T; Martens, G; Laureys, S; Chatelle, C

    2018-01-01

    Spasticity is a frequent complication after severe brain injury, which may prevent the rehabilitation process and worsen the patients' quality of life. In this study, we investigated the correlation between spasticity, muscle contracture, and the frequency of physical therapy (PT) in subacute and chronic patients with disorders of consciousness (DOC). 109 patients with subacute and chronic disorders of consciousness (Vegetative state/Unresponsive wakefulness syndrome - VS/UWS; minimally conscious state - MCS and patients who emerged from MCS - EMCS) were included in the study (39 female; mean age: 40±13.5y; 60 with traumatic etiology; 35 VS/UWS, 68 MCS, 6 EMCS; time since insult: 38±42months). The number of PT sessions (i.e., 20 to 30 minutes of conventional stretching of the four limbs) was collected based on patients' medical record and varied between 0 to 6 times per week (low PT = 0-3 and high PT = 4-6 sessions per week). Spasticity was measured with the Modified Ashworth Scale (MAS) on every segment for both upper (UL) and lower limbs (LL). The presence of muscle contracture was assessed in every joint. We tested the relationship between spasticity and muscle contracture with the frequency of PT as well as other potential confounders such as time since injury or anti-spastic medication intake. We identified a negative correlation between the frequency of PT and MAS scores as well as the presence of muscle contracture. We also identified that patients who received less than four sessions per week were more likely to be spastic and suffer from muscle contracture than patients receiving 4 sessions or more. When separating subacute (3 to 12 months post-insult) and chronic (>12months post-insult) patients, these negative correlations were only observed in chronic patients. A logit regression model showed that frequency of PT influenced spasticity, whereas neither time since insult nor medication had a significant impact on the presence of spasticity. On

  6. Psychopharmacology of 5-HT{sub 1A} receptors

    Energy Technology Data Exchange (ETDEWEB)

    Cowen, Philip J

    2000-07-01

    Serotonin{sub 1A} (5-HT{sub 1A}) receptors are located on both 5-HT cell bodies where they act as inhibitory autoreceptors and at postsynaptic sites where they mediate the effects of 5-HT released from nerve terminals. The sensitivity of 5-HT{sub 1A} receptors in humans can be measured using the technique of pharmacological challenge. For example, acute administration of a selective 5-HT{sub 1A} receptor agonist, such as ipsapirone, decreases body temperature and increases plasma cortisol through activation of pre- and postsynaptic 5-HT{sub 1A} receptors, respectively. Use of this technique has demonstrated that unmedicated patients with major depression have decreased sensitivity of both pre- and postsynaptic 5-HT{sub 1A} receptors. Treatment with selective serotonin reuptake inhibitors further down-regulates 5-HT{sub 1A} receptor activity. Due to the hypotheses linking decreased sensitivity of 5-HT{sub 1A} autoreceptors with the onset of antidepressant activity, there is current interest in the therapeutic efficacy of combined treatment with selective serotonin reuptake inhibitors and 5-HT{sub 1A} receptor antagonists.

  7. TL1A regulates TCRγδ+ intraepithelial lymphocytes and gut microbial composition

    DEFF Research Database (Denmark)

    Tougaard, Peter; Skov, S.; Pedersen, A. E.

    2015-01-01

    TL1A is a proinflammatory cytokine, which is prevalent in the gut. High TL1A concentrations are present in patients with inflammatory bowel disease (IBD) and in IBD mouse models. However, the role of TL1A during steady‐state conditions is relatively unknown. Here, we used TL1A knockout (KO) mice ...

  8. Minimum Data Set Q1a Report

    Data.gov (United States)

    U.S. Department of Health & Human Services — The MDS Q1a report summarizes, by state and county, percentages of residents that answered Yes to Q1a - Residents expresses or indicates preference to return to the...

  9. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

    NARCIS (Netherlands)

    Rudick, R.A.; Stuart, W.H.; Calabresi, P.A.; Confavreux, C.; Galetta, S.L.; Radue, E.W.; Lublin, F.D.; Weinstock-Guttman, B.; Wynn, D.R.; Lynn, F.; Panzara, M.A.; Sandrock, A.W.

    2006-01-01

    BACKGROUND: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies.

  10. PPARGC1A is upregulated and facilitates lung cancer metastasis.

    Science.gov (United States)

    Li, Jin-Dong; Feng, Qing-Chuan; Qi, Yu; Cui, Guanghui; Zhao, Song

    2017-10-15

    Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence it is imperative to determine reliable biomarkers for lung cancer prognosis. We performed quantitative real-time PCR (qRT-PCR) analysis to explore epithelial-mesenchymal transition (EMT) inducers that regulate EMT process in three patients with advanced lung cancer disease. Peroxisome proliferator-activated receptor gamma (PPARGC1A) was uniformly the topmost overexpressed gene in all three human non-small cell lung cancer (NSCLC) patient samples. Further evaluation in human normal lung and metastatic lung cancer cell lines revealed that the expression of PPARGC1A was upregulated in metastatic lung cancer cell lines. Metagenomic analysis revealed direct correlation among PPARGC1A, zinc-finger transcription factor snail homolog 1 (SNAI1), and metastatic lung disease. Upregulation of PPARGC1A transcript expression was independent of a differential upregulation of the upstream AMP-dependent protein kinase (AMPK) activation or steady state expression of the silent mating type information regulation 2 homolog 1 (SIRT1). Xenograft tail vein colonization assays proved that the high expression of PPARGC1A was a prerequisite for metastatic progression of lung cancer to brain. Our results indicate that PPARGC1A might be a potential biomarker for lung cancer prognosis. Copyright © 2017. Published by Elsevier Inc.

  11. Invasive and non-invasive brain stimulation for treatment of neuropathic pain in patients with spinal cord injury: a review.

    Science.gov (United States)

    Nardone, Raffaele; Höller, Yvonne; Leis, Stefan; Höller, Peter; Thon, Natasha; Thomschewski, Aljoscha; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

    2014-01-01

    Past evidence has shown that invasive and non-invasive brain stimulation may be effective for relieving central pain. To perform a topical review of the literature on brain neurostimulation techniques in patients with chronic neuropathic pain due to traumatic spinal cord injury (SCI) and to assess the current evidence for their therapeutic efficacy. A MEDLINE search was performed using following terms: "Spinal cord injury", "Neuropathic pain", "Brain stimulation", "Deep brain stimulation" (DBS), "Motor cortex stimulation" (MCS), "Transcranial magnetic stimulation" (TMS), "Transcranial direct current stimulation" (tDCS), "Cranial electrotherapy stimulation" (CES). Invasive neurostimulation therapies, in particular DBS and epidural MCS, have shown promise as treatments for neuropathic and phantom limb pain. However, the long-term efficacy of DBS is low, while MCS has a relatively higher potential with lesser complications that DBS. Among the non-invasive techniques, there is accumulating evidence that repetitive TMS can produce analgesic effects in healthy subjects undergoing laboratory-induced pain and in chronic pain conditions of various etiologies, at least partially and transiently. Another very safe technique of non-invasive brain stimulation - tDCS - applied over the sensory-motor cortex has been reported to decrease pain sensation and increase pain threshold in healthy subjects. CES has also proved to be effective in managing some types of pain, including neuropathic pain in subjects with SCI. A number of studies have begun to use non-invasive neuromodulatory techniques therapeutically to relieve neuropathic pain and phantom phenomena in patients with SCI. However, further studies are warranted to corroborate the early findings and confirm different targets and stimulation paradigms. The utility of these protocols in combination with pharmacological approaches should also be explored.

  12. Predictors of health-related quality of life in patients with irritable bowel syndrome. A cross-sectional study in Norway.

    Science.gov (United States)

    Michalsen, Vilde Lehne; Vandvik, Per Olav; Farup, Per G

    2015-07-30

    Reduced quality of life (QoL) is often the main problem for patients with irritable bowel syndrome (IBS). This study aimed at finding predictors of reduced physical and mental quality of life (QoL) accessible for intervention. Consecutive patients with IBS (according to the Rome II criteria) visiting a general practitioner were included in a prospective cohort study and followed up for 6-9 months. At the last visit, information about sociodemographic characteristics, abdominal complaints, QoL and a range of physical and mental comorbidities were collected. Physical and mental QoL were measured with the generic QoL instrument Short Form-12 Physical Component Score (SF-12 PCS) and Short Form-12 Mental Component Score (SF-12 MCS) respectively. The normal scores are 50. This cross-sectional study used data from the last visit. Out of 208 patients included in the cohort study, 149 (female/male: 105/44) with a mean age of 52 years (SD 15.3) were available for the analyses. Physical and mental QoL were reduced, the mean SF-12 PCS and SF-12 MCS scores were 38.4 (SD 11.9) and 45.0 (SD 11.3) respectively. The main independent predictors of low SF-12 PCS and SF-12 MCS were subjective health complaints and organic diseases, and affective disorders respectively. The severity of IBS symptoms was of minor clinical importance. To help patients with IBS and reduced QoL, treatment should focus on QoL and not on relief of IBS symptoms. The different causes of reduced physical and mental QoL make an individually directed treatment necessary.

  13. Lactose intolerance in irritable bowel syndrome patients with diarrhoea: the roles of anxiety, activation of the innate mucosal immune system and visceral sensitivity.

    Science.gov (United States)

    Yang, J; Fox, M; Cong, Y; Chu, H; Zheng, X; Long, Y; Fried, M; Dai, N

    2014-02-01

    Irritable bowel syndrome patients with diarrhoea (IBS-D) often report intolerance to milk; however, the mechanism underlying these symptoms is unknown. To assess the role of psychological factors, immune activation and visceral sensitivity on the development of lactose intolerance (LI) in IBS-D patients. Fifty-five IBS-D patients and 18 healthy controls (HCs) with lactase deficiency underwent a 20-g lactose hydrogen breath test (LHBT). Patients were categorised as lactose malabsorption (LM; malabsorption only) or LI [malabsorption plus increase in total symptom score (TSS). Measurements included (i) psychological status; (ii) enteric biopsies with quantification of mast cells (MCs), T-lymphocytes and enterochromaffin cells; (iii) serum cytokines; (iv) rectal sensitivity before and after lactose ingestion. LI was more prevalent in IBS-D patients than HCs [25/55 (46%) vs. 3/18 (17%), P = 0.029]. IBS-D patients with LI had (i) higher levels of anxiety than those with LM (P = 0.017) or HCs (P = 0.006); (ii) increased mucosal MCs compared with LM (P = 0.006) and HCs (P lactose ingestion compared with LM (P lactose ingestion was associated with the increase in visceral sensitivity after lactose intake (r = 0.629, P lactose intolerence are characterised by anxiety, mucosal immune activation and increased visceral sensitivity after lactose ingestion. The presence of these biomarkers may indicate an IBS phenotype that responds to dietary therapy and/or mast cell stabilisers. © 2013 John Wiley & Sons Ltd.

  14. Mutations in pseudohypoparathyroidism 1a and pseudopseudohypoparathyroidism in ethnic Chinese.

    Directory of Open Access Journals (Sweden)

    Yi-Lei Wu

    Full Text Available An inactivating mutation in the GNAS gene causes either pseudohypoparathyroidism 1a (PHP1A when it is maternally inherited or pseudopseudohypoparathyroidism (PPHP when it is paternally inherited. We investigated clinical manifestations and mutations of the GNAS gene in ethnic Chinese patients with PHP1A or PPHP. Seven patients from 5 families including 4 girls and 2 boys with PHP1A and 1 girl with PPHP were studied. All PHP1A patients had mental retardation. They were treated with calcitriol and CaCO3 with regular monitoring of serum Ca levels, urinary Ca/Cr ratios, and renal sonography. Among them, 5 patients also had primary hypothyroidism suggesting TSH resistance. One female patient had a renal stone which was treated with extracorporeal shockwave lithotripsy. She had an increased urinary Ca/Cr ratio of 0.481 mg/mg when the stone was detected. We detected mutations using PCR and sequencing as well as analysed a splice acceptor site mutation using RT-PCR, sequencing, and minigene construct. We detected 5 mutations: c.85C>T (Q29*, c.103C>T (Q35*, c.840-2A>G (R280Sfs*21, c.1027_1028delGA (D343*, and c.1174G>A (E392K. Mutations c.840-2A>G and c.1027_1028delGA were novel. The c.840-2A>G mutation at the splice acceptor site of intron 10 caused retention of intron 10 in the minigene construct but skipping of exon 11 in the peripheral blood cells. The latter was the most probable mechanism which caused a frameshift, changing Arg to Ser at residue 280 and invoking a premature termination of translation at codon 300 (R280Sfs*21. Five GNAS mutations in ethnic Chinese with PHP1A and PPHP were reported. Two of them were novel. Mutation c.840-2A>G destroyed a spice acceptor site and caused exon skipping. Regular monitoring and adjustment in therapy are mandatory to achieve optimal therapeutic effects and avoid nephrolithiasis in patients with PHP1A.

  15. Multiple fMRI system-level baseline connectivity is disrupted in patients with consciousness alterations.

    Science.gov (United States)

    Demertzi, Athena; Gómez, Francisco; Crone, Julia Sophia; Vanhaudenhuyse, Audrey; Tshibanda, Luaba; Noirhomme, Quentin; Thonnard, Marie; Charland-Verville, Vanessa; Kirsch, Murielle; Laureys, Steven; Soddu, Andrea

    2014-03-01

    In healthy conditions, group-level fMRI resting state analyses identify ten resting state networks (RSNs) of cognitive relevance. Here, we aim to assess the ten-network model in severely brain-injured patients suffering from disorders of consciousness and to identify those networks which will be most relevant to discriminate between patients and healthy subjects. 300 fMRI volumes were obtained in 27 healthy controls and 53 patients in minimally conscious state (MCS), vegetative state/unresponsive wakefulness syndrome (VS/UWS) and coma. Independent component analysis (ICA) reduced data dimensionality. The ten networks were identified by means of a multiple template-matching procedure and were tested on neuronality properties (neuronal vs non-neuronal) in a data-driven way. Univariate analyses detected between-group differences in networks' neuronal properties and estimated voxel-wise functional connectivity in the networks, which were significantly less identifiable in patients. A nearest-neighbor "clinical" classifier was used to determine the networks with high between-group discriminative accuracy. Healthy controls were characterized by more neuronal components compared to patients in VS/UWS and in coma. Compared to healthy controls, fewer patients in MCS and VS/UWS showed components of neuronal origin for the left executive control network, default mode network (DMN), auditory, and right executive control network. The "clinical" classifier indicated the DMN and auditory network with the highest accuracy (85.3%) in discriminating patients from healthy subjects. FMRI multiple-network resting state connectivity is disrupted in severely brain-injured patients suffering from disorders of consciousness. When performing ICA, multiple-network testing and control for neuronal properties of the identified RSNs can advance fMRI system-level characterization. Automatic data-driven patient classification is the first step towards future single-subject objective diagnostics

  16. Lipoprotein composition in HNF1A-MODY: differentiating between HNF1A-MODY and type 2 diabetes.

    Science.gov (United States)

    McDonald, Tim J; McEneny, Jane; Pearson, Ewan R; Thanabalasingham, Gaya; Szopa, Magdalena; Shields, Beverley M; Ellard, Sian; Owen, Katharine R; Malecki, Maciej T; Hattersley, Andrew T; Young, Ian S

    2012-05-18

    The young-onset diabetes seen in HNF1A-MODY is often misdiagnosed as Type 2 diabetes. Type 2 diabetes, unlike HNF1A-MODY, is associated with insulin resistance and a characteristic dyslipidaemia. We aimed to compare the lipid profiles in HNF1A-MODY, Type 2 diabetes and control subjects and to determine if lipids can be used to aid the differential diagnosis of diabetes sub-type. 1) 14 subjects in each group (HNF1A-MODY, Type 2 diabetes and controls) were matched for gender and BMI. Fasting lipid profiles and HDL lipid constituents were compared in the 3 groups. 2) HDL-cholesterol was assessed in a further 267 patients with HNF1A-MODY and 297 patients with a diagnosis of Type 2 diabetes to determine its discriminative value. 1) In HNF1A-MODY subjects, plasma-triglycerides were lower (1.36 vs. 1.93 mmol/l, p = 0.07) and plasma-HDL-cholesterol was higher than in subjects with Type 2 diabetes (1.47 vs. 1.15 mmol/l, p = 0.0008), but was similar to controls. Furthermore, in the isolated HDL; HDL-phospholipid and HDL-cholesterol ester content were higher in HNF1A-MODY, than in Type 2 diabetes (1.59 vs. 1.33 mmol/L, p = 0.04 and 1.10 vs. 0.83 mmol/L, p = 0.019, respectively), but were similar to controls (1.59 vs. 1.45 mmol/L, p = 0.35 and 1.10 vs. 1.21 mmol/L, p = 0.19, respectively). 2) A plasma-HDL-cholesterol > 1.12 mmol/L was 75% sensitive and 64% specific (ROC AUC = 0.76) at discriminating HNF1A-MODY from Type 2 diabetes. The plasma-lipid profiles of HNF1A-MODY and the lipid constituents of HDL are similar to non-diabetic controls. However, HDL-cholesterol was higher in HNF1A-MODY than in Type 2 diabetes and could be used as a biomarker to aid in the identification of patients with HNF1A-MODY. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Cross-cultural adaptation, reliability, internal consistency and validation of the Hand Function Sort (HFS©) for French speaking patients with upper limb complaints.

    Science.gov (United States)

    Konzelmann, M; Burrus, C; Hilfiker, R; Rivier, G; Deriaz, O; Luthi, F

    2015-03-01

    Functional evaluation of upper limb is not only based on clinical findings but requires self-administered questionnaires to address patients' perspective. The Hand Function Sort (HFS©) was only validated in English. The aim of this study was the French cross cultural adaptation and validation of the HFS© (HFS-F). 150 patients with various upper limbs impairments were recruited in a rehabilitation center. Translation and cross-cultural adaptation were made according to international guidelines. Construct validity was estimated through correlations with Disabilities Arm Shoulder and Hand (DASH) questionnaire, SF-36 mental component summary (MCS),SF-36 physical component summary (PCS) and pain intensity. Internal consistency was assessed by Cronbach's α and test-retest reliability by intraclass correlation. Cronbach's α was 0.98, test-retest reliability was excellent at 0.921 (95 % CI 0.871-0.971) same as original HFS©. Correlations with DASH were-0.779 (95 % CI -0.847 to -0.685); with SF 36 PCS 0.452 (95 % CI 0.276-0.599); with pain -0.247 (95 % CI -0.429 to -0.041); with SF 36 MCS 0.242 (95 % CI 0.042-0.422). There were no floor or ceiling effects. The HFS-F has the same good psychometric properties as the original HFS© (internal consistency, test retest reliability, convergent validity with DASH, divergent validity with SF-36 MCS, and no floor or ceiling effects). The convergent validity with SF-36 PCS was poor; we found no correlation with pain. The HFS-F could be used with confidence in a population of working patients. Other studies are necessary to study its psychometric properties in other populations.

  18. Comparison of the CBA-H and SF-36 for the screening of the psychological and behavioural variables in chronic dialysis patients.

    Science.gov (United States)

    De Pasquale, Concetta; Conti, Daniela; Pistorio, Maria Luisa; Fatuzzo, Pasquale; Veroux, Massimiliano; Di Nuovo, Santo

    2017-01-01

    The aim of the study was to perform an analysis of the emotional reactions, perception of stressful life and behavioural changes related to Haemodialysis (HD) in order to identify those variables that can improve lifestyle and the adherence to treatment. Some psychometric assessment, such as the Cognitive Behavioural Assessment, Hospital Form, (CBA-H) and the Health Survey (SF-36), which provides two indexes: the Physical Component Score (PCS) and the Mental Component Score (MCS), are suitable to assess a patient's psychological and behavioural style and their health-related quality of life. The study involved 37 Italian out-patients with end-stage renal disease under HD therapy. We calculated the Spearman correlation between variables of CBA-H, SF-36, age and time on HD. We also performed a multivariate linear regression using the CBA-H variables as predictors and PCS and MCS as dependent variables. From the CBA-H, 95% of participants self-reported psychological characteristics comparable to Type A personality, which identifies an anxious, hyperactive and hostile subject. Physical limitations were found to be directly proportional to the time on dialysis (rs = -0.42). The condition of perceived stress worsens the state of mental health (rs = -0.68) and general health perception (rs = -0.44). The condition of vital exhaustion correlates both the PCS and the MCS (ppsychological wellbeing of a dialyzed patient could be due to the combination of several factors, including life parameters, the positive perception of psychosocial outcomes, and the perceived quality of life. A multidisciplinary team (neurologists, psychiatrists, psychologists, and nurses) is essential to plan effective psychological and psychotherapeutic interventions to improve a mind-body integration.

  19. Mesenchymal chondrosarcoma of bone and soft tissue: a systematic review of 107 patients in the past 20 years.

    Directory of Open Access Journals (Sweden)

    Jie Xu

    Full Text Available Mesenchymal chondrosarcoma(MCS is a rare high-grade variant of chondrosarcoma. Consensus has not been reached on its optimal management. Resection with wide margins is usually recommended, but the effect of margins has been demonstrated by little positive evidence. Moreover, the effectiveness of adjuvant chemo- and/or radiotherapy remains controversial.To describe the clinical characteristics and outcomes of MCS of bone and soft tissue, to assess the efficacies of surgery, chemotherapy and radiation, and finally to deliver a more appropriate therapy.We reviewed EMBASE-, MEDLINE-, Cochrane-, Ovid- and PubMed-based to find out all cases of MCS of bone and soft tissue described between April 1994 and April 2014. Description of treatment and regular follow-up was required for each study. Language was restricted to English and Chinese. Issues of age, gender, location, metastasis, and treatment were all evaluated for each case. Kaplan-Meier Method and Cox Proportional Hazard Regression Model were used in the survival analysis.From the 630 identified publications, 18 meeting the inclusion criteria were selected, involving a total of 107 patients. Based on these data, the 5-, 10-and 20-year overall survival are 55.0%, 43.5% and 15.7% respectively. The 5-, 10-, 20- year event-free survival rates are 45.0%, 27.2% and 8.1%, respectively. Treatment without surgery is associated with poorer overall survival and event-free survival. Negative surgical margins could significantly bring down the local-recurrence rate and are associated with a higher event-free survival rate. Chemotherapy regime based on anthracyclines does not benefit the overall survival. The addition of radiation therapy is not significantly associated with the overall or event-free survival. However, we recommend radiation as the salvage therapy for patients with positive margin so as to achieve better local control.This review shows that surgery is essential in the management of MCS of bone

  20. Identifying Psoriasis and Psoriatic Arthritis Patients in Retrospective Databases When Diagnosis Codes Are Not Available: A Validation Study Comparing Medication/Prescriber Visit-Based Algorithms with Diagnosis Codes.

    Science.gov (United States)

    Dobson-Belaire, Wendy; Goodfield, Jason; Borrelli, Richard; Liu, Fei Fei; Khan, Zeba M

    2018-01-01

    Using diagnosis code-based algorithms is the primary method of identifying patient cohorts for retrospective studies; nevertheless, many databases lack reliable diagnosis code information. To develop precise algorithms based on medication claims/prescriber visits (MCs/PVs) to identify psoriasis (PsO) patients and psoriatic patients with arthritic conditions (PsO-AC), a proxy for psoriatic arthritis, in Canadian databases lacking diagnosis codes. Algorithms were developed using medications with narrow indication profiles in combination with prescriber specialty to define PsO and PsO-AC. For a 3-year study period from July 1, 2009, algorithms were validated using the PharMetrics Plus database, which contains both adjudicated medication claims and diagnosis codes. Positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of the developed algorithms were assessed using diagnosis code as the reference standard. Chosen algorithms were then applied to Canadian drug databases to profile the algorithm-identified PsO and PsO-AC cohorts. In the selected database, 183,328 patients were identified for validation. The highest PPVs for PsO (85%) and PsO-AC (65%) occurred when a predictive algorithm of two or more MCs/PVs was compared with the reference standard of one or more diagnosis codes. NPV and specificity were high (99%-100%), whereas sensitivity was low (≤30%). Reducing the number of MCs/PVs or increasing diagnosis claims decreased the algorithms' PPVs. We have developed an MC/PV-based algorithm to identify PsO patients with a high degree of accuracy, but accuracy for PsO-AC requires further investigation. Such methods allow researchers to conduct retrospective studies in databases in which diagnosis codes are absent. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  1. Large-scale structural alteration of brain in epileptic children with SCN1A mutation

    Directory of Open Access Journals (Sweden)

    Yun-Jeong Lee

    2017-01-01

    Significance: This study showed large-scale developmental brain changes in patients with epilepsy and SCN1A gene mutation, which may be associated with the core symptoms of the patients. Further longitudinal MRI studies with larger cohorts are required to confirm the effect of SCN1A gene mutation on structural brain development.

  2. Relationship between optimism and quality of life in patients with two chronic rheumatic diseases: axial spondyloarthritis and chronic low back pain: a cross sectional study of 288 patients.

    Science.gov (United States)

    Kreis, Sarah; Molto, Anna; Bailly, Florian; Dadoun, Sabrina; Fabre, Stéphanie; Rein, Christopher; Hudry, Christophe; Zenasni, Franck; Rozenberg, Sylvie; Pertuiset, Edouard; Fautrel, Bruno; Gossec, Laure

    2015-06-10

    Axial Spondyloarthritis (AxSpA) and chronic low back pain are rheumatic diseases that impact patients' health-related quality of life (HRQoL). In other chronic conditions, HRQoL was positively associated with dispositional optimism, a personality trait. The objective was to explore the relationship between optimism and HRQoL in these two diseases. A cross-sectional study was performed in 2 tertiary care hospitals and 2 private practices in France. Patients had definite AxSpA or chronic low back pain according to the rheumatologist. A generic HRQoL questionnaire (Short Form, SF-12) with physical and mental composite scores (PCS and MCS respectively) and an optimism questionnaire (the Life Orientation Test-revised, LOT-R) were collected. Analyses included non-parametric correlations and multiple regression analyses to study the effect of optimism on PCS and MCS. In all, 288 (199 AxSpA and 89 low back pain) patients were included: mean age, 47.3 ± 11.9 years, 48.6 % were males. Pain levels (0-10) were 4.5 ± 2.4 and 4.3 ± 2.4 in AxSpA and LOW BACK PAIN patients, respectively. HRQoL was similarly altered in both diseases, for both physical and mental composite scores (mean PCS: 43.7 ± 8.2 vs. 41.9 ± 7.1; mean 45.9 ± 7.8 vs. 46.7 ± 8.1 for AxSpA and low back pain respectively). Optimism was moderate and similar in both populations. Optimism was positively correlated to MCS in both diseases (rho = 0.54 and 0.58, respectively, both p Optimism was similar in these 2 chronic diseases and was an explanatory factor of the mental component of HRQoL, but not physical HRQoL. Physical HRQoL may reflect more the disease process than character traits.

  3. Determinants of quality of life in patients with fibromyalgia: A structural equation modeling approach.

    Science.gov (United States)

    Lee, Jeong-Won; Lee, Kyung-Eun; Park, Dong-Jin; Kim, Seong-Ho; Nah, Seong-Su; Lee, Ji Hyun; Kim, Seong-Kyu; Lee, Yeon-Ah; Hong, Seung-Jae; Kim, Hyun-Sook; Lee, Hye-Soon; Kim, Hyoun Ah; Joung, Chung-Il; Kim, Sang-Hyon; Lee, Shin-Seok

    2017-01-01

    Health-related quality of life (HRQOL) in patients with fibromyalgia (FM) is lower than in patients with other chronic diseases and the general population. Although various factors affect HRQOL, no study has examined a structural equation model of HRQOL as an outcome variable in FM patients. The present study assessed relationships among physical function, social factors, psychological factors, and HRQOL, and the effects of these variables on HRQOL in a hypothesized model using structural equation modeling (SEM). HRQOL was measured using SF-36, and the Fibromyalgia Impact Questionnaire (FIQ) was used to assess physical dysfunction. Social and psychological statuses were assessed using the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), the Arthritis Self-Efficacy Scale (ASES), and the Social Support Scale. SEM analysis was used to test the structural relationships of the model using the AMOS software. Of the 336 patients, 301 (89.6%) were women with an average age of 47.9±10.9 years. The SEM results supported the hypothesized structural model (χ2 = 2.336, df = 3, p = 0.506). The final model showed that Physical Component Summary (PCS) was directly related to self-efficacy and inversely related to FIQ, and that Mental Component Summary (MCS) was inversely related to FIQ, BDI, and STAI. In our model of FM patients, HRQOL was affected by physical, social, and psychological variables. In these patients, higher levels of physical function and self-efficacy can improve the PCS of HRQOL, while physical function, depression, and anxiety negatively affect the MCS of HRQOL.

  4. Determinants of quality of life in patients with fibromyalgia: A structural equation modeling approach.

    Directory of Open Access Journals (Sweden)

    Jeong-Won Lee

    Full Text Available Health-related quality of life (HRQOL in patients with fibromyalgia (FM is lower than in patients with other chronic diseases and the general population. Although various factors affect HRQOL, no study has examined a structural equation model of HRQOL as an outcome variable in FM patients. The present study assessed relationships among physical function, social factors, psychological factors, and HRQOL, and the effects of these variables on HRQOL in a hypothesized model using structural equation modeling (SEM.HRQOL was measured using SF-36, and the Fibromyalgia Impact Questionnaire (FIQ was used to assess physical dysfunction. Social and psychological statuses were assessed using the Beck Depression Inventory (BDI, the State-Trait Anxiety Inventory (STAI, the Arthritis Self-Efficacy Scale (ASES, and the Social Support Scale. SEM analysis was used to test the structural relationships of the model using the AMOS software.Of the 336 patients, 301 (89.6% were women with an average age of 47.9±10.9 years. The SEM results supported the hypothesized structural model (χ2 = 2.336, df = 3, p = 0.506. The final model showed that Physical Component Summary (PCS was directly related to self-efficacy and inversely related to FIQ, and that Mental Component Summary (MCS was inversely related to FIQ, BDI, and STAI.In our model of FM patients, HRQOL was affected by physical, social, and psychological variables. In these patients, higher levels of physical function and self-efficacy can improve the PCS of HRQOL, while physical function, depression, and anxiety negatively affect the MCS of HRQOL.

