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Sample records for high-dose simian immunodeficiency

  1. Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine

    International Nuclear Information System (INIS)

    Sparger, Ellen E.; Dubie, Robert A.; Shacklett, Barbara L.; Cole, Kelly S.; Chang, W.L.; Luciw, Paul A.

    2008-01-01

    Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-γ enzyme-linked immunospot responses of low magnitude were observed after immunization with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus

  2. Stability of the gorilla microbiome despite simian immunodeficiency virus infection

    OpenAIRE

    Moeller, A. H.; Peeters, Martine; Ayouba, Ahidjo; Ngole, E. M.; Esteban, A.; Hahn, B. H.; Ochman, H.

    2015-01-01

    Simian immunodeficiency viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in faecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. H...

  3. CCR5 Signal Transduction in Macrophages by Human Immunodeficiency Virus and Simian Immunodeficiency Virus Envelopes

    OpenAIRE

    Arthos, James; Rubbert, Andrea; Rabin, Ronald L.; Cicala, Claudia; Machado, Elizabeth; Wildt, Kathryne; Hanbach, Meredith; Steenbeke, Tavis D.; Swofford, Ruth; Farber, Joshua M.; Fauci, Anthony S.

    2000-01-01

    The capacity of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) envelopes to transduce signals through chemokine coreceptors on macrophages was examined by measuring the ability of recombinant envelope proteins to mobilize intracellular calcium stores. Both HIV and SIV envelopes mobilized calcium via interactions with CCR5. The kinetics of these responses were similar to those observed when macrophages were treated with MIP-1β. Distinct differences in the capacity o...

  4. Electrostatic potential of human immunodeficiency virus type 2 and rhesus macaque simian immunodeficiency virus capsid proteins

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    Katarzyna eBozek

    2012-06-01

    Full Text Available Human immunodeficiency virus type 2 (HIV-2 and simian immunodeficiency virus isolated from a macaque monkey (SIVmac are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (SIVsm. Despite their close similarity in genome structure, HIV-2 and SIVmac show different sensitivities to TRIM5α, a host restriction factor against retroviruses. The replication of HIV-2 strains is potently restricted by rhesus (Rh monkey TRIM5α, while that of SIVmac strain 239 (SIVmac239 is not. Viral capsid protein is the determinant of this differential sensitivity to TRIM5α, as the HIV-2 mutant carrying SIVmac239 capsid protein evaded Rh TRIM5α-mediated restriction. However, the molecular determinants of this restriction mechanism are unknown. Electrostatic potential on the protein-binding site is one of the properties regulating protein-protein interactions. In this study, we investigated the electrostatic potential on the interaction surface of capsid protein of HIV-2 strain GH123 and SIVmac239. Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between α-helices 4 and 5 (L4/5. As L4/5 is one of the major determinants of Rh TRIM5α sensitivity of these viruses, the present results suggest that the binding site of the Rh TRIM5α may show complementarity to the HIV-2 GH123 capsid surface charge distribution.

  5. Stability of the gorilla microbiome despite simian immunodeficiency virus infection.

    Science.gov (United States)

    Moeller, Andrew H; Peeters, Martine; Ayouba, Ahidjo; Ngole, Eitel Mpoudi; Esteban, Amadine; Hahn, Beatrice H; Ochman, Howard

    2015-02-01

    Simian immunodeficiency viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in faecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. Here, we examine the effects of SIVgor, a close relative of SIVcpz of chimpanzees and HIV-1 of humans, on the gut bacterial communities residing within wild gorillas, revealing that gorilla gut microbiomes are exceptionally robust to SIV infection. In contrast to the microbiomes of HIV-1-infected humans and SIVcpz-infected chimpanzees, SIVgor-infected gorilla microbiomes exhibit neither rises in the frequencies of opportunistic pathogens nor elevated rates of microbial turnover within individual hosts. Regardless of SIV infection status, gorilla microbiomes assort into enterotypes, one of which is compositionally analogous to those identified in humans and chimpanzees. The other gorilla enterotype appears specialized for a leaf-based diet and is enriched in environmentally derived bacterial genera. We hypothesize that the acquisition of this gorilla-specific enterotype was enabled by lowered immune system control over the composition of the microbiome. Our results indicate differences between the pathology of SIVgor and SIVcpz/HIV-1 infections, demonstrating the utility of investigating host microbial ecology as a means for studying disease in wild primates of high conservation priority. © 2014 John Wiley & Sons Ltd.

  6. SIVdrl detection in captive mandrills: are mandrills infected with a third strain of simian immunodeficiency virus?

    NARCIS (Netherlands)

    van der Kuyl, Antoinette C.; van den Burg, Remco; Hoyer, Mark J.; Gruters, Rob A.; Osterhaus, Albert D. M. E.; Berkhout, Ben

    2004-01-01

    A pol-fragment of simian immunodeficiency virus (SIV) that is highly related to SIVdrl-pol from drill monkeys (Mandrillus leucophaeus) was detected in two mandrills (Mandrillus sphinx) from Amsterdam Zoo. These captivity-born mandrills had never been in contact with drill monkeys, and were unlikely

  7. Functional simian immunodeficiency virus Gag-specific CD8+ intraepithelial lymphocytes in the mucosae of SIVmac251- or simian-human immunodeficiency virus KU2-infected macaques

    International Nuclear Information System (INIS)

    Stevceva, Liljana; Moniuszko, Marcin; Alvarez, Xavier; Lackner, Andrew A.; Franchini, Genoveffa

    2004-01-01

    The vaginal and rectal mucosae are the first line of cellular immune defense to sexually transmitted human immunodeficiency virus type 1 (HIV-1) entry. Thus, intraepithelial lymphocytes (IELs) may be important in the immune response to HIV infection. Here we investigated whether functional IELs in mucosal compartments could be visualized by direct staining with a tetrameric complex specific for the simian immunodeficiency virus (SIV) immunodominant Gag epitope in either separated IEL cells or tissues of macaques infected with SIVmac251. Of the 15 Mamu-A*01-positive macaques studied here, eight were chronically infected with either SIVmac251 or simian-human immunodeficiency virus (SHIV) KU2 and the remaining seven were exposed mucosally to SIVmac251 and sacrificed within 48 h to assess the local immune response. Gag-specific CD8+ T-cells were found in separated IELs from the rectum, colon, jejunum, and vagina of most infected animals. Direct staining of tetramers also revealed their presence in intact tissue. These Gag-specific IELs expressed the activation marker CD69 and produced IFN-γ, suggesting an active immune response in this locale

  8. JST Thesaurus Headwords and Synonyms: simian immunodeficiency virus [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term simian immunodeficiency virus 名詞 ...一般 * * * * サル免疫不全ウイルス サルメンエキフゼンウイルス サルメンエキフゼンウイルス Thesaurus2015 200906068937985410 C LS07 UNKNOWN_2 simian immunodeficiency virus

  9. Induction of Mucosal Homing Virus-Specific CD8+ T Lymphocytes by Attenuated Simian Immunodeficiency Virus

    OpenAIRE

    Cromwell, Mandy A.; Veazey, Ronald S.; Altman, John D.; Mansfield, Keith G.; Glickman, Rhona; Allen, Todd M.; Watkins, David I.; Lackner, Andrew A.; Johnson, R. Paul

    2000-01-01

    Induction of virus-specific T-cell responses in mucosal as well as systemic compartments of the immune system is likely to be a critical feature of an effective AIDS vaccine. We investigated whether virus-specific CD8+ lymphocytes induced in rhesus macaques by immunization with attenuated simian immunodeficiency virus (SIV), an approach that is highly effective in eliciting protection against mucosal challenge, express the mucosa-homing receptor α4β7 and traffic to the intestinal mucosa. SIV-...

  10. Understanding the Process of Envelope Glycoprotein Incorporation into Virions in Simian and Feline Immunodeficiency Viruses

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    José L. Affranchino

    2014-01-01

    Full Text Available The lentiviral envelope glycoproteins (Env mediate virus entry by interacting with specific receptors present at the cell surface, thereby determining viral tropism and pathogenesis. Therefore, Env incorporation into the virions formed by assembly of the viral Gag polyprotein at the plasma membrane of the infected cells is a key step in the replication cycle of lentiviruses. Besides being useful models of human immunodeficiency virus (HIV infections in humans and valuable tools for developing AIDS therapies and vaccines, simian and feline immunodeficiency viruses (SIV and FIV, respectively are relevant animal retroviruses; the study of which provides important information on how lentiviral replication strategies have evolved. In this review, we discuss the molecular mechanisms underlying the incorporation of the SIV and FIV Env glycoproteins into viral particles.

  11. Induction of Mucosal and Systemic Immunity to a Recombinant Simian Immunodeficiency Viral Protein

    Science.gov (United States)

    Lehner, T.; Bergmeier, L. A.; Panagiotidi, C.; Tao, L.; Brookes, R.; Klavinskis, L. S.; Walker, P.; Walker, J.; Ward, R. G.; Hussain, L.; Gearing, A. J. H.; Adams, S. E.

    1992-11-01

    Heterosexual transmission through the cervico-vaginal mucosa is the principal route of human immunodeficiency virus (HIV) infection in Africa and is increasing in the United States and Europe. Vaginal immunization with simian immunodeficiency virus (SIV) had not yet been studied in nonhuman primates. Immune responses in macaques were investigated by stimulation of the genital and gut-associated lymphoid tissue with a recombinant, particulate SIV antigen. Vaginal, followed by oral, administration of the vaccine elicited three types of immunity: (i) gag protein p27-specific, secretory immunoglobulin A (IgA) and immunoglobulin G (IgG) in the vaginal fluid, (ii) specific CD4^+ T cell proliferation and helper function in B cell p27-specific IgA synthesis in the genital lymph nodes, and (iii) specific serum IgA and IgG, with CD4^+ T cell proliferative and helper functions in the circulating blood.

  12. SIVdrl detection in captive mandrills: are mandrills infected with a third strain of simian immunodeficiency virus?

    Directory of Open Access Journals (Sweden)

    Osterhaus Albert DME

    2004-11-01

    Full Text Available Abstract A pol-fragment of simian immunodeficiency virus (SIV that is highly related to SIVdrl-pol from drill monkeys (Mandrillus leucophaeus was detected in two mandrills (Mandrillus sphinx from Amsterdam Zoo. These captivity-born mandrills had never been in contact with drill monkeys, and were unlikely to be hybrids. Their mitochondrial haplotype suggested that they descended from founder animals in Cameroon or northern Gabon, close to the habitat of the drill. SIVdrl has once before been found in a wild-caught mandrill from the same region, indicating that mandrills are naturally infected with a SIVdrl-like virus. This suggests that mandrills are the first primate species to be infected with three strains of SIV: SIVmnd1, SIVmnd2, and SIVdrl.

  13. Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses

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    Ryan P. McNamara

    2018-02-01

    Full Text Available Extracellular vesicles (EVs or exosomes have been implicated in the pathophysiology of infections and cancer. The negative regulatory factor (Nef encoded by simian immunodeficiency virus (SIV and human immunodeficiency virus (HIV plays a critical role in the progression to AIDS and impairs endosomal trafficking. Whether HIV-1 Nef can be loaded into EVs has been the subject of controversy, and nothing is known about the connection between SIV Nef and EVs. We find that both SIV and HIV-1 Nef proteins are present in affinity-purified EVs derived from cultured cells, as well as in EVs from SIV-infected macaques. Nef-positive EVs were functional, i.e., capable of membrane fusion and depositing their content into recipient cells. The EVs were able to transfer Nef into recipient cells. This suggests that Nef readily enters the exosome biogenesis pathway, whereas HIV virions are assembled at the plasma membrane. It suggests a novel mechanism by which lentiviruses can influence uninfected and uninfectable, i.e., CD4-negative, cells.

  14. Seroprevalence of simian immunodeficiency virus in wild and captive born Sykes' monkeys (Cercopithecus mitis) in Kenya

    OpenAIRE

    Otsyula Moses G; Robinson James; Elliott Debra; Munene Elephas; Ellis Brett R; Michael Scott F

    2004-01-01

    Abstract Background The Sykes' monkey and related forms (Cercopithecus mitis) make up an abundant, widespread and morphologically diverse species complex in eastern Africa that naturally harbors a distinct simian immunodeficiency virus (SIVsyk). We carried out a retrospective serological survey of SIV infection from both wild and captive Sykes' monkeys from Kenya. We compared two commercially available, cross-reactive ELISA tests using HIV antigens with a novel SIVsyk antigen-specific Western...

  15. Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Nef Proteins Show Distinct Patterns and Mechanisms of Src Kinase Activation

    Science.gov (United States)

    Greenway, Alison L.; Dutartre, Hélène; Allen, Kelly; McPhee, Dale A.; Olive, Daniel; Collette, Yves

    1999-01-01

    The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases. We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity. Unexpectedly, however, the interaction of SIV Nef with human Lck or Hck is not mediated via its consensus proline motif, which is known to mediate HIV-1 Nef binding to Src homology 3 (SH3) domains, and various experimental analyses failed to show significant interaction of SIV Nef with the SH3 domain of either kinase. Instead, SIV Nef can bind Lck and Hck SH2 domains, and its N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation. Our results provide evidence for multiple mechanisms by which Nef binds to and regulates Src kinases. PMID:10364375

  16. A brief history of the discovery of natural simian immunodeficiency virus (SIV) infections in captive sooty mangabey monkeys.

    Science.gov (United States)

    Gormus, Bobby J; Martin, Louis N; Baskin, Gary B

    2004-01-01

    Experimental leprosy studies using Mycobacterium leprae inoculum isolated from a sooty mangabey monkey (SMM) resulted in the accidental discovery that SMM's asymptomatically carry simian immunodeficiency virus (SIV) that is pathogenic in macaques. We showed that the SMM virus, SIVDelta, was antigenically related to SIVmac, which had been identified in macaques, and to the human immunodeficiency virus (HIV). Similar asymptomatic natural SIV infections had been reported in African green monkeys (AGM). Our results together with observations of others led us to propose that both SIVmac and SIVDelta originated in SMM and that SIV emerged in humans as a result of early African nonhuman primate SIV trans-species infections in humans.

  17. Evaluation of recombinant influenza virus-simian immunodeficiency virus vaccines in macaques.

    Science.gov (United States)

    Sexton, Amy; De Rose, Robert; Reece, Jeanette C; Alcantara, Sheilajen; Loh, Liyen; Moffat, Jessica M; Laurie, Karen; Hurt, Aeron; Doherty, Peter C; Turner, Stephen J; Kent, Stephen J; Stambas, John

    2009-08-01

    There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.