  5. Identification and functional characterization of a novel bipartite nuclear localization sequence in ARID1A

    Energy Technology Data Exchange (ETDEWEB)

    Bateman, Nicholas W. [Women' s Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA (United States); The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda 20889, MD (United States); Shoji, Yutaka [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids 49503, MI (United States); Conrads, Kelly A.; Stroop, Kevin D. [Women' s Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA (United States); Hamilton, Chad A. [Women' s Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA (United States); The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda 20889, MD (United States); Gynecologic Oncology Service, Department of Obstetrics and Gynecology, Walter Reed National Military Medical Center, 8901 Wisconsin Ave, MD, Bethesda, 20889 (United States); Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda 20814, MD (United States); Darcy, Kathleen M. [Women' s Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA (United States); The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda 20889, MD (United States); Maxwell, George L. [Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Falls Church, VA 22042 (United States); Risinger, John I. [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids 49503, MI (United States); and others

    2016-01-01

    AT-rich interactive domain-containing protein 1A (ARID1A) is a recently identified nuclear tumor suppressor frequently altered in solid tumor malignancies. We have identified a bipartite-like nuclear localization sequence (NLS) that contributes to nuclear import of ARID1A not previously described. We functionally confirm activity using GFP constructs fused with wild-type or mutant NLS sequences. We further show that cyto-nuclear localized, bipartite NLS mutant ARID1A exhibits greater stability than nuclear-localized, wild-type ARID1A. Identification of this undescribed functional NLS within ARID1A contributes vital insights to rationalize the impact of ARID1A missense mutations observed in patient tumors. - Highlights: • We have identified a bipartite nuclear localization sequence (NLS) in ARID1A. • Confirmation of the NLS was performed using GFP constructs. • NLS mutant ARID1A exhibits greater stability than wild-type ARID1A.

  6. Ectopic Calcification as Discernible Manifestation in Neonates with Pseudohypoparathyroidism Type 1a

    Directory of Open Access Journals (Sweden)

    Masanori Adachi

    2009-01-01

    Full Text Available The diagnosis of pseudohypoparathyroidism type 1a (PHP1a is challenging, because both the osteodystrophy, such as brachydactyly and round face, and the symptomatic hypocalcemia usually develop beyond infancy. Although ectopic calcification may be an early sign of PHP1a, there are no systematic reviews regarding the time of its appearance. We here report on two PHP1a patients who presented with subcutaneous calcification in neonatal period.

  7. UDP-glucuronosyltransferases 1A6 and 1A10 catalyze reduced menadione glucuronidation

    International Nuclear Information System (INIS)

    Nishiyama, Takahito; Ohnuma, Tomokazu; Inoue, Yuu; Kishi, Takehiko; Ogura, Kenichiro; Hiratsuka, Akira

    2008-01-01

    Menadione (2-methyl-1,4-naphthoquine), also known as vitamin K3, has been widely used as a model compound in the field of oxidative stress-related research. The metabolism of menadione has been studied, and it is known that menadione undergoes a two-electron reduction by NAD(P)H:Quinone oxidoreductase 1 (NQO1) after which the reduced form of menadione (2-methyl-1,4-naphthalenediol, menadiol) is glucuronidated and excreted in urine. To investigate which human UDP-glucuronosyltransferase (UGT) isoforms participate in the glucuronidation of menadiol reduced by NQO1 from menadione, we first constructed heterologously expressed NQO1 in Sf9 cells and tested the menadiol glucuronidating activity of 16 human recombinant UGT isoforms. Of the 16 UGT isoforms, UGTs 1A6, 1A7, 1A8, 1A9, and 1A10 catalyzed menadiol glucuronidation, and, of these, UGTs 1A6 and 1A10 catalyzed menadiol glucuronidation at much higher rates than the other UGTs. Menadiol was regioselectively glucuronidated in the manner of 4-position > 1-position by UGTs 1A7, 1A8, 1A9, and 1A10. In contrast to these UGTs, only UGT1A6 exhibited 1-menadiol-preferential glucuronidating activity. The results suggest possible detoxification pathways for quinones via NQO1 reduction followed by UGT glucuronidation

  8. Factors Associated with Pain, Disability and Quality of Life in Patients Suffering from Frozen Shoulder

    Directory of Open Access Journals (Sweden)

    Farshid Bagheri

    2016-07-01

    Full Text Available Background: Frozen shoulder is resulting in limb disability and reduction of quality of life but the factors associated with patients’ disability and quality of life is not clear. To assess pain, disability, the quality of life and factors associated with them in patients suffering from frozen shoulder.  Methods: We enrolled 120 patients (37 men and 83 women with phase-II idiopathic frozen shoulder in our cross-sectional study. Demographic data were collected and shoulder range of motion was measured in four different directions (elevation, abduction, external and internal rotation in both upper limbs. Patients were asked to fill out Visual Analog Scale for pain (VAS and, Short-Form Health Survey questionnaire (SF-36 as well as Disabilities of the Arm, Shoulder and Hand (DASH questionnaires. We asked the patients to fill out the Hamilton anxiety and depression questionnaires. Results: The mean of VAS pain, DASH, PCS, and MCS scores were 69(18, 53(17, 35(8.0, and 42(10 respectively. All the domains of SF36 questionnaires where below the normal population except physical function. VAS pain score was correlated to Hamilton depression scores in both bivariate and mulivarilable analysis. DASH score were correlated to sex, age, ROM, and both Hamilton anxiety and depression scores; However, DASH score only impact with Hamilton anxiety and ROM independently. PCS is correlated to age and MCS to Hamilton depression. Conclusion: Patient with frozen shoulder are more suffering from pain and disability secondary to psychiatric parameters such as depression and anxiety than demographic features or even restriction of range of motion.

  9. n kommunikasiestrategie vir kleinboeront- wikkeling1/a ...

    African Journals Online (AJOL)

    Ian

    WIKKELING1/A COMMUNICATION STRATEGY FOR. SMALL FARMER DEVELOPMENT1. H.C. Viljoen2, J. Laubscher3 and G.J.O. Marincowitz4. UITTREKSEL. Enige doeltreffende voorligting- en inligtingstelsel moet op die behoeftes en idioom van die boer berus. Aangesien die inligtingsbehoeftes van die kommersiële ...

  10. Genetic polymorphisms of cytochrome P450-1A2 (CYP1A2 among Emiratis.

    Directory of Open Access Journals (Sweden)

    Mohammad M Al-Ahmad

    Full Text Available Cytochrome P450 1A2 (CYP1A2 is one of the CYP450 mixed-function oxidase system that is of clinical importance due to the large number of drug interactions associated with its induction and inhibition. In addition, significant inter-individual differences in the elimination of drugs metabolized by CYP1A2 enzyme have been observed which are largely due to the highly polymorphic nature of CYP1A2 gene. However, there are limited studies on CYP1A2 phenotypes and CYP1A2 genotypes among Emiratis and thus this study was carried out to fill this gap. Five hundred and seventy six non-smoker Emirati subjects were asked to consume a soft drink containing caffeine (a non-toxic and reliable probe for predicting CYP1A2 phenotype and then provide a buccal swab along with a spot urine sample. Taq-Man Real Time PCR was used to determine the CYP1A2 genotype of each individual. Phenotyping was carried out by analyzing the caffeine metabolites using High Performance Liquid Chromatography (HPLC analysis. We found that 1.4%, 16.3% and 82.3% of the Emirati subjects were slow, intermediate and rapid CYP1A2 metabolizers, respectively. In addition, we found that 1.4% of the subjects were homozygote for derived alleles while 16.1% were heterozygote and 82.5% were homozygote for the ancestral allele. The genotype frequency of the ancestral allele, CYP1A2*1A/*1A, is the highest in this population, followed by CYP1A2 *1A/*1C and CYP1A2 *1A/*1K genotypes, with frequencies of 0.825, 0.102 and 0.058, respectively. The degree of phenotype/genotype concordance was equal to 81.6%. The CYP1A2*1C/*1C and CYP1A2*3/*3 genotypes showed significantly the lowest enzyme phenotypic activity. The frequency of slow activity CYP1A2 enzyme alleles is very low among Emiratis which correlates with the presence of low frequencies of derived alleles in CYP1A2 gene.

  11. Racial differences in health-related quality of life and functional ability in patients with gout.

    Science.gov (United States)

    Singh, Jasvinder A; Bharat, Aseem; Khanna, Dinesh; Aquino-Beaton, Cleopatra; Persselin, Jay E; Duffy, Erin; Elashoff, David; Khanna, Puja P

    2017-01-01

    To compare the health-related quality of life (HRQOL) and the functional ability by race in patients with gout. In a 9-month prospective cohort multicentre study, patients with gout self-reported race, dichotomized as Caucasian or African American (others excluded). We calculated HRQOL/function scores adjusted for age, study site and college education for Short Form-36 (SF-36; generic HRQOL), Gout Impact Scale (GIS; disease-specific HRQOL) and HAQ-disability index (HAQ-DI; functional ability). Longitudinally adjusted scores were computed using multivariable mixed-effect regression models with a random patient effect and fixed sequential visit effect (3-monthly visits). Compared with Caucasians (n = 107), African Americans (n = 60) with gout were younger (61.1 vs 67.3 years) and had higher median baseline serum urate (9.0 vs 7.9 mg/dl) (P gout had worse HRQOL scores on three SF-36 domains, the mental component summary (MCS) and two of the five GIS scales than Caucasians [mean (se); P ⩽ 0.02 for all]: SF-36 mental health, 39.7 (1.1) vs 45.2 (0.9); SF-36 role emotional, 42.1 (4.2) vs 51.4 (4.2); SF-36 social functioning, 36.0 (1.1) vs 40.0 (0.9) (P = 0.04); SF-36 MCS, 43.2 (3.1) vs 50.0 (3.2); GIS unmet treatment need, 37.6 (1.6) vs 31.5 (1.4); and GIS concern during attacks, 53.3 (3.7) vs 47.4 (3.7). Differences between the respective HAQ-DI total scores were not statistically significant; 0.98 (0.1) vs 0.80 (1.0) (P = 0.11). Racial differences in SF-36 mental health, role emotional and MCS scales exceeded, and for HAQ-DI approached, the minimal clinically important difference thresholds. African Americans with gout have significantly worse HRQOL compared with Caucasians. Further research is necessary in the form of studies targeted at African Americans on how best to improve these outcomes. Published by Oxford University Press on behalf of the British Society for Rheumatology 2016. This work is written by US Government employees and is in the public domain in the

  12. Earth and Sky, Unit 1A

    DEFF Research Database (Denmark)

    Gammelgaard Nielsen, Anders

    2011-01-01

    The assignment known as ‘Earth and sky’ is the final first year course at Unit 1a. The aim of the assignment is to strengthen the student’s abilities to manage a project process individu- ally. The process involves develop- ing the ability to make independent decisions.The point of departure...... for the ‘Earth and sky’ assignment is ex- perience students acquired during their group study tour to Austra- lia. Building in particular on the re- search conducted on the Sydney Opera House and the architectur- al principles of spatial creation that this building represents....

  13. Pitfalls in genetic testing: the story of missed SCN1A mutations.

    Science.gov (United States)

    Djémié, Tania; Weckhuysen, Sarah; von Spiczak, Sarah; Carvill, Gemma L; Jaehn, Johanna; Anttonen, Anna-Kaisa; Brilstra, Eva; Caglayan, Hande S; de Kovel, Carolien G; Depienne, Christel; Gaily, Eija; Gennaro, Elena; Giraldez, Beatriz G; Gormley, Padhraig; Guerrero-López, Rosa; Guerrini, Renzo; Hämäläinen, Eija; Hartmann, Corinna; Hernandez-Hernandez, Laura; Hjalgrim, Helle; Koeleman, Bobby P C; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes R; Leu, Costin; Marini, Carla; McMahon, Jacinta M; Mei, Davide; Møller, Rikke S; Muhle, Hiltrud; Myers, Candace T; Nava, Caroline; Serratosa, Jose M; Sisodiya, Sanjay M; Stephani, Ulrich; Striano, Pasquale; van Kempen, Marjan J A; Verbeek, Nienke E; Usluer, Sunay; Zara, Federico; Palotie, Aarno; Mefford, Heather C; Scheffer, Ingrid E; De Jonghe, Peter; Helbig, Ingo; Suls, Arvid

    2016-07-01

    Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated in epilepsy, are found in the majority of Dravet syndrome (DS) patients, we focused on missed SCN1A mutations. We sent out a survey to 16 genetic centers performing SCN1A testing. We collected data on 28 mutations initially missed using Sanger sequencing. All patients were falsely reported as SCN1A mutation-negative, both due to technical limitations and human errors. We illustrate the pitfalls of Sanger sequencing and most importantly provide evidence that SCN1A mutations are an even more frequent cause of DS than already anticipated.

  14. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood

    DEFF Research Database (Denmark)

    Heinzen, Erin L; Swoboda, Kathryn J; Hitomi, Yuki

    2012-01-01

    and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation...... affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3....

  15. UPWIND 1A2 Metrology. Final Report

    DEFF Research Database (Denmark)

    Eecen, P.J.; Wagenaar, J.W.; Stefanatos, N.

    . Since this problem covers many areas of wind energy, the work package is defined as a crosscutting activity. The objectives of the metrology work package are to develop metrology tools in wind energy to significantly enhance the quality of measurement and testing techniques. The first deliverable...... is a valuable tool for the further assessment and interest has been shown from other work packages, such as Training. This report describes the activities that have been carried out in the Work Package 1A2 Metrology of the UpWind project. Activities from Risø are described in a separate report: T.F. Pedersen...... was to perform a state of the art assessment to identify all relevant measurands. The required accuracies and required sampling frequencies have been identified from the perspective of the users of the data (the other work packages in UpWind). This work led to the definition of the Metrology Database, which...

  16. A novel CYP1A1 gene polymorphism and the risk of head and neck ...

    African Journals Online (AJOL)

    Several polymorphisms in the CYP1A1 locus have been identified and their genotypes appear to exhibit population frequencies that depend on ethnicity. In this study, we assessed the role of CYP1A1 genotype in 388 head and neck cancer patients in Pakistani population via a case-control study. Polymerase chain reaction ...

  17. Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis

    Science.gov (United States)

    Xu, Sen-Lin; Liu, Sha; Cui, Wei; Shi, Yu; Liu, Qin; Duan, Jiang-Jie; Yu, Shi-Cang; Zhang, Xia; Cui, You-Hong; Kung, Hsiang-Fu; Bian, Xiu-Wu

    2015-01-01

    Glioma is the most aggressive brain tumor with high invasiveness and poor prognosis. More reliable, sensitive and practical biomarkers to reveal glioma high invasiveness remain to be explored for the guidance of therapy. We herein evaluated the diagnostic and prognostic value of aldehyde dehydrogenase 1A1 (ALDH1A1) in the glioma specimens from 237 patients, and found that ADLH1A1 was frequently overexpressed in the high-grade glioma (WHO grade III-IV) as compared to the low-grade glioma (WHO grade I-II) patients. The tumor cells with ALDH1A1 expression were more abundant in the region between tumor and the borderline of adjacent tissue as compared to the central part of the tumor. ALDH1A1 overexpression was associated with poor differentiation and dismal prognosis. Notably, the overall and disease-free survivals of the patients who had ALDH1A1+ tumor cells sparsely located in the adjacent tissue were much worse. Furthermore, ALDH1A1 expression was correlated with the “classical-like” (CL) subtype as we examined GBM specimens from 72 patients. Multivariate Cox regression analysis revealed that ALDH1A1 was an independent marker for glioma patients’ outcome. Mechanistically, both in vitro and in vivo studies revealed that ALDH1A1+ cells isolated from either a glioblastoma cell line U251 or primary glioblastoma cells displayed significant invasiveness, clonogenicity, and proliferation as compared to ALDH1A1- cells, due to increased levels of mRNA and protein for matrix metalloproteinase 2, 7 and 9 (MMP2, MMP7 and MMP9). These results indicate that ALDH1A1+ cells contribute to the progression of glioma including invasion, proliferation and poor prognosis, and suggest that targeting ALDH1A1 may have important implications for the treatment of highly invasive glioma. PMID:26101711

  18. Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A): implications for autism

    LENUS (Irish Health Repository)

    Tansey, Katherine E

    2011-03-31

    Abstract Background Arginine vasopressin (AVP) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. The arginine vasopressin receptor 1A gene (AVPR1A) is widely expressed in the brain and is considered to be a key receptor for regulation of social behaviour. Moreover, genetic variation at AVPR1A has been reported to be associated with autism. Evidence from non-human mammals implicates variation in the 5\\'-flanking region of AVPR1A in variable gene expression and social behaviour. Methods We examined four tagging single nucleotide polymorphisms (SNPs) (rs3803107, rs1042615, rs3741865, rs11174815) and three microsatellites (RS3, RS1 and AVR) at the AVPR1A gene for association in an autism cohort from Ireland. Two 5\\'-flanking region polymorphisms in the human AVPR1A, RS3 and RS1, were also tested for their effect on relative promoter activity. Results The short alleles of RS1 and the SNP rs11174815 show weak association with autism in the Irish population (P = 0.036 and P = 0.008, respectively). Both RS1 and RS3 showed differences in relative promoter activity by length. Shorter repeat alleles of RS1 and RS3 decreased relative promoter activity in the human neuroblastoma cell line SH-SY5Y. Conclusions These aligning results can be interpreted as a functional route for this association, namely that shorter alleles of RS1 lead to decreased AVPR1A transcription, which may proffer increased susceptibility to the autism phenotype.

  19. UVA1 a promising approach for scleroderma

    Science.gov (United States)

    Keyal, Uma; Bhatta, Anil Kumar; Wang, Xiu Li

    2017-01-01

    Scleroderma is a complex connective tissue disease characterized by fibrosis, vasculopathy, and immune system dysfunction. The heterogeneity of disease presentation and poorly understood etiology has made the management of scleroderma difficult. The available treatment options like immunosuppressive agents are associated with potentially hazardous side effects and physiotherapy, which to a certain degree helps to minimize the loss of function in digits and limbs, has only limited success. Also, studies investigating antifibrotic therapies have failed to report any significant improvement. Hence, there is currently no effective therapy for scleroderma. Recently, phototherapy has been extensively studied and found to be effective in treating scleroderma. Initially psoralen + ultraviolet A (PUVA) significantly enriched the therapeutic panel, but more recently ultraviolet A1 (UVA1) is seen to replace PUVA therapy. This might be because of UVA1 therapy being free of side effects seen with psoralens such as nausea, vomiting or photokeratitis. In addition, UVA1 is seen to lower risk of phototoxic reactions with deeper penetration of radiation. The present review will put some light on the use of UVA1 for treating cutaneous lesion in scleroderma and we aim to find the most benefitted group of patients and most effective dose of UVA1 for different types of scleroderma. PMID:28979701

  20. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood

    Science.gov (United States)

    Heinzen, Erin L.; Swoboda, Kathryn J.; Hitomi, Yuki; Gurrieri, Fiorella; Nicole, Sophie; de Vries, Boukje; Tiziano, F. Danilo; Fontaine, Bertrand; Walley, Nicole M.; Heavin, Sinéad; Panagiotakaki, Eleni; Fiori, Stefania; Abiusi, Emanuela; Di Pietro, Lorena; Sweney, Matthew T.; Newcomb, Tara M.; Viollet, Louis; Huff, Chad; Jorde, Lynn B.; Reyna, Sandra P.; Murphy, Kelley J.; Shianna, Kevin V.; Gumbs, Curtis E.; Little, Latasha; Silver, Kenneth; Ptác̆ek, Louis J.; Haan, Joost; Ferrari, Michel D.; Bye, Ann M.; Herkes, Geoffrey K.; Whitelaw, Charlotte M.; Webb, David; Lynch, Bryan J.; Uldall, Peter; King, Mary D.; Scheffer, Ingrid E.; Neri, Giovanni; Arzimanoglou, Alexis; van den Maagdenberg, Arn M.J.M.; Sisodiya, Sanjay M.; Mikati, Mohamad A.; Goldstein, David B.; Nicole, Sophie; Gurrieri, Fiorella; Neri, Giovanni; de Vries, Boukje; Koelewijn, Stephany; Kamphorst, Jessica; Geilenkirchen, Marije; Pelzer, Nadine; Laan, Laura; Haan, Joost; Ferrari, Michel; van den Maagdenberg, Arn; Zucca, Claudio; Bassi, Maria Teresa; Franchini, Filippo; Vavassori, Rosaria; Giannotta, Melania; Gobbi, Giuseppe; Granata, Tiziana; Nardocci, Nardo; De Grandis, Elisa; Veneselli, Edvige; Stagnaro, Michela; Gurrieri, Fiorella; Neri, Giovanni; Vigevano, Federico; Panagiotakaki, Eleni; Oechsler, Claudia; Arzimanoglou, Alexis; Nicole, Sophie; Giannotta, Melania; Gobbi, Giuseppe; Ninan, Miriam; Neville, Brian; Ebinger, Friedrich; Fons, Carmen; Campistol, Jaume; Kemlink, David; Nevsimalova, Sona; Laan, Laura; Peeters-Scholte, Cacha; van den Maagdenberg, Arn; Casaer, Paul; Casari, Giorgio; Sange, Guenter; Spiel, Georg; Boneschi, Filippo Martinelli; Zucca, Claudio; Bassi, Maria Teresa; Schyns, Tsveta; Crawley, Francis; Poncelin, Dominique; Vavassori, Rosaria

    2012-01-01

    Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurologic manifestations. AHC is usually a sporadic disorder with unknown etiology. Using exome sequencing of seven patients with AHC, and their unaffected parents, we identified de novo nonsynonymous mutations in ATP1A3 in all seven AHC patients. Subsequent sequence analysis of ATP1A3 in 98 additional patients revealed that 78% of AHC cases have a likely causal ATP1A3 mutation, including one inherited mutation in a familial case of AHC. Remarkably, six ATP1A3 mutations explain the majority of patients, including one observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset-dystonia-parkinsonism, AHC-causing mutations revealed consistent reductions in ATPase activity without effects on protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC, and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in this gene. PMID:22842232

  1. Differences in UGT1A1, UGT1A7, and UGT1A9 polymorphisms between Uzbek and Japanese populations.

    Science.gov (United States)

    Maeda, Hiromichi; Hazama, Shoichi; Shavkat, Abdiev; Okamoto, Ken; Oba, Koji; Sakamoto, Junichi; Takahashi, Kenichi; Oka, Masaki; Nakamura, Daisuke; Tsunedomi, Ryouichi; Okayama, Naoko; Mishima, Hideyuki; Kobayashi, Michiya

    2014-06-01

    Uridine-diphosphate glucuronosyltransferase 1A (UGT1A) is a key enzyme involved in irinotecan metabolism, and polymorphisms in the UGT1A gene are associated with irinotecan-induced toxicity. The aim of this study was to elucidate the allele frequencies of UGT1A polymorphisms in healthy Uzbek volunteers, and to compare them with those of the Japanese population. A total of 97 healthy volunteers from Uzbekistan were enrolled and blood samples were collected from each participant. Genotyping analysis was performed by fragment size analysis for UGT1A1*28, direct sequencing for UGT1A7*3 and UGT1A9*22, and TaqMan assays for UGT1A1*93, UGT1A1*6, UGT1A1*27, UGT1A1*60, and UGT1A7*12. The frequencies of polymorphisms were compared with the Japanese population by using the data previously reported from our study group. When the Uzbek and Japanese populations were compared, heterozygotes or homozygotes for UGT1A1*28, UGT1A1*60, and UGT1A1*93 were significantly more frequent in the Uzbek population (P Japanese population (P Japanese population. A comprehensive study of the influence of UGT1A1 polymorphisms on the risk of irinotecan-induced toxicity is necessary for optimal use of irinotecan treatment.

  2. Health related quality of life in patients with newly diagnosed anti-neutrophil cytoplasm antibody associated vasculitis

    Science.gov (United States)

    Walsh, Michael; Mukhtyar, Chetan; Mahr, Alfred; Herlyn, Karen; Luqmani, Raashid; Merkel, Peter A.; Jayne, David R. W.

    2011-01-01

    Background Anti-neutrophil cytoplasm antibody-associated vasculitis (AAV) can present with a broad spectrum of signs and symptoms. The relative effects of different manifestations on health related quality of life (HRQOL) is unknown. Methods We conducted an individual patient data meta-analysis of baseline Short Form 36 (SF-36) scores from four randomized controlled trials of patients with newly diagnosed AAV. We determined the associations between organ manifestations at trial entry and the SF-36 Physical Composite Score (PCS) and Mental Composite Score (MCS) using mixed effects models adjusted for demographic factors. Associations with each of the 8 domains of the SF-36 were further explored using multivariate multiple regression. Results SF-36 data was available from 346 patients. Older age (−0.11 points/year; 95% Confidence Interval [CI] −0.21 to −0.012; p=0.029) and neurologic involvement (−5.84, p<0.001) at baseline were associated with lower Physical Composite Scores. Physical Function scores were the most affected and older age (−0.25 points per year, 95% Confidence Interval [CI] −0.38 to −0.11; p<0.001) scores and neurologic involvement (−8.48 points, 95% CI −12.90 to −4.06; p<0.001) had the largest effects. The MCS was negatively affected only by chest involvement (p=0.027) but this effect was not exerted in any particular domain. Conclusions HRQOL in patients with newly diagnosed AAV are complex and incompletely explained by their organ system manifestations. PMID:21452254

  3. Minocycline added to subcutaneous interferon β-1a in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, P S; Sellebjerg, F; Lycke, J

    2016-01-01

    BACKGROUND AND PURPOSE: Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) β-1a therapy. METHODS: This was a double......-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN β-1a 44 μg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN β-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying...... were assessed. RESULTS: One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence...

  4. Neck exercises, physical and cognitive behavioural-graded activity as a treatment for adult whiplash patients with chronic neck pain: Design of a randomised controlled trial

    DEFF Research Database (Denmark)

    Ris Hansen, Inge; Søgaard, Karen; Christensen, Robin Daniel Kjersgaard

    2011-01-01

    scale for pain bothersomeness (0-10), SF-36 Mental Component Summary (MCS), TAMPA scale of Kinesiophobia (17-68), Impact of Event Scale (0-45), EuroQol (0-1), craniocervical flexion test (22 mmHg - 30 mmHg), joint position error test and cervical range of movement. The SF36 scales are scored using norm......ABSTRACT: BACKGROUND: Many patients suffer from chronic neck pain following a whiplash injury. A combination of cognitive, behavioural therapy with physiotherapy interventions has been indicated to be effective in the management of patients with chronic whiplash-associated disorders. The objective...... is to present the design of a randomised controlled trial (RCT) aimed at evaluating the effectiveness of a combined individual physical and cognitive behavioural-graded activity program on self-reported general physical function, in addition to neck function, pain, disability and quality of life in patients...

  5. Genomic and proteomic characterization of ARID1A chromatin remodeller in ampullary tumors.

    Science.gov (United States)

    Nastase, Anca; Teo, Jin Yao; Heng, Hong Lee; Ng, Cedric Chuan Young; Myint, Swe Swe; Rajasegaran, Vikneswari; Loh, Jia Liang; Lee, Ser Yee; Ooi, London Lucien; Chung, Alexander Yaw Fui; Chow, Pierce Kah Hoe; Cheow, Peng Chung; Wan, Wei Keat; Azhar, Rafy; Khoo, Avery; Xiu, Sam Xin; Alkaff, Syed Muhammad Fahmy; Cutcutache, Ioana; Lim, Jing Quan; Ong, Choon Kiat; Herlea, Vlad; Dima, Simona; Duda, Dan G; Teh, Bin Tean; Popescu, Irinel; Lim, Tony Kiat Hon

    2017-01-01

    AT rich interactive domain 1A (ARID1A) is one of the most commonly mutated genes in a broad variety of tumors. The mechanisms that involve ARID1A in ampullary cancer progression remains elusive. Here, we evaluated the frequency of ARID1A and KRAS mutations in ampullary adenomas and adenocarcinomas and in duodenal adenocarcinomas from two cohorts of patients from Singapore and Romania, correlated with clinical and pathological tumor features, and assessed the functional role of ARID1A . In the ampullary adenocarcinomas, the frequency of KRAS and ARID1A mutations was 34.7% and 8.2% respectively, with a loss or reduction of ARID1A protein in 17.2% of the cases. ARID1A mutational status was significantly correlated with ARID1A protein expression level (P=0.023). There was a significant difference in frequency of ARID1A mutation between Romania and Singapore (2.7% versus 25%, P=0.04), suggestive of different etiologies. One somatic mutation was detected in the ampullary adenoma group. In vitro studies indicated the tumor suppressive role of ARID1A . Our results warrant further investigation of this chromatin remodeller as a potential early biomarker of the disease, as well as identification of therapeutic targets in ARID1A mutated ampullary cancers.

  6. Scoliosis in osteogenesis imperfecta caused by COL1A1/COL1A2 mutations - genotype-phenotype correlations and effect of bisphosphonate treatment.

    Science.gov (United States)

    Sato, Atsuko; Ouellet, Jean; Muneta, Takeshi; Glorieux, Francis H; Rauch, Frank

    2016-05-01

    Bisphosphonates are widely used to treat children with osteogenesis imperfecta (OI), a bone fragility disorder that is most often caused by mutations in COL1A1 or COL1A2. However, it is unclear whether this treatment decreases the risk of developing scoliosis. We retrospectively evaluated spine radiographs and charts of 437 patients (227 female) with OI caused by mutations in COL1A1 or COL1A2 and compared the relationship between scoliosis, genotype and bisphosphonate treatment history. At the last follow-up (mean age 11.9 [SD: 5.9] years), 242 (55%) patients had scoliosis. The prevalence of scoliosis was highest in OI type III (89%), followed by OI type IV (61%) and OI type I (36%). Moderate to severe scoliosis (Cobb angle ≥25°) was rare in individuals with COL1A1 haploinsufficiency mutations but was present in about two fifth of patients with triple helical glycine substitutions or C-propeptide mutations. During the first 2 to 4years of bisphosphonate therapy, patients with OI type III had lower Cobb angle progression rates than before bisphosphonate treatment, whereas in OI types I and IV bisphosphonate treatment was not associated with a change in Cobb angle progression rates. At skeletal maturity, the prevalence of scoliosis (Cobb angle >10°) was similar in patients who had started bisphosphonate treatment early in life (before 5.0years of age) and in patients who had started therapy later (after the age of 10.0years) or had never received bisphosphonate therapy. Bisphosphonate treatment decreased progression rate of scoliosis in OI type III but there was no evidence of a positive effect on scoliosis in OI types I and IV. The prevalence of scoliosis at maturity was not influenced by the bisphosphonate treatment history in any OI type. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a.

    Science.gov (United States)

    Rudick, R A; Pace, A; Rani, M R S; Hyde, R; Panzara, M; Appachi, S; Shrock, J; Maurer, S L; Calabresi, P A; Confavreux, C; Galetta, S L; Lublin, F D; Radue, E-W; Ransohoff, R M

    2009-06-09

    Findings from a small clinical study suggested that statins may counteract the therapeutic effects of interferon beta (IFNbeta) in patients with relapsing-remitting multiple sclerosis (RRMS). We conducted a post hoc analysis of data from the Safety and Efficacy of Natalizumab in Combination With IFNbeta-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) study to determine the effects of statins on efficacy of IFNbeta. SENTINEL was a prospective trial of patients with RRMS treated with natalizumab (Tysabri, Biogen Idec, Inc., Cambridge, MA) plus IM IFNbeta-1a (Avonex, Biogen Idec, Inc.) 30 microg compared with placebo plus IM IFNbeta-1a 30 microg. Clinical and MRI outcomes in patients treated with IM IFNbeta-1a only (no-statins group, n = 542) were compared with those of patients taking IM IFNbeta-1a and statins at doses used to treat hyperlipidemia (statins group, n = 40). No significant differences were observed between treatment groups in adjusted annualized relapse rate (p = 0.937), disability progression (p = 0.438), number of gadolinium-enhancing lesions (p = 0.604), or number of new or enlarging T2-hyperintense lesions (p = 0.802) at 2 years. More patients in the statins group reported fatigue, extremity pain, muscle aches, and increases in hepatic transaminases compared with patients in the no-statins group. Statin treatment had no ex vivo or in vitro effect on induction of IFN-stimulated genes. Statin therapy does not appear to affect clinical effects of IM interferon beta-1a in patients with relapsing-remitting multiple sclerosis or the primary molecular response to interferon beta treatment.

  8. Casein Kinase 2 Is a Novel Regulator of the Human Organic Anion Transporting Polypeptide 1A2 (OATP1A2) Trafficking.

    Science.gov (United States)

    Chan, Ting; Cheung, Florence Shin Gee; Zheng, Jian; Lu, Xiaoxi; Zhu, Ling; Grewal, Thomas; Murray, Michael; Zhou, Fanfan

    2016-01-04

    Human organic anion transporting polypeptides (OATPs) mediate the influx of many important drugs into cells. Casein kinase 2 (CK2) is a critical protein kinase that phosphorylates >300 protein substrates and is dysregulated in a number of disease states. Among the CK2 substrates are several transporters, although whether this includes human OATPs has not been evaluated. The current study was undertaken to evaluate the regulation of human OATP1A2 by CK2. HEK-239T cells in which OATP1A2 was overexpressed were treated with CK2 specific inhibitors or transfected with CK2 specific siRNA, and the activity, expression, and subcellular trafficking of OATP1A2 was evaluated. CK2 inhibition decreased the uptake of the prototypic OATP1A2 substrate estrone-3-sulfate (E3S). Kinetic studies revealed that this was due to a decrease in the maximum velocity (Vmax) of E3S uptake, while the Michaelis constant was unchanged. The cell surface expression, but not the total cellular expression of OATP1A2, was impaired by CK2 inhibition and knockdown of the catalytic α-subunits of CK2. CK2 inhibition decreased the internalization of OATP1A2 via a clathrin-dependent pathway, decreased OATP1A2 recycling, and likely impaired OATP1A2 targeting to the cell surface. Consistent with these findings, CK2 inhibition also disrupted the colocalization of OATP1A2 and Rab GTPase (Rab)4-, Rab8-, and Rab9-positive endosomal and secretory vesicles. Taken together, CK2 has emerged as a novel regulator of the subcellular trafficking and stability of OATP1A2. Because OATP1A2 transports many molecules of physiological and pharmacological importance, the present data may inform drug selection in patients with diseases in which CK2 and OATP1A2 are dysregulated.

  9. Scutellarin inhibits cytochrome P450 isoenzyme 1A2 (CYP1A2) in rats.

    Science.gov (United States)

    Jian, Tun-Yu; He, Jian-Chang; He, Gong-Hao; Feng, En-Fu; Li, Hong-Liang; Bai, Min; Xu, Gui-Li

    2012-08-01

    Scutellarin is the most important flavone glycoside in the herbal drug Erigeron breviscapus (Vant.) Hand.-Mazz. It is used frequently in the clinic to treat ischemic vascular diseases in China. However, the direct relationship between scutellarin and cytochrome P450 (CYP450) is unclear. The present study investigated the in vitro and in vivo effects of scutellarin on cytochrome P450 1A2 (CYP 1A2) metabolism. According to in vitro experiments, scutellarin (10-250 µM) decreased the formation of 4-acetamidophenol in a concentration-dependent manner, with an IC₅₀ value of 108.20 ± 0.657 µM. Furthermore, scutellarin exhibited a weak mixed-type inhibition against the activity of CYP1A2 in rat liver microsomes, with a K(i) value of 95.2 µM. Whereas in whole animal studies, scutellarin treatment for 7 days (at 5, 15, 30 mg/kg, i.p.) decreased the clearance (CL), and increased the T(1/2) (at 15, 30 mg/kg, i.p.), it did not affect the V(d) of phenacetin. Scutellarin treatment (at 5, 15, 30 mg/kg, i.p.) increased the AUC(0-∞) by 14.3%, 67.3% and 159.2%, respectively. Scutellarin at 30 mg/kg also weakly inhibited CYP1A2 activity, in accordance with our in vitro study. Thus, the results indicate that CYP1A2 is inhibited directly, but weakly, by scutellarin in vivo, and provide useful information on the safe and effective use of scutellarin in clinical practice. Copyright © 2012 John Wiley & Sons, Ltd.

  10. ELISA-based assay of immunoglobulin G antibodies against mammalian cell entry 1A (Mce1A) protein: a novel diagnostic approach for leprosy.

    Science.gov (United States)

    Lima, Filipe R; Takenami, Iukary; Cavalcanti, Maurílio Al; Riley, Lee W; Arruda, Sérgio

    2017-12-01

    Leprosy is a chronic infectious disease caused by the obligate intracellular bacillus Mycobacterium leprae. Because leprosy diagnosis is complex and requires professional expertise, new tools and methodologies are needed to detect cases in early stages and prevent transmission. The M. leprae genome contains mce1A, which encodes a putative mammalian cell entry protein (Mce1A). We hypothesised that the presence of Mce1A on the cell surface could be detected by the host's immune system. The aim of this study was to evaluate antibody responses against the Mce1A protein in leprosy patients, household contacts of patients, and the general population to present an addition tool for leprosy diagnosis. A cross-sectional study involving 89 volunteers [55 leprosy cases, 12 household contacts (HHC) and 22 endemic controls (EC)] was conducted at Couto Maia Hospital, in Salvador, Bahia (BA), Brazil. The median anti-Mce1A IgA was significantly higher in multibacillary (MB) and paucibacillary (PB) cases than in EC (p leprosy cases, IgG enzyme-linked immunosorbent assay sensitivity and specificity were 92.7% and 97.1%, respectively. IgG positivity was confirmed in 92.1% and 94.1% of MB and PB patients, respectively. This novel diagnostic approach presents an easy, non-invasive, and inexpensive method for leprosy screening, which may be applicable in endemic areas.

  11. Peginterferon beta-1a – nowa postać interferonu beta-1a

    Directory of Open Access Journals (Sweden)

    Zdzisław Maciejek

    2015-11-01

    Full Text Available W 2014 roku, po zakończeniu próby klinicznej III fazy ADVANCE, do leczenia postaci rzutowo-remisyjnej stwardnienia rozsianego wprowadzono nową pegylowaną postać interferonu beta-1a o wydłużonym czasie działania. Do badania zakwalifikowano 1512 chorych ze 183 ośrodków z 26 krajów (500 uczestników przyjmowało placebo, 512 – peginterferon beta-1a w dawce 125 µg podawany podskórnie co 2 tygodnie, 500 – peginterferon beta-1a w dawce 125 µg podawany podskórnie co 4 tygodnie. Grupy były zbliżone pod względem wieku, płci, czasu trwania choroby i niepełnosprawności ocenianej w Expanded Disability Status Scale. Cel badania stanowiła ocena skuteczności i bezpieczeństwa pegylowanego interferonu beta-1a po 2 latach terapii w porównaniu z grupą placebo, która w drugim roku również otrzymywała ten lek. Skuteczność peginterferonu beta-1a podawanego co 2 tygodnie w porównaniu z placebo przejawiała się redukcją rocznego wskaźnika rzutów (o 37%, liczby nowych lub powiększonych ognisk T2-zależnych (o 67%, ryzyka wystąpienia rzutu (o 39% i ryzyka utrwalonej 12-tygodniowej progresji niepełnosprawności (o 33%. Najczęstsze działania niepożądane towarzyszące kuracji (94% chorych to odczyn w miejscu wkłucia, objawy grypopodobne, gorączka i bóle głowy. U 16% osób przyjmujących lek co 2 tygodnie i 22% otrzymujących go co 4 tygodnie odnotowano poważne objawy niepożądane (rzuty, zapalenie płuc, infekcje dróg moczowych. Reasumując: leczenie peginterferonem beta-1a cechowały skuteczność, dobra tolerancja i bezpieczeństwo.

  12. [Detection of UGT1A1*28 Polymorphism Using Fragment Analysis].

    Science.gov (United States)

    Huang, Ying; Su, Jian; Huang, Xiaosui; Lu, Danxia; Xie, Zhi; Yang, Suqing; Guo, Weibang; Lv, Zhiyi; Wu, Hongsui; Zhang, Xuchao

    2017-12-20

    Uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1), UGT1A1*28 polymorphism can reduce UGT1A1 enzymatic activity, which may lead to severe toxicities in patients who receive irinotecan. This study tries to build a fragment analysis method to detect UGT1A1*28 polymorphism. A total of 286 blood specimens from the lung cancer patients who were hospitalized in Guangdong General Hospital between April 2014 to May 2015 were detected UGT1A1*28 polymorphism by fragment analysis method. Comparing with Sanger sequencing, precision and accuracy of the fragment analysis method were 100%. Of the 286 patients, 236 (82.5% harbored TA6/6 genotype, 48 (16.8%) TA 6/7 genotype and 2 (0.7%) TA7/7 genotype. Our data suggest hat the fragment analysis method is robust for detecting UGT1A1*28 polymorphism in clinical practice. It's simple, time-saving, and easy-to-carry.

  13. Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome.

    Directory of Open Access Journals (Sweden)

    Anna Ka-Yee Kwong

    Full Text Available BACKGROUND: Dravet syndrome is a severe form of epilepsy. Majority of patients have a mutation in SCN1A gene, which encodes a voltage-gated sodium channel. A recent study has demonstrated that 16% of SCN1A-negative patients have a mutation in PCDH19, the gene encoding protocadherin-19. Mutations in other genes account for only a very small proportion of families. TSPYL4 is a novel candidate gene within the locus 6q16.3-q22.31 identified by linkage study. OBJECTIVE: The present study examined the mutations in epileptic Chinese children with emphasis on Dravet syndrome. METHODS: A hundred children with severe epilepsy were divided into Dravet syndrome and non-Dravet syndrome groups and screened for SCN1A mutations by direct sequencing. SCN1A-negative Dravet syndrome patients and patients with phenotypes resembling Dravet syndrome were checked for PCDH19 and TSPYL4 mutations. RESULTS: Eighteen patients (9 males, 9 females were diagnosed to have Dravet syndrome. Among them, 83% (15/18 had SCN1A mutations including truncating (7, splice site (2 and missense mutations (6. The truncating/splice site mutations were associated with moderate to severe degree of intellectual disability (p<0.05. During the progression of disease, 73% (11/15 had features fitting into the diagnostic criteria of autism spectrum disorder and 53% (8/15 had history of vaccination-induced seizures. A novel PCDH19 p.D377N mutation was identified in one SCN1A-negative female patient with Dravet syndrome and a known PCDH19 p.N340S mutation in a female non-Dravet syndrome patient. The former also inherited a TSPYL4 p.G60R variant. CONCLUSION: A high percentage of SCN1A mutations was identified in our Chinese cohort of Dravet syndrome patients but none in the rest of patients. We demonstrated that truncating/splice site mutations were linked to moderate to severe intellectual disability in these patients. A de novo PCDH19 missense mutation together with an inherited TSPYL4 missense

  14. Specific collaborative group intervention for patients with medically unexplained symptoms in general practice: a cluster randomized controlled trial.

    Science.gov (United States)

    Schaefert, R; Kaufmann, C; Wild, B; Schellberg, D; Boelter, R; Faber, R; Szecsenyi, J; Sauer, N; Guthrie, E; Herzog, W

    2013-01-01

    Patients with medically unexplained symptoms (MUS) are frequent in primary care and substantially impaired in their quality of life (QoL). Specific training of general practitioners (GPs) alone did not demonstrate sustained improvement at later follow-up in current reviews. We evaluated a collaborative group intervention. We conducted a cluster randomized controlled trial. Thirty-five GPs recruited 304 MUS patients (intervention group: 170; control group: 134). All GPs were trained in diagnosis and management of MUS (control condition). Eighteen randomly selected intervention GPs participated in training for a specific collaborative group intervention. They conducted 10 weekly group sessions and 2 booster meetings in their practices, together with a psychosomatic specialist. Six and 12 months after baseline, QoL was assessed with the Short-Form 36. The primary outcome was the physical composite score (PCS), and the secondary outcome was the mental composite score (MCS). At 12 months, intention-to-treat analyses showed a significant between-group effect for the MCS (p = 0.023) but not for the PCS (p = 0.674). This effect was preceded by a significant reduction of somatic symptom severity (15-item somatic symptom severity scale of the Patient Health Questionnaire, PHQ-15) at 6 months (p = 0.008) that lacked significance at 12 months (p = 0.078). As additional between-group effects at 12 months, per-protocol analyses showed less health anxiety (Whiteley-7; p = 0.038) and less psychosocial distress (PHQ; p = 0.024); GP visits were significantly (p = 0.042) reduced in the intervention group. Compared to pure GP training, collaborative group intervention achieved a progressive, clinically meaningful improvement in mental but not physical QoL. It could bridge gaps between general practice and mental health care. Copyright © 2012 S. Karger AG, Basel.

  15. Use of Monte Carlo Simulations to Determine Optimal Carbapenem Dosing in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapy.

    Science.gov (United States)

    Lewis, Susan J; Kays, Michael B; Mueller, Bruce A

    2016-10-01

    Pharmacokinetic/pharmacodynamic analyses with Monte Carlo simulations (MCSs) can be used to integrate prior information on model parameters into a new renal replacement therapy (RRT) to develop optimal drug dosing when pharmacokinetic trials are not feasible. This study used MCSs to determine initial doripenem, imipenem, meropenem, and ertapenem dosing regimens for critically ill patients receiving prolonged intermittent RRT (PIRRT). Published body weights and pharmacokinetic parameter estimates (nonrenal clearance, free fraction, volume of distribution, extraction coefficients) with variability were used to develop a pharmacokinetic model. MCS of 5000 patients evaluated multiple regimens in 4 different PIRRT effluent/duration combinations (4 L/h × 10 hours or 5 L/h × 8 hours in hemodialysis or hemofiltration) occurring at the beginning or 14-16 hours after drug infusion. The probability of target attainment (PTA) was calculated using ≥40% free serum concentrations above 4 times the minimum inhibitory concentration (MIC) for the first 48 hours. Optimal doses were defined as the smallest daily dose achieving ≥90% PTA in all PIRRT combinations. At the MIC of 2 mg/L for Pseudomonas aeruginosa, optimal doses were doripenem 750 mg every 8 hours, imipenem 1 g every 8 hours or 750 mg every 6 hours, and meropenem 1 g every 12 hours or 1 g pre- and post-PIRRT. Ertapenem 500 mg followed by 500 mg post-PIRRT was optimal at the MIC of 1 mg/L for Streptococcus pneumoniae. Incorporating data from critically ill patients receiving RRT into MCS resulted in markedly different carbapenem dosing regimens in PIRRT from those recommended for conventional RRTs because of the unique drug clearance characteristics of PIRRT. These results warrant clinical validation. © 2016, The American College of Clinical Pharmacology.

  16. Eating behaviors in obese children with pseudohypoparathyroidism type 1a: a cross-sectional study.

    Science.gov (United States)

    Wang, Lulu; Shoemaker, Ashley H

    2014-01-01

    Children with pseudohypoparathyroidism type 1a (PHP-1a) develop early-onset obesity. These children have decreased resting energy expenditure but it is unknown if hyperphagia contributes to their obesity. We conducted a survey assessment of patients 2 to 12 years old with PHP-1a and matched controls using the Hyperphagia Questionnaire (HQ) and Children's Eating Behavior Questionnaire (CEBQ). Results of the PHP-1a group were also compared with an obese control group and normal weight sibling group. We enrolled 10 patients with PHP-1a and 9 matched controls. There was not a significant difference between the PHP-1a group and matched controls for total HQ score (p = 0.72), Behavior (p = 0.91), Drive (p = 0.48) or Severity (p = 0.73) subset scores. There was also no difference between the PHP-1a group and matched controls on the CEBQ. In a secondary analysis, the PHP-1a group was compared with obese controls (n = 30) and normal weight siblings (n = 6). Caregivers reported an increased interest in food before age 2 years in 6 of 10 PHP-1a patients (60%), 9 of 30 obese controls (30%) and none of the siblings (p = 0.04). The sibling group had a significantly lower Positive Eating Behavior score than the PHP-1a group (2.6 [2.4, 2.9] vs. 3.5 [3.1, 4.0], p PHP-1a and obese controls (p = 0.35). The sibling group had a lower Desire to Drink score than both the PHP-1a group (1.8 [1.6, 2.7] vs. 4.3 [3.3, 5.0], p PHP-1a and obese control Desire to Drink scores (p = 0.11). Patients with PHP-1a demonstrate hyperphagic symptoms similar to matched obese controls.

  17. Risk factors for fear of falling in elderly patients with severe knee osteoarthritis before and one year after total knee arthroplasty.

    Science.gov (United States)

    Tsonga, Theano; Michalopoulou, Maria; Kapetanakis, Stylianos; Giovannopoulou, Eirini; Malliou, Paraskevi; Godolias, George; Soucacos, Panagiotis

    2016-12-01

    To evaluate the regression of fear of falling (FOF) and identify its risk factors in patients with severe knee osteoarthritis before and one year after total knee arthroplasty (TKA). 11 men and 57 women with a mean age of 73 years and a mean body mass index of 30.36 kg/m2 who had severe (grade 3 or 4) knee osteoarthritis and knee pain of ≥1 year were included. Two weeks before and one year after TKA, patients were asked about their FOF status and falls history. Patients were asked to complete the Physical Activity Scale for the Elderly, Short Form 36 (SF-36), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaires. Clinical performance was assessed using the Berg Balance Scale and Timed Up and Go (TUG) test. Of the 68 patients, 56 (82.4%) had FOF preoperatively and 30 (44.1%) had FOF one year after TKA (p<0.001). The strongest predictors for FOF preoperatively were fallers (odds ratio [OR]=9.83, p=0.028), mental component summary (MCS) score of SF-36 (OR=0.88, p=0.024), and TUG (OR=3.4, p=0.013). The strongest predictors for FOF one year postoperatively were fallers (OR=16.51, p=0.041), patients with ≥2 chronic diseases (OR=17.33, p=0.011), physical function score of WOMAC (OR=1.015, p=0.005), and MCS score of SF-36 (OR=0.86, p=0.015). TKA positively affected FOF and gradually reduced the FOF rate over a year period after TKA in an elderly population.

  18. Association of CYP1A1 gene polymorphism with chronic kidney disease: a case control study.

    Science.gov (United States)

    Siddarth, Manushi; Datta, Sudip K; Ahmed, Rafat S; Banerjee, Basu D; Kalra, Om P; Tripathi, Ashok K

    2013-07-01

    CYP1A1 is an important xenobiotic metabolizing enzyme, present in liver and kidney. Expression of CYP1A1 enzyme increases manifold when kidney cells are exposed to nephrotoxins/chemicals leading to oxidative stress-induced cell damage. To study the association of CYP1A1 gene polymorphism in patients of chronic kidney disease with unknown etiology (CKDU), we recruited 334 CKDU patients and 334 age and sex matched healthy controls. CYP1A1*2A and *2C polymorphisms were studied by PCR-RFLP and allele specific-PCR respectively. Subjects carrying at least one mutant allele of CYP1A1*2A (TC, CC) and *2C (AG, GG) were shown to be associated with 1.4-2-fold increased risk of CKDU. Also, genotypic combinations of hetero-/homozygous mutants of CYP1A1*2A (TC, CC) with hetero-/homozygous mutant genotypes of CYP1A1*2C (AG, GG) i.e. TC/AG (pCKDU with an odd ratio ranging 1.8-3.3 times approximately. This study demonstrates association of CYP1A1 polymorphisms with CKDU. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Visualisation of serotonin-1A (5-HT1A) receptors in the central nervous system

    International Nuclear Information System (INIS)

    Passchier, J.; Waarde, A. van

    2001-01-01

    The 5-HT 1A subtype of receptors for the neurotransmitter serotonin is predominantly located in the limbic forebrain and is involved in the modulation of emotion and the function of the hypothalamus. Since 5-HT 1A receptors are implicated in the pathogenesis of anxiety, depression, hallucinogenic behaviour, motion sickness and eating disorders, they are an important target for drug therapy. Here, we review the radioligands which are available for visualisation and quantification of this important neuroreceptor in the human brain, using positron emission tomography (PET) or single-photon emission tomography (SPET). More than 20 compounds have been labelled with carbon-11 (half-life 20 min), fluorine-18 (half-life 109.8 min) or iodine-123 (half-life 13.2 h): structural analogues of the agonist, 8-OH-DPAT, structural analogues of the antagonist, WAY 100635, and apomorphines. The most successful radioligands thus far are [carbonyl- 11 C] WAY-100635 (WAY), [carbonyl- 11 C]desmethyl-WAY-100635 (DWAY), p-[ 18 F]MPPF and [ 11 C]robalzotan (NAD-299). The high-affinity ligands WAY and DWAY produce excellent images of 5-HT 1A receptor distribution in the brain (even the raphe nuclei are visualised), but they cannot be distributed to remote facilities and they probably cannot be used to measure changes in endogenous serotonin. Binding of the moderate-affinity ligands MPPF and NAD-299 may be more sensitive to serotonin competition and MPPF can be distributed to PET centres within a flying distance of a few hours. Future research should be directed towards: (a) improvement of the metabolic stability in primates; (b) development of a fluorinated radioligand which can be produced in large quantities and (c) production of a radioiodinated or technetium-labelled ligand for SPET. (orig.)

  20. A secure mobile crowdsensing (MCS) location tracker for elderly in smart city

    Science.gov (United States)

    Shien, Lau Khai; Singh, Manmeet Mahinderjit

    2017-10-01

    According to the UN's (United Nations) projection, Malaysia will achieve ageing population status by 2030. The challenge of the growing ageing population is health and social care services. As the population lives longer, the costs of institutional care rises and elderly who not able live independently in their own homes without caregivers. Moreover, it restricted their activity area, safety and freedom in their daily life. Hence, a tracking system is worthy for their caregivers to track their real-time location with efficient. Currently tracking and monitoring systems are unable to satisfy the needs of the community. Hence, Indoor-Outdoor Elderly Secure and Tracking care system (IOET) proposed to track and monitor elderly. This Mobile Crowdsensing type of system is using indoor and outdoor positioning system to locate elder which utilizes the RFID, NFC, biometric system and GPS aim to secure the safety of elderly within indoors and outdoors environment. A mobile application and web-based application to be designed for this system. This system able to real-time tracking by combining GPS and NFC for outdoor coverage where ideally in smart city. In indoor coverage, the system utilizes active RFID tracking elderly movement. The system will prompt caregiver wherever elderly movement or request by using the notification service which provided the real-time notify. Caregiver also can review the place that visited by elderly and trace back elderly movement.

  1. Graphical interface between the CIRSSE testbed and CimStation software with MCS/CTOS

    Science.gov (United States)

    Hron, Anna B.

    1992-01-01

    This research is concerned with developing a graphical simulation of the testbed at the Center for Intelligent Robotic Systems for Space Exploration (CIRSSE) and the interface which allows for communication between the two. Such an interface is useful in telerobotic operations, and as a functional interaction tool for testbed users. Creating a simulated model of a real world system, generates inevitable calibration discrepancies between them. This thesis gives a brief overview of the work done to date in the area of workcell representation and communication, describes the development of the CIRSSE interface, and gives a direction for future work in the area of system calibration. The CimStation software used for development of this interface, is a highly versatile robotic workcell simulation package which has been programmed for this application with a scale graphical model of the testbed, and supporting interface menu code. A need for this tool has been identified for the reasons of path previewing, as a window on teleoperation and for calibration of simulated vs. real world models. The interface allows information (i.e., joint angles) generated by CimStation to be sent as motion goal positions to the testbed robots. An option of the interface has been established such that joint angle information generated by supporting testbed algorithms (i.e., TG, collision avoidance) can be piped through CimStation as a visual preview of the path.

  2. Nuclear spectrum data acquisition intelligent interface based on MCS-51 single chip microcomputer

    International Nuclear Information System (INIS)

    Xia Songjiang; Su Qin

    1991-01-01

    The intelligent interface consists of multichannel buffer and communication interface. It can acquire 4096 channels nuclear spectrum data. By connecting to a main computer, the data acquisition system has high resolution and foreground, background operating functions. The system features simple structure, reliable communication, convenient operation and high cost performance

  3. Standardization of 137mCs+137mBa by Liquid Scintillation

    International Nuclear Information System (INIS)

    Rodriguez, L.; Los Arcos, J.M.; Grau, A.

    1995-01-01

    A procedure for the preparation of a stable, homogeneous solution of 137Cs+''137mBa, for use in liquid scintillation measurements, is described. Its count rate stability and spectral time evolution has been followed for several weeks. The solution has been standardised by the CIEMAT/NIST method in both Ultima-Gold and Insta-Gel, to a combined uncertainty lower than 0,51 % (k=l). (Author) 5 refs

  4. Motivation, Challenges, Support (MCS) Cycle Model for the Development of PBL Tutors

    Science.gov (United States)

    Constantinou, Costas S.; Nicolaou, Stella A.

    2018-01-01

    Problem-Based Learning (PBL) is well known for enhancing students' problem solving skills and teamwork, while the role of PBL tutors is to facilitate discussion rather than teach. This study used four focus groups to explore PBL tutors' motivation, challenges and support mechanisms, and the relationship between these. The study found that there…

  5. 242-A MCS Logic Acceptance Test Report for Year 2000 Upgrade

    International Nuclear Information System (INIS)

    TEATS, M.C.

    1999-01-01

    242-A Evaporator distributive control system upgrade to D/3 version 9.0-2 for year 2000 compliance. Testing was performed per test procedure HNF-3568. There were no unresolved exceptions. The system responded correctly to all testing and meets the requirements to operate the 242-A This report documents the acceptance test results for the Evaporator facility

  6. Evolución de 1 año de un paciente rehabilitado con implantes oseointegrados de carga inmediata después de la resección quirúrgica de un cementoblastoma: Reporte clínico Clinical Report: Patient's progress one year after being treated with immediate loading bone integrated implants after removal of cementoblastomas

    Directory of Open Access Journals (Sweden)

    E.J. de Moraes

    2009-12-01

    Full Text Available Se presenta un caso clínico correspondiente a un paciente con diágnostico de dos cementoblastomas, en el cual, posterior a la resección quirúrgica de ambos tumores, se rehabilitó con una prótesis sobre implantes de carga inmediata. Para esto instalaron 4 implantes, utilizando el sistema de Carga Inmediata Speed Máster (Conexão Sistema de Prótesis- São Paulo- Brazil con la instalación de la prótesis 48 horas después de la cirugía. La evolución clínica y radiográfica fue seguida por 14 meses, comprobando que los implantes mantenían una condición adecuadaThe authors present a clinical case of a patient with two cementoblastomas who was treated with four implants installed using Speed Master System. The prosthesis was seated 48 hours after surgery. The clinical and radiographic follow-up was performed 14 months later and it was determined that the implants were in satisfactory conditions.

  7. DNA segment containing C/sub β1/, a gene for the constant region of the β chain of the T-cell antigen receptor, was inserted into chromosome 6 in cells from one patients with human T-cell leukemia

    International Nuclear Information System (INIS)

    Ino, T.; Kurosawa, Y.; Yoshida, M.C.; Hirano, M.