  18. Primary simian immunodeficiency virus SIVmnd-2 infection in mandrills (Mandrillus sphinx).

    Science.gov (United States)

    Onanga, Richard; Souquière, Sandrine; Makuwa, Maria; Mouinga-Ondeme, Augustin; Simon, François; Apetrei, Cristian; Roques, Pierre

    2006-04-01

    Mandrills are the only nonhuman primate (NHP) naturally infected by two types of simian immunodeficiency virus (SIV): SIVmnd-1 and SIVmnd-2. We have already reported that the high SIVmnd-1 replication during primary infection contrasts with only transient changes in CD4+ and CD8+ cell counts. Since early virus-host interactions predict viral control and disease progression in human immunodeficiency virus-infected patients, we investigated the dynamics of SIVmnd-2 primary infection in mandrills to examine the impact on immune effectors in blood and lymph nodes (LNs). To avoid in vitro strain selection, all mandrills in this study received plasma from SIVmnd-2-infected mandrills. SIVmnd-2 plasma viremia peaked at 10(7) to 10(8) RNA copies/ml between days 7 and 10. This peak was followed in all four monkeys by a decline in virus replication, with a set point level of 10(5) to 10(6) RNA copies/ml at day 42 postinfection (p.i.). Viral DNA load in PBMC and LNs also peaked between days 7 and 10 (10(5) to 10(6) DNA copies/10(6) cells) and stabilized at 10(3) to 10(4) DNA copies/10(6) cells during the chronic phase. Anti-SIVmnd-2 antibodies were detected starting from days 28 to 32. A transitory decline of CD3+ CD4+ cells in the LNs occurred in animals with high peak VLs. CD4+ and CD8+ T-cell activation in blood and LNs was noted between days 5 and 17 p.i., surrounding the peak of viral replication. This was most significant in the LNs. Activation markers then returned to preinfection values despite continuous and active viral replication during the chronic infection. The dynamics of SIVmnd-2 infection in mandrills showed a pattern similar to that of SIVmnd-1 infection. This might be a general feature of nonpathogenic SIV natural African NHP models.

  19. Immunovirological analyses of chronically simian immunodeficiency virus SIVmnd-1- and SIVmnd-2-infected mandrills (Mandrillus sphinx).

    Science.gov (United States)

    Apetrei, Cristian; Sumpter, Beth; Souquiere, Sandrine; Chahroudi, Ann; Makuwa, Maria; Reed, Patricia; Ribeiro, Ruy M; Pandrea, Ivona; Roques, Pierre; Silvestri, Guido

    2011-12-01

    Simian immunodeficiency virus (SIV) infection in African nonhuman primate (NHP) natural hosts is usually nonpathogenic, despite high levels of virus replication. We have previously shown that chronic SIV infection in sooty mangabeys (SMs) and African green monkeys (AGMs) is associated with low levels of immune activation and bystander T cell apoptosis. To compare these features with those observed in another natural host, the mandrill (MND), we conducted a cross-sectional survey of the 23 SIV-infected and 25 uninfected MNDs from the only semifree colony of mandrills available worldwide. Viral loads (VLs) were determined and phenotypic and functional analysis of peripheral blood- and lymph node-derived lymphocytes was performed. We found that mandrills chronically infected with SIVmnd-1 or SIVmnd-2 have similar levels of viral replication, and we observed a trend toward lower CD4+ T cell counts in chronically SIVmnd-2-infected MNDs than SIVmnd-1-infected MNDs. No correlation between CD4+ T cell counts and VLs in SIV-infected MNDs could be established. Of note, the levels of T cell activation, proliferation, and apoptosis were comparable between SIVmnd-1- and SIVmnd-2-infected MNDs and to those observed in uninfected animals, with the only exception being an increase in tumor necrosis factor alpha-producing CD8+ T cells in SIVmnd-2-infected MNDs. Overall, these findings recapitulate previous observations in SIV-infected SMs and AGMs and lend further evidence to the hypothesis that low levels of immune activation protect natural SIV hosts from disease progression.

  20. Seroprevalence of simian immunodeficiency virus in wild and captive born Sykes' monkeys (Cercopithecus mitis in Kenya

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    Otsyula Moses G

    2004-10-01

    Full Text Available Abstract Background The Sykes' monkey and related forms (Cercopithecus mitis make up an abundant, widespread and morphologically diverse species complex in eastern Africa that naturally harbors a distinct simian immunodeficiency virus (SIVsyk. We carried out a retrospective serological survey of SIV infection from both wild and captive Sykes' monkeys from Kenya. We compared two commercially available, cross-reactive ELISA tests using HIV antigens with a novel SIVsyk antigen-specific Western blot assay and analyzed the data by origin, subspecies, age and sex. Results The SIVsyk antigen-specific Western blot assay detected more serum samples as positive than either of the cross-reactive ELISA assays. Using this assay, we found that seroprevalence is higher than previously reported, but extremely variable in wild populations (from 0.0 to 90.9%. Females were infected more often than males in both wild and captive populations. Seropositive infants were common. However, no seropositive juveniles were identified. Conclusion We have developed a specific and sensitive Western blot assay for anti-SIVsyk antibody detection. Sykes' monkeys are commonly infected with SIVsyk, but with extremely variable prevalence in the wild. Higher infection prevalence in females suggests predominantly sexual transmission. High infection prevalence in infants, but none in juveniles, suggests maternal antibodies, but little or no vertical transmission.

  1. B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers.

    Science.gov (United States)

    Fukazawa, Yoshinori; Lum, Richard; Okoye, Afam A; Park, Haesun; Matsuda, Kenta; Bae, Jin Young; Hagen, Shoko I; Shoemaker, Rebecca; Deleage, Claire; Lucero, Carissa; Morcock, David; Swanson, Tonya; Legasse, Alfred W; Axthelm, Michael K; Hesselgesser, Joseph; Geleziunas, Romas; Hirsch, Vanessa M; Edlefsen, Paul T; Piatak, Michael; Estes, Jacob D; Lifson, Jeffrey D; Picker, Louis J

    2015-02-01

    Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation. Here we show that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly restricted to CD4(+) follicular helper T (TFH) cells, suggesting that these EC monkeys' highly effective SIV-specific CD8(+) T cells can effectively clear productive SIV infection from extrafollicular sites, but their relative exclusion from B cell follicles prevents their elimination of productively infected TFH cells. CD8(+) lymphocyte depletion in EC monkeys resulted in a dramatic re-distribution of productive SIV infection to non-TFH cells, with restriction of productive infection to TFH cells resuming upon CD8(+) T cell recovery. Thus, B cell follicles constitute 'sanctuaries' for persistent SIV replication in the presence of potent anti-viral CD8(+) T cell responses, potentially complicating efforts to cure HIV infection with therapeutic vaccination or T cell immunotherapy.

  2. Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia.

    Science.gov (United States)

    Reeves, Daniel B; Peterson, Christopher W; Kiem, Hans-Peter; Schiffer, Joshua T

    2017-07-01

    Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient. IMPORTANCE HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the "Berlin patient" remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact

  3. Adaptive evolution of simian immunodeficiency viruses isolated from two conventional progressor macaques with neuroaids

    Energy Technology Data Exchange (ETDEWEB)

    Foley, Brian T [Los Alamos National Laboratory; Korber, Bette T [Los Alamos National Laboratory

    2008-01-01

    Simian immunodeficiency virus infection of macaques may result in neuroAIDS, a feature more commonly observed in macaques with rapid progressive disease than in those with conventional disease. This is the first report of two conventional progressors (H631 and H636) with encephalitis in rhesus macaques inoculated with a derivative of SIVsmES43-3. Phylogenetic analyses of viruses isolated from the cerebral spinal fluid (CSF) and plasma from both animals demonstrated tissue compartmentalization. Additionally, virus from the central nervous system (CNS) was able to infect primary macaque monocyte-derived macrophages more efficiently than virus from plasma. Conversely, virus isolated from plasma was able to replicate better in peripheral blood mononuclear cells than virus from CNS. We speculate that these viruses were under different selective pressures in their separate compartments. Furthermore, these viruses appear to have undergone adaptive evolution to preferentially replicate in their respective cell targets. Analysis of the number of potential N-linked glycosylation sites (PNGS) in gp160 showed that there was a statistically significant loss of PNGS in viruses isolated from CNS in both macaques compared to SIVsmE543-3. Moreover, virus isolated from the brain in H631, had statistically significant loss of PNGS compared to virus isolated from CSF and plasma of the same animal. It is possible that the brain isolate may have adapted to decrease the number of PNGS given that humoral immune selection pressure is less likely to be encountered in the brain. These viruses provide a relevant model to study the adaptations required for SIV to induce encephalitis.

  4. Optimization of the doxycycline-dependent simian immunodeficiency virus through in vitro evolution

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    Piatak Mike

    2008-06-01

    Full Text Available Abstract Background Vaccination of macaques with live attenuated simian immunodeficiency virus (SIV provides significant protection against the wild-type virus. The use of a live attenuated human immunodeficiency virus (HIV as AIDS vaccine in humans is however considered unsafe because of the risk that the attenuated virus may accumulate genetic changes during persistence and evolve to a pathogenic variant. We earlier presented a conditionally live HIV-1 variant that replicates exclusively in the presence of doxycycline (dox. Replication of this vaccine strain can be limited to the time that is needed to provide full protection through transient dox administration. Since the effectiveness and safety of such a conditionally live virus vaccine should be tested in macaques, we constructed a similar dox-dependent SIV variant. The Tat-TAR transcription control mechanism in this virus was inactivated through mutation and functionally replaced by the dox-inducible Tet-On regulatory system. This SIV-rtTA variant replicated in a dox-dependent manner in T cell lines, but not as efficiently as the parental SIVmac239 strain. Since macaque studies will likely require an efficiently replicating variant, we set out to optimize SIV-rtTA through in vitro viral evolution. Results Upon long-term culturing of SIV-rtTA, additional nucleotide substitutions were observed in TAR that affect the structure of this RNA element but that do not restore Tat binding. We demonstrate that the bulge and loop mutations that we had introduced in the TAR element of SIV-rtTA to inactivate the Tat-TAR mechanism, shifted the equilibrium between two alternative conformations of TAR. The additional TAR mutations observed in the evolved variants partially or completely restored this equilibrium, which suggests that the balance between the two TAR conformations is important for efficient viral replication. Moreover, SIV-rtTA acquired mutations in the U3 promoter region. We demonstrate

  5. Suppression of a Natural Killer Cell Response by Simian Immunodeficiency Virus Peptides.

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    Jamie L Schafer

    2015-09-01

    Full Text Available Natural killer (NK cell responses in primates are regulated in part through interactions between two highly polymorphic molecules, the killer-cell immunoglobulin-like receptors (KIRs on NK cells and their major histocompatibility complex (MHC class I ligands on target cells. We previously reported that the binding of a common MHC class I molecule in the rhesus macaque, Mamu-A1*002, to the inhibitory receptor Mamu-KIR3DL05 is stabilized by certain simian immunodeficiency virus (SIV peptides, but not by others. Here we investigated the functional implications of these interactions by testing SIV peptides bound by Mamu-A1*002 for the ability to modulate Mamu-KIR3DL05+ NK cell responses. Twenty-eight of 75 SIV peptides bound by Mamu-A1*002 suppressed the cytolytic activity of primary Mamu-KIR3DL05+ NK cells, including three immunodominant CD8+ T cell epitopes previously shown to stabilize Mamu-A1*002 tetramer binding to Mamu-KIR3DL05. Substitutions at C-terminal positions changed inhibitory peptides into disinhibitory peptides, and vice versa, without altering binding to Mamu-A1*002. The functional effects of these peptide variants on NK cell responses also corresponded to their effects on Mamu-A1*002 tetramer binding to Mamu-KIR3DL05. In assays with mixtures of inhibitory and disinhibitory peptides, low concentrations of inhibitory peptides dominated to suppress NK cell responses. Consistent with the inhibition of Mamu-KIR3DL05+ NK cells by viral epitopes presented by Mamu-A1*002, SIV replication was significantly higher in Mamu-A1*002+ CD4+ lymphocytes co-cultured with Mamu-KIR3DL05+ NK cells than with Mamu-KIR3DL05- NK cells. These results demonstrate that viral peptides can differentially affect NK cell responses by modulating MHC class I interactions with inhibitory KIRs, and provide a mechanism by which immunodeficiency viruses may evade NK cell responses.

  6. Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir.

    Science.gov (United States)

    Avalos, Claudia R; Abreu, Celina M; Queen, Suzanne E; Li, Ming; Price, Sarah; Shirk, Erin N; Engle, Elizabeth L; Forsyth, Ellen; Bullock, Brandon T; Mac Gabhann, Feilim; Wietgrefe, Stephen W; Haase, Ashley T; Zink, M Christine; Mankowski, Joseph L; Clements, Janice E; Gama, Lucio

    2017-08-15

    A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring virus that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation and neuronal damage in cerebrospinal fluid (CSF) of HIV-infected individuals demonstrate continued effects of HIV in brain and suggest that the central nervous system (CNS) may serve as a viral reservoir. Using a simian immunodeficiency virus (SIV)/macaque model for HIV encephalitis and AIDS, we evaluated whether infected cells persist in brain despite ART. Eight SIV-infected pig-tailed macaques were virally suppressed with ART, and plasma and CSF viremia levels were analyzed longitudinally. To assess whether virus persisted in brain macrophages (BrMΦ) in these macaques, we used a macrophage quantitative viral outgrowth assay (MΦ-QVOA), PCR, and in situ hybridization (ISH) to measure the frequency of infected cells and the levels of viral RNA and DNA in brain. Viral RNA in brain tissue of suppressed macaques was undetectable, although viral DNA was detected in all animals. The MΦ-QVOA demonstrated that the majority of suppressed animals contained latently infected BrMΦ. We also showed that virus produced in the MΦ-QVOAs was replication competent, suggesting that latently infected BrMΦ are capable of reestablishing productive infection upon treatment interruption. This report provides the first confirmation of the presence of replication-competent SIV in BrMΦ of ART-suppressed macaques and suggests that the highly debated issue of viral latency in macrophages, at least in brain, has been addressed in SIV-infected macaques treated with ART. IMPORTANCE Resting CD4 + T cells are currently the only cells that fit the definition of a latent reservoir. However, recent evidence suggests that HIV

  7. High throughput generation and characterization of replication-competent clade C transmitter-founder simian human immunodeficiency viruses.

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    Debashis Dutta

    Full Text Available Traditional restriction endonuclease-based cloning has been routinely used to generate replication-competent simian-human immunodeficiency viruses (SHIV and simian tropic HIV (stHIV. This approach requires the existence of suitable restriction sites or the introduction of nucleotide changes to create them. Here, using an In-Fusion cloning technique that involves homologous recombination, we generated SHIVs and stHIVs based on epidemiologically linked clade C transmitted/founder HIV molecular clones from Zambia. Replacing vif from these HIV molecular clones with vif of SIVmac239 resulted in chimeric genomes used to generate infectious stHIV viruses. Likewise, exchanging HIV env genes and introducing N375 mutations to enhance macaque CD4 binding site and cloned into a SHIVAD8-EO backbone. The generated SHIVs and stHIV were infectious in TZMbl and ZB5 cells, as well as macaque PBMCs. Therefore, this method can replace traditional methods and be a valuable tool for the rapid generation and testing of molecular clones of stHIV and SHIV based on primary clinical isolates will be valuable to generate rapid novel challenge viruses for HIV vaccine/cure studies.