    1987-01-01

    DNA rearrangements that occurred in the vicinity of T-cell antigen receptor β-chain gene clusters residing on chromosome 7 were examined in human T-cell acute lymphoblastic leukemia cells. In one patient, it was observed that, for the T-cell receptor β-chain genes, a D/sub β 1/-J/sub β2.3/ (where D is diversity and J is joining) junction was found on one chromosome, while the other chromosome kept the germ-line configuration. If this D/sub β/-J/sub β/ junction was formed by the customary deletion mechanism, the C/sub β1/ gene (where C is constant) located between the D/sub β1/ and J/sub Β2.3/ loci should have disappeared from this chromosome. The C/sub β1/ gene indeed was absent from the rearranged chromosome 7, but it was found on chromosome 6 as an inserted segment. The implications of the observations are discussed

  8. Cytosolic 5′-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis

    Science.gov (United States)

    Rietveld, A; Pye, S R; Mariampillai, K; Benveniste, O; Peeters, M T J; Miller, J A L; Hanna, M G; Machado, P M; Parton, M J; Gheorghe, K R; Badrising, U A; Lundberg, I E; Sacconi, S; Herbert, M K; McHugh, N J; Lecky, B R F; Brierley, C; Hilton-Jones, D; Lamb, J A; Roberts, M E; Cooper, R G; Saris, C G J; Pruijn, G J M; Chinoy, H; van Engelen, B G M

    2017-01-01

    Objectives Autoantibodies directed against cytosolic 5′-nucleotidase 1A have been identified in many patients with inclusion body myositis. This retrospective study investigated the association between anticytosolic 5′-nucleotidase 1A antibody status and clinical, serological and histopathological features to explore the utility of this antibody to identify inclusion body myositis subgroups and to predict prognosis. Materials and methods Data from various European inclusion body myositis registries were pooled. Anticytosolic 5′-nucleotidase 1A status was determined by an established ELISA technique. Cases were stratified according to antibody status and comparisons made. Survival and mobility aid requirement analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression. Results Data from 311 patients were available for analysis; 102 (33%) had anticytosolic 5′-nucleotidase 1A antibodies. Antibody-positive patients had a higher adjusted mortality risk (HR 1.89, 95% CI 1.11 to 3.21, p=0.019), lower frequency of proximal upper limb weakness at disease onset (8% vs 23%, adjusted OR 0.29, 95% CI 0.12 to 0.68, p=0.005) and an increased prevalence of excess of cytochrome oxidase deficient fibres on muscle biopsy analysis (87% vs 72%, adjusted OR 2.80, 95% CI 1.17 to 6.66, p=0.020), compared with antibody-negative patients. Interpretation Differences were observed in clinical and histopathological features between anticytosolic 5′-nucleotidase 1A antibody positive and negative patients with inclusion body myositis, and antibody-positive patients had a higher adjusted mortality risk. Stratification of inclusion body myositis by anticytosolic 5′-nucleotidase 1A antibody status may be useful, potentially highlighting a distinct inclusion body myositis subtype with a more severe phenotype. PMID:28122761

  9. Cytosolic 5'-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis.

    Science.gov (United States)

    Lilleker, J B; Rietveld, A; Pye, S R; Mariampillai, K; Benveniste, O; Peeters, M T J; Miller, J A L; Hanna, M G; Machado, P M; Parton, M J; Gheorghe, K R; Badrising, U A; Lundberg, I E; Sacconi, S; Herbert, M K; McHugh, N J; Lecky, B R F; Brierley, C; Hilton-Jones, D; Lamb, J A; Roberts, M E; Cooper, R G; Saris, C G J; Pruijn, G J M; Chinoy, H; van Engelen, B G M

    2017-05-01

    Autoantibodies directed against cytosolic 5'-nucleotidase 1A have been identified in many patients with inclusion body myositis. This retrospective study investigated the association between anticytosolic 5'-nucleotidase 1A antibody status and clinical, serological and histopathological features to explore the utility of this antibody to identify inclusion body myositis subgroups and to predict prognosis. Data from various European inclusion body myositis registries were pooled. Anticytosolic 5'-nucleotidase 1A status was determined by an established ELISA technique. Cases were stratified according to antibody status and comparisons made. Survival and mobility aid requirement analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression. Data from 311 patients were available for analysis; 102 (33%) had anticytosolic 5'-nucleotidase 1A antibodies. Antibody-positive patients had a higher adjusted mortality risk (HR 1.89, 95% CI 1.11 to 3.21, p=0.019), lower frequency of proximal upper limb weakness at disease onset (8% vs 23%, adjusted OR 0.29, 95% CI 0.12 to 0.68, p=0.005) and an increased prevalence of excess of cytochrome oxidase deficient fibres on muscle biopsy analysis (87% vs 72%, adjusted OR 2.80, 95% CI 1.17 to 6.66, p=0.020), compared with antibody-negative patients. Differences were observed in clinical and histopathological features between anticytosolic 5'-nucleotidase 1A antibody positive and negative patients with inclusion body myositis, and antibody-positive patients had a higher adjusted mortality risk. Stratification of inclusion body myositis by anticytosolic 5'-nucleotidase 1A antibody status may be useful, potentially highlighting a distinct inclusion body myositis subtype with a more severe phenotype. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  10. Inhibitory Effects of Commonly Used Herbal Extracts on UDP-Glucuronosyltransferase 1A4, 1A6, and 1A9 Enzyme Activities

    Science.gov (United States)

    Mohamed, Mohamed-Eslam F.

    2011-01-01

    The aim of this study was to investigate the effect of commonly used botanicals on UDP-glucuronosyltransferase (UGT) 1A4, UGT1A6, and UGT1A9 activities in human liver microsomes. The extracts screened were black cohosh, cranberry, echinacea, garlic, ginkgo, ginseng, milk thistle, saw palmetto, and valerian in addition to the green tea catechin epigallocatechin gallate (EGCG). Formation of trifluoperazine glucuronide, serotonin glucuronide, and mycophenolic acid phenolic glucuronide was used as an index reaction for UGT1A4, UGT1A6, and UGT1A9 activities, respectively, in human liver microsomes. Inhibition potency was expressed as the concentration of the inhibitor at 50% activity (IC50) and the volume in which the dose could be diluted to generate an IC50-equivalent concentration [volume/dose index (VDI)]. Potential inhibitors were EGCG for UGT1A4, milk thistle for both UGT1A6 and UGT1A9, saw palmetto for UGT1A6, and cranberry for UGT1A9. EGCG inhibited UGT1A4 with an IC50 value of (mean ± S.E.) 33.8 ± 3.1 μg/ml. Milk thistle inhibited both UGT1A6 and UGT1A9 with IC50 values of 59.5 ± 3.6 and 33.6 ± 3.1 μg/ml, respectively. Saw palmetto and cranberry weakly inhibited UGT1A6 and UGT1A9, respectively, with IC50 values >100 μg/ml. For each inhibition, VDI was calculated to determine the potential of achieving IC50-equivalent concentrations in vivo. VDI values for inhibitors indicate a potential for inhibition of first-pass glucuronidation of UGT1A4, UGT1A6, and UGT1A9 substrates. These results highlight the possibility of herb-drug interactions through modulation of UGT enzyme activities. Further clinical studies are warranted to investigate the in vivo extent of the observed interactions. PMID:21632963

  11. Large-scale structural alteration of brain in epileptic children with SCN1A mutation

    OpenAIRE

    Lee, Yun-Jeong; Yum, Mi-Sun; Kim, Min-Jee; Shim, Woo-Hyun; Yoon, Hee Mang; Yoo, Il Han; Lee, Jiwon; Lim, Byung Chan; Kim, Ki Joong; Ko, Tae-Sung

    2017-01-01

    Objective: Mutations in SCN1A gene encoding the alpha 1 subunit of the voltage gated sodium channel are associated with several epilepsy syndromes including genetic epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). However, in most patients with SCN1A mutation, brain imaging has reported normal or non-specific findings including cerebral or cerebellar atrophy. The aim of this study was to investigate differences in brain morphometry in epileptic chil...

  12. Are the changes in observed functioning after multi-disciplinary rehabilitation of patients with fibromyalgia associated with changes in pain self-efficacy?

    DEFF Research Database (Denmark)

    Rasmussen, Marianne Uggen; Amris, Kirstine; Rydahl Hansen, Susan

    2017-01-01

    OBJECTIVE: To examine the hypothesis that change in pain self-efficacy is associated with observed and self-reported activity, pain intensity, catastrophizing, and quality of life after multi-disciplinary rehabilitation of fibromyalgia patients. DESIGN: In-depth analyses of secondary outcomes...... of a randomized-controlled trial. SUBJECTS: Women (N = 187) with fibromyalgia. METHODS: Outcomes were Pain Self-Efficacy, Assessment of Motor and Process Skills (AMPS), SF-36 Physical Function (SF-36-PF), pain intensity, and SF-36 Mental Composite Score (SF-36-MCS) to assess quality of life and pain...... catastrophizing. Individual and group associations between outcomes were examined. RESULTS: Individual changes in pain self-efficacy were not associated with changes in observed activity: AMPS motor (rs = 0.08, p = 0.27) and process (rs = 0.12, p = 0.11), not even in those patients with a clinically relevant...

  13. Apo-ghrelin receptor (apo-GHSR1a Regulates Dopamine Signaling in the Brain

    Directory of Open Access Journals (Sweden)

    Andras eKern

    2014-08-01

    Full Text Available The orexigenic peptide hormone ghrelin is synthesized in the stomach and its receptor growth hormone secretagogue receptor (GHSR1a is expressed mainly in the central nervous system (CNS. In this review we confine our discussion to the physiological role of GHSR1a in the brain. Paradoxically, despite broad expression of GHSR1a in the CNS, other than trace amounts in the hypothalamus, ghrelin is undetectable in the brain. In our efforts to elucidate the function of the ligand-free ghrelin receptor (apo-GHSR1a we identified subsets of neurons that co-express GHSR1a and dopamine receptors. In this review we focus on interactions between apo-GHSR1a and dopamine-2 receptor (DRD2 and formation of GHSR1a:DRD2 heteromers in hypothalamic neurons that regulate appetite, and discuss implications for the treatment of Prader-Willi syndrome. GHSR1a antagonists of distinct chemical structures, a quinazolinone and a triazole, respectively enhance and inhibit dopamine signaling through GHSR1a:DRD2 heteromers by an allosteric mechanism. This finding illustrates a potential strategy for designing the next generation of drugs for treating eating disorders as well as psychiatric disorders caused by abnormal dopamine signaling. Treatment with a GHSR1a antagonist that enhances dopamine/DRD2 activity in GHSR1a:DRD2 expressing hypothalamic neurons has the potential to inhibit the uncontrollable hyperphagia associated with Prader-Willi syndrome. DRD2 antagonists are prescribed for treating schizophrenia, but these block dopamine signaling in all DRD2 expressing neurons and are associated with adverse side effects, including enhanced appetite and excessive weight gain. A GHSR1a antagonist of structural class that allosterically blocks dopamine/DRD2 action in GHSR1a:DRD2 expressing neurons would have no effect on neurons expressing DRD2 alone; therefore, the side effects of DRD2 antagonists would potentially be reduced thereby enhancing patient compliance.

  14. Health-related quality of life is related to cytokine levels at 12 months in patients with chronic heart failure

    DEFF Research Database (Denmark)

    Mommersteeg, Paula M C; Kupper, Nina; Schoormans, Dounya

    2010-01-01

    for the MLHFQ, the SF-36 mental component summary (MCS) and the physical component summary (PCS), controlling for age, sex, BMI, smoking, co morbidity, NYHA-class and 6min walk test. Baseline MLHFQ was associated with increased levels of baseline sTNFR2, and 12-month sTNFR1 12month sTNFR2. Baseline MCS...

  15. A novel index for quantifying the risk of early complications for patients undergoing cervical spine surgeries.

    Science.gov (United States)

    Passias, Peter G; Diebo, Bassel G; Marascalchi, Bryan J; Jalai, Cyrus M; Horn, Samantha R; Zhou, Peter L; Paltoo, Karen; Bono, Olivia J; Worley, Nancy; Poorman, Gregory W; Challier, Vincent; Dixit, Anant; Paulino, Carl; Lafage, Virginie

    2017-11-01

    OBJECTIVE It is becoming increasingly necessary for surgeons to provide evidence supporting cost-effectiveness of surgical treatment for cervical spine pathology. Anticipating surgical risk is critical in accurately evaluating the risk/benefit balance of such treatment. Determining the risk and cost-effectiveness of surgery, complications, revision procedures, and mortality rates are the most significant limitations. The purpose of this study was to determine independent risk factors for medical complications (MCs), surgical complications (SCs), revisions, and mortality rates following surgery for patients with cervical spine pathology. The most relevant risk factors were used to structure an index that will help quantify risk and anticipate failure for such procedures. METHODS The authors of this study performed a retrospective review of the National Inpatient Sample (NIS) database for patients treated surgically for cervical spine pathology between 2001 and 2010. Multivariate models were performed to calculate the odds ratio (OR) of the independent risk factors that led to MCs and repeated for SCs, revisions, and mortality. The models controlled for age ( 65 years old), sex, race, revision status (except for revision analysis), surgical approach, number of levels fused/re-fused (2-3, 4-8, ≥ 9), and osteotomy utilization. ORs were weighted based on their predictive category: 2 times for revision surgery predictors and 4 times for mortality predictors. Fifty points were distributed among the predictors based on their cumulative OR to establish a risk index. RESULTS Discharges for 362,989 patients with cervical spine pathology were identified. The mean age was 52.65 years, and 49.47% of patients were women. Independent risk factors included medical comorbidities, surgical parameters, and demographic factors. Medical comorbidities included the following: pulmonary circulation disorder, coagulopathy, metastatic cancer, renal failure, congestive heart failure

  16. 5-HT 1A polymorphism and self-transcendence in mood disorders.

    Science.gov (United States)

    Lorenzi, Cristina; Serretti, Alessandro; Mandelli, Laura; Tubazio, Viviana; Ploia, Cristina; Smeraldi, Enrico

    2005-08-05

    Recently, an association between serotonin 1A receptor binding potential and self-transcendence scores at the temperament and character inventory (TCI) has been reported. We tested involvement of 5-HT(1A) gene in this trait, in a sample of 40 remitted mood disorder patients. Subjects with the 5-HT(1A)*C/C genotype showed significantly lower scores at the total self-transcendence and at the sub-scales of transpersonal identification and spiritual acceptance. Our preliminary results further support the involvement of the serotoninergic pattern in the self-transcendence character trait. (c) 2005 Wiley-Liss, Inc.

  17. Quality of life, clinical outcomes and safety of early prophylactic levothyroxine administration in patients with Graves' hyperthyroidism undergoing radioiodine therapy: a randomized controlled study.

    Science.gov (United States)

    Taïeb, David; Bournaud, Claire; Eberle, Marie-Claude; Catargi, Bogdan; Schvartz, Claire; Cavarec, Marie-Béatrice; Faugeron, Isabelle; Toubert, Marie-Elisabeth; Benisvy, Danielle; Archange, Cendrine; Mundler, Olivier; Caron, Philippe; Abdullah, Ahmad Esmaeel; Baumstarck, Karine

    2016-04-01

    While radioiodine therapy is commonly used for treating Graves' disease, a prolonged and clinical hypothyroidism may result in disabling symptoms leading to deterioration of quality of life (QoL) of patients. Introducing levothyroxine (LT4) treatment in the early post-therapeutic period may be an interesting approach to limit this phenomenon. A multicenter, prospective, open-label randomized controlled trial enrolled 94 patients with Graves' hyperthyroidism randomly assigned to the experimental group (n=46) (group A: early prophylactic LT4 treatment) or the control group (n=48) (group B: standard follow-up). The primary endpoint was the 6-month QoL. The secondary endpoints were other QoL scores such as Graves' ophthalmopathy (GO) outcomes, thyroid function tests and safety. The primary endpoint at 6 months was achieved: the mental composite score (MCS) of Short Form 36 (SF-36) was significantly higher in group A compared to group B (P=0.009). Four other dimension scores of the SF-36 and four dimension scores of the thyroid-specific patient-reported outcome (ThyPRO) significantly differed between the two groups, indicating better QoL in group A. After adjustment for variables, the early LT4 administration strategy was found as an independent factor for only two scores of SF-36: the MCS and the general health (GH) score. There were no differences in GO, final thyroid status and changes in the anti-TSH receptor antibodies (TRAbs) levels between the two groups. No adverse cardiovascular event was reported. Early LT4 administration post-radioactive iodine (RAI) could represent a safe potential benefit for patients with regard to QoL. The optimal strategy taking into account administered RAI activities and LT4 treatment dosage and timing remains to be determined. © 2016 European Society of Endocrinology.

  18. Association between helplessness, disability, and disease activity with health-related quality of life among rheumatoid arthritis patients in a multiethnic Asian population.

    Science.gov (United States)

    Kwan, Yu Heng; Koh, Ee Tzun; Leong, Khai Pang; Wee, Hwee-Lin

    2014-08-01

    To investigate the association between helplessness, disability, and disease activity with health-related quality of life (HRQoL) in a multiethnic cohort of rheumatoid arthritis (RA) patients in Singapore. This cross-sectional study was conducted at Tan Tock Seng Hospital, Department of Rheumatology, Allergy and Immunology, from October 2010 to October 2011. All patients fulfilled the American College of Rheumatology 1987 criteria for RA. Socio-demographics, clinical, and patient-reported outcome (PRO) variables were collected. HRQoL outcomes were Short Form 36 (SF-36) physical and mental component summary (PCS and MCS) scores and Short Form 6 Dimensions (SF-6D) utilities. Stepwise multiple linear regression analyses were performed using HRQoL outcomes as dependent variables in separate models and with adjustment for helplessness (Rheumatology Attitudes Index, RAI), disability (Health Assessment Questionnaire, HAQ), and disease activity (Disease Activity in 28 joints) followed by socio-demographic, clinical, and PRO variables. Complete data were provided by 473 consenting subjects [mean (SD) age: 60.02 (11.04) years, 85 % female, 77 % Chinese]. After adjustment for all measured covariates, only RAI and HAQ scores remained significantly associated with SF-36 MCS (β: -0.9, p < 0.001; β: -7.0, p < 0.001) and SF-6D utilities (β: -0.005, p < 0.001; β: -0.081, p < 0.001), respectively, while only HAQ scores were significantly associated with SF-36 PCS (β: -7.7, p < 0.001). Interventions to address the sense of helplessness and to prevent or reduce disability could improve HRQoL of RA patients.

  19. Single-use autoinjector for once-weekly intramuscular injection of IFNβ-1a.

    Science.gov (United States)

    Limmroth, Volker; Gerbershagen, Kathrin

    2014-12-01

    IFNβ products and glatiramer acetate are established treatment first-line options in long-term disease-modifying therapy of multiple sclerosis (MS). These self-injectable medications are used once weekly to once daily. Injection-related issues are common patient-cited reasons for nonadherence. Autoinjectors have been shown to support long-term adherence to injectable medications. The ability to self-inject in MS patients has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patient independence. The recently introduced easy-to-use prefilled once-weekly pen is a safe and effective device for intramuscular (IM) IFNβ-1a application and provides a convenient method for self-injection. We reviewed the available published evidence on the characteristics of this device. The once-weekly pen facilitates self-injection and was preferred over prefilled syringes by patients in a prospective open-label, multicenter Phase IIIb trial in MS patients who had been using IM IFNβ-1a in prefilled syringes. The simple and safe handling, shielded short needle, single-use disposable design and virtually painless injection by the device may contribute to adherence, quality of life and independence in patients using IM IFNβ-1a.

  20. The presence of both serotonin 1A receptor (HTR1A and dopamine transporter (DAT1 gene variants increase the risk of borderline personality disorder

    Directory of Open Access Journals (Sweden)

    Peter R Joyce

    2014-01-01

    Full Text Available Dysfunction in the dopaminergic and serotonergic neurotransmitter systems has been demonstrated to be important in the aetiology of Borderline personality disorder (BPD. We investigated the relationship of two BPD risk factors, the HTR1A promoter polymorphism -1019C>G (rs6295 and the DAT1 repeat allele, with BPD in a major depressive disorder cohort of 367 patients. Out-patients with major depressive disorder were recruited for two treatment trials and assessed for personality disorders, including BPD. DNA samples were collected and the rs6295 polymorphism was detected with a TaqMan® assay. The DAT1 repeat allele was genotyped using a modified PCR method. The impact of polymorphisms on BPD was statistically analysed using uncontrolled logistic and multiple logistic regression models. BPD patients had higher frequencies of the DAT1 9,9 (OR=2.67 and 9,10 (OR=3.67 genotypes and also those homozygous HTR1A G allele (OR=2.03. No significant interactions between HTR1A and DAT1 genotypes, were observed; however, an increased risk of BPD was observed for those patients who were either 9,10; G,G (OR=6.64 and 9,9; C,G (OR=5.42. Furthermore, the odds of BPD in patients exhibiting high-risk variants of these two genes differed from those of patients in low-risk groups by up to a factor of 9. Our study provides evidence implicating the importance of the serotonergic and dopaminergic systems in BPD and that the interaction between genes from different neurotransmitters may play a role in the susceptibility to BPD.

  1. Large-scale structural alteration of brain in epileptic children with SCN1A mutation.

    Science.gov (United States)

    Lee, Yun-Jeong; Yum, Mi-Sun; Kim, Min-Jee; Shim, Woo-Hyun; Yoon, Hee Mang; Yoo, Il Han; Lee, Jiwon; Lim, Byung Chan; Kim, Ki Joong; Ko, Tae-Sung

    2017-01-01

    Mutations in SCN1A gene encoding the alpha 1 subunit of the voltage gated sodium channel are associated with several epilepsy syndromes including genetic epilepsy with febrile seizures plus (GEFS +) and severe myoclonic epilepsy of infancy (SMEI). However, in most patients with SCN1A mutation, brain imaging has reported normal or non-specific findings including cerebral or cerebellar atrophy. The aim of this study was to investigate differences in brain morphometry in epileptic children with SCN1A mutation compared to healthy control subjects. We obtained cortical morphology (thickness, and surface area) and brain volume (global, subcortical, and regional) measurements using FreeSurfer (version 5.3.0, https://surfer.nmr.mgh.harvard.edu) and compared measurements of children with epilepsy and SCN1A gene mutation ( n  = 21) with those of age and gender matched healthy controls ( n  = 42). Compared to the healthy control group, children with epilepsy and SCN1A gene mutation exhibited smaller total brain, total gray matter and white matter, cerebellar white matter, and subcortical volumes, as well as mean surface area and mean cortical thickness. A regional analysis revealed significantly reduced gray matter volume in the patient group in the bilateral inferior parietal, left lateral orbitofrontal, left precentral, right postcentral, right isthmus cingulate, right middle temporal area with smaller surface area and white matter volume in some of these areas. However, the regional cortical thickness was not significantly different in two groups. This study showed large-scale developmental brain changes in patients with epilepsy and SCN1A gene mutation, which may be associated with the core symptoms of the patients. Further longitudinal MRI studies with larger cohorts are required to confirm the effect of SCN1A gene mutation on structural brain development.

  2. Mutational analysis of the promoter and the coding region of the 5-HT1A gene

    Energy Technology Data Exchange (ETDEWEB)

    Erdmann, J.; Noethen, M.M.; Shimron-Abarbanell, D. [Univ. of Bonn (Germany)] [and others

    1994-09-01

    Disturbances of serotonergic pathways have been implicated in many neuropsychiatric disorders. Serotonin (5HT) receptors can be subdivided into at least three major families (5HT1, 5HT2, and 5HT3). Five human 5HT1 receptor subtypes have been cloned, namely 1A, 1D{alpha}, 1D{beta}, 1E, and 1F. Of these, the 5HT1A receptor is the best characterized subtype. In the present study we sought to identify genetic variation in the 5HT1A receptor gene which through alteration of protein function or level of expression might contribute to the genetics of neuropsychiatric diseases. The coding region and the 5{prime} promoter region of the 5HT1A gene from 159 unrelated subjects (45 schizophrenic, 46 bipolar affective, and 43 patients with Tourette`s syndrome, as well as 25 controls) were analyzed using SSCA. SSCA revealed the presence of two mutations both located in the coding region of the 5HT1A receptor gene. The first mutation is a rare silent C{r_arrow}T substitution at nucleotide position 549. The second mutation is characterized by a base pair substitution (A{r_arrow}G) at the first position of codon 28 and results in an amino acid exchange (Ile{r_arrow}Val). Since Val28 was found only in a single schizophrenic patient and in none of the other patients or controls, we decided to extend our samples and to use a restriction assay for screening a further 74 schizophrenic, 95 bipolar affective, and 49 patients with Tourette`s syndrome, as well as 185 controls, for the presence of the mutation. In total, the mutation was found in 2 schizophrenic patients, in 3 bipolars, in 1 Tourette patient, and in 5 controls. To our knowledge the Ile-28-Val substitution reported here is the first natural occuring molecular variant which has been identified for a serotonin receptor so far.

  3. Comparison of surgical treatment with direct repair versus conservative treatment in young patients with spondylolysis: a prospective, comparative, clinical trial.

    Science.gov (United States)

    Lee, Gun Woo; Lee, Sun-Mi; Ahn, Myun-Whan; Kim, Ho-Joong; Yeom, Jin S

    2015-07-01

    Although direct repair (DR) with screw fixation at the pars defect is a common surgical treatment for lumbar spondylolysis, it is unknown whether DR leads to better outcomes for young patients with spondylolysis than traditional nonsurgical treatment. The purpose of the study was to investigate whether DR was associated with better outcomes for lumbar spondylolysis in young patients than traditional conservative treatment. This is a prospective cohort study. Of 1,784 patients with low back pain in the reference period, 149 young patients with spondylolysis who followed up for at least 1 year were enrolled in the study. The primary outcome was pain intensity at the lower back measured with a Visual Analog Scale. Secondary outcomes included the functional outcome as measured with the Oswestry disability index (ODI) and the 12-item short-form health survey (SF-12) consisting of the physical component summary (PCS) and mental component summary (MCS) scores, the radiologic outcome as measured with lumbar spine radiographs and computed tomography scans, and complications of treatment. This was a prospective comparative study between two groups of patients who were treated with either conservative treatment or surgery for lumbar spondylolysis. Enrolled patients self-selected their own treatment and were allocated to either the traditional care group with conservative treatment (87 patients) or the surgery group (62 patients). All patients were followed up for at least 1 year. Pain intensity at the lower back did not differ significantly between groups at the final follow-up. Likewise, the ODI and SF-12 (PCS and MCS) scores did not differ significantly between groups (p=.13, .71, and .68, respectively). The change in the gap distance of the pars defect at the final follow-up was significantly different between groups (traditional care group: +0.8±0.4 mm; surgery group: -0.7±0.5; p=.01). The union rate at 1 year after surgical treatment was 52% (32/61). The rate of

  4. Frequency of polymorphisms and protein expression of cyclin-dependent kinase inhibitor 1A (CDKN1A in central nervous system tumors

    Directory of Open Access Journals (Sweden)

    Mev Dominguez Valentin

    Full Text Available CONTEXT AND OBJECTIVE: Genetic investigation of central nervous system (CNS tumors provides valuable information about the genes regulating proliferation, differentiation, angiogenesis, migration and apoptosis in the CNS. The aim of our study was to determine the prevalence of genetic polymorphisms (codon 31 and 3' untranslated region, 3'UTR and protein expression of the cyclin-dependent kinase inhibitor 1A (CDKN1A gene in patients with and without CNS tumors. DESIGN AND SETTING: Analytical cross-sectional study with a control group, at the Molecular Biology Laboratory, Pediatric Oncology Department, Hospital das Clínicas de Ribeirão Preto. METHODS: 41 patients with CNS tumors and a control group of 161 subjects without cancer and paires for sex, age and ethnicity were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. Protein analysis was performed on 36 patients with CNS tumors, using the Western Blotting technique. RESULTS: The frequencies of the heterozygote (Ser/Arg and polymorphic homozygote (Arg/Arg genotypes of codon 31 in the control subjects were 28.0% and 1.2%, respectively. However, the 3'UTR site presented frequencies of 24.2% (C/T and 0.6% (T/T. These frequencies were not statistically different (P > 0.05 from those seen in the patients with CNS tumors (19.4% and 0.0%, codon 31; 15.8% and 2.6%, 3'UTR site. Regarding the protein expression in ependymomas, 66.67% did not express the protein CDKN1A. The results for medulloblastomas and astrocytomas were similar: neither of them expressed the protein (57.14% and 61.54%, respectively. CONCLUSION: No significant differences in protein expression patterns or polymorphisms of CDKN1A in relation to the three types of CNS tumors were observed among Brazilian subjects.

  5. Methionine synthase A2756G and reduced folate carrier1 A80G ...

    African Journals Online (AJOL)

    Maha Moustafa

    2015-10-09

    Oct 9, 2015 ... folate carrier (RFC1) A80G gene polymorphisms on the maternal risk for DS. Patients: This ... Peer review under responsibility of Ain Shams University. ... Folate is the general term for a water-soluble B vitamin (vita- min B9) ...