  8. Evolution of nef variants in gut associated lymphoid tissue of rhesus macaques during primary simian immunodeficiency virus infection

    International Nuclear Information System (INIS)

    Ndolo, Thomas; Syvanen, Michael; Ellison, Thomas; Dandekar, Satya

    2005-01-01

    We utilized the simian immunodeficiency virus model of AIDS to examine evolution of nef gene in gut-associated lymphoid tissue (GALT) during primary and early asymptomatic stages of infection. Macaques were infected with a cloned virus, SIVmac239/nef-stop harboring a premature stop codon in the nef gene. Restoration of the nef open reading frame occurred in GALT early at 3 days post-infection. Analysis of nef sequences by phylogenetic tools showed that evolution of nef was neutral thereafter, as evidenced by the ratio of synonymous to nonsynonymous substitutions, a star pattern in unrooted trees and distribution of amino acid replacements fitting a simple Poisson process. Two regions encoding for a nuclear localization signal and a CTL epitope were conserved. Thus, GALT was a site for strong positive selection of functional nef during initial stages of infection. However, evolution of the nef gene thereafter was neutral during early asymptomatic stage of infection

  9. Pathogenic infection of Macaca nemestrina with a CCR5-tropic subtype-C simian-human immunodeficiency virus

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    Song Ruijiang

    2009-07-01

    Full Text Available Abstract Background Although pig-tailed macaques (Macaca nemestrina have been used in AIDS research for years, less is known about the early immunopathogenic events in this species, as compared to rhesus macaques (Macaca mulatta. Similarly, the events in early infection are well-characterized for simian immunodeficiency viruses (SIV, but less so for chimeric simian-human immunodeficiency viruses (SHIV, although the latter have been widely used in HIV vaccine studies. Here, we report the consequences of intrarectal infection with a CCR5-tropic clade C SHIV-1157ipd3N4 in pig-tailed macaques. Results Plasma and cell-associated virus was detectable in peripheral blood and intestinal tissues of all four pig-tailed macaques following intrarectal inoculation with SHIV-1157ipd3N4. We also observed a rapid and irreversible loss of CD4+ T cells at multiple mucosal sites, resulting in a marked decrease of CD4:CD8 T cell ratios 0.5–4 weeks after inoculation. This depletion targeted subsets of CD4+ T cells expressing the CCR5 coreceptor and having a CD28-CD95+ effector memory phenotype, consistent with the R5-tropism of SHIV-1157ipd3N4. All three animals that were studied beyond the acute phase seroconverted as early as week 4, with two developing cross-clade neutralizing antibody responses by week 24. These two animals also demonstrated persistent plasma viremia for >48 weeks. One of these animals developed AIDS, as shown by peripheral blood CD4+ T-cell depletion starting at 20 weeks post inoculation. Conclusion These findings indicate that SHIV-1157ipd3N4-induced pathogenesis in pig-tailed macaques followed a similar course as SIV-infected rhesus macaques. Thus, R5 SHIV-C-infection of pig-tailed macaques could provide a useful and relevant model for AIDS vaccine and pathogenesis research.

  10. Structural improvement of unliganded simian immunodeficiency virus gp120 core by normal-mode-based X-ray crystallographic refinement

    International Nuclear Information System (INIS)

    Chen, Xiaorui; Lu, Mingyang; Poon, Billy K.; Wang, Qinghua; Ma, Jianpeng

    2009-01-01

    The structural model of the unliganded and fully glycosylated simian immunodeficiency virus gp120 core determined to 4.0 Å resolution was substantially improved using a recently developed normal-mode-based anisotropic B-factor refinement method. The envelope protein gp120/gp41 of simian and human immunodeficiency viruses plays a critical role in viral entry into host cells. However, the extraordinarily high structural flexibility and heavy glycosylation of the protein have presented enormous difficulties in the pursuit of high-resolution structural investigation of some of its conformational states. An unliganded and fully glycosylated gp120 core structure was recently determined to 4.0 Å resolution. The rather low data-to-parameter ratio limited refinement efforts in the original structure determination. In this work, refinement of this gp120 core structure was carried out using a normal-mode-based refinement method that has been shown in previous studies to be effective in improving models of a supramolecular complex at 3.42 Å resolution and of a membrane protein at 3.2 Å resolution. By using only the first four nonzero lowest-frequency normal modes to construct the anisotropic thermal parameters, combined with manual adjustments and standard positional refinement using REFMAC5, the structural model of the gp120 core was significantly improved in many aspects, including substantial decreases in R factors, better fitting of several flexible regions in electron-density maps, the addition of five new sugar rings at four glycan chains and an excellent correlation of the B-factor distribution with known structural flexibility. These results further underscore the effectiveness of this normal-mode-based method in improving models of protein and nonprotein components in low-resolution X-ray structures

  11. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques

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    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A.; Veazey, Ronald S.

    2015-01-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit+IL-7Rα+ (CD117+CD127+) cells. These ILC3 cells highly expressed CD90 (∼63%) and aryl hydrocarbon receptor and produced IL-17 (∼63%), IL-22 (∼36%), and TNF-α (∼72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4+ T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues.—Xu, H., Wang, X., Lackner, A. A., Veazey, R. S. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques. PMID:26283536

  12. Cytotoxic T-Lymphocyte Escape Does Not Always Explain the Transient Control of Simian Immunodeficiency Virus SIVmac239 Viremia in Adenovirus-Boosted and DNA-Primed Mamu-A*01-Positive Rhesus Macaques

    Science.gov (United States)

    McDermott, Adrian B.; O'Connor, David H.; Fuenger, Sarah; Piaskowski, Shari; Martin, Sarah; Loffredo, John; Reynolds, Matthew; Reed, Jason; Furlott, Jessica; Jacoby, Timothy; Riek, Cara; Dodds, Elizabeth; Krebs, Kendall; Davies, Mary-Ellen; Schleif, William A.; Casimiro, Danilo R.; Shiver, John W.; Watkins, D. I.

    2005-01-01

    Adenovirus 5 (Ad5) vectors show promise as human immunodeficiency virus vaccine candidates. Indian rhesus macaques vaccinated with Ad5-gag controlled simian-human immunodeficiency virus SHIV89.6P viral replication in the absence of Env immunogens that might elicit humoral immunity. Here we immunized 15 macaques using either a homologous Ad5-gag/Ad5-gag (Ad5/Ad5) or a heterologous DNA-gag/Ad5-gag (DNA/Ad5) prime-boost regimen and challenged them with a high dose of simian immunodeficiency virus SIVmac239. Macaques vaccinated with the DNA/Ad5 regimen experienced a brief viral load nadir of less than 10,000 viral copies per ml blood plasma that was not seen in Mamu-A*01-negative DNA/Ad5 vaccinees, Mamu-A*01-positive Ad5/Ad5 vaccinees, or vaccine-naive controls. Interestingly, most of these animals were not durably protected from disease progression when challenged with SIVmac239. To investigate the reasons underlying this short-lived vaccine effect, we investigated breadth of the T-cell response, immunogenetic background, and viral escape from CD8+ lymphocytes that recognize immunodominant T-cell epitopes. We show that these animals do not mount unusually broad cellular immune response, nor do they express unusual major histocompatibility complex class I alleles. Viral recrudescence occurred in four of the five Mamu-A*01-positive vaccinated macaques. However, only a single animal in this group demonstrated viral escape in the immunodominant Gag181-189CM9 response. These results suggest that viral “breakthrough” in vaccinated animals and viral escape are not inextricably linked and underscore the need for additional research into the mechanisms of vaccine failure. PMID:16306626

  13. Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication

    International Nuclear Information System (INIS)

    Watanabe, Mamoru; Chen, Zheng W.; Tsubota, Hiroshi; Lord, C.I.; Levine, C.G.; Letvin, N.L.

    1991-01-01

    Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIV mac ) demonstrate significant virologic and clinical improvement as a result of treatment with human recombinant soluble CD4 (rsCD4). The authors show that human rsCD4 does not efficiently inhibit SIV mac replication in bone marrow macrophages of rhesus monkeys and does not significantly augment bone marrow hematopoietic colony formation in vitro. However, plasma of human rsCD4-treated rhesus monkeys does exhibit significant anti-SIV mac activity in vitro. Plasma of these animals efficiently blocks SIV mac replicaton in peripheral blood lymphocytes and bone marrow macrophages. It also increases granulocyte/macrophage colony formation in vitro by bone marrow cells of SIV mac -infected monkeys. This plasma and the IgG fraction of plasma from a rhesus monkey immunized with human rsCD4 in adjuvant demonstrate reactivity with a soluble form of the rhesus monkey CD4 molecule, exhibit binding to CD4 + but not CD8 + concanavalin A-activated rhesus monkey peripheral blood lymphocytes, and precipitate the CD4 molecule from surface-labeled activated rhesus monkey peripheral blood lymphocytes. Moreover, anti-viral activity is demonstrable in the IgG fraction of plasma from a human rsCD4-immunized monkey. These studies raise the possibility that a modified human CD4 molecule serving as an immunogen might elicit an antibody response that could potentially induce a beneficial therapeutic response in human immunodeficiency virus-infected individuals

  14. Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques

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    John K. Maxi

    2016-11-01

    Full Text Available Alcohol use disorders (AUD exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+ patients. We have shown that chronic binge alcohol (CBA administration (13–14 g EtOH/kg/wk prior to and during simian immunodeficiency virus (SIV infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; n = 2 macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; n = 2 macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 months post-SIV inoculation were analyzed to determine differentially expressed genes. MetaCore from Thomson Reuters revealed enrichment of genes involved in inflammation, immune responses, and neurodevelopment. Functional relevance of these alterations was examined in vitro by exposing murine neural progenitor cells (NPCs to ethanol (EtOH and HIV trans-activator of transcription (Tat protein. EtOH impaired NPC differentiation as indicated by decreased βIII tubulin expression. These findings suggest a role for neuroinflammation and neurogenesis in CBA/SIV neuropathogenesis and warrant further investigation of their potential contribution to CBA-mediated neurobehavioral deficits.

  15. Revisiting a quarter of a century of simian immunodeficiency virus (SIV-associated cardiovascular diseases at the German Primate Center

    Directory of Open Access Journals (Sweden)

    M. Mietsch

    2017-06-01

    Full Text Available Human immunodeficiency virus (HIV comorbidities have become clinically more important due to antiretroviral therapy. Although therapy increases life expectancy, it does not completely suppress immune activation and its associated complications. The simian immunodeficiency virus (SIV-infected rhesus macaque (Macaca mulatta represents a valuable model for the investigation of SIV-associated diseases. Although cardiovascular (CV changes are common in HIV-infected patients, there are only a few reports on the incidence of CV findings in SIV-infected animals. In addition, potential associations between pathohistological findings and hematological parameters are still unclear. We therefore conducted a retrospective analysis of 195 SIV-infected rhesus macaques that were euthanized with AIDS-related symptoms at the German Primate Center, Goettingen, over a 25-year period. Pathological findings were correlated with hematological data. The main findings included myocarditis (12.8 %, endocarditis (9.7 %, and arteriopathy (10.3 % in various organs. Thrombocytopenia occurred more frequently in macaques with endocarditis or arteriopathy than in macaques without CV disease (80 % in animals with endocarditis, 60 % in animals with arteriopathy, p < 0. 0001 and p = 0. 0016, respectively. Further investigations of the interaction between coagulation markers, proinflammatory cytokines, and biomarkers associated with endothelial dysfunction (e.g., D-dimers and histological data (vascular wall structure may unravel the mechanisms underlying HIV/SIV-associated CV comorbidities.

  16. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques.

    Science.gov (United States)

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S

    2015-12-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit(+)IL-7Rα(+) (CD117(+)CD127(+)) cells. These ILC3 cells highly expressed CD90 (∼ 63%) and aryl hydrocarbon receptor and produced IL-17 (∼ 63%), IL-22 (∼ 36%), and TNF-α (∼ 72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4(+) T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues. © FASEB.

  17. Immunogenicity of NYVAC Prime-Protein Boost Human Immunodeficiency Virus Type 1 Envelope Vaccination and Simian-Human Immunodeficiency Virus Challenge of Nonhuman Primates.

    Science.gov (United States)

    Saunders, Kevin O; Santra, Sampa; Parks, Robert; Yates, Nicole L; Sutherland, Laura L; Scearce, Richard M; Balachandran, Harikrishnan; Bradley, Todd; Goodman, Derrick; Eaton, Amanda; Stanfield-Oakley, Sherry A; Tartaglia, James; Phogat, Sanjay; Pantaleo, Giuseppe; Esteban, Mariano; Gomez, Carmen E; Perdiguero, Beatriz; Jacobs, Bertram; Kibler, Karen; Korber, Bette; Montefiori, David C; Ferrari, Guido; Vandergrift, Nathan; Liao, Hua-Xin; Tomaras, Georgia D; Haynes, Barton F

    2018-04-15

    A preventive human immunodeficiency virus type 1 (HIV-1) vaccine is an essential part of the strategy to eradicate AIDS. A critical question is whether antibodies that do not neutralize primary isolate (tier 2) HIV-1 strains can protect from infection. In this study, we investigated the ability of an attenuated poxvirus vector (NYVAC) prime-envelope gp120 boost to elicit potentially protective antibody responses in a rhesus macaque model of mucosal simian-human immunodeficiency virus (SHIV) infection. NYVAC vector delivery of a group M consensus envelope, trivalent mosaic envelopes, or a natural clade B isolate B.1059 envelope elicited antibodies that mediated neutralization of tier 1 viruses, cellular cytotoxicity, and phagocytosis. None of the macaques made neutralizing antibodies against the tier 2 SHIV SF162P3 used for mucosal challenge. Significant protection from infection was not observed for the three groups of vaccinated macaques compared to unvaccinated macaques, although binding antibody to HIV-1 Env correlated with decreased viremia after challenge. Thus, NYVAC Env prime-gp120 boost vaccination elicited polyfunctional, nonneutralizing antibody responses with minimal protective activity against tier 2 SHIV mucosal challenge. IMPORTANCE The antibody responses that confer protection against HIV-1 infection remain unknown. Polyfunctional antibody responses correlated with time to infection in previous macaque studies. Determining the ability of vaccines to induce these types of responses is critical for understanding how to improve upon the one efficacious human HIV-1 vaccine trial completed thus far. We characterized the antibody responses induced by a NYVAC-protein vaccine and determined the protective capacity of polyfunctional antibody responses in an R5, tier 2 mucosal SHIV infection model. Copyright © 2018 American Society for Microbiology.

  18. Superior Efficacy of a Human Immunodeficiency Virus Vaccine Combined with Antiretroviral Prevention in Simian-Human Immunodeficiency Virus-Challenged Nonhuman Primates.