  6. CD1a expression in psoriatic skin following treatment with propylthiouracil, an antithyroid thioureylene

    Directory of Open Access Journals (Sweden)

    Barr Ronald J

    2003-07-01

    Full Text Available Abstract Background The antithyroid thioureylenes, propylthiouracil (PTU and methimazole (MMI, are effective in the treatment of patients with plaque psoriasis. The mechanism of action of the drugs in psoriasis is unknown. Since the drugs reduce circulating IL-12 levels in patients with Graves' hyperthyroidism, the effect of propylthiouracil on CD1a expression in psoriatic lesions was examined in biopsy samples of patients with plaque psoriasis. CD1a is a marker of differentiated skin antigen presenting cells (APC, Langerhans cells. Langerhans cells and skin monocyte/macrophages are the source of IL-12, a key cytokine involved in the events that lead to formation of the psoriatic plaque. Methods Biopsy specimens were obtained from six patients with plaque psoriasis who were treated with 300 mg propylthiouracil (PTU daily for three months. Clinical response to PTU as assessed by PASI scores, histological changes after treatment, and CD1a expression in lesional skin before and after treatment were studied. Results Despite significant improvement in clinical and histological parameters the expression of CD1a staining cells in the epidermis did not decline with propylthiouracil treatment. Conclusions It appears that the beneficial effect of propylthiouracil in psoriasis is mediated by mechanisms other than by depletion of skin antigen-presenting cells.

  7. Methionine synthase A2756G and reduced folate carrier1 A80G ...

    African Journals Online (AJOL)

    Aim of the study: To analyze the effect of methionine synthase (MTR) A2756G, and reduced folate carrier (RFC1) A80G gene polymorphisms on the maternal risk for DS. Patients: This study was conducted in the Medical Genetics Center, Ain-Shams University hospitals, on a total of 170 mothers of children, diagnosed with ...

  8. Variable phenotypes associated with 10q23 microdeletions involving the PTEN and BMPR1A genes.

    NARCIS (Netherlands)

    Menko, F.H.; Kneepkens, C.M.; Leeuw, N. de; Peeters, E.A.; Maldergem, L. van; Kamsteeg, E.J.; Davidson, R.; Rozendaal, L.; Lasham, C.A.; Peeters-Scholte, C.M.; Jansweijer, M.C.E.; Hilhorst-Hofstee, Y.; Gille, J.J.P.; Heins, Y.M.; Nieuwint, A.W.; Sistermans, E.A.

    2008-01-01

    Infantile juvenile polyposis is a rare disease with severe gastrointestinal symptoms and a grave clinical course. Recently, 10q23 microdeletions involving the PTEN and BMPR1A genes were found in four patients with infantile juvenile polyposis. It was hypothesized that a combined and synergistic

  9. 12 CFR 528.1a - Supplementary guidelines.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Supplementary guidelines. 528.1a Section 528.1a Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY NONDISCRIMINATION REQUIREMENTS § 528.1a Supplementary guidelines. The Office's policy statement found at 12 CFR 528.9 supplements...

  10. Cystatin C is not a good candidate biomarker for HNF1A-MODY.

    Science.gov (United States)

    Nowak, Natalia; Szopa, Magdalena; Thanabalasingham, Gaya; McDonald, Tim J; Colclough, Kevin; Skupien, Jan; James, Timothy J; Kiec-Wilk, Beata; Kozek, Elzbieta; Mlynarski, Wojciech; Hattersley, Andrew T; Owen, Katharine R; Malecki, Maciej T

    2013-10-01

    Cystatin C is a marker of glomerular filtration rate (GFR). Its level is influenced, among the others, by CRP whose concentration is decreased in HNF1A-MODY. We hypothesized that cystatin C level might be altered in HNF1A-MODY. We aimed to evaluate cystatin C in HNF1A-MODY both as a diagnostic marker and as a method of assessing GFR. We initially examined 51 HNF1A-MODY patients, 56 subjects with type 1 diabetes (T1DM), 39 with type 2 diabetes (T2DM) and 43 non-diabetic individuals (ND) from Poland. Subjects from two UK centres were used as replication panels: including 215 HNF1A-MODY, 203 T2DM, 39 HNF4A-MODY, 170 GCK-MODY, 17 HNF1B-MODY and 58 T1DM patients. The data were analysed with additive models, adjusting for gender, age, BMI and estimated GFR (creatinine). In the Polish subjects, adjusted cystatin C level in HNF1A-MODY was lower compared with T1DM, T2DM and ND (p MODY, while the two GFR estimates were similar or cystatin C-based lower in the other groups. In the UK subjects, there were no differences in cystatin C between HNF1A-MODY and the other diabetic subgroups, except HNF1B-MODY. In UK HNF1A-MODY, cystatin C-based GFR estimate was higher than the creatinine-based one (p MODY. In HNF1A-MODY, the cystatin C-based GFR estimate is higher than the creatinine-based one.

  11. UGT1A6 polymorphisms modulated lung cancer risk in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Ley-Fang Kua

    Full Text Available Uridine diphosphoglucuronosyltransferases (UGTs 1A6 is the only UGT1A isoform expressed in lung tissue. It is responsible for the detoxification of carcinogens such as benezo[a]pyrene from cigarette smoke. The purpose of this study was to evaluate the association of UGT1A6 polymorphisms and haplotypes with lung cancer risk and to evaluate the functional significance of UGT1A6 polymorphisms. Genomic DNA was isolated from leukocytes. Eight UGT1A6 polymorphisms were sequenced in a test set of 72 Chinese lung cancer patients and 62 healthy controls. Potential risk modifying alleles were validated in a separate set of 95 Chinese lung cancer patients and 100 healthy controls. UGT1A6 19T>G, 541A>G and 552A>C showed significant association with increased lung cancer risk, while UGT1A6 105C>T and IVS1+130G>T were significantly associated with reduced lung cancer risk. Multivariate logistic regression analysis demonstrated a significant association of lung cancer with UGT1A6 541A>G (OR: 3.582, 95% CI: 1.27-10.04, p = 0.015, 552A>C (OR: 5.364, 95% CI: 1.92-14.96, p = 0.001 and IVS1+130G>T (OR: 0.191, 95% CI: 0.09-0.36, pT increased mRNA stability, providing a plausible explanation of its association with reduced lung cancer risk. Thus UGT1A6 polymorphisms may be used to identify people with increased risk of developing lung cancer.

  12. Impact of demographic and comorbid conditions on quality of life of hemodialysis patients: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Qusay Mohammed Mandoorah

    2014-01-01

    Full Text Available To assess the quality of life (QOL of Saudi Arabian patients undergoing hemo-dialysis (HD and to determine the impact of gender, age, education and comorbidities on the QOL of these patients, we conducted a cross-sectional study and used the short form-36 (SF-36 questionnaire, a generic instrument for measuring QOL. This questionnaire is composed of eight scales that summarize the physical component scale (PCS and mental component scale (MCS of health status. We calculated the PCS and MCS scores for each patient. We studied 205 HD patients (123 men; ages 18-75 years from the King Fahd General Hospital, Jeddah, Saudi Arabia. The mean SF-36 score was 59.4 ± 21.7 in men and 41.9 ± 20.9 in women (P <0.0001. Patients older than 60 years had the worst score (41.5 ± 21.2, followed by patients aged 40-59 years (53.6 ± 22.8; patients aged 18-39 years had the best SF-36 score (57.5 ± 22.5; P <0.0001. Education had a positive impact on QOL (P <0.0001, whereas comorbid conditions had a nega-tive impact. Peripheral vascular disease was associated with the worst outcome (SF-36 score, 40.4 ± 23.0; P <0.0001, followed by dyslipidemia (42.9 ± 22.4; P = 0.001 and diabetes mellitus (45.0 ± 22.0; P = 0.012. Among the comorbid conditions, hypertension was associated with the best SF-36 score (50.6 ± 22.7; P = 0.034. We conclude that old age, female gender, poor education and comorbid conditions have a negative impact on the QOL of HD patients in Saudi Arabia. These findings indicate a general need for social support for female patients on HD and early diagnosis and management of comorbid conditions.

  13. High-sensitivity CRP discriminates HNF1A-MODY from other subtypes of diabetes.

    Science.gov (United States)

    McDonald, Tim J; Shields, Beverley M; Lawry, Jane; Owen, Katharine R; Gloyn, Anna L; Ellard, Sian; Hattersley, Andrew T

    2011-08-01

    Maturity-onset diabetes of the young (MODY) as a result of mutations in hepatocyte nuclear factor 1-α (HNF1A) is often misdiagnosed as type 1 diabetes or type 2 diabetes. Recent work has shown that high-sensitivity C-reactive protein (hs-CRP) levels are lower in HNF1A-MODY than type 1 diabetes, type 2 diabetes, or glucokinase (GCK)-MODY. We aim to replicate these findings in larger numbers and other MODY subtypes. hs-CRP levels were assessed in 750 patients (220 HNF1A, 245 GCK, 54 HNF4-α [HNF4A], 21 HNF1-β (HNF1B), 53 type 1 diabetes, and 157 type 2 diabetes). hs-CRP was lower in HNF1A-MODY (median [IQR] 0.3 [0.1-0.6] mg/L) than type 2 diabetes (1.40 [0.60-3.45] mg/L; P MODY (1.45 [0.46-2.88] mg/L; P MODY (0.60 [0.30-1.80] mg/L; P MODY (0.60 [0.10-2.8] mg/L; P = 0.07). hs-CRP discriminated HNF1A-MODY from type 2 diabetes with hs-CRP MODY than other forms of diabetes and may be used as a biomarker to select patients for diagnostic HNF1A genetic testing.

  14. CYP1A1, CYP1A2, SULT1A1 AND SULT1E1 ALLELIC POLYMORPHISM IN CASE OF GENITAL ENDOMETRIOSIS

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    Konstantin Sergeevich Kublinskiy

    2016-02-01

    Up-to-date molecular and genetic analyses reveal that women predisposed to genital endometriosis possess Allele G and Genotypes AG and GG of the polymorphic option A-4889G of the CYP1A1 gene and Allele A and Genotypes CA and AA of the polymorphic option C-734A of the CYP1A2 gene. The polymorphism of the promoter regions of the SULT1A1 (G-638A and SULT1E1 (C-174T genes is not associated with genital endometriosis in women.

  15. Novel POC1A mutation in primordial dwarfism reveals new insights for centriole biogenesis.

    Science.gov (United States)

    Koparir, Asuman; Karatas, Omer F; Yuceturk, Betul; Yuksel, Bayram; Bayrak, Ali O; Gerdan, Omer F; Sagiroglu, Mahmut S; Gezdirici, Alper; Kirimtay, Koray; Selcuk, Ece; Karabay, Arzu; Creighton, Chad J; Yuksel, Adnan; Ozen, Mustafa

    2015-10-01

    POC1A encodes a WD repeat protein localizing to centrioles and spindle poles and is associated with short stature, onychodysplasia, facial dysmorphism and hypotrichosis (SOFT) syndrome. These main features are related to the defect in cell proliferation of chondrocytes in growth plate. In the current study, we aimed at identifying the molecular basis of two patients with primordial dwarfism (PD) in a single family through utilization of whole-exome sequencing. A novel homozygous p.T120A missense mutation was detected in POC1A in both patients, a known causative gene of SOFT syndrome, and confirmed using Sanger sequencing. To test the pathogenicity of the detected mutation, primary fibroblast cultures obtained from the patients and a control individual were used. For evaluating the global gene expression profile of cells carrying p.T120A mutation in POC1A, we performed the gene expression array and compared their expression profiles to those of control fibroblast cells. The gene expression array analysis showed that 4800 transcript probes were significantly deregulated in cells with p.T120A mutation in comparison to the control. GO term association results showed that deregulated genes are mostly involved in the extracellular matrix and cytoskeleton. Furthermore, the p.T120A missense mutation in POC1A caused the formation of abnormal mitotic spindle structure, including supernumerary centrosomes, and changes in POC1A were accompanied by alterations in another centrosome-associated WD repeat protein p80-katanin. As a result, we identified a novel mutation in POC1A of patients with PD and showed that this mutation causes the formation of multiple numbers of centrioles and multipolar spindles with abnormal chromosome arrangement. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Association of IL1A and IL1B loci with primary open angle glaucoma

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    Mukhopadhyay Indranil

    2010-06-01

    Full Text Available Abstract Background Recent studies suggest that glaucoma is a neurodegenerative disease in which secondary degenerative losses occur after primary insult by raised Intraocular pressure (IOP or by other associated factors. It has been reported that polymorphisms in the IL1A and IL1B genes are associated with Primary Open Angle Glaucoma (POAG. The purpose of our study was to investigate the role of these polymorphisms in eastern Indian POAG patients. Methods The study involved 315 unrelated POAG patients, consisting of 116 High Tension Glaucoma (HTG patients with intra ocular pressure (IOP > 21 mmHg and 199 non-HTG patients (presenting IOP IL1A (-889C/T; rs1800587, IL1B (-511C/T; rs16944 and IL1B (3953C/T; rs1143634. Haplotype frequency was determined by Haploview 4.1 software. The association of individual SNPs and major haplotypes was evaluated using chi-square statistics. The p-value was corrected for multiple tests by Bonferroni method. Results No significant difference was observed in the allele and genotype frequencies for IL1A and IL1B SNPs between total pool of POAG patients and controls. However, on segregating the patient pool to HTG and non-HTG groups, weak association was observed for IL1A polymorphism (-889C/T where -889C allele was found to portray risk (OR = 1.380; 95% CI = 1.041-1.830; p = 0.025 for non-HTG patients. Similarly, 3953T allele of IL1B polymorphism (+3953C/T was observed to confer risk to HTG group (OR = 1.561; 95% CI = 1.022-2.385; p = 0.039. On haplotype analysis it was observed that TTC was significantly underrepresented in non-HTG patients (OR = 0.538; 95% CI = 0.356- 0.815; p = 0.003 while TCT haplotype was overrepresented in HTG patients (OR = 1.784; 95% CI = 1.084- 2.937; p = 0.022 compared to control pool. However, after correction for multiple tests by Bonferroni method, an association of only TTC haplotype with non-HTG cases sustained (pcorrected = 0.015 and expected to confer protection. Conclusion The study

  17. EХPERIENCE IN INTERFERON β-1A USE FOR TREATMENT OF MULTIPLE SCLEROSIS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    L. M. Kuzenkova

    2013-01-01

    Full Text Available Aim: to evaluate the impact of subcutaneous interferon β-1a on matrix metalloproteinases 3, 8, 9 (MMP, cytokines (tumor necrosis factor α — TNF α, and transforming growth factor β1 — TGF β1 levels in serum of children with relapsing-remitting multiple sclerosis. Patients and methods: the results of treatment of 32 patients with relapsing-remitting multiple sclerosis aged 12–18 years (22 girls and 10 boys were analyzed. Treatment efficacy was assessed by the number of relapsing-remitting multiple sclerosis exacerbations during 12 months, MRI data, MMP and cytokines dynamics in serum. Results: statistical evidence acquired for MMPs, their tissue inhibitor and cytokines levels decrease (p < 0,005 in patients receiving therapy with subcutaneous INF β-1a. Conclusions: subcutaneous interferon β-1а is highly efficient in treatment of relapsing-remitting multiple sclerosis in children and adolescents.

  18. Factors associated with quality of life among hemodialysis patients in Malaysia.

    Directory of Open Access Journals (Sweden)

    Nor Baizura Md Yusop

    Full Text Available Although hemodialysis treatment has greatly increased the life expectancy of end stage renal disease patients, low quality of life among hemodialysis patients is frequently reported. This cross-sectional study aimed to determine the relationship between medical history, hemodialysis treatment and nutritional status with the mental and physical components of quality of life in hemodialysis patients. Respondents (n=90 were recruited from Hospital Kuala Lumpur and dialysis centres of the National Kidney Foundation of Malaysia. Data obtained included socio-demography, medical history, hemodialysis treatment and nutritional status. Mental and physical quality of life were measured using the Mental Composite Summary (MCS and Physical Composite Summary (PCS of the Short-Form Health Survey 36-items, a generic core of the Kidney Disease Quality of Life Short Form. Two summary measures and total SF-36 was scored as 0-100, with a higher score indicating better quality of life. Approximately 26 (30% of respondents achieved the body mass index (24 kg/m(2 and more than 80% (n=77 achieved serum albumin level (>35.0 mg/dL recommended for hemodialysis patients. The majority of respondents did not meet the energy (n=72, 80% and protein (n=68,75% recommendations. The total score of SF-36 was 54.1 ± 19.2, while the score for the mental and physical components were 45.0 ± 8.6 and 39.6 ± 8.6, respectively. Factors associated with a higher MCS score were absence of diabetes mellitus (p=0.000 and lower serum calcium (p=0.004, while higher blood flow (p=0.000, higher serum creatinine (p=0.000 and lower protein intake (p=0.006 were associated with a higher PCS score. To improve the overall quality of life of hemodialysis patients, a multidisciplinary intervention that includes medical, dietetic and psychosocial strategies that address factors associated with mental and physical quality of life are warranted to reduce further health complications and to improve quality

  19. Factors associated with quality of life among hemodialysis patients in Malaysia.

    Science.gov (United States)

    Md Yusop, Nor Baizura; Yoke Mun, Chan; Shariff, Zalilah Mohd; Beng Huat, Choo

    2013-01-01

    Although hemodialysis treatment has greatly increased the life expectancy of end stage renal disease patients, low quality of life among hemodialysis patients is frequently reported. This cross-sectional study aimed to determine the relationship between medical history, hemodialysis treatment and nutritional status with the mental and physical components of quality of life in hemodialysis patients. Respondents (n=90) were recruited from Hospital Kuala Lumpur and dialysis centres of the National Kidney Foundation of Malaysia. Data obtained included socio-demography, medical history, hemodialysis treatment and nutritional status. Mental and physical quality of life were measured using the Mental Composite Summary (MCS) and Physical Composite Summary (PCS) of the Short-Form Health Survey 36-items, a generic core of the Kidney Disease Quality of Life Short Form. Two summary measures and total SF-36 was scored as 0-100, with a higher score indicating better quality of life. Approximately 26 (30%) of respondents achieved the body mass index (24 kg/m(2)) and more than 80% (n=77) achieved serum albumin level (>35.0 mg/dL) recommended for hemodialysis patients. The majority of respondents did not meet the energy (n=72, 80%) and protein (n=68,75%) recommendations. The total score of SF-36 was 54.1 ± 19.2, while the score for the mental and physical components were 45.0 ± 8.6 and 39.6 ± 8.6, respectively. Factors associated with a higher MCS score were absence of diabetes mellitus (p=0.000) and lower serum calcium (p=0.004), while higher blood flow (p=0.000), higher serum creatinine (p=0.000) and lower protein intake (p=0.006) were associated with a higher PCS score. To improve the overall quality of life of hemodialysis patients, a multidisciplinary intervention that includes medical, dietetic and psychosocial strategies that address factors associated with mental and physical quality of life are warranted to reduce further health complications and to improve quality of

  20. CD25+ B-1a Cells Express Aicda

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    Hiroaki Kaku

    2017-06-01

    Full Text Available B-1a cells are innate-like B-lymphocytes producing natural antibodies. Activation-induced cytidine deaminase (AID, a product of the Aicda gene, plays a central role in class-switch recombination and somatic hypermutation in B cells. Although a role for Aicda in B-1a cells has been suggested on the basis of experiments with knock out (KO mice, whether B-1a cells express Aicda, and if so, which B-1a cell subpopulation expresses Aicda, remains unknown. Here, we demonstrate that B-1 cells express Aicda, but at a level below that expressed by germinal center (GC B cells. We previously reported that B-1a cells can be subdivided based on CD25 expression. We show here that B-1a cell Aicda expression is concentrated in the CD25+ B-1a cell subpopulation. These results suggest the possibility that previous studies of memory B cells identified on the basis of Aicda expression may have inadvertently included an unknown number of CD25+ B-1a cells. Although B-1a cells develop normally in the absence of Aicda, a competitive reconstitution assay reveals enhanced vigor for AID KO B-1a cell bone marrow (BM progenitors, as compared with wild-type BM B-1 cell progenitors. These results suggest that AID inhibits the development of B-1a cells from BM B-1 cell progenitors in a competitive environment.

  1. Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.

    Science.gov (United States)

    Lal, Dennis; Reinthaler, Eva M; Dejanovic, Borislav; May, Patrick; Thiele, Holger; Lehesjoki, Anna-Elina; Schwarz, Günter; Riesch, Erik; Ikram, M Arfan; van Duijn, Cornelia M; Uitterlinden, Andre G; Hofman, Albert; Steinböck, Hannelore; Gruber-Sedlmayr, Ursula; Neophytou, Birgit; Zara, Federico; Hahn, Andreas; Gormley, Padhraig; Becker, Felicitas; Weber, Yvonne G; Cilio, Maria Roberta; Kunz, Wolfram S; Krause, Roland; Zimprich, Fritz; Lemke, Johannes R; Nürnberg, Peter; Sander, Thomas; Lerche, Holger; Neubauer, Bernd A

    2016-01-01

    The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.

  2. Strong synergistic induction of CYP1A1 expression by andrographolide plus typical CYP1A inducers in mouse hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Jaruchotikamol, Atika [Department of Toxicology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Jarukamjorn, Kanokwan [Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002 (Thailand); Sirisangtrakul, Wanna [Department of Toxicology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002 (Thailand); Sakuma, Tsutomu; Kawasaki, Yuki [Department of Toxicology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Nemoto, Nobuo [Department of Toxicology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan)

    2007-10-15

    The effects of andrographolide, the major diterpenoid constituent of Andrographis paniculata, on the expression of cytochrome P450 superfamily 1 members, including CYP1A1, CYP1A2, and CYP1B1, as well as on aryl hydrocarbon receptor (AhR) expression in primary cultures of mouse hepatocytes were investigated in comparison with the effects of typical CYP1A inducers, including benz[a]anthracene, {beta}-naphthoflavone, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Andrographolide significantly induced the expression of CYP1A1 and CYP1A2 mRNAs in a concentration-dependent manner, as did the typical CYP1A inducers, but did not induce that of CYP1B1 or AhR. Interestingly, andrographolide plus the typical CYP1A inducers synergistically induced CYP1A1 expression, and the synergism was blocked by an AhR antagonist, resveratrol. The CYP1A1 enzyme activity showed a similar pattern of induction. This is the first report that shows that andrographolide has a potency to induce CYP1A1 enzyme and indicates that andrographolide could be a very useful compound for investigating the regulatory mechanism of the CYP1A1 induction pathway. In addition, our findings suggest preparing advice for rational administration of A. paniculata, according to its ability to induce CYP1A1 expression.

  3. Strong synergistic induction of CYP1A1 expression by andrographolide plus typical CYP1A inducers in mouse hepatocytes

    International Nuclear Information System (INIS)

    Jaruchotikamol, Atika; Jarukamjorn, Kanokwan; Sirisangtrakul, Wanna; Sakuma, Tsutomu; Kawasaki, Yuki; Nemoto, Nobuo

    2007-01-01

    The effects of andrographolide, the major diterpenoid constituent of Andrographis paniculata, on the expression of cytochrome P450 superfamily 1 members, including CYP1A1, CYP1A2, and CYP1B1, as well as on aryl hydrocarbon receptor (AhR) expression in primary cultures of mouse hepatocytes were investigated in comparison with the effects of typical CYP1A inducers, including benz[a]anthracene, β-naphthoflavone, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Andrographolide significantly induced the expression of CYP1A1 and CYP1A2 mRNAs in a concentration-dependent manner, as did the typical CYP1A inducers, but did not induce that of CYP1B1 or AhR. Interestingly, andrographolide plus the typical CYP1A inducers synergistically induced CYP1A1 expression, and the synergism was blocked by an AhR antagonist, resveratrol. The CYP1A1 enzyme activity showed a similar pattern of induction. This is the first report that shows that andrographolide has a potency to induce CYP1A1 enzyme and indicates that andrographolide could be a very useful compound for investigating the regulatory mechanism of the CYP1A1 induction pathway. In addition, our findings suggest preparing advice for rational administration of A. paniculata, according to its ability to induce CYP1A1 expression

  4. Case report of novel CACNA1A gene mutation causing episodic ataxia type 2

    Directory of Open Access Journals (Sweden)

    David Alan Isaacs

    2017-05-01

    Full Text Available Background: Episodic ataxia type 2 (OMIM 108500 is an autosomal dominant channelopathy characterized by paroxysms of ataxia, vertigo, nausea, and other neurologic symptoms. More than 50 mutations of the CACNA1A gene have been discovered in families with episodic ataxia type 2, although 30%–50% of all patients with typical episodic ataxia type 2 phenotype have no detectable mutation of the CACNA1A gene. Case: A 46-year-old Caucasian man, with a long history of bouts of imbalance, vertigo, and nausea, presented to our hospital with 2 weeks of ataxia and headache. Subsequent evaluation revealed a novel mutation in the CACNA1A gene: c.1364 G > A Arg455Gln. Acetazolamide was initiated with symptomatic improvement. Conclusion: This case report expands the list of known CACNA1A mutations associated with episodic ataxia type 2.

  5. Health-related quality of life, work productivity, and indirect costs among patients with irritable bowel syndrome with diarrhea.

    Science.gov (United States)

    Buono, Jessica L; Carson, Robyn T; Flores, Natalia M

    2017-02-14

    Irritable bowel syndrome (IBS) affects 10-15% of adults in the US, and is associated with significant impairment in health-related quality of life (HRQoL); however, information specific to the diarrhea subtype (IBS-D) is lacking. We assessed the impact of IBS-D on HRQoL, work productivity, and daily activities, and the associated indirect costs, among a sample of the US population. Respondents (≥18 years) from the 2012 US National Health and Wellness Survey who reported an IBS-D diagnosis by a physician or symptoms consistent with Rome II criteria for IBS-D were identified as having IBS-D. Controls included respondents without IBS-D or inflammatory bowel disease. HRQoL was assessed via the Short Form 36 Health Survey version 2 questionnaire and summarized into Mental and Physical Component Summary (MCS; PCS) scores and a Short Form-6 dimension (SF-6D) utility score. Work and activity impairment were assessed via the Work Productivity and Activity Impairment Questionnaire: General Health version (WPAI:GH), which measures absenteeism, presenteeism, overall work productivity loss, and daily activity impairment. Indirect costs were calculated using unit cost data from the Bureau of Labor Statistics and variables from the WPAI:GH. Generalized linear models were used to examine differences in health outcomes between respondents with IBS-D and controls, controlling for demographic and health characteristics. In total, 66,491 respondents (1102 IBS-D; 65,389 controls) were analyzed. Mean age was 48.7 years; 50% were female. Compared with controls, the IBS-D cohort reported significantly lower HRQoL (mean MCS: 45.16 vs. 49.48; p work productivity loss (20.7% vs. 13.2%; p work and daily activities, and higher indirect costs, imposing a substantial burden on patients and employers. These findings suggest a significant unmet need exists for effective IBS-D treatments.

  6. Severe fatigue and reduced quality of life in children with hereditary motor and sensory neuropathy 1A

    NARCIS (Netherlands)

    Jagersma, Elbrich; Jeukens-Visser, Martine; van Paassen, Barbara W.; Meester-Delver, Anke; Nollet, Frans

    2013-01-01

    Severe fatigue and low quality of life are reported by a majority of adult patients with hereditary motor and sensory neuropathy 1A. In children with hereditary motor and sensory neuropathy 1A, the prevalence and impact of fatigue have not been studied yet. In this questionnaire survey, 55 Dutch

  7. Recurrent spontaneous hip dislocation in a patient with neurofibromatosis type 1: a case report.

    LENUS (Irish Health Repository)

    Galbraith, John G

    2011-01-01

    Neurofibromatosis type-1 is a common genetic disorder which often affects the skeleton. Skeletal manifestations of neurofibromatosis type-1 include scoliosis, congenital pseudarthrosis of the tibia and intraosseous cystic lesions. Dislocation of the hip associated with neurofibromatosis type-1 is a rare occurrence and is underreported in the literature.

  8. Recurrent spontaneous hip dislocation in a patient with neurofibromatosis type 1: a case report

    Directory of Open Access Journals (Sweden)

    Harty James A

    2011-03-01

    Full Text Available Abstract Introduction Neurofibromatosis type-1 is a common genetic disorder which often affects the skeleton. Skeletal manifestations of neurofibromatosis type-1 include scoliosis, congenital pseudarthrosis of the tibia and intraosseous cystic lesions. Dislocation of the hip associated with neurofibromatosis type-1 is a rare occurrence and is underreported in the literature. Case presentation We report a case of hip dislocation resulting from an intra-articular neurofibroma in an 18-year-old Caucasian woman following minor trauma. This was originally suggested by the abnormalities on early radiographs of her pelvis and later confirmed with computed tomography and magnetic resonance imaging. Treatment was successful with skeletal traction for six weeks with no further hip dislocations at a 12-year follow-up. Conclusion This case illustrates the radiological features of this rare complication of neurofibromatosis type-1 using the modalities of plain radiograph, magnetic resonance imaging and computed tomography reconstruction. The radiological images give a clear insight into the mechanism by which neurofibromatosis type-1 leads to hip dislocation. It also demonstrates one treatment option with excellent results on long-term follow-up.

  9. Facial Plexiform neurofibromatosis in a patient with neurofibromatosis type1: a case report

    Directory of Open Access Journals (Sweden)

    Iffat Hassan

    2012-01-01

    Full Text Available Plexiform neurofibroma is a poorly circumscribed, diffuse enlargement of neural sheets that typically involves major nerve trunks of the head and neck region because of the rich innervations of this area. It is a benign tumor and is a virtually pathognomonic and often disabling feature of neurofibromatosis type 1 (NF-1 or Von Recklinghausen’s disease. We hereby report a case of facial neurofibroma in an adult female with neurofibromatosis type 1 (NF-1.

  10. Homer1a protein expression in schizophrenia, bipolar disorder, and major depression.

    Science.gov (United States)

    Leber, Stefan L; Llenos, Ida C; Miller, Christine L; Dulay, Jeannette R; Haybaeck, Johannes; Weis, Serge

    2017-10-01

    In recent years, there was growing interest in postsynaptic density proteins in the central nervous system. Of the most important candidates of this specialized region are proteins belonging to the Homer protein family. This family of scaffolding proteins is suspected to participate in the pathogenesis of a variety of diseases. The present study aims to compare Homer1a expression in the hippocampus and cingulate gyrus of patients with major psychiatric disorders including schizophrenia, bipolar disorder and major depression. Immunohistochemistry was used to analyze changes of Homer1a protein expression in the hippocampal formation and the cingulate gyrus from the respective disease groups. Glial cells of the cingulate gyrus gray matter showed decreased Homer1a levels in bipolar disorder when compared to controls. The same results were seen when comparing cingulate gyrus gray matter glial cells in bipolar disorder with major depression. Stratum oriens glial cells of the hippocampus showed decreased Homer1a levels in bipolar disorder when compared to controls and major depression. Stratum lacunosum glial cells showed decreased Homer1a levels in bipolar disorder when compared to major depression. In stratum oriens interneurons Homer1a levels were increased in all disease groups when compared to controls. Stratum lucidum axons showed decreased Homer1a levels in bipolar disorder when compared to controls. Our data demonstrate altered Homer1a levels in specific brain regions and cell types of patients suffering from schizophrenia, bipolar disorder and major depression. These findings support the role of Homer proteins as interesting candidates in neuropsychiatric pathophysiology and treatment.

  11. Distinct patterns of ALDH1A1 expression predict metastasis and poor outcome of colorectal carcinoma

    Science.gov (United States)

    Xu, Sen-Lin; Zeng, Dong-Zu; Dong, Wei-Guo; Ding, Yan-Qing; Rao, Jun; Duan, Jiang-Jie; Liu, Qing; Yang, Jing; Zhan, Na; Liu, Ying; Hu, Qi-Ping; Zhang, Xia; Cui, You-Hong; Kung, Hsiang-Fu; Yu, Shi-Cang; Bian, Xiu-Wu

    2014-01-01

    Purpose: Aldehyde dehydrogenase 1A1 (ALDH1A1) has been proposed as a candidate biomarker for colorectal carcinoma (CRC). However, the heterogeneity of its expression makes it difficult to predict the outcome of CRC. The aim of this study was to evaluate the diagnostic and prognostic value of this molecule in CRC. Methods and Results: In this study, we examined ALDH1A1 expression by immunohistochemistry including 406 cases of primary CRC with corresponding adjacent mucosa, with confirmation of real-time PCR and Western blotting. We found that the expression patterns of ALDH1A1 were heterogeneous in the CRC and corresponding adjacent tissues. We defined the ratio of ALDH1A1 level in adjacent mucosa to that in tumor tissues as RA/C and found that the capabilities of tumor invasion and metastasis in the tumors with RA/C < 1 were significantly higher than those with RA/C ≥ 1. Follow-up data showed the worse prognoses in the CRC patients with RA/C < 1. For understanding the underlying mechanism, the localization of β-catenin was detected in the CRC tissues with different patterns of ALDH1A1 expression from 221 patients and β-catenin was found preferentially expressed in cell nuclei of the tumors with RA/C < 1 and ALDH1A1high expression of HT29 cell line, indicating that nuclear translocation of β-catenin might contribute to the increased potentials of invasion and metastasis. Conclusion: Our results indicate that RA/C is a novel biomarker to reflect the distinct expression patterns of ALDH1A1 for predicting metastasis and prognosis of CRC. PMID:25031716

  12. Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms.

    LENUS (Irish Health Repository)

    Murphy, Therese M

    2012-02-01

    BACKGROUND: Suicidal behaviour is known to aggregate in families. Patients with psychiatric disorders are at higher risk for suicide attempts (SA), however protective and risk genetic variants for suicide appear to be independent of underlying psychiatric disorders. Here we investigate genetic variants in genes important for neurobiological pathways linked to suicidal behaviour and\\/or associated endophenotypes, for association with SA among patients with co-existing psychiatric illness. Selected gene-gene and gene-environment interactions were also tested. METHODS: DNA was obtained from bloods of 159 patients (76 suicide attempters and 83 non-attempters), who were profiled for DSM-IV Axis I psychiatric diagnosis. Twenty-eight single nucleotide polymorphisms (SNPs) from 18 candidate genes (COMT, 5-HT2A, 5-HT1A, 5-HTR1B, TPH1, MAO-A, TPH2, DBH, CNR1, BDNF, ABCG1, GABRA5, GABRG2, GABRB2, SLC1A2, SLC1A3, NTRK2, CRHR1) were genotyped. Genotyping was performed by KBioscience. Tests of association between genetic variants and SA were conducted using Chi squared and Armitage Trend tests. Binary logistical regression analyses were performed to evaluate the contribution of individual genetic variants to the prediction of SA, and to examine SNPs for potential gene-gene and gene-environment interactions. RESULTS: Our analysis identified 4 SNPs (rs4755404, rs2269272, rs6296 and rs1659400), which showed evidence of association with SA compared to a non-attempter control group. We provide evidence of a 3-locus gene-gene interaction, and a putative gene-environment interaction, whereby genetic variation at the NTRK2 locus may moderate the risk associated with history of childhood abuse. CONCLUSION: Preliminary findings suggest that allelic variability in SLC1A2\\/3, 5-HTR1B and NTRK2 may be relevant to the underlying diathesis for suicidal acts.

  13. Mutations in HNF1A Result in Marked Alterations of Plasma Glycan Profile

    Science.gov (United States)

    Thanabalasingham, Gaya; Huffman, Jennifer E.; Kattla, Jayesh J.; Novokmet, Mislav; Rudan, Igor; Gloyn, Anna L.; Hayward, Caroline; Adamczyk, Barbara; Reynolds, Rebecca M.; Muzinic, Ana; Hassanali, Neelam; Pucic, Maja; Bennett, Amanda J.; Essafi, Abdelkader; Polasek, Ozren; Mughal, Saima A.; Redzic, Irma; Primorac, Dragan; Zgaga, Lina; Kolcic, Ivana; Hansen, Torben; Gasperikova, Daniela; Tjora, Erling; Strachan, Mark W.J.; Nielsen, Trine; Stanik, Juraj; Klimes, Iwar; Pedersen, Oluf B.; Njølstad, Pål R.; Wild, Sarah H.; Gyllensten, Ulf; Gornik, Olga; Wilson, James F.; Hastie, Nicholas D.; Campbell, Harry; McCarthy, Mark I.; Rudd, Pauline M.; Owen, Katharine R.; Lauc, Gordan; Wright, Alan F.

    2013-01-01

    A recent genome-wide association study identified hepatocyte nuclear factor 1-α (HNF1A) as a key regulator of fucosylation. We hypothesized that loss-of-function HNF1A mutations causal for maturity-onset diabetes of the young (MODY) would display altered fucosylation of N-linked glycans on plasma proteins and that glycan biomarkers could improve the efficiency of a diagnosis of HNF1A-MODY. In a pilot comparison of 33 subjects with HNF1A-MODY and 41 subjects with type 2 diabetes, 15 of 29 glycan measurements differed between the two groups. The DG9-glycan index, which is the ratio of fucosylated to nonfucosylated triantennary glycans, provided optimum discrimination in the pilot study and was examined further among additional subjects with HNF1A-MODY (n = 188), glucokinase (GCK)-MODY (n = 118), hepatocyte nuclear factor 4-α (HNF4A)-MODY (n = 40), type 1 diabetes (n = 98), type 2 diabetes (n = 167), and nondiabetic controls (n = 98). The DG9-glycan index was markedly lower in HNF1A-MODY than in controls or other diabetes subtypes, offered good discrimination between HNF1A-MODY and both type 1 and type 2 diabetes (C statistic ≥0.90), and enabled us to detect three previously undetected HNF1A mutations in patients with diabetes. In conclusion, glycan profiles are altered substantially in HNF1A-MODY, and the DG9-glycan index has potential clinical value as a diagnostic biomarker of HNF1A dysfunction. PMID:23274891

  14. Analysis list: Hif1a [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Hif1a Blood,Embryo + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Hif1a.1.tsv http://dbarchi...ve.biosciencedbc.jp/kyushu-u/mm9/target/Hif1a.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Hi...f1a.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Hif1a.Blood.tsv,http://dbarchi...ve.biosciencedbc.jp/kyushu-u/mm9/colo/Hif1a.Embryo.tsv http://dbarchive.bi...osciencedbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Embryo.gml ...

  15. Serotonin type-1A receptor imaging in depression

    International Nuclear Information System (INIS)

    Drevets, Wayne C.; Frank, Ellen; Price, Julie C.; Kupfer, David J.; Greer, Phil J.; Mathis, Chester

    2000-01-01

    Regional 5-hydroxytryptamine 1A (5-HT 1A ) receptor binding potential (BP) of depressed subjects with primary, recurrent, familial mood disorders was compared to that of healthy controls by using positron emission tomography and [carbonyl- 11 C]WAY-100635 {[ 11 C]N-(2-(4-(2-methoxyphenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide}. The mean 5-HT 1A receptor BP was reduced 42% in the midbrain raphe and 25-33% in limbic and neocortical areas in the mesiotemporal, occipital, and parietal cortex. The magnitude of these abnormalities was most prominent in bipolar depressives and unipolar depressives who had bipolar relatives. These abnormal reductions in 5-HT 1A receptor BP are consistent with in vivo evidence that 5-HT 1A receptor sensitivity is reduced in major depressive disorder and postmortem data showing a widespread deficit of 5-HT 1A receptor expression in primary mood disorders

  16. Analysis list: Ptf1a [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Ptf1a Embryo,Pancreas + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/P...tf1a.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Ptf1a.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/mm9/target/Ptf1a.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Ptf1a.Embryo.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Ptf1a.Pancreas.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Embryo.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Pancreas.gml ...

  17. Analysis list: DYRK1A [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DYRK1A Neural,Uterus + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/...DYRK1A.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/DYRK1A.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/target/DYRK1A.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/DYRK1A.Neural....tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/DYRK1A.Uterus.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Neural.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Uterus.gml ...

  18. FUNCTIONAL STATUS IN PATIENTS WITH CHRONIC KIDNEY DISEASE BEING TREATED WITH HEMODIALYSIS IN PKU MUHAMMADIYAH HOSPITAL, YOGYAKARTA, INDONESIA

    Directory of Open Access Journals (Sweden)

    Adiyati Mardiyah

    2017-08-01

    Full Text Available Background: Hemodialysis process is useful for patients with end-stage renal disease. However, this is a situation of abject dependence on a machine, a procedure and a group of qualified medical professionals for the rest of their lives that may influence their functional status. Objective: This study aims to describe the functional status of patients with chronic kidney disease undergoing hemodialysis. Method: This was a descriptive study with cross-sectional design, which conducted in the PKU Muhammadiyah Hospital Yogyakarta on March 2017. There were 78 patients selected using purposive sampling. Functional status was measured using SF-36 questionnaire. Descriptive statistic was performed for data analysis Result:. The total average of functional status level was 42.92, with Physical Component Scale (PCS of 42.31 and Mental Component Scale (MCS of 45.78. Conclusion: There were functional deficiencies in both physical and mental status in patients with CKD undergoing hemodialysis. Thus, it is suggested that pharmacological management of these patients need stringent monitoring on part of the psychiatrist to deal with mental health problems, and the interdisciplinary team need to do great efforts to improve functional status and quality of life of patients with CKD.

  19. Identification of CYP1A inducing compounds in crude oil

    Energy Technology Data Exchange (ETDEWEB)

    Khan, C.W.; Hodson, P.V. [Queen' s Univ., Kingston, ON (Canada). Dept. of Biology; Hollebone, B.P.; Wang, Z. [Environment Canada, Ottawa, ON (Canada). Environmental Technology Advancement Directorate; Brown, R.S. [Queen' s Univ., Kingston, ON (Canada). Dept. of Chemistry

    2004-07-01

    One of the major sources of polycyclic aromatic hydrocarbons (PAHs) in aquatic ecosystems is crude oil. PAHs are responsible for developmental malformations in the early life stages of fish. The induction of CYP1A enzyme is characteristic of developmental toxicity caused by crude oil. As such, it is an effective biomarker of PAH uptake. It is not known which PAHs cause toxicity because of the complex chemical composition of crude oil. In this study, an approach called Toxicity Identification and Evaluation (TIE) was used with different crude oils to separate bioavailable PAHs into petroleum sub-fractions. The extent of CYP1A induction in rainbow trout was measured after 48 hour exposures to each fraction. Low temperature vacuum distillation was used to create white gas, kerosene, coal tar/bitumen and wax fractions. Hepatic CYP1A activity was induced by whole oil and some fractions. The highest PAH concentration was found in the coal tar/bitumen fraction which accounted for most CYP1A induction in whole oil. The wax fraction also caused moderate CYP1A induction, but the white gas fraction did not cause any CYP1A induction. The hypothesis that alkyl PAH may be the most significant source of CYP1A inducers in the coal tar/bitumen fraction was supported by chemical analysis of CYP1A induction potency. Results showed that benzo[a]pyrene accounts for nearly all of the CYP1A induction caused by the wax fraction.

  20. Novel mutations in the SCNN1A gene causing Pseudohypoaldosteronism type 1.

    Directory of Open Access Journals (Sweden)

    Jian Wang

    Full Text Available Pseudohypoaldosteronism type 1 (PHA1 is a rare inherited disease characterized by resistance to the actions of aldosterone. Mutations in the subunit genes (SCNN1A, SCNN1B, SCNN1G of the epithelial sodium channel (ENaC and the NR3C2 gene encoding the mineralocorticoid receptor, result in systemic PHA1 and renal PHA1 respectively. Common clinical manifestations of PHA1 include salt wasting, hyperkalaemia, metabolic acidosis and elevated plasma aldosterone levels in the neonatal period. In this study, we describe the clinical and biochemical manifestations in two Chinese patients with systemic PHA1. Sequence analysis of the SCNN1A gene revealed a compound heterozygous mutation (c.1311delG and c.1439+1G>C in one patient and a homozygous mutation (c.814_815insG in another patient, all three variants are novel. Further analysis of the splicing pattern in a minigene construct showed that the c.1439+1G>C mutation can lead to the retainment of intron 9 as the 5'-donor splice site disappears during post-transcriptional processing of mRNA. In conclusion, our study identified three novel SCNN1A gene mutations in two Chinese patients with systemic PHA1.

  1. Inhibition of SLC1A5 sensitizes colorectal cancer to cetuximab.

    Science.gov (United States)

    Ma, Huanrong; Wu, Zhenzhen; Peng, Jianjun; Li, Yang; Huang, Hongxiang; Liao, Yi; Zhou, Minyu; Sun, Li; Huang, Na; Shi, Min; Bin, Jianping; Liao, Yulin; Rao, Jinjun; Wang, Lin; Liao, Wangjun

    2018-06-15

    Cetuximab resistance is a key barrier in treating metastatic colorectal cancer (mCRC). Targeting of metabolic resources import could resensitize drug-resistant cancer cells to anticancer treatments. Here we showed that the expression of the glutamine transporter solute carrier 1 family member 5 (SLC1A5) in clinical CRC samples of patients resisted to cetuximab was significantly higher than in those of patients responded to cetuximab. Inhibition of SLC1A5 by shRNA-mediated gene silencing or pharmacological inhibitor significantly suppressed the growth of CRC. Moreover, inhibition of SLC1A5 significantly enhanced the inhibitory efficacy of cetuximab on CRC proliferation both in vitro and in vivo. Mechanistically, SLC1A5 inhibition facilitated EGFR degradation through the ubiquitin-proteasome pathway, and decreased the expression of nuclear EGFR, both of which might have contribution to the improved response to cetuximab. This study provides the metabolic molecule SLC1A5 as a potential therapeutic target to increase the efficacy of cetuximab on CRC. © 2018 UICC.

  2. Minocycline added to subcutaneous interferon β-1a in multiple sclerosis: randomized RECYCLINE study.

    Science.gov (United States)

    Sørensen, P S; Sellebjerg, F; Lycke, J; Färkkilä, M; Créange, A; Lund, C G; Schluep, M; Frederiksen, J L; Stenager, E; Pfleger, C; Garde, E; Kinnunen, E; Marhardt, K

    2016-05-01

    Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) β-1a therapy. This was a double-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN β-1a 44 μg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN β-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying relapse. Secondary efficacy endpoints were the annualized relapse rate for qualifying relapses, the number of new/enlarging T2-weighted lesions and change in brain volume [magnetic resonance imaging (MRI) was performed only in a few selected centres]. In addition, a number of tertiary efficacy endpoints were assessed. One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence interval 0.53, 1.35; log-rank = 0.50; P = 0.48). There were no statistically significant differences between the two groups on other efficacy endpoints, although some numerical trends in favour of minocycline were observed. No unexpected adverse events were reported, but more patients discontinued because of adverse events with minocycline versus placebo. Minocycline showed no statistically significant beneficial effect when added to sc IFN β-1a therapy. © 2016 EAN.

  3. The water avoidance stress induces bladder pain due to a prolonged alpha1A adrenoceptor stimulation.

    Science.gov (United States)

    Matos, Rita; Serrão, Paula; Rodriguez, Larissa; Birder, Lori Ann; Cruz, Francisco; Charrua, Ana

    2017-08-01

    Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) remains an elusive disease with the cause for the pain unclear. BPS/IC patients present increased sympathetic activity and high levels of urinary noradrenaline. At the experimental level, it has been shown that chronic adrenergic stimulation produces pain and bladder changes through an alpha 1A adrenoceptor mediated mechanism. Water avoidance stress (WAS) in rodents reproduces signs of nociception and bladder changes seen in BPS/IC patients. In this study, we explore the possible role of alpha 1A adrenoceptor in bladder pain and morphological changes. WAS was induced in a group of female Wistar rats. A separate WAS group received 0.2 mg/kg day silodosin (WAS + S). Lower abdominal pain was determined by performing sensitivity to Von Frey filaments. Bladder reflex activity was determined by cystometry in anaesthetised animals. Urine was collected for noradrenaline quantification by HPLC. Bladders were harvested and stained with Haematoxylin-eosin (to analyse urothelial morphology and to determine the disruption of surface umbrella cells) or with Toluidine Blue 0.1% to analyse mast cell infiltration. WAS increased urinary noradrenaline level and bladder frequency and decreased mechanical pain threshold, which was reversed by silodosin. WAS induced lymphocytic and mast cells infiltration in the mucosa and mild urothelial disruption, which was absent in WAS + S group. Alpha 1A adrenoceptor stimulation has an important role in the appearance of bladder pain in rats. Since BPS/IC patients present high levels of noradrenaline, alpha 1A stimulation may be an additional trigger for bladder dysfunction presented by these patients. Further studies will determine the clinical relevance of this finding in the treatment of BPS/IC patients.

  4. Skeletal muscle PGC-1a is required for maintaining an acute LPS-induced TNFa response

    DEFF Research Database (Denmark)

    Olesen, Jesper; Larsson, Signe; Iversen, Ninna

    2012-01-01

    Many lifestyle-related diseases are associated with low-grade inflammation and peroxisome proliferator activated receptor ¿ coactivator (PGC)-1a has been suggested to be protective against low-grade inflammation. However, whether these anti-inflammatory properties affect acute inflammation is not...... does not exert anti-inflammatory effects during acute inflammation. Lack of skeletal muscle PGC-1a seems however to impair the acute TNFa response, which may reflect a phenotype more susceptible to infections as also observed in type 2 diabetes patients....

  5. Role of casein kinase 1A1 in the biology and targeted therapy of del(5q) MDS

    Science.gov (United States)

    Schneider, Rebekka K.; Ademà, Vera; Heckl, Dirk; Järås, Marcus; Mallo, Mar; Lord, Allegra M.; Chu, Lisa P.; McConkey, Marie E.; Kramann, Rafael; Mullally, Ann; Bejar, Rafael; Solé, Francesc; Ebert, Benjamin L.

    2014-01-01

    Summary The Casein kinase 1A1 gene (CSNK1A1) is a putative tumor suppressor gene located in the common deleted region for del(5q) myelodysplastic syndrome (MDS). We generated a murine model with conditional inactivation of Csnk1a1 and found that Csnk1a1 haploinsufficiency induces hematopoietic stem cell expansion and a competitive repopulation advantage whereas homozygous deletion induces hematopoietic stem cell failure. Based on this finding, we found that heterozygous inactivation of Csnk1a1 sensitizes cells to a CSNK1 inhibitor relative to cells with two intact alleles. In addition, we identified recurrent somatic mutations in CSNK1A1 on the non-deleted allele of patients with del(5q) MDS. These studies demonstrate that CSNK1A1 plays a central role in the biology of del(5q) MDS and is a promising therapeutic target. PMID:25242043

  6. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zehua; Cui, Feifei; Yu, Fudong; Peng, Xiao; Jiang, Tao; Chen, Dawei [Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Lu, Su [Department of Pathology, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Tang, Huamei, E-mail: tanghuamei@gmail.com [Department of Pathology, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Peng, Zhihai, E-mail: zhihai.peng@hotmail.com [Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China)

    2014-06-27

    Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) was significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation.

  7. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    International Nuclear Information System (INIS)

    Wu, Zehua; Cui, Feifei; Yu, Fudong; Peng, Xiao; Jiang, Tao; Chen, Dawei; Lu, Su; Tang, Huamei; Peng, Zhihai

    2014-01-01

    Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) was significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation

  8. Phenotypes and genotypes in individuals with SMC1A variants

    DEFF Research Database (Denmark)

    Huisman, Sylvia; Mulder, Paul A; Redeker, Egbert

    2017-01-01

    , stereotypic movements, and (in some) regression. Their missense, nonsense, and frameshift mutations are evenly spread over the gene. We conclude that SMC1A variants can result in a phenotype resembling CdLS and a phenotype resembling Rett syndrome. Resemblances between the SMC1A group and the NIPBL group...

  9. Role of pelvic lymphadenectomy in stage 1A endometrial carcinoma ...

    African Journals Online (AJOL)

    Hossam Hassan Aly Hassan El Sokkary

    2013-10-31

    Oct 31, 2013 ... phadenectomy in managing stage 1A diagnosed preoperatively, we try to evaluate this need. Objective: To ... Methods: 60 Cases of endometrial carcinoma diagnosed by fractional curettage and proved to be stage 1A .... The strongest argument for routine staging is the avoidance of pelvic radiation therapy ...

  10. GSTP1 A>G polymorphism and chemosensitivity of osteosarcoma: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Fengfeng Wu

    2016-01-01

    Full Text Available The association between GSTP1 A>G polymorphism and chemosensitivity of osteosarcoma is controversial according to previously published studies. We conducted this meta-analysis to further investigate the role of GSTP1 A>G genetic variation in response to chemotherapy resistance in patients with osteosarcoma. Using the electronic databases of Pubmed, Wanfang and CNIK were searched to find the studies related to the GSTP1 A>G polymorphism and chemosensitivity of osteosarcoma. The genotype of AA, AG and GG were extracted from the chemotherapy sensitivity and chemotherapy resistance group. The association between GSTP1 A>G polymorphism and chemosensitivity was calculated by STATA11.0 software. The correlation between GSTP1 A>G polymorphism and chemotherapy response was assessed by odds ratio (OR and its 95% confidence interval (95%CI. Four studies with 681 cases were finally included in this meta-analysis. The pooled data indicated that there was no significant association between GSTP1 A>G polymorphism and chemosensitivity in patients with osteosarcoma [Homozygous genetic model (GG vs AA: OR=0.53, 95%CI: 0.25-1.12, P=0.10; recessive genetic model (GG vs GA+AA: OR=0.61, 95%CI:0.34-1.11,P=0.11; and dominant genetic model (GG+AG vs AA: OR=0.67, 95%CI:0.42-1.07,P=0.10]. No correlation between GSTP1 A>G polymorphism and chemosensitivity was found according to this present meta-analysis. However, the small number of cases in each included study and significant statistical heterogeneity among the trials means the conclusion should be regarded as conservative.

  11. Combined assessment of DYRK1A, BDNF and homocysteine levels as diagnostic marker for Alzheimer's disease.

    Science.gov (United States)

    Janel, N; Alexopoulos, P; Badel, A; Lamari, F; Camproux, A C; Lagarde, J; Simon, S; Feraudet-Tarisse, C; Lamourette, P; Arbones, M; Paul, J L; Dubois, B; Potier, M C; Sarazin, M; Delabar, J M

    2017-06-20

    Early identification of Alzheimer's disease (AD) risk factors would aid development of interventions to delay the onset of dementia, but current biomarkers are invasive and/or costly to assess. Validated plasma biomarkers would circumvent these challenges. We previously identified the kinase DYRK1A in plasma. To validate DYRK1A as a biomarker for AD diagnosis, we assessed the levels of DYRK1A and the related markers brain-derived neurotrophic factor (BDNF) and homocysteine in two unrelated AD patient cohorts with age-matched controls. Receiver-operating characteristic curves and logistic regression analyses showed that combined assessment of DYRK1A, BDNF and homocysteine has a sensitivity of 0.952, a specificity of 0.889 and an accuracy of 0.933 in testing for AD. The blood levels of these markers provide a diagnosis assessment profile. Combined assessment of these three markers outperforms most of the previous markers and could become a useful substitute to the current panel of AD biomarkers. These results associate a decreased level of DYRK1A with AD and challenge the use of DYRK1A inhibitors in peripheral tissues as treatment. These measures will be useful for diagnosis purposes.

  12. Vacuum assisted closure improves the quality of life in patients with diabetic foot.

    Science.gov (United States)

    Karatepe, O; Eken, I; Acet, E; Unal, O; Mert, M; Koc, B; Karahan, S; Filizcan, U; Ugurlucan, M; Aksoy, M

    2011-01-01

    Diabetes Mellitus (DM) is the most common endocrine disease worldwide. One of the most important chronic complications of this disease is the development of diabetic foot. The management of diabetic foot wounds is quite important with respect to public health. To determine the effect of Vacuum Assisted Closure (VAC) therapy on the quality of life in the treatment of diabetic foot ulcers and compare it with standart wound care. Between May 2007 to December 2008, 67 consecutive patients with diabetic foot ulcers were randomly assigned to VAC therapy (Group 1, n : 30) or standart wound care (Group 2, n : 37). The SF-36 questionnaire was administered the day before and in the month following wound healing. Global analyses of the 8 domains and 2 comprehensive indexes of SF-36, Physical Component Summary (PCS) and Mental Component Summary (MCS) were performed. Clinical measures included standard antidiabetic treatment, daily wound care including antiseptic bath, debridement, toe removal for gangrene when necessary, and wound care with conventional methods or VAC. Healing time was calculated as the time from hospital admission to the time of re-epithelization. There were no differences in the mean age, ulcer size and pulse status of the patients in both groups. Healing time in the VAC group was significantly reduced (p VAC therapy. Vacuum Assisted Closure therapy was found to be effective in the treatment of chronic diabetic ulcers. The improvement of quality of life demonstrates a clear-cut indication in this particular group of patients.

  13. Nutritional status independently affects quality of life of patients with systemic immunoglobulin light-chain (AL) amyloidosis.

    Science.gov (United States)

    Caccialanza, Riccardo; Palladini, Giovanni; Klersy, Catherine; Cereda, Emanuele; Bonardi, Chiara; Cameletti, Barbara; Montagna, Elisabetta; Russo, Paola; Foli, Andrea; Milani, Paolo; Lavatelli, Francesca; Merlini, Giampaolo

    2012-03-01

    Nutritional status is an independent prognostic factor in immunoglobulin light-chain amyloidosis (AL), but its influence on quality of life (QoL) is unknown. The aim of this cross-sectional study was to investigate the association between nutritional status and QoL in AL patients at diagnosis. One hundred and fifty consecutive patients with biopsy-proven AL were assessed for nutritional status by anthropometry [body mass index, unintentional weight loss (WL) in the previous 6 months and mid-arm muscle circumference (MAMC)], biochemistry (serum prealbumin), and semiquantitative food intake at referral. QoL was assessed by the Medical Outcomes Study 36-item Short Form General Health Survey. The composite physical component summary (PCS) and the mental component summary (MCS) for AL outpatients were 36.2 ± 10.1 and 44.9 ± 11.3, respectively (p performance status, the number of organs involved, the severity of cardiac damage, C-reactive protein, energy intake, and WL, PCS was significantly lower for serum prealbumin Nutritional status independently affects QoL in AL patients since diagnosis. Nutritional evaluation should be integral part of the clinical assessment of AL patients. Nutritional support intervention trials are warranted in such patients' population.

  14. The effects of epistaxis on health-related quality of life in patients with hereditary hemorrhagic telangiectasia.

    Science.gov (United States)

    Merlo, Christian A; Yin, Linda X; Hoag, Jeffrey B; Mitchell, Sally E; Reh, Douglas D

    2014-11-01

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease mainly characterized by epistaxis in more than 96% of patients. Recently, a validated questionnaire known as the HHT Epistaxis Severity Score (ESS) was developed. However, little is known about the relationship between epistaxis and quality of life. We hypothesize that epistaxis severity is a major factor predicting health-related quality of life (HR-QoL) in HHT patients. This is a cross-sectional study. The ESS questionnaire and Medical Outcomes Study 36-item short form (SF-36) were administered to subjects through an Internet survey. All participants had a definitive diagnosis of HHT through Curaçao criteria or genetic testing. Demographic information, genetics, and extensive histories were also collected. Descriptive analyses were performed with calculations of means and standard deviations (SDs) for continuous variables and proportions for categorical variables. Linear regressions were then performed to assess the association between HR-QoL and ESS. A total of 604 subjects participated between April and August 2008. All patients reported epistaxis, 285 (47.2%) had telangiectasias, and 545 (90.2%) had a family history of HHT; 167 (27.6%) patients had mild epistaxis (ESS epistaxis (≥4 ESS epistaxis (ESS ≥7). Patients with severe epistaxis had lower scores for both the Physical Component Summary (PCS) and the Mental Component Summary (MCS) of HR-QoL when compared to those with mild epistaxis (p epistaxis. © 2014 ARS-AAOA, LLC.