    Science.gov (United States)

    Le Grand, Roger; Dereuddre-Bosquet, Nathalie; Dispinseri, Stefania; Gosse, Leslie; Desjardins, Delphine; Shen, Xiaoying; Tolazzi, Monica; Ochsenbauer, Christina; Saidi, Hela; Tomaras, Georgia; Prague, Mélanie; Barnett, Susan W; Thiebaut, Rodolphe; Cope, Alethea; Scarlatti, Gabriella; Shattock, Robin J

    2016-06-01

    Although vaccines and antiretroviral (ARV) prevention have demonstrated partial success against human immunodeficiency virus (HIV) infection in clinical trials, their combined introduction could provide more potent protection. Furthermore, combination approaches could ameliorate the potential increased risk of infection following vaccination in the absence of protective immunity. We used a nonhuman primate model to determine potential interactions of combining a partially effective ARV microbicide with an envelope-based vaccine. The vaccine alone provided no protection from infection following 12 consecutive low-dose intravaginal challenges with simian-HIV strain SF162P3, with more animals infected compared to naive controls. The microbicide alone provided a 68% reduction in the risk of infection relative to that of the vaccine group and a 45% reduction relative to that of naive controls. The vaccine-microbicide combination provided an 88% reduction in the per-exposure risk of infection relative to the vaccine alone and a 79% reduction relative to that of the controls. Protected animals in the vaccine-microbicide group were challenged a further 12 times in the absence of microbicide and demonstrated a 98% reduction in the risk of infection. A total risk reduction of 91% was observed in this group over 24 exposures (P = 0.004). These important findings suggest that combined implementation of new biomedical prevention strategies may provide significant gains in HIV prevention. There is a pressing need to maximize the impact of new biomedical prevention tools in the face of the 2 million HIV infections that occur each year. Combined implementation of complementary biomedical approaches could create additive or synergistic effects that drive improved reduction of HIV incidence. Therefore, we assessed a combination of an untested vaccine with an ARV-based microbicide in a nonhuman primate vaginal challenge model. The vaccine alone provided no protection (and may have

  19. Tolerance to Chronic Delta-9-Tetrahydrocannabinol (Δ9-THC) in Rhesus Macaques Infected With Simian Immunodeficiency Virus

    Science.gov (United States)

    Winsauer, Peter J.; Molina, Patricia E.; Amedee, Angela M.; Filipeanu, Catalin M.; McGoey, Robin R.; Troxclair, Dana A.; Walker, Edith M.; Birke, Leslie L.; Stouwe, Curtis Vande; Howard, Jessica M.; Leonard, Stuart T.; Moerschbaecher, Joseph M.; Lewis, Peter B.

    2011-01-01

    Although Δ9-THC has been approved to treat anorexia and weight loss associated with AIDS, it may also reduce well-being by disrupting complex behavioral processes or enhancing HIV replication. To investigate these possibilities, four groups of male rhesus macaques were trained to respond under an operant acquisition and performance procedure, and administered vehicle or Δ9-THC before and after inoculation with simian immunodeficiency virus(SIVmac251, 100 TCID50/ml, i.v.). Prior to chronic Δ9-THC and SIV inoculation, 0.032– 0.32 mg/kg of Δ9-THC produced dose-dependent rate-decreasing effects and small, sporadic error-increasing effects in the acquisition and performance components in each subject. Following 28 days of chronic Δ9-THC (0.32 mg/kg, i.m.) or vehicle twice daily, delta-9-THC-treated subjects developed tolerance to the rate-decreasing effects, and this tolerance was maintained during the initial 7–12 months irrespective of SIV infection (i.e., +THC/−SIV, +THC/+SIV). Full necropsy was performed on all SIV subjects an average of 329 days post-SIV inoculation, with postmortem histopathology suggestive of a reduced frequency of CNS pathology as well as opportunistic infections in delta-9-THC-treated subjects. Chronic Δ9-THC also significantly reduced CB-1 and CB-2 receptor levels in the hippocampus, attenuated the expression of a proinflammatory cytokine (MCP-1), and did not increase viral load in plasma, cerebrospinal fluid, or brain tissue compared to vehicle-treated subjects with SIV. Together, these data indicate that chronic Δ9-THC produces tolerance to its behaviorally disruptive effects on complex tasks while not adversely affecting viral load or other markers of disease progression during the early stages of infection. PMID:21463073

  20. Differential Impact of In Vivo CD8+ T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques.

    Science.gov (United States)

    Chowdhury, Ankita; Hayes, Timothy L; Bosinger, Steven E; Lawson, Benton O; Vanderford, Thomas; Schmitz, Joern E; Paiardini, Mirko; Betts, Michael; Chahroudi, Ann; Estes, Jacob D; Silvestri, Guido

    2015-09-01

    Numerous studies have demonstrated that CD8(+) T lymphocytes suppress virus replication during human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. However, the mechanisms underlying this activity of T cells remain incompletely understood. Here, we conducted CD8(+) T lymphocyte depletion in 15 rhesus macaques (RMs) infected intravenously (i.v.) with SIVmac239. At day 70 postinfection, the animals (10 progressors with high viremia and 5 controllers with low viremia) were CD8 depleted by i.v. administration of the antibody M-T807R1. As expected, CD8 depletion resulted in increased virus replication, more prominently in controllers than progressors, which correlated inversely with predepletion viremia. Of note, the feature of CD8(+) T lymphocyte predepletion that correlated best with the increase in viremia postdepletion was the level of CD8(+) T-bet(+) lymphocytes. We next found that CD8 depletion resulted in a homogenous increase of SIV RNA in superficial and mesenteric lymph nodes, spleen, and the gastrointestinal tract of both controllers and progressors. Interestingly, the level of SIV DNA increased postdepletion in both CD4(+) central memory T lymphocytes (TCM) and CD4(+) effector memory T lymphocytes (TEM) in progressor RMs but decreased in the CD4(+) TCM of 4 out of 5 controllers. Finally, we found that CD8 depletion is associated with a greater increase in CD4(+) T lymphocyte activation (measured by Ki-67 expression) in controllers than in progressors. Overall, these data reveal a differential impact of CD8(+) T lymphocyte depletion between controller and progressor SIV-infected RMs, emphasizing the complexity of the in vivo antiviral role of CD8(+) T lymphocytes. In this study, we further dissect the impact of CD8(+) T lymphocytes on HIV/SIV replication during SIV infection. CD8(+) T lymphocyte depletion leads to a relatively homogenous increase in viral replication in peripheral blood and tissues. CD8(+) T lymphocyte depletion

  1. Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Matusali, G.; Dereuddre-Bosquet, N.; Le Tortorec, A.; Moreau, M.; Satie, A.-P.; Mahé, D.; Roumaud, P.; Bourry, O.; Sylla, N.; Bernard-Stoecklin, S.; Pruvost, A.; Le Grand, R.

    2015-01-01

    ABSTRACT A number of men receiving prolonged suppressive highly active antiretroviral therapy (HAART) still shed human immunodeficiency virus (HIV) in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with simian immunodeficiency virus mac251 (SIVmac251) who were treated for 4 months with HAART, which was intensified over the last 7 weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen or in testis, epididymis, seminal vesicles, and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA-positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of nonproductively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly in the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organ infection in long-term-treated infected individuals. IMPORTANCE A substantial subset of men receiving prolonged HAART suppressing viral loads in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV

  2. Structure of Simian Immunodeficiency Virus Envelope Spikes Bound with CD4 and Monoclonal Antibody 36D5.

    Science.gov (United States)

    Hu, Guiqing; Liu, Jun; Roux, Kenneth H; Taylor, Kenneth A

    2017-08-15

    The human immunodeficiency virus type 1 (HIV-1)/simian immunodeficiency virus (SIV) envelope spike (Env) mediates viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the coreceptor binding site and is a target for neutralizing antibodies. We used cryo-electron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody (MAb) 36D5 to gp120 of the SIV Env trimer. Our results show that 36D5 binds gp120 at the base of the V3 loop and suggest that the antibody exerts its neutralization effect by blocking the coreceptor binding site. The antibody does this without altering the dynamics of the spike motion between closed and open states when CD4 is bound. The interaction between 36D5 and SIV gp120 is similar to the interaction between some broadly neutralizing anti-V3 loop antibodies and HIV-1 gp120. Two conformations of gp120 bound with CD4 are revealed, suggesting an intrinsic dynamic nature of the liganded Env trimer. CD4 binding substantially increases the binding of 36D5 to gp120 in the intact Env trimer, consistent with CD4-induced changes in the conformation of gp120 and the antibody binding site. Binding by MAb 36D5 does not substantially alter the proportions of the two CD4-bound conformations. The position of MAb 36D5 at the V3 base changes little between conformations, indicating that the V3 base serves as a pivot point during the transition between these two states. IMPORTANCE Glycoprotein spikes on the surfaces of SIV and HIV are the sole targets available to the immune system for antibody neutralization. Spikes evade the immune system by a combination of a thick layer of polysaccharide on the surface (the glycan shield) and movement between spike domains that masks the epitope conformation. Using SIV virions whose spikes were "decorated" with the primary cellular receptor (CD4) and an antibody (36D5) at part of the coreceptor binding site, we visualized multiple conformations trapped by the

  3. Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection.

    Science.gov (United States)

    Byrareddy, Siddappa N; Kallam, Brianne; Arthos, James; Cicala, Claudia; Nawaz, Fatima; Hiatt, Joseph; Kersh, Ellen N; McNicholl, Janet M; Hanson, Debra; Reimann, Keith A; Brameier, Markus; Walter, Lutz; Rogers, Kenneth; Mayne, Ann E; Dunbar, Paul; Villinger, Tara; Little, Dawn; Parslow, Tristram G; Santangelo, Philip J; Villinger, Francois; Fauci, Anthony S; Ansari, Aftab A

    2014-12-01

    α4β7 integrin-expressing CD4(+) T cells preferentially traffic to gut-associated lymphoid tissue (GALT) and have a key role in HIV and simian immunodeficiency virus (SIV) pathogenesis. We show here that the administration of an anti-α4β7 monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with SIVmac251. In treated animals that became infected, the GALT was significantly protected from infection and CD4(+) T cell numbers were maintained in both the blood and the GALT. Thus, targeting α4β7 reduces mucosal transmission of SIV in macaques.

  4. Lentiviral Gag assembly analyzed through the functional characterization of chimeric simian immunodeficiency viruses expressing different domains of the feline immunodeficiency virus capsid protein.

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    María J Esteva

    Full Text Available To gain insight into the functional relationship between the capsid (CA domains of the Gag polyproteins of simian and feline immunodeficiency viruses (SIV and FIV, respectively, we constructed chimeric SIVs in which the CA-coding region was partially or totally replaced by the equivalent region of the FIV CA. The phenotypic characterization of the chimeras allowed us to group them into three categories: the chimeric viruses that, while being assembly-competent, exhibit a virion-associated unstable FIV CA; a second group represented only by the chimeric SIV carrying the N-terminal domain (NTD of the FIV CA which proved to be assembly-defective; and a third group constituted by the chimeric viruses that produce virions exhibiting a mature and stable FIV CA protein, and which incorporate the envelope glycoprotein and contain wild-type levels of viral genome RNA and reverse transcriptase. Further analysis of the latter group of chimeric SIVs demonstrated that they are non-infectious due to a post-entry impairment, such as uncoating of the viral core, reverse transcription or nuclear import of the preintegration complex. Furthermore, we show here that the carboxyl-terminus domain (CTD of the FIV CA has an intrinsic ability to dimerize in vitro and form high-molecular-weight oligomers, which, together with our finding that the FIV CA-CTD is sufficient to confer assembly competence to the resulting chimeric SIV Gag polyprotein, provides evidence that the CA-CTD exhibits more functional plasticity than the CA-NTD. Taken together, our results provide relevant information on the biological relationship between the CA proteins of primate and nonprimate lentiviruses.

  5. The simian immunodeficiency virus targets central cell cycle functions through transcriptional repression in vivo.

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    Carl-Magnus Hogerkorp

    Full Text Available A massive and selective loss of CD4+ memory T cells occurs during the acute phase of immunodeficiency virus infections. The mechanism of this depletion is poorly understood but constitutes a key event with implications for progression. We assessed gene expression of purified T cells in Rhesus Macaques during acute SIVmac239 infection in order to define mechanisms of pathogenesis. We observe a general transcriptional program of over 1,600 interferon-stimulated genes induced in all T cells by the infection. Furthermore, we identify 113 transcriptional changes that are specific to virally infected cells. A striking downregulation of several key cell cycle regulator genes was observed and shared promotor-region E2F binding sites in downregulated genes suggested a targeted transcriptional control of an E2F regulated cell cycle program. In addition, the upregulation of the gene for the fundamental regulator of RNA polymerase II, TAF7, demonstrates that viral interference with the cell cycle and transcriptional regulation programs may be critical components during the establishment of a pathogenic infection in vivo.

  6. Antifibrotic Therapy in Simian Immunodeficiency Virus Infection Preserves CD4+ T-Cell Populations and Improves Immune Reconstitution With Antiretroviral Therapy

    Science.gov (United States)

    Estes, Jacob D.; Reilly, Cavan; Trubey, Charles M.; Fletcher, Courtney V.; Cory, Theodore J.; Piatak, Michael; Russ, Samuel; Anderson, Jodi; Reimann, Thomas G.; Star, Robert; Smith, Anthony; Tracy, Russell P.; Berglund, Anna; Schmidt, Thomas; Coalter, Vicky; Chertova, Elena; Smedley, Jeremy; Haase, Ashley T.; Lifson, Jeffrey D.; Schacker, Timothy W.

    2015-01-01

    Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4+ T cells/µL, and CD4+ T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4+ T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4+ T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4+ T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution. PMID:25246534

  7. Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV vaccinated rhesus macaques

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    Pahar Bapi

    2012-08-01

    Full Text Available Abstract Background An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV vector – simian immunodeficiency virus (SIV envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1. Findings The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals. Conclusions Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.

  8. The impact of early immune destruction on the kinetics of postacute viral replication in rhesus monkey infected with the simian-human immunodeficiency virus 89.6P

    International Nuclear Information System (INIS)

    Zhang Zhiqiang; Schleif, William A.; Casimiro, Danilo R.; Handt, Larry; Chen, Minchun; Davies, Mary-Ellen; Liang Xiaoping; Fu Tongming; Tang Aimin; Wilson, Keith A.; McElhaugh, Michael; Carella, Anthony; Tan, Charles; Connolly, Brett; Hill, Susan; Klein, Hilton; Emini, Emilio A.; Shiver, John W.

    2004-01-01

    Set-point viral load is positively correlated with the extent of initial viral replication in pathogenic simian-human immunodeficiency virus (SHIV) infection. To elucidate the mechanisms underlying the correlation, we conducted a systematic investigation in rhesus monkeys infected with the highly pathogenic SHIV 89.6P. This model is widely used in the preclinical evaluation of AIDS vaccine candidates and a thorough understanding of the model's biology is important to the proper interpretation of these evaluations. We found that the levels of peak viremia were positively correlated not only with the levels of set-point viremia but, importantly, with the extent of initial overall immune destruction as indicated by the degree of CD4 + T cell depletion and lymph node germinal center (GC) formation. The extent of initial overall immune destruction was inversely correlated with subsequent development and maintenance of virus-specific cellular and humoral immune responses. Thus, these data suggest that the extent of early immune damage determines the development and durability of virus-specific immunity, thereby playing a critical role in establishing the levels of set-point viral replication in SHIV infection. Vaccines that limit both the initial viral replication and the extent of early immune damage will therefore mediate long-term virus replication control and mitigation of long-term immune destruction in this model of immunodeficiency virus infection

  9. A Macaque Model for Rectal Lymphogranuloma Venereum and Non-Lymphogranuloma Venereum Chlamydia trachomatis: Impact on Rectal Simian/Human Immunodeficiency Virus Acquisition.

    Science.gov (United States)

    Vishwanathan, Sundaram Ajay; Aubert, Rachael D; Morris, Monica R; Zhao, Chunxia; Philips, Christi; Khalil, George M; Deyounks, Frank; Kelley, Kristen; Ritter, Jana M; Chen, C Y; Kersh, Ellen N; McNicholl, Janet M

    2017-09-01

    Sustained genital tract inflammation caused by sexually transmitted infections (STIs) is known to increase risk of vaginal human immunodeficiency virus (HIV) infections but, to our knowledge, there are no nonhuman primate studies that have evaluated its link to rectal HIV acquisition. Rhesus macaques inoculated with Chlamydia trachomatis (CT) (serovars LGV-L2 and CT-E; n = 7) or saline (n = 7) received up to 20 rectal challenges twice a week of simian/HIV immunodeficiency virus (SHIVSF162p3). SHIV viremia was determined by real-time PCR and Chlamydia infection by APTIMA Combo 2 testing. The rectal cytokine-chemokine levels were evaluated by multiplex bead assays. Rectal Chlamydia infection was maintained throughout the study. We did not observe significant differences (P = 1.0) in frequency of SHIV acquisition between the STI and control arms. It took fewer SHIV challenges to infect the STI animals although the difference was not significant (P = 0.59). There were no significant differences in peak plasma viremia between STI and control arms (P = 0.63). The association of plasma viremia with rectal shedding was significantly different by arm (P = 0.038). In the first such study in a macaque model, we did not observe an increased risk of SHIV acquisition due to rectal Chlamydia coinfection. This macaque model can be further developed and expanded to better investigate the impact of different rectal STIs on HIV acquisition.

  10. Loss of memory CD4+ T-cells in semi-wild mandrills (Mandrillus sphinx) naturally infected with species-specific simian immunodeficiency virus SIVmnd-1.

    Science.gov (United States)

    Greenwood, Edward J D; Schmidt, Fabian; Liégeois, Florian; Kondova, Ivanela; Herbert, Anaïs; Ngoubangoye, Barthelemy; Rouet, François; Heeney, Jonathan L

    2014-01-01

    Simian immunodeficiency virus (SIV) infection is found in a number of African primate species and is thought to be generally non-pathogenic. However, studies of wild primates are limited to two species, with SIV infection appearing to have a considerably different outcome in each. Further examination of SIV-infected primates exposed to their natural environment is therefore warranted. We performed a large cross-sectional study of a cohort of semi-wild mandrills with naturally occurring SIV infection, including 39 SIV-negative and 33 species-specific SIVmnd-1-infected animals. This study was distinguished from previous reports by considerably greater sample size, examination of exclusively naturally infected animals in semi-wild conditions and consideration of simian T-lymphotropic virus (STLV) status in addition to SIVmnd-1 infection. We found that SIVmnd-1 infection was associated with a significant and progressive loss of memory CD4(+) T-cells. Limited but significant increases in markers of immune activation in the T-cell populations, significant increases in plasma neopterin and changes to B-cell subsets were also observed in SIV-infected animals. However, no increase in plasma soluble CD14 was observed. Histological examination of peripheral lymph nodes suggested that SIVmnd-1 infection was not associated with a significant disruption of the lymph node architecture. Whilst this species has evolved numerous strategies to resist the development of AIDS, significant effects of SIV infection could be observed when examined in a natural environment. STLVmnd-1 infection also had significant effects on some markers relevant to understanding SIV infection and thus should be considered in studies of SIV infection of African primates where present.

  11. Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.

    Science.gov (United States)

    Simon, Liz; Song, Keijing; Vande Stouwe, Curtis; Hollenbach, Andrew; Amedee, Angela; Mohan, Mahesh; Winsauer, Peter; Molina, Patricia

    2016-03-01

    Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Δ9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.

  12. Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus

    International Nuclear Information System (INIS)

    Kaur, Amitinder; Sanford, Hannah B.; Garry, Deirdre; Lang, Sabine; Klumpp, Sherry A.; Watanabe, Daisuke; Bronson, Roderick T.; Lifson, Jeffrey D.; Rosati, Margherita; Pavlakis, George N.; Felber, Barbara K.; Knipe, David M.; Desrosiers, Ronald C.

    2007-01-01

    The immunogenicity and protective capacity of replication-defective herpes simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol-Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti-Gag and anti-Env cellular responses were detected in all six macaques. Following intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma viremia levels were significantly lower in vaccinated compared to control macaques. Plasma SIV RNA in vaccinated macaques was inversely correlated with anti-Rev ELISPOT responses on the day of challenge (P value < 0.05), anti-Tat ELISPOT responses at 2 weeks post challenge (P value < 0.05) and peak neutralizing antibody titers pre-challenge (P value 0.06). These findings support continued study of recombinant herpesviruses as a vaccine approach for AIDS

  13. High-throughput gene expression profiling indicates dysregulation of intestinal cell cycle mediators and growth factors during primary simian immunodeficiency virus infection

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    George, Michael D; Sankaran, Sumathi; Reay, Elizabeth; Gelli, Angie C; Dandekar, Satya

    2003-07-20

    During primary simian immunodeficiency virus (SIV) infection, CD4+ T cells are severely depleted in gut-associated lymphoid tissue (GALT), while CD8+ T-cell numbers dramatically increase. To gain an understanding of the molecular basis of this disruption in T-cell homeostasis, host gene expression was monitored in longitudinal jejunum tissue biopsies from SIV-infected rhesus macaques by DNA microarray analysis. Transcription of cyclin E1, CDC2, retinoblastoma, transforming growth factor (TGF), fibroblast growth factor (FGF), and interleukin-2 was repressed while cyclins B1 and D2 and transcription factor E2F were upregulated, indicating a complex dysregulation of growth and proliferation within the intestinal mucosa. Innate, cell-mediated, and humoral immune responses were markedly upregulated in animals that significantly reduced their viral loads and retained more intestinal CD4+ T cells. We conclude that the alterations in intestinal gene expression during primary SIV infection were characteristic of a broad-range immune response, and reflective of the efficacy of viral suppression.

  14. High-throughput gene expression profiling indicates dysregulation of intestinal cell cycle mediators and growth factors during primary simian immunodeficiency virus infection

    International Nuclear Information System (INIS)

    George, Michael D.; Sankaran, Sumathi; Reay, Elizabeth; Gelli, Angie C.; Dandekar, Satya

    2003-01-01

    During primary simian immunodeficiency virus (SIV) infection, CD4+ T cells are severely depleted in gut-associated lymphoid tissue (GALT), while CD8+ T-cell numbers dramatically increase. To gain an understanding of the molecular basis of this disruption in T-cell homeostasis, host gene expression was monitored in longitudinal jejunum tissue biopsies from SIV-infected rhesus macaques by DNA microarray analysis. Transcription of cyclin E1, CDC2, retinoblastoma, transforming growth factor (TGF), fibroblast growth factor (FGF), and interleukin-2 was repressed while cyclins B1 and D2 and transcription factor E2F were upregulated, indicating a complex dysregulation of growth and proliferation within the intestinal mucosa. Innate, cell-mediated, and humoral immune responses were markedly upregulated in animals that significantly reduced their viral loads and retained more intestinal CD4+ T cells. We conclude that the alterations in intestinal gene expression during primary SIV infection were characteristic of a broad-range immune response, and reflective of the efficacy of viral suppression

  15. Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatability complex class I-mediated control

    Science.gov (United States)

    Beck, Sarah E.; Queen, Suzanne E.; Viscidi, Raphael; Johnson, Darius; Kent, Stephen J.; Adams, Robert J.; Tarwater, Patrick M.; Mankowski, Joseph L.

    2016-01-01

    In the fourth decade of the HIV epidemic, the relationship between host immunity and HIV central nervous system (CNS) disease remains incompletely understood. Using a simian immunodeficiency virus (SIV)/macaque model, we examined CNS outcomes in pigtailed macaques expressing the MHC class I allele Mane-A1*084:01 which confers resistance to SIV-induced CNS disease and induces the prototypic viral escape mutation Gag K165R. Insertion of gag K165R into the neurovirulent clone SIV/17E-Fr reduced viral replication in vitro compared to SIV/17E-Fr. We also found lower CSF, but not plasma, viral loads in macaques inoculated with SIV/17E-Fr K165R versus those inoculated with wildtype. Although escape mutation K165R was genotypically stable in plasma, it rapidly reverted to wildtype Gag KP9 in both CSF and in microglia cultures. We induced robust Gag KP9-specific CTL tetramer responses by vaccinating Mane-A*084:01-positive pigtailed macaques with a Gag KP9 virus-like particle (VLP) vaccine. Upon SIV/17E-Fr challenge, vaccinated animals had lower SIV RNA in CSF compared to unvaccinated controls, but showed no difference in plasma viral loads. These data clearly demonstrate that viral fitness in the CNS is distinct from the periphery and underscores the necessity of understanding the consequences of viral escape in CNS disease with the advent of new therapeutic vaccination strategies. PMID:26727909

  16. Simian immunodeficiency virus infection induces severe loss of intestinal central memory T cells which impairs CD4+ T-cell restoration during antiretroviral therapy.

    Science.gov (United States)

    Verhoeven, D; Sankaran, S; Dandekar, S

    2007-08-01

    Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4(+) T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4(+) memory subsets or lost and fail to regenerate during ART. Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. Changes in proliferative CD4(+) memory subsets during infection accelerated their depletion. This reduced the central memory CD4(+) T-cell pool and contributed to slow CD4(+) T-cell restoration during ART. There was a lack of restoration of the CD4(+) central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.

  17. Discovery and full genome characterization of two highly divergent simian immunodeficiency viruses infecting black-and-white colobus monkeys (Colobus guereza) in Kibale National Park, Uganda.

    Science.gov (United States)

    Lauck, Michael; Switzer, William M; Sibley, Samuel D; Hyeroba, David; Tumukunde, Alex; Weny, Geoffrey; Taylor, Bill; Shankar, Anupama; Ting, Nelson; Chapman, Colin A; Friedrich, Thomas C; Goldberg, Tony L; O'Connor, David H

    2013-10-21

    African non-human primates (NHPs) are natural hosts for simian immunodeficiency viruses (SIV), the zoonotic transmission of which led to the emergence of HIV-1 and HIV-2. However, our understanding of SIV diversity and evolution is limited by incomplete taxonomic and geographic sampling of NHPs, particularly in East Africa. In this study, we screened blood specimens from nine black-and-white colobus monkeys (Colobus guereza occidentalis) from Kibale National Park, Uganda, for novel SIVs using a combination of serology and "unbiased" deep-sequencing, a method that does not rely on genetic similarity to previously characterized viruses. We identified two novel and divergent SIVs, tentatively named SIVkcol-1 and SIVkcol-2, and assembled genomes covering the entire coding region for each virus. SIVkcol-1 and SIVkcol-2 were detected in three and four animals, respectively, but with no animals co-infected. Phylogenetic analyses showed that SIVkcol-1 and SIVkcol-2 form a lineage with SIVcol, previously discovered in black-and-white colobus from Cameroon. Although SIVkcol-1 and SIVkcol-2 were isolated from the same host population in Uganda, SIVkcol-1 is more closely related to SIVcol than to SIVkcol-2. Analysis of functional motifs in the extracellular envelope glycoprotein (gp120) revealed that SIVkcol-2 is unique among primate lentiviruses in containing only 16 conserved cysteine residues instead of the usual 18 or more. Our results demonstrate that the genetic diversity of SIVs infecting black-and-white colobus across equatorial Africa is greater than previously appreciated and that divergent SIVs can co-circulate in the same colobine population. We also show that the use of "unbiased" deep sequencing for the detection of SIV has great advantages over traditional serological approaches, especially for studies of unknown or poorly characterized viruses. Finally, the detection of the first SIV containing only 16 conserved cysteines in the extracellular envelope protein

  18. The nonnucleoside reverse transcription inhibitor MIV-160 delivered from an intravaginal ring, but not from a carrageenan gel, protects against simian/human immunodeficiency virus-RT Infection.

    Science.gov (United States)

    Aravantinou, Meropi; Singer, Rachel; Derby, Nina; Calenda, Giulia; Mawson, Paul; Abraham, Ciby J; Menon, Radhika; Seidor, Samantha; Goldman, Daniel; Kenney, Jessica; Villegas, Guillermo; Gettie, Agegnehu; Blanchard, James; Lifson, Jeffrey D; Piatak, Michael; Fernández-Romero, José A; Zydowsky, Thomas M; Teleshova, Natalia; Robbiani, Melissa

    2012-11-01

    We previously showed that a carrageenan (CG) gel containing 50 μM MIV-150 (MIV-150/CG) reduced vaginal simian/human immunodeficiency virus (SHIV)-RT infection of macaques (56%, p>0.05) when administered daily for 2 weeks with the last dose given 8 h before challenge. Additionally, when 100 mg of MIV-150 was loaded into an intravaginal ring (IVR) inserted 24 h before challenge and removed 2 weeks after challenge, >80% protection was observed (p<0.03). MIV-160 is a related NNRTI with a similar IC(50), greater aqueous solubility, and a shorter synthesis. To objectively compare MIV-160 with MIV-150, herein we evaluated the antiviral effects of unformulated MIV-160 in vitro as well as the in vivo protection afforded by MIV-160 delivered in CG (MIV-160/CG gel) and in an IVR under regimens used with MIV-150 in earlier studies. Like MIV-150, MIV-160 exhibited potent antiviral activity against SHIV-RT in macaque vaginal explants. However, formulated MIV-160 exhibited divergent effects in vivo. The MIV-160/CG gel offered no protection compared to CG alone, whereas the MIV-160 IVRs protected significantly. Importantly, the results of in vitro release studies of the MIV-160/CG gel and the MIV-160 IVR suggested that in vivo efficacy paralleled the amount of MIV-160 released in vitro. Hundreds of micrograms of MIV-160 were released daily from IVRs while undetectable amounts of MIV-160 were released from the CG gel. Our findings highlight the importance of testing different modalities of microbicide delivery to identify the optimal formulation for efficacy in vivo.

  19. Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by tenofovir gel and its relationship to drug levels in tissue.