  15. Serotonin-1A receptors in major depression quantified using PET: controversies, confounds, and recommendations.

    Science.gov (United States)

    Shrestha, Saurav; Hirvonen, Jussi; Hines, Christina S; Henter, Ioline D; Svenningsson, Per; Pike, Victor W; Innis, Robert B

    2012-02-15

    The serotonin-1A (5-HT(1A)) receptor is of particular interest in human positron emission tomography (PET) studies of major depressive disorder (MDD). Of the eight studies investigating this issue in the brains of patients with MDD, four reported decreased 5-HT(1A) receptor density, two reported no change, and two reported increased 5-HT(1A) receptor density. While clinical heterogeneity may have contributed to these differing results, methodological factors by themselves could also explain the discrepancies. This review highlights several of these factors, including the use of the cerebellum as a reference region and the imprecision of measuring the concentration of parent radioligand in arterial plasma, the method otherwise considered to be the 'gold standard'. Other potential confounds also exist that could restrict or unexpectedly affect the interpretation of results. For example, the radioligand may be a substrate for an efflux transporter - like P-gp - at the blood-brain barrier; furthermore, the binding of the radioligand to the receptor in various stages of cellular trafficking is unknown. Efflux transport and cellular trafficking may also be differentially expressed in patients compared to healthy subjects. We believe that, taken together, the existing disparate findings do not reliably answer the question of whether 5-HT(1A) receptors are altered in MDD or in subgroups of patients with MDD. In addition, useful meta-analysis is precluded because only one of the imaging centers acquired all the data necessary to address these methodological concerns. We recommend that in the future, individual centers acquire more thorough data capable of addressing methodological concerns, and that multiple centers collaborate to meaningfully pool their data for meta-analysis. Published by Elsevier Inc.

  16. Mechanisms of prickle1a function in zebrafish epilepsy and retinal neurogenesis

    Directory of Open Access Journals (Sweden)

    Xue Mei

    2013-05-01

    Epilepsy is a complex neurological disorder characterized by unprovoked seizures. The etiology is heterogeneous with both genetic and environmental causes. Genes that regulate neurotransmitters and ion channels in the central nervous system have been associated with epilepsy. However, a recent screening in human epilepsy patients identified mutations in the PRICKLE1 (PK1 locus, highlighting a potentially novel mechanism underlying seizures. PK1 is a core component of the planar cell polarity network that regulates tissue polarity. Zebrafish studies have shown that Pk1 coordinates cell movement, neuronal migration and axonal outgrowth during embryonic development. Yet how dysfunction of Pk1 relates to epilepsy is unknown. To address the mechanism underlying epileptogenesis, we used zebrafish to characterize Pk1a function and epilepsy-related mutant forms. We show that knockdown of pk1a activity sensitizes zebrafish larva to a convulsant drug. To model defects in the central nervous system, we used the retina and found that pk1a knockdown induces neurite outgrowth defects; yet visual function is maintained. Furthermore, we characterized the functional and biochemical properties of the PK1 mutant forms identified in human patients. Functional analyses demonstrate that the wild-type Pk1a partially suppresses the gene knockdown retinal defects but not the mutant forms. Biochemical analysis reveals increased ubiquitylation of one mutant form and decreased translational efficiency of another mutant form compared with the wild-type Pk1a. Taken together, our results indicate that mutation of human PK1 could lead to defects in neurodevelopment and signal processing, providing insight into seizure predisposition in these patients.

  17. Pitfalls in genetic testing: the story of missed SCN1A mutations

    OpenAIRE

    Djémié, T.; Weckhuysen, S.; von Spiczak, S.; Carvill, G. L.; Jaehn, J.; Anttonen, A-K; Brilstra, E.; Caglayan, H. S.; de Kovel, C. G.; Depienne, C.; Gaily, E.; Gennaro, E.; Giraldez, B. G.; Gormley, P.; Guerrero-López, R.

    2016-01-01

    BACKGROUND: Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated ...

  18. Pitfalls in genetic testing : the story of missed SCN1A mutations

    OpenAIRE

    Djémié, Tania; Weckhuysen, Sarah; von Spiczak, Sarah; Carvill, Gemma L; Jaehn, Johanna; Anttonen, Anna-Kaisa; Brilstra, Eva; Caglayan, Hande S; de Kovel, Carolien G; Depienne, Christel; Gaily, Eija; Gennaro, Elena; Giraldez, Beatriz G; Gormley, Padhraig; Guerrero-López, Rosa

    2016-01-01

    BACKGROUND: Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated ...

  19. Increased de novo lipogenesis and delayed conversion of large VLDL into intermediate density lipoprotein particles contribute to Hyperlipidemia in glycogen storage disease type 1a

    NARCIS (Netherlands)

    Bandsma, Robert H. J.; Prinsen, Berthil H.; Van Der Velden, Monique De Sain; Rake, Jan-Peter; Boer, Theo; Smit, G. Peter A.; Reijngoud, Dirk-Jan; Kuipers, Folkert

    Glycogen storage disease type 1a (GSD-1a) is a metabolic disorder characterized by fasting-induced hypoglycemia, hepatic steatosis, and hyperlipidemia. The mechanisms underlying the lipid abnormalities are largely unknown. To investigate these mechanisms seven GSD-1a patients and four healthy

  20. The Algorithm Theoretical Basis Document for Level 1A Processing

    Science.gov (United States)

    Jester, Peggy L.; Hancock, David W., III

    2012-01-01

    The first process of the Geoscience Laser Altimeter System (GLAS) Science Algorithm Software converts the Level 0 data into the Level 1A Data Products. The Level 1A Data Products are the time ordered instrument data converted from counts to engineering units. This document defines the equations that convert the raw instrument data into engineering units. Required scale factors, bias values, and coefficients are defined in this document. Additionally, required quality assurance and browse products are defined in this document.

  1. Serotonin type-1A receptor imaging in depression

    Energy Technology Data Exchange (ETDEWEB)

    Drevets, Wayne C. E-mail: drevets@pet.upmc.edu; Frank, Ellen; Price, Julie C.; Kupfer, David J.; Greer, Phil J.; Mathis, Chester

    2000-07-01

    Regional 5-hydroxytryptamine{sub 1A} (5-HT{sub 1A}) receptor binding potential (BP) of depressed subjects with primary, recurrent, familial mood disorders was compared to that of healthy controls by using positron emission tomography and [carbonyl-{sup 11}C]WAY-100635 {l_brace}[{sup 11}C]N-(2-(4-(2-methoxyphenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide{r_brace}. The mean 5-HT{sub 1A} receptor BP was reduced 42% in the midbrain raphe and 25-33% in limbic and neocortical areas in the mesiotemporal, occipital, and parietal cortex. The magnitude of these abnormalities was most prominent in bipolar depressives and unipolar depressives who had bipolar relatives. These abnormal reductions in 5-HT{sub 1A} receptor BP are consistent with in vivo evidence that 5-HT{sub 1A} receptor sensitivity is reduced in major depressive disorder and postmortem data showing a widespread deficit of 5-HT{sub 1A} receptor expression in primary mood disorders.

  2. Tryptase-positive mast cells correlate with angiogenesis in early breast cancer patients.

    Science.gov (United States)

    Ranieri, Girolamo; Ammendola, Michele; Patruno, Rosa; Celano, Giuseppe; Zito, Francesco Alfredo; Montemurro, Severino; Rella, Addolorata; Di Lecce, Valentina; Gadaleta, Cosmo Damiano; Battista De Sarro, Giovanni; Ribatti, Domenico

    2009-07-01

    Literature data indicate that mast cells (MCs) are involved in tumor angiogenesis due to the release of several pro-angiogenetic factors among which tryptase, a serine protease stored in MCs granules, is one of the most active. However, no data are available concerning the role of MCs in angiogenesis in primary human breast cancer. In this study, we have evaluated the correlations between the number of MCs positive to tryptase (MCDPT), the area occupied by MCs positive to tryptase (MCAPT) and microvascular density (MVD) and endothelial area (EA) in a series of 88 primary T1-3, N0-2 M0 female breast cancer, by means of immunohistochemistry and image analysis methods. Data demonstrated a significant (r = from 0.78 to 0.89; p-value from 0.001 to 0.002 by Pearson's analysis respectively) correlation between MCDPT, MCAPT, MVD, EA to each other. No correlation concerning MCDPT, MCAPT, MVD, EA and the main clinicopathological features was found. Our results suggest that tryptase-positive MCs play a role in breast cancer angiogenesis. In this context several tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated in clinical trials as a new anti-angiogenetic approach.

  3. CHANGES IN TUMOR NECROSIS FACTOR ALFA DURING TREATMENT OF PATIENTS WITH MULTIPLE SCLEROSIS BY TRANSIMMUNIZATION METHOD

    Directory of Open Access Journals (Sweden)

    A. V. Kil'dyushevskiy

    2016-01-01

    Full Text Available Background: Despite the availability of a  large number of treatments for multiple sclerosis with various targets, these treatments are not always effective. According to the literature, experimental studies have shown a  significant decrease in tumor necrosis factor alfa (TNF-α with the use of extracorporeal photochemotherapy. Aim: To assess changes in TNF-α in patients with multiple sclerosis during treatment with transimmunization. Materials and methods: The study recruited 13 adult patients with multiple sclerosis. Serum TNF-α was measured by immunochemiluminescence analysis (IMMULITE 1000, Siemens. The patients were treated by transimmunization, i.e. a  modified photopheresis. Two hours before the procedure, Ammifurin (8-methoxypsoralene was administered to all the patients, then their mononuclear cells were isolated under PBSC protocol with Haemonetics MCS+ cell separator. Thereafter, mononuclear cells were irradiated with ultraviolet for 90  minutes and incubated for 20 hours at 37 °С. The next day the cells were re-infused to the patients. The procedure was performed 2  times per week for 6  months, then once per 4  months. Results: Before transimmunization, mean TNF-α level in adult patients with multiple sclerosis was 9.958±0.812  pg/mL (normal, below 8.1 pg/mL. After transimmunization, its level was 6.992±0.367  pg/mL (р<0.05. Conclusion: Ultraviolet irradiation of peripheral blood monocytes with their subsequent incubation (transimmunization led to a 30% decrease of serum TNF-α in patients with multiple sclerosis. This indicates a suppressive effect of transimmunization on TNF-α. Hence, in patients with multiple sclerosis transimmunization exerts an anti-inflammatory effect.

  4. Mast cell distribution in normal adult skin.

    Science.gov (United States)

    Janssens, A S; Heide, R; den Hollander, J C; Mulder, P G M; Tank, B; Oranje, A P

    2005-03-01

    To investigate mast cell distribution in normal adult skin to provide a reference range for comparison with mastocytosis. Mast cells (MCs) were counted in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders in adults. There was an uneven distribution of MCs in different body sites using the anti-tryptase monoclonal antibody technique. Numbers of MCs on the trunk, upper arm, and upper leg were similar, but were significantly different from those found on the lower leg and forearm. Two distinct groups were formed--proximal and distal. There were 77.0 MCs/mm2 at proximal body sites and 108.2 MCs/mm2 at distal sites. Adjusted for the adjacent diagnosis and age, this difference was consistent. The numbers of MCs in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders were not different from those in the control group. Differences in the numbers of MCs between the distal and the proximal body sites must be considered when MCs are counted for a reliable diagnosis of mastocytosis. A pilot study in patients with mastocytosis underlined the variation in the numbers of MCs in mastocytosis and normal skin, but showed a considerable overlap. The observed numbers of MCs in adults cannot be extrapolated to children. MC numbers varied significantly between proximal and distal body sites and these differences must be considered when MCs are counted for a reliable diagnosis of mastocytosis. There was a considerable overlap between the numbers of MCs in mastocytosis and normal skin.

  5. Dendritiform Keratopathy Associated with Exposure to Polyquarternium-1, a Common Ophthalmic Preservative.

    Science.gov (United States)

    Matoba, Alice Y; Peterson, Jeff R; Wilhelmus, Kirk R

    2016-03-01

    To describe dendritiform keratopathy associated with exposure to polyquaternium-1, a common preservative found in contact lens solutions and tear replacement products. Case series. Sixteen patients who demonstrated dendritiform keratopathy during topical ophthalmic exposure to polyquaternium-1. Records were reviewed of all patients diagnosed with dendritiform keratopathy between 1999 and 2014 who had documented exposure to contact lens care disinfecting solutions or artificial tear solutions containing polyquaternium-1. Patients were excluded who had coexisting potential causes for dendritiform keratopathy, such as prior herpes simplex keratitis, varicella-zoster viral keratitis, the linear form of Thygeson's superficial keratitis, epithelial regeneration line, Acanthamoeba keratitis, mucus plaque keratopathy, medication-related keratopathy, or limbal stem cell deficiency characterized by conjunctivalization of the corneal epithelium. Effect of discontinuation of exposure to polyquaternium-1 on the dendritiform keratopathy. Sixteen patients demonstrated dendritiform keratopathy after exposure to the preservative polyquaternium-1. Thirteen patients had a history of recent exposure to contact lens disinfecting solutions (Opti-Free, Equate) containing polyquaternium-1. Three patients used a tear replacement product (Systane) containing a polyquaternium-1 preservative. Four patients were treated with antiviral medications for presumed herpes simplex keratitis; 4 patients underwent diagnostic testing for Acanthamoeba keratitis. Two additional patients were diagnosed sequentially with herpes simplex keratitis, then Acanthamoeba keratitis before referral. All dendritiform lesions resolved within 2 to 6 weeks after elimination of exposure to polyquaternium-1. Ophthalmic products containing polyquaternium-1 may cause dendritiform keratopathy that may be confused with infections of the superficial cornea, such as herpes simplex virus keratitis or Acanthamoeba keratitis

  6. OAS1: a multiple sclerosis susceptibility gene that influences disease severity.

    LENUS (Irish Health Repository)

    O'Brien, M

    2012-02-01

    BACKGROUND: Type 1 interferons upregulate oligoadenylate synthetase 1 (OAS1). A single nucleotide polymorphism (SNP) in exon 7 of OAS1 results in differential RNAseL enzyme activity, the A allele coding for a truncated form with low activity and the G conferring high activity. We hypothesized that OAS1 genotypes would influence both susceptibility to multiple sclerosis (MS) and disease activity with the AA genotype being overrepresented and the GG genotype underrepresented in relapsing-remitting MS (RRMS) with increased disease activity. METHODS: We examined OAS1 genotype distribution in 401 patients with MS, 394 healthy controls, and 178 patients with RRMS receiving interferon-beta (IFNbeta) assessed as 1) having no or minimal disease activity on IFNbeta, 2) having disease activity despite IFNbeta, and 3) 65 patients with RRMS with highly active disease. RESULTS: The OAS1 genotype distribution differed between patients with MS and controls (p = 0.000003), with lower frequency of GG homozygotes in patients with MS (6%) compared with controls (17%). In relation to disease severity, 34 (32%) patients with no or minimal disease activity on IFNbeta had the AA and 8 (8%) the GG genotype; of patients with disease activity despite IFNbeta, 27 (51%) were AA, while only 1 (2%) was GG (p = 0.03). Median time to first relapse on IFNbeta was 24 months in patients with RRMS with AA genotype and 33 months with AG or GG genotype (p = 0.04). The GG genotype was absent in 65 patients with highly active RRMS (p = 0.03). CONCLUSIONS: A functional OAS1 SNP, AA genotype, confers susceptibility to MS and the GG genotype may protect against increased disease activity.

  7. The Factors Influencing Depression Endpoints Research (FINDER study: final results of Italian patients with depression

    Directory of Open Access Journals (Sweden)

    Quail Deborah

    2010-07-01

    Full Text Available Abstract Background Factors Influencing Depression Endpoints Research (FINDER is a 6-month, prospective, observational study carried out in 12 European countries aimed at investigating health-related quality of life (HRQoL in outpatients receiving treatment for a first or new depressive episode. The Italian HRQoL data at 6 months is described in this report, and the factors associated with HRQoL changes were determined. Methods Data were collected at baseline, 3 and 6 months of treatment. HRQoL was measured using components of the 36-item Short Form Health Survey (SF-36; mental component summary (MCS, physical component summary (PCS and the European Quality of Life-5 Dimensions (EQ-5D; visual analogue scale (VAS and health status index (HSI. The Hospital Anxiety and Depression Scale (HADS was adopted to evaluate depressive symptoms, while somatic and painful physical symptoms were assessed by using the 28-item Somatic Symptom Inventory (SSI-28 and a VAS. Results Of the initial 513 patients, 472 completed the 3-month observation and 466 the 6-month observation. The SF-36 and EQ-5D mean (± SD scores showed HRQoL improvements at 3 months and a further smaller improvement at 6 months, with the most positive effects for SF-36 MCS (baseline 22.0 ± 9.2, 3 months 34.6 ± 10.0; 6 months 39.3 ± 9.5 and EQ-5D HSI (baseline 0.4 ± 0.3; 3 months 0.7 ± 0.3; 6 months 0.7 ± 0.2. Depression and anxiety symptoms (HADS-D mean at baseline 13.3 ± 4.2; HADS-A mean at baseline 12.2 ± 3.9 consistently decreased during the first 3 months (8.7 ± 4.3; 7.5 ± 3.6 and showed a further positive change at 6 months (6.9 ± 4.3; 5.8 ± 3.4. Somatic and painful symptoms (SSI and VAS significantly decreased, with the most positive changes in the SSI-28 somatic item (mean at baseline 2.4 ± 0.7; mean change at 3 months: -0.5; 95% CI -0.6 to -0.5; mean change at 6 months: -0.7; 95% CI -0.8 to -0.7; in 'interference of overall pain with daily activities' (mean at baseline 45

  8. Apolipoprotein M can discriminate HNF1A-MODY from Type 1 diabetes.

    Science.gov (United States)

    Mughal, S A; Park, R; Nowak, N; Gloyn, A L; Karpe, F; Matile, H; Malecki, M T; McCarthy, M I; Stoffel, M; Owen, K R

    2013-02-01

    Missed diagnosis of maturity-onset diabetes of the young (MODY) has led to an interest in biomarkers that enable efficient prioritization of patients for definitive molecular testing. Apolipoprotein M (apoM) was suggested as a biomarker for hepatocyte nuclear factor 1 alpha (HNF1A)-MODY because of its reduced expression in Hnf1a(-/-) mice. However, subsequent human studies examining apoM as a biomarker have yielded conflicting results. We aimed to evaluate apoM as a biomarker for HNF1A-MODY using a highly specific and sensitive ELISA. ApoM concentration was measured in subjects with HNF1A-MODY (n = 69), Type 1 diabetes (n = 50), Type 2 diabetes (n = 120) and healthy control subjects (n = 100). The discriminative accuracy of apoM and of the apoM/HDL ratio for diabetes aetiology was evaluated. Mean (standard deviation) serum apoM concentration (μmol/l) was significantly lower for subjects with HNF1A-MODY [0.86 (0.29)], than for those with Type 1 diabetes [1.37 (0.26), P = 3.1 × 10(-18) ) and control subjects [1.34 (0.22), P = 7.2 × 10(-19) ). There was no significant difference in apoM concentration between subjects with HNF1A-MODY and Type 2 diabetes [0.89 (0.28), P = 0.13]. The C-statistic measure of discriminative accuracy for apoM was 0.91 for HNF1A-MODY vs. Type 1 diabetes, indicating high discriminative accuracy. The apoM/HDL ratio was significantly lower in HNF1A-MODY than other study groups. However, this ratio did not perform well in discriminating HNF1A-MODY from either Type 1 diabetes (C-statistic = 0.79) or Type 2 diabetes (C-statistic = 0.68). We confirm an earlier report that serum apoM levels are lower in HNF1A-MODY than in controls. Serum apoM provides good discrimination between HNF1A-MODY and Type 1 diabetes and warrants further investigation for clinical utility in diabetes diagnostics. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  9. Extra Virgin Olive Oil Improves Oxidative Stress, Functional Capacity, and Health-Related Psychological Status in Patients With Fibromyalgia: A Preliminary Study.

    Science.gov (United States)

    Rus, Alma; Molina, Francisco; Ramos, Manuel Miguel; Martínez-Ramírez, María Josefa; Del Moral, María Luisa

    2016-07-21

    Fibromyalgia (FM) is a chronic disease that imposes physical, psychological, and social limitations. We have reported that oxidative stress may play a role in the pathophysiology of FM. Olive oil has been shown to be effective treatment against the oxidative stress associated with several diseases. The aim of this study was to investigate the effect of olive oil on oxidative stress and health-related parameters in FM. This preliminary study was performed on blood samples of 23 women diagnosed with FM who consumed 50 ml of organic olive oil daily for 3 weeks. Subjects were randomized into two groups: one ingested extra virgin olive oil (EVOO) and the other refined olive oil (ROO), which have different antioxidant content. The patients' oxidative (lipid, protein, and DNA oxidation) and antioxidative (antioxidant enzyme activities and compounds) profiles were examined before and after the treatment period. Functional capacity and physical and mental health status were assessed using the Fibromyalgia Impact Questionnaire (FIQ) and the Physical Component (PCS-12) and Mental Component Summaries (MCS-12) of the Short Form-12 Health Survey, respectively. Significant differences were found in pre-post change between the EVOO and ROO groups for protein carbonyls, lipid peroxidation, and FIQ and MCS-12 scores. Differences between groups approached statistical significance for oxidative DNA damage and levels of the antioxidant compound zinc. EVOO may protect women with FM against oxidative stress in addition to improving functional capacity and health-related psychological status. Findings suggest that olive oil may be a valuable therapeutic support in FM. © The Author(s) 2016.

  10. Neck exercises, physical and cognitive behavioural-graded activity as a treatment for adult whiplash patients with chronic neck pain: Design of a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Hansen Inge

    2011-12-01

    Full Text Available Abstract Background Many patients suffer from chronic neck pain following a whiplash injury. A combination of cognitive, behavioural therapy with physiotherapy interventions has been indicated to be effective in the management of patients with chronic whiplash-associated disorders. The objective is to present the design of a randomised controlled trial (RCT aimed at evaluating the effectiveness of a combined individual physical and cognitive behavioural-graded activity program on self-reported general physical function, in addition to neck function, pain, disability and quality of life in patients with chronic neck pain following whiplash injury compared with a matched control group measured at baseline and 4 and 12 months after baseline. Methods/Design The design is a two-centre, RCT-study with a parallel group design. Included are whiplash patients with chronic neck pain for more than 6 months, recruited from physiotherapy clinics and an out-patient hospital department in Denmark. Patients will be randomised to either a pain management (control group or a combined pain management and training (interventiongroup. The control group will receive four educational sessions on pain management, whereas the intervention group will receive the same educational sessions on pain management plus 8 individual training sessions for 4 months, including guidance in specific neck exercises and an aerobic training programme. Patients and physiotherapists are aware of the allocation and the treatment, while outcome assessors and data analysts are blinded. The primary outcome measures will be Medical Outcomes Study Short Form 36 (SF36, Physical Component Summary (PCS. Secondary outcomes will be Global Perceived Effect (-5 to +5, Neck Disability Index (0-50, Patient Specific Functioning Scale (0-10, numeric rating scale for pain bothersomeness (0-10, SF-36 Mental Component Summary (MCS, TAMPA scale of Kinesiophobia (17-68, Impact of Event Scale (0-45, EuroQol (0

  11. Factors influencing the health-related quality of life of Chinese advanced cancer patients and their spousal caregivers: a cross-sectional study.

    Science.gov (United States)

    Li, Qiuping; Xu, Yinghua; Zhou, Huiya; Loke, Alice Yuen

    2016-08-02

    Cancer and its treatment have a major impact on the lives of patients and their intimate partners, such as on their health-related quality of life (HRQOL). The aims of this study are to: (i) assess the HRQOL of advanced cancer patients and spousal caregivers, and explore the relationship between the HRQOL of cancer patients and that of their spousal caregivers; (ii) detect factors influencing the HRQOL of cancer patients and spousal caregivers; and (iii) explore the impact of anxiety and depression on the HRQOL of couples. A total of 131 couples where one of the partners was hospitalized for advanced cancer were invited to complete a survey to assess their demographic and background information, HRQOL, and anxiety and depression. HRQOL was measured using the SF-12, while anxiety and depression were measured using the Hospital Anxiety and Depression Scale. Data were analyzed using a T-test, Pearson correlations, multiple linear regressions, and structural equation modeling. In general, the spousal caregivers had higher levels of HRQOL (seven out of eight SF-12 domains and two SF-12 dimensions) p = 0.038-0.000, anxiety (p = 0.002), and depression (p = 0.011) than patients. Correlations of HRQOL between patients and spouses were small to moderate (r = 0.193-0.398). Multiple independent factors influencing the physical component summary (PCS), mental component summary (MCS), vitality (VT), and role emotional (RE) sections of the SF-12 were identified, including: gender, time since diagnosis, levels of education, working status, the extent to which spousal caregivers were informed about the disease, improved marital relationship after the diagnosis of cancer, and anxiety and depression. For both patients and spousal caregivers, the strongest independent factor influencing HRQOL (SF-12 PCS, MCS, VT, and RE) was anxiety and depression. Anxiety and depression may have both actor and partner effects on the HRQOL of couples to various degrees. The findings of

  12. Genetic Polymorphism of Secretoglobin SCGB1A1 and Development of Lung Pathology in Children

    Directory of Open Access Journals (Sweden)

    N.K. Malaya

    2014-02-01

    Full Text Available The purpose of investigation — to study of A(38G genetic polymorphism of the first exon of secretoglobin SCGB1A1 in Crimean children and to identify the possible correlation between the degree of polymorphism and development of lung pathology (bronchial asthma and recurrent bronchitis. There were investigated DNA samples from children with bronchial asthma (75 persons, recurrent bronchitis (19 persons and healthy children (20 persons aged from 6 to 16 years. The genetic polymorphism was determined by polymerase chain reaction with method of allele discrimination with registration the results by electrophoresis. Frequency of allele combinations of genetic variants of studied polymorphism was different in patients with bronchial asthma, recurrent bronchitis and in control group. Thus, among patients with bronchial asthma the frequency of homozygous allele AA carriers is lower, and among patients with recurrent bronchitis it is higher then in control group. Contrary, the frequency of AG heterozygotes was higher among patients with bronchial asthma then in patients with recurrent bronchitis and in control group. Also the frequency of AG heterozygotes in patients with recurrent bronchitis is much lower than homozygotes. The obtained results can be used for prognostic purpose to evaluate the prospects of the obstructive syndrome development.

  13. Radium-226 in certified uranium reference ores DL-1a, BL-4a, DH-1a and BL-5

    International Nuclear Information System (INIS)

    Smith, C.W.; Steger, H.F.

    1983-05-01

    Radium-226 radioactivity in uranium reference ores BL-4a and BL-5 and uranium-thorium reference ores DL-1a and DH-1a was determined in an interlaboratory program. Twelve of thirteen participants used certified radium solutions from the United States National Bureau of Standards (NBS) for calibration purposes. Recommended values of sup(226)Ra activity and associated parameters were calculated by statistical treatment of the results. In all cases, the recommended values are within 2 percent of activities predicted assuming secular equilibrium in the sup(238)U decay series. The recommended values for radium activity are 1.40, 15.5, 31.5 and 857 Bq/ for DL-1a, BL-4a, DH-1a and BL-5, respectively

  14. Porcine EEF1A1 and EEF1A2 genes: genomic structure, polymorphism, mapping and expression

    Czech Academy of Sciences Publication Activity Database

    Svobodová, K.; Horák, Pavel; Stratil, Antonín; Bartenschlager, H.; Van Poucke, M.; Chalupová, P.; Dvořáková, Věra; Knorr, Ch.; Stupka, R.; Čítek, J.; Šprysl, M.; Palánová, Anna; Peelman, L. J.; Geldermann, H.; Knoll, A.

    2015-01-01

    Roč. 42, č. 8 (2015), s. 1257-1264 ISSN 0301-4851 R&D Projects: GA ČR(CZ) GA523/06/1302; GA ČR GA523/09/0844 Institutional support: RVO:67985904 Keywords : EEF1A1 * EEF1A2 * gene expression Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.698, year: 2015

  15. Smoking and risk of treatment-induced neutralizing antibodies to interferon β-1a.

    Science.gov (United States)

    Hedström, Anna Karin; Ryner, Malin; Fink, Katarina; Fogdell-Hahn, Anna; Alfredsson, Lars; Olsson, Tomas; Hillert, Jan

    2014-04-01

    Neutralizing antibodies (NAbs) to interferon β (IFNβ) products that develop during treatment are associated with a loss of clinical efficacy. The aim of this study was to investigate the influence of smoking habits on the risk of developing NAbs to IFNβ, in the treatment of multiple sclerosis (MS). This report is based on 695 MS patients treated with IFNβ-1a, included in two Swedish case-control studies that collected information on smoking habits. Using logistic regression, the development of NAbs to IFNβ-1a among current smokers was compared with that of non-smokers, by calculating the odds ratio (OR) with a 95% confidence interval (CI). Current smokers showed an increased risk of developing NAbs to IFNβ-1a, compared with non-smokers (OR 1.9; 95% CI 1.3-2.8; p = 0.002). There were no gender differences. We observed no association between past smoking and the risk of developing NAbs to IFNβ-1a. The finding that current smokers have an increased risk of developing NAbs to IFNβ-1a has implications, both for the practical care and the treatment of MS; it also provides an interesting perspective of the lungs as an immune-reactive organ, reacting upon irritation.