    Science.gov (United States)

    Dobard, Charles; Sharma, Sunita; Martin, Amy; Pau, Chou-Pong; Holder, Angela; Kuklenyik, Zsuzsanna; Lipscomb, Jonathan; Hanson, Debra L; Smith, James; Novembre, Francis J; García-Lerma, J Gerardo; Heneine, Walid

    2012-01-01

    A vaginal gel containing 1% tenofovir (TFV) was found to be safe and effective in reducing HIV infection in women when used pericoitally. Because of the long intracellular half-life of TFV and high drug exposure in vaginal tissues, we hypothesized that a vaginal gel containing TFV may provide long-lasting protection. Here, we performed delayed-challenge experiments and showed that vaginal 1% TFV gel protected 4/6 macaques against vaginal simian-human immunodeficiency virus (SHIV) exposures occurring 3 days after gel application, demonstrating long-lasting protection. Despite continued gel dosing postinfection, neither breakthrough infection had evidence of drug resistance by ultrasensitive testing of SHIV in plasma and vaginal lavage. Analysis of the active intracellular tenofovir diphosphate (TFV-DP) in vaginal lymphocytes collected 4 h to 3 days after gel dosing persistently showed high TFV-DP levels (median, 1,810 fmol/10(6) cells) between 4 and 24 h that exceed the 95% inhibitory concentration (IC(95)), reflecting rapid accumulation and long persistence. In contrast to those in peripheral blood mononuclear cells (PBMCs) following oral dosing, TFV-DP levels in vaginal lymphocytes decreased approximately 7-fold by 3 days, exhibiting a much higher rate of decay. We observed a strong correlation between intracellular TFV-DP in vaginal lymphocytes, in vitro antiviral activity, and in vivo protection, suggesting that TFV-DP above the in vitro IC(95) in vaginal lymphocytes is a good predictor of high efficacy. Data from this model reveal an extended window of protection by TFV gel that supports coitus-independent use. The identification of protective TFV-DP concentrations in vaginal lymphocytes may facilitate the evaluation of improved delivery methods of topical TFV and inform clinical studies.

  20. Simian Immunodeficiency Virus (SIV-Specific Chimeric Antigen Receptor-T Cells Engineered to Target B Cell Follicles and Suppress SIV Replication

    Directory of Open Access Journals (Sweden)

    Kumudhini Preethi Haran

    2018-03-01

    Full Text Available There is a need to develop improved methods to treat and potentially cure HIV infection. During chronic HIV infection, replication is concentrated within T follicular helper cells (Tfh located within B cell follicles, where low levels of virus-specific CTL permit ongoing viral replication. We previously showed that elevated levels of simian immunodeficiency virus (SIV-specific CTL in B cell follicles are linked to both decreased levels of viral replication in follicles and decreased plasma viral loads. These findings provide the rationale to develop a strategy for targeting follicular viral-producing (Tfh cells using antiviral chimeric antigen receptor (CAR T cells co-expressing the follicular homing chemokine receptor CXCR5. We hypothesize that antiviral CAR/CXCR5-expressing T cells, when infused into an SIV-infected animal or an HIV-infected individual, will home to B cell follicles, suppress viral replication, and lead to long-term durable remission of SIV and HIV. To begin to test this hypothesis, we engineered gammaretroviral transduction vectors for co-expression of a bispecific anti-SIV CAR and rhesus macaque CXCR5. Viral suppression by CAR/CXCR5-transduced T cells was measured in vitro, and CXCR5-mediated migration was evaluated using both an in vitro transwell migration assay, as well as a novel ex vivo tissue migration assay. The functionality of the CAR/CXCR5 T cells was demonstrated through their potent suppression of SIVmac239 and SIVE660 replication in in vitro and migration to the ligand CXCL13 in vitro, and concentration in B cell follicles in tissues ex vivo. These novel antiviral immunotherapy products have the potential to provide long-term durable remission (functional cure of HIV and SIV infections.

  1. Experimental Oral Herpes Simplex Virus-1 (HSV-1 Co-infection in Simian Immunodeficiency Virus (SIV-Infected Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Meropi Aravantinou

    2017-12-01

    Full Text Available Herpes simplex virus 1 and 2 (HSV-1/2 similarly initiate infection in mucosal epithelia and establish lifelong neuronal latency. Anogenital HSV-2 infection augments the risk for sexual human immunodeficiency virus (HIV transmission and is associated with higher HIV viral loads. However, whether oral HSV-1 infection contributes to oral HIV susceptibility, viremia, or oral complications of HIV infection is unknown. Appropriate non-human primate (NHP models would facilitate this investigation, yet there are no published studies of HSV-1/SIV co-infection in NHPs. Thus, we performed a pilot study for an oral HSV-1 infection model in SIV-infected rhesus macaques to describe the feasibility of the modeling and resultant immunological changes. Three SIV-infected, clinically healthy macaques became HSV-1-infected by inoculation with 4 × 108 pfu HSV-1 McKrae on buccal, tongue, gingiva, and tonsils after gentle abrasion. HSV-1 DNA was shed in oral swabs for up to 21 days, and shedding recurred in association with intra-oral lesions after periods of no shedding during 56 days of follow up. HSV-1 DNA was detected in explant cultures of trigeminal ganglia collected at euthanasia on day 56. In the macaque with lowest baseline SIV viremia, SIV plasma RNA increased following HSV-1 infection. One macaque exhibited an acute pro-inflammatory response, and all three animals experienced T cell activation and mobilization in blood. However, T cell and antibody responses to HSV-1 were low and atypical. Through rigorous assessesments, this study finds that the virulent HSV-1 strain McKrae resulted in a low level HSV-1 infection that elicited modest immune responses and transiently modulated SIV infection.

  2. Variability of bio-clinical parameters in Chinese-origin Rhesus macaques infected with simian immunodeficiency virus: a nonhuman primate AIDS model.

    Directory of Open Access Journals (Sweden)

    Song Chen

    Full Text Available BACKGROUND: Although Chinese-origin Rhesus macaques (Ch RhMs infected with simian immunodeficiency virus (SIV have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established. METHODOLOGY/PRINCIPAL FINDINGS: By randomizing 150 (78 male and 72 female Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group challenged with intrarectal (i.r. SIVmac239, intravenous (i.v. SIVmac239, or i.v. SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1-2 weeks. Plasma viral load (VL peaked at weeks 1-2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68. The rates of progression to AIDS or death were more rapid in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with i.r. or i.v. SIVmac239. The variability (standard deviation in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (i.r. or i.v. than in those infected with SIVmac251 (i.v., allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251. CONCLUSION/SIGNIFICANCE: These results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies.

  3. Anti-retroviral therapy fails to restore the severe Th-17: Tc-17 imbalance observed in peripheral blood during simian immunodeficiency virus infection.

    Science.gov (United States)

    Kader, M; Bixler, S; Piatak, M; Lifson, J; Mattapallil, J J

    2009-10-01

    Human immuno deficiency virus and simian immunodeficiency virus infections are characterized by a severe loss of Th-17 cells (IL-17(+)CD4(+) T cells) that has been associated with disease progression and systemic dissemination of bacterial infections. Anti-retroviral therapy (ART) has led to repopulation of CD4(+) T cells in peripheral tissues with little sustainable repopulation in mucosal tissues. Given the central importance of Th-17 cells in mucosal homeostasis, it is not known if the failure of ART to permanently repopulate mucosal tissues is associated with a failure to restore Th-17 cells that are lost during infection. Dynamics of alpha4(+)beta7(hi) CD4(+) T cells in peripheral blood of SIV infected rhesus macaques were evaluated and compared to animals that were treated with ART. The frequency of Th-17 and Tc-17 cells was determined following infection and after therapy. Relative expression of IL-21, IL-23, and TGFbeta was determined using Taqman PCR. Treatment of SIV infected rhesus macaques with anti-retroviral therapy was associated with a substantial repopulation of mucosal homing alpha4(+)beta7(hi)CD4(+) T cells in peripheral blood. This repopulation, however, was not accompanied by a restoration of Th-17 responses. Interestingly, SIV infection was associated with an increase in Tc-17 responses (IL-17(+)CD8(+) T cells) suggesting to a skewing in the ratio of Th-17: Tc-17 cells from a predominantly Th-17 phenotype to a predominantly Tc-17 phenotype. Surprisingly, Tc-17 responses remained high during the course of therapy suggesting that ART failed to correct the imbalance in Th-17 : Tc-17 responses induced following SIV infection. ART was associated with substantial repopulation of alpha4(+)beta7(hi) CD4(+) T cells in peripheral blood with little or no rebound of Th-17 cells. On the other hand, repopulation of alpha4(+)beta7(hi) CD4(+) T cells was accompanied by persistence of high levels of Tc-17 cells in peripheral blood. The dysregulation of Th-17

  4. A single amino acid substitution within the transmembrane domain of the human immunodeficiency virus type 1 Vpu protein renders simian-human immunodeficiency virus (SHIVKU-1bMC33) susceptible to rimantadine

    International Nuclear Information System (INIS)

    Hout, David R.; Gomez, Lisa M.; Pacyniak, Erik; Miller, Jean-Marie; Hill, M. Sarah; Stephens, Edward B.

    2006-01-01

    Previous studies from our laboratory have shown that the transmembrane domain (TM) of the Vpu protein of human immunodeficiency virus type 1 (HIV-1) contributes to the pathogenesis of SHIV KU-1bMC33 in macaques and that the TM domain of Vpu could be replaced with the M2 protein viroporin from influenza A virus. Recently, we showed that the replacement of the TM domain of Vpu with that of the M2 protein of influenza A virus resulted in a virus (SHIV M2 ) that was sensitive to rimantadine [Hout, D.R., Gomez, M.L., Pacyniak, E., Gomez, L.M., Inbody, S.H., Mulcahy, E.R., Culley, N., Pinson, D.M., Powers, M.F., Wong, S.W., Stephens, E.B., 2006. Substitution of the transmembrane domain of Vpu in simian human immunodeficiency virus (SHIV KU-1bMC33 ) with that of M2 of influenza A results in a virus that is sensitive to inhibitors of the M2 ion channel and is pathogenic for pig-tailed macaques. Virology 344, 541-558]. Based on previous studies of the M2 protein which have shown that the His-X-X-X-Trp motif within the M2 is essential to the function of the M2 proton channel, we have constructed a novel SHIV in which the alanine at position 19 of the TM domain was replaced with a histidine residue resulting in the motif His-Ile-Leu-Val-Trp. The SHIV VpuA19H replicated with similar kinetics as the parental SHIV KU-1bMC33 and pulse-chase analysis revealed that the processing of viral proteins was similar to SHIV KU-1bMC33 . This SHIV VpuA19H virus was found to be more sensitive to the M2 ion channel blocker rimantadine than SHIV M2 . Electron microscopic examination of SHIV VpuA19H -infected cells treated with rimantadine revealed an accumulation of viral particles at the cell surface and within intracellular vesicles, which was similar to that previously observed to SHIV M2 -infected cells treated with rimantadine. These data indicate that the Vpu protein of HIV-1 can be converted into a rimantadine-sensitive ion channel with the alteration of one amino acid and provide

  5. Insights into the Impact of CD8+ Immune Modulation on Human Immunodeficiency Virus Evolutionary Dynamics in Distinct Anatomical Compartments by Using Simian Immunodeficiency Virus-Infected Macaque Models of AIDS Progression.

    Science.gov (United States)

    Rife Magalis, Brittany; Nolan, David J; Autissier, Patrick; Burdo, Tricia H; Williams, Kenneth C; Salemi, Marco

    2017-12-01

    A thorough understanding of the role of human immunodeficiency virus (HIV) intrahost evolution in AIDS pathogenesis has been limited by the need for longitudinally sampled viral sequences from the vast target space within the host, which are often difficult to obtain from human subjects. CD8 + lymphocyte-depleted macaques infected with simian immunodeficiency virus (SIV) provide an increasingly utilized model of pathogenesis due to clinical manifestations similar to those for HIV-1 infection and AIDS progression, as well as a characteristic rapid disease onset. Comparison of this model with SIV-infected non-CD8 + lymphocyte-depleted macaques also provides a unique opportunity to investigate the role of CD8 + cells in viral evolution and population dynamics throughout the duration of infection. Using several different phylogenetic methods, we analyzed viral gp120 sequences obtained from extensive longitudinal sampling of multiple tissues and enriched leukocyte populations from SIVmac251-infected macaques with or without CD8 + lymphocyte depletion. SIV evolutionary and selection patterns in non-CD8 + lymphocyte-depleted animals were characterized by sequential population turnover and continual viral adaptation, a scenario readily comparable to intrahost evolutionary patterns during human HIV infection in the absence of antiretroviral therapy. Alternatively, animals that were depleted of CD8 + lymphocytes exhibited greater variation in population dynamics among tissues and cell populations over the course of infection. Our findings highlight the major role for CD8 + lymphocytes in prolonging disease progression through continual control of SIV subpopulations from various anatomical compartments and the potential for greater independent viral evolutionary behavior among these compartments in response to immune modulation. IMPORTANCE Although developments in combined antiretroviral therapy (cART) strategies have successfully prolonged the time to AIDS onset in HIV-1

  6. Changes in soluble factor-mediated CD8+ cell-derived antiviral activity in cynomolgus macaques infected with simian immunodeficiency virus SIVmac251: relationship to biological markers of progression.

    Science.gov (United States)

    Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

    2006-01-01

    Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of beta-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and alpha-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells.

  7. Changes in Soluble Factor-Mediated CD8+ Cell-Derived Antiviral Activity in Cynomolgus Macaques Infected with Simian Immunodeficiency Virus SIVmac251: Relationship to Biological Markers of Progression†

    Science.gov (United States)

    Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

    2006-01-01

    Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of β-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and α-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells. PMID:16352548

  8. Simian Immunodeficiency Virus Targeting of CXCR3+ CD4+ T Cells in Secondary Lymphoid Organs Is Associated with Robust CXCL10 Expression in Monocyte/Macrophage Subsets.

    Science.gov (United States)

    Fujino, Masayuki; Sato, Hirotaka; Okamura, Tomotaka; Uda, Akihiko; Takeda, Satoshi; Ahmed, Nursarat; Shichino, Shigeyuki; Shiino, Teiichiro; Saito, Yohei; Watanabe, Satoru; Sugimoto, Chie; Kuroda, Marcelo J; Ato, Manabu; Nagai, Yoshiyuki; Izumo, Shuji; Matsushima, Kouji; Miyazawa, Masaaki; Ansari, Aftab A; Villinger, Francois; Mori, Kazuyasu

    2017-07-01

    Glycosylation of Env defines pathogenic properties of simian immunodeficiency virus (SIV). We previously demonstrated that pathogenic SIVmac239 and a live-attenuated, quintuple deglycosylated Env mutant (Δ5G) virus target CD4 + T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4 + T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Here, we studied the host responses relevant to SIV targeting of CXCR3 + CCR5 + CD4 + T cells in SLOs. Genome-wide transcriptome analyses revealed that Th1-polarized inflammatory responses, defined by expression of CXCR3 chemokines, were distinctly induced in the SIVmac239-infected animals. Consistent with robust expression of CXCL10, CXCR3 + T cells were depleted from blood in the SIVmac239-infected animals. We also discovered that elevation of CXCL10 expression in blood and SLOs was secondary to the induction of CD14 + CD16 + monocytes and MAC387 + macrophages, respectively. Since the significantly higher levels of SIV infection in SLOs occurred with a massive accumulation of infiltrated MAC387 + macrophages, T cells, dendritic cells (DCs), and residential macrophages near high endothelial venules, the results highlight critical roles of innate/inflammatory responses in SIVmac239 infection. Restricted infection in SLOs by Δ5G also suggests that glycosylation of Env modulates innate/inflammatory responses elicited by cells of monocyte/macrophage/DC lineages. IMPORTANCE We previously demonstrated that a pathogenic SIVmac239 virus and a live-attenuated, deglycosylated mutant Δ5G virus infected distinct CD4 + T cell subsets in SLOs and the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Accordingly, infections with SIVmac239, but not with Δ5G, deplete CXCR3

  9. High-dose interferon-alpha2a exerts potent activity against human immunodeficiency virus type 1 not associated with antitumor activity in subjects with Kaposi's sarcoma

    NARCIS (Netherlands)

    Frissen, P. H.; de Wolf, F.; Reiss, P.; Bakker, P. J.; Veenhof, C. H.; Danner, S. A.; Goudsmit, J.; Lange, J. M.

    1997-01-01

    Anti-human immunodeficiency virus type 1 (HIV-1) activity was assessed in HIV-1-infected homosexual and bisexual men receiving 18-36 MIU/day of recombinant interferon (IFN)-alpha2a for Kaposi's sarcoma (KS). The median baseline HIV-1 RNA level was 4.99 log10 copies/mL. Seventeen subjects (68%)

  10. Toxicity and efficacy of 2',3'-dideoxycytidine in clinical trials of pigtailed macaques infected with simian retrovirus type 2.

    OpenAIRE

    Tsai, C C; Follis, K E; Yarnall, M; Blakley, G A

    1989-01-01

    Four dosing regimens of 2',3'-dideoxycytidine (ddC) were administered intravenously for 10 to 28 days to 18 pigtailed macaques with simian acquired immunodeficiency syndrome. Ten macaques naturally infected with simian acquired immunodeficiency syndrome retrovirus serotype 2 (SRV-2), the etiologic agent of simian acquired immunodeficiency syndrome, received ddC by continuous intravenous infusion or by a daily bolus injection for 10 to 12 days. Another eight macaques that were negative for SRV...

  11. Antibodies with High Avidity to the gp120 Envelope Protein in Protection from Simian Immunodeficiency Virus SIVmac251 Acquisition in an Immunization Regimen That Mimics the RV-144 Thai Trial

    Science.gov (United States)

    Pegu, Poonam; Vaccari, Monica; Gordon, Shari; Keele, Brandon F.; Doster, Melvin; Guan, Yongjun; Ferrari, Guido; Pal, Ranajit; Ferrari, Maria Grazia; Whitney, Stephen; Hudacik, Lauren; Billings, Erik; Rao, Mangala; Montefiori, David; Tomaras, Georgia; Alam, S. Munir; Fenizia, Claudio; Lifson, Jeffrey D.; Stablein, Donald; Tartaglia, Jim; Michael, Nelson; Kim, Jerome; Venzon, David

    2013-01-01

    The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8+ T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIVmac251 that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4+ and CD8+ T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIVmac251 acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIVmac251-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIVmac251 infectivity in cells that express high levels of α4β7 integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines. PMID:23175374

  12. Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial.

    Science.gov (United States)

    Pegu, Poonam; Vaccari, Monica; Gordon, Shari; Keele, Brandon F; Doster, Melvin; Guan, Yongjun; Ferrari, Guido; Pal, Ranajit; Ferrari, Maria Grazia; Whitney, Stephen; Hudacik, Lauren; Billings, Erik; Rao, Mangala; Montefiori, David; Tomaras, Georgia; Alam, S Munir; Fenizia, Claudio; Lifson, Jeffrey D; Stablein, Donald; Tartaglia, Jim; Michael, Nelson; Kim, Jerome; Venzon, David; Franchini, Genoveffa

    2013-02-01

    The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8(+) T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIV(mac251) that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4(+) and CD8(+) T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIV(mac251) acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIV(mac251)-specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIV(mac251) infectivity in cells that express high levels of α(4)β(7) integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines.

  13. Antiviral therapy during primary simian immunodeficiency virus infection fails to prevent acute loss of CD4+ T cells in gut mucosa but enhances their rapid restoration through central memory T cells.

    Science.gov (United States)

    Verhoeven, David; Sankaran, Sumathi; Silvey, Melanie; Dandekar, Satya

    2008-04-01

    Gut-associated lymphoid tissue (GALT) is an early target of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) and a site for severe CD4+ T-cell depletion. Although antiretroviral therapy (ART) is effective in suppressing HIV replication and restoring CD4+ T cells in peripheral blood, restoration in GALT is delayed. The role of restored CD4+ T-cell help in GALT during ART and its impact on antiviral CD8+ T-cell responses have not been investigated. Using the SIV model, we investigated gut CD4+ T-cell restoration in infected macaques, initiating ART during either the primary stage (1 week postinfection), prior to acute CD4+ cell loss (PSI), or during the chronic stage at 10 weeks postinfection (CSI). ART led to viral suppression in GALT and peripheral blood mononuclear cells of PSI and CSI animals at comparable levels. CSI animals had incomplete CD4+ T-cell restoration in GALT. In PSI animals, ART did not prevent acute CD4+ T-cell loss by 2 weeks postinfection in GALT but supported rapid and complete CD4+ T-cell restoration thereafter. This correlated with an accumulation of central memory CD4+ T cells and better suppression of inflammation. Restoration of CD4+ T cells in GALT correlated with qualitative changes in SIV gag-specific CD8+ T-cell responses, with a dominance of interleukin-2-producing responses in PSI animals, while both CSI macaques and untreated SIV-infected controls were dominated by gamma interferon responses. Thus, central memory CD4+ T-cell levels and qualitative antiviral CD8+ T-cell responses, independent of viral suppression, were the immune correlates of gut mucosal immune restoration during ART.

  14. High-dose chemotherapy and immunotherapy in adult Burkitt lymphoma: comparison of results in human immunodeficiency virus-infected and noninfected patients.

    Science.gov (United States)

    Oriol, Albert; Ribera, Josep-Maria; Bergua, Juan; Giménez Mesa, Eduardo; Grande, Carlos; Esteve, Jordi; Brunet, Salut; Moreno, Maria-Jose; Escoda, Lourdes; Hernandez-Rivas, Jesus-Maria; Hoelzer, Dieter

    2008-07-01

    It has been recognized that cure is possible for human immunodeficiency virus (HIV)-infected patients with Burkitt lymphoma/leukemia (BL) if appropriate chemotherapy is used. The introduction of rituximab in BL therapeutic schemes has been scarcely explored. The outcome and toxicity of HIV-positive patients with BL treated in a rituximab and intensive chemotherapy-based trial was evaluated. Thirty-six consecutive patients, 15 to 55 years of age, diagnosed with advanced stage BL were recruited from July 2003 to August 2006, stratified according to HIV infection status and treated with 6 cycles of intensive chemotherapy including 8 doses of rituximab. Nineteen of the patients (53%) were HIV-infected. Their clinical characteristics were comparable to those of the HIV-negative patients. Complete remission (CR) rates were 88% and 84%, respectively, for HIV-negative and -positive patients. Twenty-seven patients (82% and 68%, respectively, for HIV-negative and -positive patients) completed the 6 protocol scheduled cycles. HIV-infected patients presented higher incidences of grade 3-4 mucositis (27% vs 7% of cycles, P = .0005) and severe infectious episodes (26% vs 8%, P = .0025). However, there were no statistically significant differences in 2-year overall survival (82%, 95% confidence interval [CI], 65%-99% and 73%, 95% CI, 54%-92%, respectively) or 2-year disease-free survival (93%, 95% CI, 82%-99% and 87%, 95% CI 72%-99%, respectively). Intensive immunochemotherapy can be administered safely to patients with HIV infection. Despite a higher incidence of severe mucositis and infections the remission and survival rates are comparable to those observed in HIV-negative patients. (Copyright) 2008 American Cancer Society.

  15. Improved survival in rhesus macaques immunized with modified vaccinia virus Ankara recombinants expressing simian immunodeficiency virus envelope correlates with reduction in memory CD4+ T-cell loss and higher titers of neutralizing antibody.

    Science.gov (United States)

    Ourmanov, Ilnour; Kuwata, Takeo; Goeken, Robert; Goldstein, Simoy; Iyengar, Ranjani; Buckler-White, Alicia; Lafont, Bernard; Hirsch, Vanessa M

    2009-06-01

    Previous studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high viremia and AIDS following challenge with a pathogenic strain of SIV. Although all animals became infected, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines compared with animals that received nonrecombinant MVA. Most importantly, the reduction in viremia resulted in a significant increase in median and cumulative survival. Continued analysis of these animals over the subsequent 9 years has shown that they maintain a survival advantage, although all but two of the macaques have progressed to AIDS. Importantly, improved survival correlated with preservation of memory CD4(+) T cells in the peripheral blood. The greatest survival advantage was observed in macaques immunized with regimens containing SIV Env, and the titer of neutralizing antibodies to the challenge virus prior to or shortly following challenge correlated with preservation of CD4(+) T cells. These data are consistent with a role for neutralizing antibodies in nonsterilizing protection from high viremia and associated memory CD4(+) T-cell loss.

  16. Significant Depletion of CD4+ T Cells Occurs in the Oral Mucosa during Simian Immunodeficiency Virus Infection with the Infected CD4+ T Cell Reservoir Continuing to Persist in the Oral Mucosa during Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Jeffy George

    2015-01-01

    Full Text Available Human and simian immunodeficiency virus (HIV and SIV infections are characterized by manifestation of numerous opportunistic infections and inflammatory conditions in the oral mucosa. The loss of CD4+ T cells that play a critical role in maintaining mucosal immunity likely contributes to this process. Here we show that CD4+ T cells constitute a minor population of T cells in the oral mucosa and display a predominantly central memory phenotype mirroring other mucosal sites such as the rectal mucosa. Chronic SIV infection was associated with a near total depletion of CD4+ T cells in the oral mucosa that appear to repopulate during antiretroviral therapy (ART. Repopulating CD4+ T cells harbored a large fraction of Th17 cells suggesting that ART potentially reconstitutes oral mucosal immunity. However, a minor fraction of repopulating CD4+ T cells harbored SIV DNA suggesting that the viral reservoir continues to persist in the oral mucosa during ART. Therapeutic approaches aimed at obtaining sustainable CD4+ T cell repopulation in combination with strategies that can eradicate the latent viral reservoir in the oral mucosa are essential for better oral health and long-term outcome in HIV infected patients.

  17. Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV in macaques vaccinated with replication-deficient viral vectors

    Directory of Open Access Journals (Sweden)

    Strasak Alexander

    2009-06-01

    Full Text Available Abstract Background We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens. Results Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p Conclusion The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.

  18. Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid

    Science.gov (United States)

    Boyer, Jean D.; Robinson, Tara M.; Kutzler, Michele A.; Vansant, Gordon; Hokey, David A.; Kumar, Sanjeev; Parkinson, Rose; Wu, Ling; Sidhu, Maninder K.; Pavlakis, George N.; Felber, Barbara K.; Brown, Charles; Silvera, Peter; Lewis, Mark G.; Monforte, Joseph; Waldmann, Thomas A.; Eldridge, John; Weiner, David B.

    2007-01-01

    The cell-mediated immune profile induced by a recombinant DNA vaccine was assessed in the simian/HIV (SHIV) and macaque model. The vaccine strategy included coimmunization of a DNA-based vaccine alone or in combination with an optimized plasmid encoding macaque IL-15 (pmacIL-15). We observed strong induction of vaccine-specific IFN-γ-producing CD8+ and CD4+ effector T cells in the vaccination groups. Animals were subsequently challenged with 89.6p. The vaccine groups were protected from ongoing infection, and the IL-15 covaccinated group showed a more rapidly controlled infection than the group treated with DNA vaccine alone. Lymphocytes isolated from the group covaccinated with pmacIL-15 had higher cellular proliferative responses than lymphocytes isolated from the macaques that received SHIV DNA alone. Vaccine antigen activation of lymphocytes was also studied for a series of immunological molecules. Although mRNA for IFN-γ was up-regulated after antigen stimulation, the inflammatory molecules IL-8 and MMP-9 were down-regulated. These observed immune profiles are potentially reflective of the ability of the different groups to control SHIV replication. This study demonstrates that an optimized IL-15 immune adjuvant delivered with a DNA vaccine can impact the cellular immune profile in nonhuman primates and lead to enhanced suppression of viral replication. PMID:18000037

  19. A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge.

    Science.gov (United States)

    Andrews, Chasity D; Yueh, Yun Lan; Spreen, William R; St Bernard, Leslie; Boente-Carrera, Mar; Rodriguez, Kristina; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Ford, Susan; Mohri, Hiroshi; Cheng-Mayer, Cecilia; Hong, Zhi; Ho, David D; Markowitz, Martin

    2015-01-14

    Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human immunodeficiency virus) rhesus macaque challenge model. We examined the pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera (depot medroxyprogesterone acetate), which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with GSK744 LA (50 mg/kg) monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were fivefold lower on average in cervical tissues than in rectal tissues. Eight female rhesus macaques were treated with GSK744 LA at week 0, and four female rhesus macaques served as controls. All animals received a high-dose challenge of SHIV162P3 at week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas viremia was detected 1 to 2 weeks after SHIV challenge in all control animals. The GSK744 LA-treated rhesus macaques were given a second administration of drug at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected six of eight female rhesus macaques against three high-dose SHIV challenges, whereas all control animals became infected after the first challenge (P = 0.0003, log-rank test). These results support further clinical development of GSK744 LA for PrEP. Copyright © 2015, American Association for the Advancement of Science.

  20. Sequential priming with simian immunodeficiency virus (SIV) DNA vaccines, with or without encoded cytokines, and a replicating adenovirus-SIV recombinant followed by protein boosting does not control a pathogenic SIVmac251 mucosal challenge.