  16. CD1a presentation of endogenous antigens by group 2 innate lymphoid cells.

    Science.gov (United States)

    Hardman, Clare S; Chen, Yi-Ling; Salimi, Maryam; Jarrett, Rachael; Johnson, David; Järvinen, Valtteri J; Owens, Raymond J; Repapi, Emmanouela; Cousins, David J; Barlow, Jillian L; McKenzie, Andrew N J; Ogg, Graham

    2017-12-22

    Group 2 innate lymphoid cells (ILC2) are effectors of barrier immunity, with roles in infection, wound healing, and allergy. A proportion of ILC2 express MHCII (major histocompatibility complex II) and are capable of presenting peptide antigens to T cells and amplifying the subsequent adaptive immune response. Recent studies have highlighted the importance of CD1a-reactive T cells in allergy and infection, activated by the presentation of endogenous neolipid antigens and bacterial components. Using a human skin challenge model, we unexpectedly show that human skin-derived ILC2 can express CD1a and are capable of presenting endogenous antigens to T cells. CD1a expression is up-regulated by TSLP (thymic stromal lymphopoietin) at levels observed in the skin of patients with atopic dermatitis, and the response is dependent on PLA2G4A. Furthermore, this pathway is used to sense Staphylococcus aureus by promoting Toll-like receptor-dependent CD1a-reactive T cell responses to endogenous ligands. These findings define a previously unrecognized role for ILC2 in lipid surveillance and identify shared pathways of CD1a- and PLA2G4A-dependent ILC2 inflammation amenable to therapeutic intervention. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  17. Analysis of CYP1A1 and COMT polymorphisms in women with cervical cancer.

    Science.gov (United States)

    Kleine, J P; Camargo-Kosugi, C M; Carvalho, C V; Silva, F C; Silva, I D C G

    2015-12-29

    The aim of this case-control study was to obtain a comprehensive panel of genetic polymorphisms present only in genes (cytochrome P-450 1A1--CYP1A1 and catechol-O-methyl transferase--COMT) within the metabolic pathway of sex steroids and determine their possible associations with the presence or absence of cervical cancer. Genotypes of 222 women were analyzed: a) 81 with cancer of the cervix treated at the Cancer Hospital Alfredo Abram, between June 2012 and May 2013, with diagnosis confirmed surgically and/or through histomorphological examination; and b) 141 healthy women who assisted at the Endocrine Gynecology and Climacteric Ambulatory, Department of Gynecology, UNIFESP-EPM. These polymorphisms were detected by polymerase chain reaction amplification-restriction fragment length polymorphism analysis and visualized on 3% agarose gels stained with ethidium bromide. We found a significant association between the frequency of the CYP1A1 polymorphism and the development of cervical cancer. A statistical difference was observed between patient and control groups for CYP1A1 polymorphism genotype distributions (P 0.05) or between other risk variables analyzed. The CYP1A1 gene involved in the metabolic pathway of sex steroids might influence the emergence of pathological conditions such as cervical cancer in women who carry a mutated allele, and result in 1.80 and 13.46 times increased risk for women with heterozygous or homozygous mutated genotypes, respectively.

  18. Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.

    Directory of Open Access Journals (Sweden)

    Dennis Lal

    Full Text Available The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic.We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients.We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%. Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1 are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test, previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.

  19. Gene-Environment Interaction in Parkinson's Disease: Coffee, ADORA2A, and CYP1A2.

    Science.gov (United States)

    Chuang, Yu-Hsuan; Lill, Christina M; Lee, Pei-Chen; Hansen, Johnni; Lassen, Christina F; Bertram, Lars; Greene, Naomi; Sinsheimer, Janet S; Ritz, Beate

    2016-01-01

    Drinking caffeinated coffee has been reported to provide protection against Parkinson's disease (PD). Caffeine is an adenosine A2A receptor (encoded by the gene ADORA2A) antagonist that increases dopaminergic neurotransmission and Cytochrome P450 1A2 (gene: CYP1A2) metabolizes caffeine; thus, gene polymorphisms in ADORA2A and CYP1A2 may influence the effect coffee consumption has on PD risk. In a population-based case-control study (PASIDA) in Denmark (1,556 PD patients and 1,606 birth year- and gender-matched controls), we assessed interactions between lifetime coffee consumption and 3 polymorphisms in ADORA2A and CYP1A2 for all subjects, and incident and prevalent PD cases separately using logistic regression models. We also conducted a meta-analysis combining our results with those from previous studies. We estimated statistically significant interactions for ADORA2A rs5760423 and heavy vs. light coffee consumption in incident (OR interaction = 0.66 [95% CI 0.46-0.94], p = 0.02) but not prevalent PD. We did not observe interactions for CYP1A2 rs762551 and rs2472304 in incident or prevalent PD. In meta-analyses, PD associations with daily coffee consumption were strongest among carriers of variant alleles in both ADORA2A and CYP1A2. We corroborated results from a previous report that described interactions between ADORA2A and CYP1A2 polymorphisms and coffee consumption. Our results also suggest that survivor bias may affect results of studies that enroll prevalent PD cases. © 2017 S. Karger AG, Basel.

  20. Sentinel-1A Product Geolocation Accuracy: Commissioning Phase Results

    Directory of Open Access Journals (Sweden)

    Adrian Schubert

    2015-07-01

    Full Text Available Sentinel-1A (S1A is an Earth observation satellite carrying a state-of-the-art Synthetic Aperture Radar (SAR imaging instrument. It was launched by the European Space Agency (ESA on 3 April 2014. With the end of the in-orbit commissioning phase having been completed at the end of September 2014, S1A data products are already consistently providing highly accurate geolocation. StripMap (SM mode products were acquired regularly and tested for geolocation accuracy and consistency during dedicated corner reflector (CR campaigns. At the completion of this phase, small geometric inconsistencies had been understood and mitigated, with the high quality of the final product geolocation estimates reflecting the mission’s success thus far. This paper describes the measurement campaign, the methods used during geolocation estimation, and presents best estimates of the product Absolute Location Error (ALE available at the beginning of S1A’s operational phase.

  1. DH-1a: a certified uranium-thorium reference ore

    International Nuclear Information System (INIS)

    Steger, H.F.; Bowman, W.S.; Zechanowitsch, G.

    1981-09-01

    A 122-kg sample of uranium-thorium ore, DH-1a, from Elliot Lake, Ontario, was prepared as a compositional reference material to replace the similar certified ore, DH-1. DH-1a was ground to minus 74μm, blended in one lot, and bottled in 200 g units. The homogeneity of DH-1a with respect to uranium was confirmed using the volumetric umpire method. The recommended value for uranium is based on the data from the confirmation of homogeneity. For thorium, twelve laboratories provided results in a free choice analytical program. A statistical analysis of the data gave a recommended value of 0.263 percent for uranium and 0.091 percent for thorium

  2. Two novel POC1A mutations in the primordial dwarfism, SOFT syndrome: Clinical homogeneity but also unreported malformations.

    Science.gov (United States)

    Barraza-García, Jimena; Iván Rivera-Pedroza, Carlos; Salamanca, Luis; Belinchón, Alberta; López-González, Vanesa; Sentchordi-Montané, Lucía; del Pozo, Ángela; Santos-Simarro, Fernando; Campos-Barros, Ángel; Lapunzina, Pablo; Guillén-Navarro, Encarna; González-Casado, Isabel; García-Miñaur, Sixto; Heath, Karen E

    2016-01-01

    Primordial dwarfism encompasses rare conditions characterized by severe intrauterine growth retardation and growth deficiency throughout life. Recently, three POC1A mutations have been reported in six families with the primordial dwarfism, SOFT syndrome (Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis). Using a custom-designed Next-generation sequencing skeletal dysplasia panel, we have identified two novel homozygous POC1A mutations in two individuals with primordial dwarfism. The severe growth retardation and the facial profiles are strikingly similar between our patients and those described previously. However, one of our patients was diagnosed with severe foramen magnum stenosis and subglottic tracheal stenosis, malformations not previously associated with this syndrome. Our findings confirm that POC1A mutations cause SOFT syndrome and that mutations in this gene should be considered in patients with severe pre- and postnatal short stature, symmetric shortening of long bones, triangular facies, sparse hair and short, thickened distal phalanges. © 2015 Wiley Periodicals, Inc.

  3. SCN1A, ABCC2 and UGT2B7 gene polymorphisms in association with individualized oxcarbazepine therapy.

    Science.gov (United States)

    Ma, Chun-Lai; Wu, Xun-Yi; Jiao, Zheng; Hong, Zhen; Wu, Zhi-Yuan; Zhong, Ming-Kang

    2015-01-01

    Associations between the effects of SCN1A, SCN2A, ABCC2 and UGT2B7 genetic polymorphisms and oxcarbazepine (OXC) maintenance doses in Han Chinese epileptic patients were investigated. Genetic polymorphisms were detected in 184 epileptic patients receiving OXC monotherapy by high-resolution melting curve and TaqMan method. Carriers of the SCN1A IVS5-91G>A, UGT2B7 c.802T>C and ABCC2 c.1249G>A variant alleles required significantly higher OXC maintenance doses than noncarriers (p GA > AA. SCN1A, UGT2B7 and ABCC2 genetic polymorphisms are associated with OXC maintenance doses and may be useful for the personalization of OXC therapy in epileptic patients. Further studies are needed. Original submitted 6 June 2014; Revision submitted 5 September 2014.

  4. Cyp1a reporter zebrafish reveals target tissues for dioxin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kun-Hee [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Park, Hye-Jeong [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Jin Hee [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Suhyun [Graduate School of Medicine, Korea University, Ansan (Korea, Republic of); Williams, Darren R. [New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju (Korea, Republic of); Kim, Myeong-Kyu [Department of Neurology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Jung, Young Do [Department of Biochemistry, Chonnam National University Medical School, Gwangju (Korea, Republic of); Teraoka, Hiroki [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Park, Hae-Chul [Graduate School of Medicine, Korea University, Ansan (Korea, Republic of); Choy, Hyon E., E-mail: hyonchoy@chonnam.ac.kr [Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Shin, Boo Ahn, E-mail: bashin@chonnam.ac.kr [Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Choi, Seok-Yong, E-mail: zebrafish@chonnam.ac.kr [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); School of Biological Sciences and Technology, Chonnam National University, Gwangju (Korea, Republic of)

    2013-06-15

    Highlights: •2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic anthropogenic substance ever identified. •Transgenic cyp1a reporter zebrafish reveals target tissues for TCDD. •The retinal bipolar cells, otic vesicle, lateral line, pancreas, cloaca and pectoral fin bud are novel targets in zebrafish for TCDD. •Our findings will further understanding of human health risks by TCDD. -- Abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the unintentional byproduct of various industrial processes, is classified as human carcinogen and could disrupt reproductive, developmental and endocrine systems. Induction of cyp1a1 is used as an indicator of TCDD exposure. We sought to determine tissues that are vulnerable to TCDD toxicity using a transgenic zebrafish (Danio rerio) model. We inserted a nuclear enhanced green fluorescent protein gene (EGFP) into the start codon of a zebrafish cyp1a gene in a fosmid clone using DNA recombineering. The resulting recombineered fosmid was then used to generate cyp1a reporter zebrafish, embryos of which were exposed to TCDD. Expression pattern of EGFP in the reporter zebrafish mirrored that of endogenous cyp1a mRNA. In addition, exposure of the embryos to TCDD at as low as 10 pM for 72 h, which does not elicit morphological abnormalities of embryos, markedly increased GFP expression. Furthermore, the reporter embryos responded to other AhR ligands as well. Exposure of the embryos to TCDD revealed previously reported (the cardiovascular system, liver, pancreas, kidney, swim bladder and skin) and unreported target tissues (retinal bipolar cells, otic vesicle, lateral line, cloaca and pectoral fin bud) for TCDD. Transgenic cyp1a reporter zebrafish we have developed can further understanding of ecotoxicological relevance and human health risks by TCDD. In addition, they could be used to identify agonists of AhR and antidotes to TCDD toxicity.

  5. A comparison of functional outcome in patients sustaining major trauma: a multicentre, prospective, international study.

    Directory of Open Access Journals (Sweden)

    Timothy H Rainer

    Full Text Available OBJECTIVES: To compare 6 month and 12 month health status and functional outcomes between regional major trauma registries in Hong Kong and Victoria, Australia. SUMMARY BACKGROUND DATA: Multicentres from trauma registries in Hong Kong and the Victorian State Trauma Registry (VSTR. METHODS: Multicentre, prospective cohort study. Major trauma patients and aged ≥18 years were included. The main outcome measures were Extended Glasgow Outcome Scale (GOSE functional outcome and risk-adjusted Short-Form 12 (SF-12 health status at 6 and 12 months after injury. RESULTS: 261 cases from Hong Kong and 1955 cases from VSTR were included. Adjusting for age, sex, ISS, comorbid status, injury mechanism and GCS group, the odds of a better functional outcome for Hong Kong patients relative to Victorian patients at six months was 0.88 (95% CI: 0.66, 1.17, and at 12 months was 0.83 (95% CI: 0.60, 1.12. Adjusting for age, gender, ISS, GCS, injury mechanism and comorbid status, Hong Kong patients demonstrated comparable mean PCS-12 scores at 6-months (adjusted mean difference: 1.2, 95% CI: -1.2, 3.6 and 12-months (adjusted mean difference: -0.4, 95% CI: -3.2, 2.4 compared to Victorian patients. Keeping age, gender, ISS, GCS, injury mechanism and comorbid status, there was no difference in the MCS-12 scores of Hong Kong patients compared to Victorian patients at 6-months (adjusted mean difference: 0.4, 95% CI: -2.1, 2.8 or 12-months (adjusted mean difference: 1.8, 95% CI: -0.8, 4.5. CONCLUSION: The unadjusted analyses showed better outcomes for Victorian cases compared to Hong Kong but after adjusting for key confounders, there was no difference in 6-month or 12-month functional outcomes between the jurisdictions.

  6. Anxiety, Depression, and Health-Related QOL in Patients Diagnosed with PAH or CTEPH.

    Science.gov (United States)

    Pfeuffer, Elena; Krannich, Holger; Halank, Michael; Wilkens, Heinrike; Kolb, Philipp; Jany, Berthold; Held, Matthias

    2017-12-01

    Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are life-threatening diseases with a high burden of symptoms. Although depression, anxiety, and reduced health related quality of life (HRQOL) have also been reported, a comparative analysis which explores these traits and their underlying factors was lacking. A retrospective analysis of depression, anxiety, and health related QOL was conducted using a Hospital anxiety and depression scale (HADS) as well as the SF-36 HRQOL questionnaire. Results from these tools were compared with haemodynamic and functional parameters in 70 PAH and 23 CTEPH outpatients from a German tertiary care center specializing in pulmonary hypertension. Although HRQOL was reduced in both cohorts of patients, individuals diagnosed with CTEPH scored lower in nearly all SF-36 parameters. Significance was noted in both "mental health" (p = 0.01) and "mental component summary score" (MCS) (p = 0.02). Depression was also more frequent in patients with CTEPH (56%) than in patients with PAH (30%), (p = 0.03). Overall, depression and anxiety correlated with most SF-36 scales in both PAH and CTEPH. In CTEPH, depression also correlated with the Borg Dyspnea Scale (r = 0.44, p = 0.01). These patients also had significantly lower pCO 2 levels than the PAH cohort reflecting more severe ventilation/perfusion mismatch. All other haemodynamic and functional parameters did not differ across the groups. While both cohorts of patients suffer from a reduced HRQOL as well as depression and anxiety, decreases in mental health parameters are more pronounced in the CTEPH cohort. This suggests a strong effort to improve early detection, especially in dyspneic patients with classical risk factors for CTEPH and PAH and argues for mental illness interventions alongside routine clinical care provided to patients diagnosed with PAH or CTEPH.

  7. Predictors of health-related quality of life in patients with chronic liver disease.

    Science.gov (United States)

    Afendy, A; Kallman, J B; Stepanova, M; Younoszai, Z; Aquino, R D; Bianchi, G; Marchesini, G; Younossi, Z M

    2009-09-01

    Patient-reported outcomes like health-related quality of life (HRQL) have become increasingly important for full assessment of patients with chronic liver diseases (CLD). To explore the relative impact of different types of liver disease on HRQL as well as predictors of HRQL domains in CLD. Our HRQL databases with Short-Form 36 (SF-36) data were used. Scores for each of SF-36 scales (PF - physical functioning, RP - role functioning, BP - bodily pain, GH - general health, VT - vitality, SF - social functioning, RE - role emotional and MH - mental health, MCS - mental component score, PCS - physical component score) were compared between different types of CLD as well as other variables. Complete data were available for 1103 CLD patients. Demographic and clinical data included: age 54.2 +/- 12.0 years, 40% female, 761 (69%) with cirrhosis. Analysis revealed that age correlated significantly (P < 0.05) with worsening HRQL on every scale of the SF-36. Female patients had more HRQL impairments in PF, RP, BP, GH, VT and MH scales of SF-36 (Delta scale score: 6.6-10.7, P < 0.05). Furthermore, cirrhotic patients had more impairment of HRQL in every scale of SF-36 (Delta scale score: 6.6-43.0, P < 0.05). In terms of diagnostic groups, non-alcoholic fatty liver disease patients showed more impairment of HRQL. Analysis of this large CLD cohort suggests that a number of important clinicodemographic factors are associated with HRQL impairment. These findings contribute to the full understanding of the total impact of CLD on patients' health.

  8. A Comparison of Functional Outcome in Patients Sustaining Major Trauma: A Multicentre, Prospective, International Study

    Science.gov (United States)

    Rainer, Timothy H.; Yeung, Hiu Hung; Gabbe, Belinda J.; Yuen, Kai Y.; Ho, Hiu F.; Kam, Chak W.; Chang, Annice; Poon, Wai S.; Cameron, Peter A.; Graham, Colin A.

    2014-01-01

    Objectives To compare 6 month and 12 month health status and functional outcomes between regional major trauma registries in Hong Kong and Victoria, Australia. Summary Background Data Multicentres from trauma registries in Hong Kong and the Victorian State Trauma Registry (VSTR). Methods Multicentre, prospective cohort study. Major trauma patients and aged ≥18 years were included. The main outcome measures were Extended Glasgow Outcome Scale (GOSE) functional outcome and risk-adjusted Short-Form 12 (SF-12) health status at 6 and 12 months after injury. Results 261 cases from Hong Kong and 1955 cases from VSTR were included. Adjusting for age, sex, ISS, comorbid status, injury mechanism and GCS group, the odds of a better functional outcome for Hong Kong patients relative to Victorian patients at six months was 0.88 (95% CI: 0.66, 1.17), and at 12 months was 0.83 (95% CI: 0.60, 1.12). Adjusting for age, gender, ISS, GCS, injury mechanism and comorbid status, Hong Kong patients demonstrated comparable mean PCS-12 scores at 6-months (adjusted mean difference: 1.2, 95% CI: −1.2, 3.6) and 12-months (adjusted mean difference: −0.4, 95% CI: −3.2, 2.4) compared to Victorian patients. Keeping age, gender, ISS, GCS, injury mechanism and comorbid status, there was no difference in the MCS-12 scores of Hong Kong patients compared to Victorian patients at 6-months (adjusted mean difference: 0.4, 95% CI: −2.1, 2.8) or 12-months (adjusted mean difference: 1.8, 95% CI: −0.8, 4.5). Conclusion The unadjusted analyses showed better outcomes for Victorian cases compared to Hong Kong but after adjusting for key confounders, there was no difference in 6-month or 12-month functional outcomes between the jurisdictions. PMID:25157522

  9. Should We Provide Life-Sustaining Treatments to Patients with Permanent Loss of Cognitive Capacities?

    Directory of Open Access Journals (Sweden)

    Ofra G. Golan

    2012-07-01

    Full Text Available A very troubling issue for health care systems today is that of life-sustaining treatment for patients who have permanently lost their cognitive capacities. These include patients in persistent vegetative state (PVS, or minimally conscious state (MCS, as well as a growing population of patients at the very end stage of dementia. These patients are totally dependent on life-sustaining treatments and are, actually, kept alive “artificially.” This phenomenon raises doubts as to the ethics of sustaining the life of patients who have lost their consciousness and cognitive capacities, and whether there is a moral obligation to do so. The problem is that the main facts concerning the experiences and well-being of such patients and their wishes are unknown. Hence the framework of the four principles—beneficence, non-maleficence, autonomy, and justice—is not applicable in these cases; therefore we examined solidarity as another moral value to which we may resort in dealing with this dilemma. This article shows that the source of the dilemma is the social attitudes towards loss of cognitive capacities, and the perception of this state as loss of personhood. Consequently, it is suggested that the principle of solidarity—which both sets an obligation to care for the worst-off, and can be used to identify obligations that appeal to an ethos of behavior—can serve as a guiding principle for resolving the dilemma. The value of solidarity can lead society to care for these patients and not deny them basic care and life-sustaining treatment when appropriate.

  10. Refining a health-related quality of life assessment strategy for solid organ transplant patients.

    Science.gov (United States)

    Feurer, Irene D; Moore, Derek E; Speroff, Theodore; Liu, Hongxia; Payne, Jerita; Harrison, Connie; Pinson, C Wright

    2004-01-01

    The psychometric properties of generic health-related quality of life (HRQOL) assessment instruments were evaluated to identify a reliable, valid, and non-redundant battery to measure longitudinal outcomes in organ transplant patients. Objective functional performance and subjective HRQOL were assessed in 371 solid organ (liver, heart, kidney, lung) transplant patients using the Karnofsky scale, the SF-36 Health Survey (SF-36), and Psychosocial Adjustment to Illness Scale (PAIS). The surveys' internal-consistency reliability, criterion-related validity, and redundancy were tested. The SF-36 mental (MCS) and physical components (PCS), and PAIS summary scales were internally consistent (all alpha > or = 0.83). Four out of seven PAIS scales (vocational, domestic, sexual, social) were collectively associated with the PCS (R = 0.65, P satisfaction) scale was not associated with the SF-36((R)). The relationship between functional performance and the PCS is stronger (r = 0.52, P global score (r = 0.37, P satisfaction inventory was indicated and was developed.

  11. Large Genomic Deletions in CACNA1A Cause Episodic Ataxia Type 2

    Directory of Open Access Journals (Sweden)

    Jijun eWan

    2011-09-01

    Full Text Available Episodic ataxia (EA syndromes are heritable diseases characterized by dramatic episodes of imbalance and incoordination. Episodic ataxia type 2 (EA2, the most common and the best characterized subtype, is caused by mostly nonsense, splice site, small indel and sometimes missense mutations in CACNA1A. Direct sequencing of CACNA1A fails to identify mutations in some patients with EA2-like features, possibly due to incomplete interrogation of CACNA1A or defects in other EA genes not yet defined. Previous reports described genomic deletions between 4-40kb in EA2. In 47 subjects with EA (26 with EA2-like features who tested negative for mutations in the known EA genes, we used Multiplex Ligation-dependent Probe Amplification (MLPA to analyze CACNA1A for exonic copy number variations. Breakpoints were further defined by long-range PCR. We identified distinct multi-exonic deletions in three probands with classic EA2-like features: episodes of prolonged vertigo and ataxia triggered by stress and fatigue, interictal nystagmus, with onset during infancy or early childhood. The breakpoints in all three probands are located in Alu sequences, indicating errors in homologous recombination of Alu sequences as the underlying mechanism. The smallest deletion spanned exons 39 and 40, while the largest deletion spanned 200kb, missing all but the first three exons. One deletion involving exons 39 through 47 arose spontaneously. The search for mutations in CACNA1A appears most fruitful in EA patients with interictal nystagmus and onset early in life. The finding of large heterozygous deletions suggests haploinsufficiency as a possible pathomechanism of EA2.

  12. Anxiety and depression mediate the health-related quality of life differently in patients with cardiovascular disease and stroke-preliminary report of the Yilan study: a population-based community health survey.

    Science.gov (United States)

    Hsu, Nai-Wei; Tsao, Hsuan-Ming; Chen, Hsi-Chung; Chou, Pesus

    2014-01-01

    Cardiovascular disease and stroke have emerged as substantial and growing health challenges to populations around the world. Besides for the survival and medical prognosis, how to improve the health-related quality of life (HRQoL) might also become one of the goals of treatment programs. There are multiple factors that influence HRQol, including comorbidity, mental function and lifestyle. However, substantial research and investigation have still not clarified these underlying pathways, which merit further attention. The purpose of this study was to determine how psychological factors affect the link between cardiovascular disease and stroke with HRQoL. A total of 1,285 elder subjects at least 65 years of age (47.2% male) were enrolled. The mental function and HRQol of each patient was then measured using the Hospital Anxiety and Depression Scale and Short Form-12. After multiple regression analysis, anxiety, depression, cardiovascular disease, stroke, education level and age were shown to be associated with both mental component score (MCS) and physical component score (PCS). In the mediation analysis using the SPSS macro provided by Preacher and Hayes, cardiovascular disease and stroke affected HRQoL via anxiety and depression, respectively. These results suggest that cardiovascular disease and stroke have negative impacts on patient MCS and PCS through different underlying pathways. Cardiovascular disease influences the HRQoL both directly and indirectly with the mediation of anxiety, and stroke influences the HRQoL by way of depression. These findings support the proposition that different combinations of both physical and psychological support are necessary to best manage these diseases.

  13. ALDH1A2 (RALDH2 genetic variation in human congenital heart disease

    Directory of Open Access Journals (Sweden)

    Mesquita Sonia MF

    2009-11-01

    Full Text Available Abstract Background Signaling by the vitamin A-derived morphogen retinoic acid (RA is required at multiple steps of cardiac development. Since conversion of retinaldehyde to RA by retinaldehyde dehydrogenase type II (ALDH1A2, a.k.a RALDH2 is critical for cardiac development, we screened patients with congenital heart disease (CHDs for genetic variation at the ALDH1A2 locus. Methods One-hundred and thirty-three CHD patients were screened for genetic variation at the ALDH1A2 locus through bi-directional sequencing. In addition, six SNPs (rs2704188, rs1441815, rs3784259, rs1530293, rs1899430 at the same locus were studied using a TDT-based association approach in 101 CHD trios. Observed mutations were modeled through molecular mechanics (MM simulations using the AMBER 9 package, Sander and Pmemd programs. Sequence conservation of observed mutations was evaluated through phylogenetic tree construction from ungapped alignments containing ALDH8 s, ALDH1Ls, ALDH1 s and ALDH2 s. Trees were generated by the Neighbor Joining method. Variations potentially affecting splicing mechanisms were cloned and functional assays were designed to test splicing alterations using the pSPL3 splicing assay. Results We describe in Tetralogy of Fallot (TOF the mutations Ala151Ser and Ile157Thr that change non-polar to polar residues at exon 4. Exon 4 encodes part of the highly-conserved tetramerization domain, a structural motif required for ALDH oligomerization. Molecular mechanics simulation studies of the two mutations indicate that they hinder tetramerization. We determined that the SNP rs16939660, previously associated with spina bifida and observed in patients with TOF, does not affect splicing. Moreover, association studies performed with classical models and with the transmission disequilibrium test (TDT design using single marker genotype, or haplotype information do not show differences between cases and controls. Conclusion In summary, our screen indicates that

  14. Passive smoking, Cyp1A1 gene polymorphism and dysmenorrhea

    Science.gov (United States)

    Liu, Hong; Yang, Fan; Li, Zhiping; Chen, Changzhong; Fang, Zhian; Wang, Lihua; Hu, Yonghua; Chen, Dafang

    2007-01-01

    Objective This study investigated whether the association between passive smoking exposure and dysmenorrhea is modified by two susceptibility genes, CYP1A1MspI and CYP1A1HincII. Methods This report includes 1645 (1124 no dysmenorrhea, 521 dysmenorrhea) nonsmoking and nondrinking newly wed female workers at Anqing, China between June 1997 and June 2000. Multiple logistic regression models were used to estimate the associations of passive smoking exposure and genetic susceptibility with dysmenorrhea, adjusting for perceived stress. Results When stratified by women genotype, the adjusted OR of dysmenorrhea was 1.6 (95%CI=1.3-2.1) for passive smoking group with Ile/Ile462 genotype, and 1.5 (95%CI=1.1-2.1) with C/C6235 genotype, compared to non passive smoking group, respectively. The data further showed that there was a significant combined effect between passive smoking and the CYP1A1 Msp1 C/C6235 and HincII Ile/Ile462 genotype (OR=2.6, 95%CI=1.3-5.2). Conclusion CYP1A1 MspI and HincII genotypes modified the association between passive smoking and dysmenorrhea. PMID:17566695

  15. Novel pyridylmethylamines as highly selective 5-HT(1A) superagonists.

    Science.gov (United States)

    Bollinger, Stefan; Hübner, Harald; Heinemann, Frank W; Meyer, Karsten; Gmeiner, Peter

    2010-10-14

    To further improve the maximal serotonergic efficacy and better understand the configurational requirements for 5-HT(1A) binding and activation, we generated and biologically investigated structural variants of the lead structure befiradol. For a bioisosteric replacement of the 3-chloro-4-fluoro moiety, a focused library of 63 compounds by solution phase parallel synthesis was developed. Target binding of our compound collection was investigated, and their affinities for 5-HT(2), α(1), and α(2)-adrenergic as well as D(1)-D(4) dopamine receptors were compared. For particularly interesting test compounds, intrinsic activities at 5-HT(1A) were examined in vitro employing a GTPγS assay. The investigation guided us to highly selective 5HT(1A) superagonists. The benzothiophene-3-carboxamide 8bt revealed almost exclusive 5HT(1A) recognition with a K(i) value of 2.7 nM and a maximal efficacy of 124%. To get insights into the bioactive conformation of our compound collection, we synthesized conformationally constrained bicyclic scaffolds when SAR data indicated a chair-type geometry and an equatorially dispositioned aminomethyl substituent for the 4,4-disubstituted piperidine moiety.

  16. Italian results for stages 1A and 2

    International Nuclear Information System (INIS)

    Di Francesca, R.

    1990-01-01

    This report presents the results on Stages 1A and 2 CRP examples. The examples have been solved by SISCO and HARMONIE codes, which are used for mechanical equilibrium calculations of fast reactor cores at ENEA Fast Reactor Department. (author). 9 figs, 12 tabs