    Science.gov (United States)

    Demberg, Thorsten; Boyer, Jean D; Malkevich, Nina; Patterson, L Jean; Venzon, David; Summers, Ebonita L; Kalisz, Irene; Kalyanaraman, V S; Lee, Eun Mi; Weiner, David B; Robert-Guroff, Marjorie

    2008-11-01

    Previously, combination DNA/nonreplicating adenovirus (Ad)- or poxvirus-vectored vaccines have strongly protected against SHIV(89.6P), DNAs expressing cytokines have modulated immunity elicited by DNA vaccines, and replication-competent Ad-recombinant priming and protein boosting has strongly protected against simian immunodeficiency virus (SIV) challenge. Here we evaluated a vaccine strategy composed of these promising components. Seven rhesus macaques per group were primed twice with multigenic SIV plasmid DNA with or without interleukin-12 (IL-12) DNA or IL-15 DNA. After a multigenic replicating Ad-SIV immunization, all groups received two booster immunizations with SIV gp140 and SIV Nef protein. Four control macaques received control DNA plasmids, empty Ad vector, and adjuvant. All vaccine components were immunogenic, but the cytokine DNAs had little effect. Macaques that received IL-15-DNA exhibited higher peak anti-Nef titers, a more rapid anti-Nef anamnestic response postchallenge, and expanded CD8(CM) T cells 2 weeks postchallenge compared to the DNA-only group. Other immune responses were indistinguishable between groups. Overall, no protection against intrarectal challenge with SIV(mac251) was observed, although immunized non-Mamu-A*01 macaques as a group exhibited a statistically significant 1-log decline in acute viremia compared to non-Mamu-A*01 controls. Possible factors contributing to the poor outcome include administration of cytokine DNAs to sites different from the Ad recombinants (intramuscular and intratracheal, respectively), too few DNA priming immunizations, a suboptimal DNA delivery method, failure to ensure delivery of SIV and cytokine plasmids to the same cell, and instability and short half-life of the IL-15 component. Future experiments should address these issues to determine if this combination approach is able to control a virulent SIV challenge.

  1. A single dose of a MIV-150/Zinc acetate gel provides 24 h of protection against vaginal simian human immunodeficiency virus reverse transcriptase infection, with more limited protection rectally 8-24 h after gel use.

    Science.gov (United States)

    Kenney, Jessica; Singer, Rachel; Derby, Nina; Aravantinou, Meropi; Abraham, Ciby J; Menon, Radhika; Seidor, Samantha; Zhang, Shimin; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Fernández-Romero, José A; Zydowsky, Thomas M; Robbiani, Melissa

    2012-11-01

    Previously we showed that repeated vaginal application of a MIV-150/zinc acetate carrageenan (MIV-150/ZA/CG) gel and a zinc acetate carrageenan (ZA/CG) gel significantly protected macaques from vaginal simian human immunodeficiency virus reverse transcriptase (SHIV-RT) infection. Gels were applied either daily for 2 weeks or every other day for 4 weeks, and the animals were challenged 4-24 h later. Herein, we examined the effects of a single vaginal dose administered either before or after virus challenge. Encouraged by the vaginal protection seen with MIV-150/ZA/CG, we also tested it rectally. Vaginal applications of MIV-150/ZA/CG, ZA/CG, and CG gel were performed once 8-24 h before, 1 h after, or 24 h before and 1 h after vaginal challenge. Rectal applications of MIV-150/ZA/CG and CG gel were performed once 8 or 24 h before rectal challenge. While vaginal pre-challenge and pre/post-challenge application of MIV-150/ZA/CG gel offered significant protection (88%, pinfection prechallenge, but not significantly, and the effect was completely lost post-challenge. Rectal application of MIV-150/ZA/CG gel afforded limited protection against rectal challenge when applied 8-24 h before challenge. Thus, MIV-150/ZA/CG gel is a highly effective vaginal microbicide that demonstrates 24 h of protection from vaginal infection and may demonstrate efficacy against rectal infection when given close to the time of HIV exposure.

  2. Mathematical modeling of ultradeep sequencing data reveals that acute CD8+ T-lymphocyte responses exert strong selective pressure in simian immunodeficiency virus-infected macaques but still fail to clear founder epitope sequences.

    Science.gov (United States)

    Love, Tanzy M T; Thurston, Sally W; Keefer, Michael C; Dewhurst, Stephen; Lee, Ha Youn

    2010-06-01

    The prominent role of antiviral cytotoxic CD8(+) T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and SIV) has rationalized the development of T-cell-based vaccines. However, the presence of escape mutations in the acute stage of infection has raised a concern that accelerated escape from vaccine-induced CD8-TL responses might undermine vaccine efficacy. We reanalyzed previously published data of 101,822 viral genomes of three CD8-TL epitopes, Nef(103-111)RM9 (RM9), Tat(28-35)SL8 (SL8), and Gag(181-189)CM9 (CM9), sampled by ultradeep pyrosequencing from eight macaques. Multiple epitope variants appeared during the resolution of acute viremia, followed by the predominance of a single mutant epitope. By fitting a mathematical model, we estimated the first acute escape rate as 0.36 day(-1) within escape-prone epitopes, RM9 and SL8, and the chronic escape rate as 0.014 day(-1) within the CM9 epitope. Our estimate of SIV acute escape rates was found to be comparable to very early HIV-1 escape rates. The timing of the first escape was more highly correlated with the timing of the peak CD8-TL response than with the magnitude of the CD8-TL response. The transmitted epitope decayed more than 400 times faster during the acute viral decline stage than predicted by a neutral evolution model. However, the founder epitope persisted as a minor population even at the viral set point; in contrast, the majority of acute escape epitopes were completely cleared. Our results suggest that a reservoir of SIV infection is preferentially formed by virus with the transmitted epitope.

  3. Scrambling of the amino acids within the transmembrane domain of Vpu results in a simian-human immunodeficiency virus (SHIVTM) that is less pathogenic for pig-tailed macaques

    International Nuclear Information System (INIS)

    Hout, David R.; Gomez, Melissa L.; Pacyniak, Erik; Gomez, Lisa M.; Inbody, Sarah H.; Mulcahy, Ellyn R.; Culley, Nathan; Pinson, David M.; Powers, Michael F.; Wong, Scott W.; Stephens, Edward B.

    2005-01-01

    Previous studies have shown that the transmembrane (TM) domain of the subtype B Vpu enhances virion release from cells and some studies have shown that this domain may form an oligomeric structure with properties of an ion channel. To date, no studies have been performed to assess the role of this domain in virus pathogenesis in a macaque model of disease. Using a pathogenic molecular clone of simian human immunodeficiency virus (SHIV KU-1bMC33 ), we have generated a novel virus in which the transmembrane domain of the Vpu protein was scrambled but maintained hydrophobic in nature (SHIV TM ), which presumably would disrupt any ion channel TM properties of this protein. Vectors expressing the Vpu as a fusion protein with the enhanced green fluorescent protein (Vpu TM EGFP) indicate that it was transported to the same intracellular compartment as the unmodified Vpu protein but did not down-regulate cell surface expression of CD4. To assess the pathogenicity of SHIV TM , three pig-tailed macaques were inoculated with the SHIV TM and monitored for 6-8 months for CD4 + T cell levels, viral loads and the stability of the sequence of the vpu gene. Our results indicated that unlike the parental SHIV KU-1bMC33 , inoculation of macaques with SHIV TM did not cause a severe CD4 + T cell loss over the course of their infections. Sequence analysis of the vpu gene analyzed from sequential PBMC samples derived from macaques revealed that the scrambled TM was stable during the course of infection. At necropsy, examination of tissues revealed low viral loads and none of the pathology commonly observed in lymphoid and non-lymphoid tissues following inoculation with the pathogenic parental SHIV KU-1bMC33 virus. Thus, these results show for the first time that the TM domain of Vpu contributes to the pathogenicity of SHIV KU-1bMC33 in pig-tailed macaques

  4. Modification of a loop sequence between α-helices 6 and 7 of virus capsid (CA protein in a human immunodeficiency virus type 1 (HIV-1 derivative that has simian immunodeficiency virus (SIVmac239 vif and CA α-helices 4 and 5 loop improves replication in cynomolgus monkey cells

    Directory of Open Access Journals (Sweden)

    Adachi Akio

    2009-08-01

    Full Text Available Abstract Background Human immunodeficiency virus type 1 (HIV-1 productively infects only humans and chimpanzees but not cynomolgus or rhesus monkeys while simian immunodeficiency virus isolated from macaque (SIVmac readily establishes infection in those monkeys. Several HIV-1 and SIVmac chimeric viruses have been constructed in order to develop an animal model for HIV-1 infection. Construction of an HIV-1 derivative which contains sequences of a SIVmac239 loop between α-helices 4 and 5 (L4/5 of capsid protein (CA and the entire SIVmac239 vif gene was previously reported. Although this chimeric virus could grow in cynomolgus monkey cells, it did so much more slowly than did SIVmac. It was also reported that intrinsic TRIM5α restricts the post-entry step of HIV-1 replication in rhesus and cynomolgus monkey cells, and we previously demonstrated that a single amino acid in a loop between α-helices 6 and 7 (L6/7 of HIV type 2 (HIV-2 CA determines the susceptibility of HIV-2 to cynomolgus monkey TRIM5α. Results In the study presented here, we replaced L6/7 of HIV-1 CA in addition to L4/5 and vif with the corresponding segments of SIVmac. The resultant HIV-1 derivatives showed enhanced replication capability in established T cell lines as well as in CD8+ cell-depleted primary peripheral blood mononuclear cells from cynomolgus monkey. Compared with the wild type HIV-1 particles, the viral particles produced from a chimeric HIV-1 genome with those two SIVmac loops were less able to saturate the intrinsic restriction in rhesus monkey cells. Conclusion We have succeeded in making the replication of simian-tropic HIV-1 in cynomolgus monkey cells more efficient by introducing into HIV-1 the L6/7 CA loop from SIVmac. It would be of interest to determine whether HIV-1 derivatives with SIVmac CA L4/5 and L6/7 can establish infection of cynomolgus monkeys in vivo.

  5. The presence of the casein kinase II phosphorylation sites of Vpu enhances the CD4+ T cell loss caused by the simian-human immunodeficiency virus SHIVKU-lbMC33 in pig-tailed macaques

    International Nuclear Information System (INIS)

    Singh, Dinesh K.; Griffin, Darcy M.; Pacyniak, Erik; Jackson, Mollie; Werle, Michael J.; Wisdom, Bo; Sun, Francis; Hout, David R.; Pinson, David M.; Gunderson, Robert S.; Powers, Michael F.; Wong, Scott W.; Stephens, Edward B.

    2003-01-01

    The simian-human immunodeficiency virus (SHIV)/ macaque model for human immunodeficiency virus type 1 has become a useful tool to assess the role of Vpu in lentivirus pathogenesis. In this report, we have mutated the two phosphorylated serine residues of the HIV-1 Vpu to glycine residues and have reconstructed a SHIV expressing this nonphosphorylated Vpu (SHIV S52,56G ). Expression studies revealed that this protein was localized to the same intracellular compartment as wild-type Vpu. To determine if this virus was pathogenic, four pig-tailed macaques were inoculated with SHIV S52,56G and virus burdens and circulating CD4 + T cells monitored up to 1 year. Our results indicate that SHIV S52,56G caused rapid loss in the circulating CD4 + T cells within 3 weeks of inoculation in one macaque (CC8X), while the other three macaques developed no or gradual numbers of CD4 + T cells and a wasting syndrome. Histological examination of tissues revealed that macaque CC8X had lesions in lymphoid tissues (spleen, lymph nodes, and thymus) that were typical for macaques inoculated with pathogenic parental SHIV KU-1bMC33 and had no lesions within the CNS. To rule out that macaque CC8X had selected for a virus in which there was reversion of the glycine residues at positions 52 and 56 to serine residues and/or compensating mutations occurred in other genes associated with CD4 down-regulation, sequence analysis was performed on amplified vpu sequences isolated from PBMC and from several lymphoid tissues at necropsy. Sequence analysis revealed a reversion of the glycine residues back to serine residues in this macaque. The other macaques maintained low virus burdens, with one macaque (P003) developing a wasting syndrome between months 9 and 11. Histological examination of tissues from this macaque revealed a thymus with severe atrophy that was similar to that of a previously reported macaque inoculated with a SHIV lacking vpu (Virology 293, 2002, 252). Sequence analysis revealed no

  6. Gamma dosimetry of high doses

    International Nuclear Information System (INIS)

    Martinez C, T.; Galvan G, A.; Canizal, G.

    1991-01-01

    The gamma dosimetry of high doses is problematic in almost all the classic dosemeters either based on the thermoluminescence, electric, chemical properties, etc., because they are saturated to very high dose and they are no longer useful. This work carries out an investigation in the interval of high doses. The solid system of heptahydrate ferrous sulfate, can be used as solid dosemeter of routine for high doses of radiation. The proposed method is simple, cheap and it doesn't require sophisticated spectrophotometers or spectrometers but expensive and not common in some laboratories

  7. Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model

    OpenAIRE

    Jiae Kim; Jiae Kim; Kristina K. Peachman; Kristina K. Peachman; Ousman Jobe; Ousman Jobe; Elaine B. Morrison; Atef Allam; Atef Allam; Linda Jagodzinski; Sofia A. Casares; Mangala Rao

    2017-01-01

    Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP) models for studying human immunodeficiency virus (HIV)-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several...

  8. Safety and tolerability of conserved region vaccines vectored by plasmid DNA, simian adenovirus and modified vaccinia virus ankara administered to human immunodeficiency virus type 1-uninfected adults in a randomized, single-blind phase I trial.

    Directory of Open Access Journals (Sweden)

    Emma-Jo Hayton

    Full Text Available HIV-1 vaccine development has advanced slowly due to viral antigenic diversity, poor immunogenicity and recently, safety concerns associated with human adenovirus serotype-5 vectors. To tackle HIV-1 variation, we designed a unique T-cell immunogen HIVconsv from functionally conserved regions of the HIV-1 proteome, which were presented to the immune system using a heterologous prime-boost combination of plasmid DNA, a non-replicating simian (chimpanzee adenovirus ChAdV-63 and a non-replicating poxvirus, modified vaccinia virus Ankara. A block-randomized, single-blind, placebo-controlled phase I trial HIV-CORE 002 administered for the first time candidate HIV-1- vaccines or placebo to 32 healthy HIV-1/2-uninfected adults in Oxford, UK and elicited high frequencies of HIV-1-specific T cells capable of inhibiting HIV-1 replication in vitro. Here, detail safety and tolerability of these vaccines are reported.Local and systemic reactogenicity data were collected using structured interviews and study-specific diary cards. Data on all other adverse events were collected using open questions. Serum neutralizing antibody titres to ChAdV-63 were determined before and after vaccination.Two volunteers withdrew for vaccine-unrelated reasons. No vaccine-related serious adverse events or reactions occurred during 190 person-months of follow-up. Local and systemic events after vaccination occurred in 27/32 individuals and most were mild (severity grade 1 and predominantly transient (<48 hours. Myalgia and flu-like symptoms were more strongly associated with MVA than ChAdV63 or DNA vectors and more common in vaccine recipients than in placebo. There were no intercurrent HIV-1 infections during follow-up. 2/24 volunteers had low ChAdV-63-neutralizing titres at baseline and 7 increased their titres to over 200 with a median (range of 633 (231-1533 post-vaccination, which is of no safety concern.These data demonstrate safety and good tolerability of the pSG2

  9. Substitution of the transmembrane domain of Vpu in simian-human immunodeficiency virus (SHIVKU1bMC33) with that of M2 of influenza A results in a virus that is sensitive to inhibitors of the M2 ion channel and is pathogenic for pig-tailed macaques

    International Nuclear Information System (INIS)

    Hout, David R.; Gomez, Melissa L.; Pacyniak, Erik; Gomez, Lisa M.; Fegley, Barbara; Mulcahy, Ellyn R.; Hill, M. Sarah; Culley, Nathan; Pinson, David M.; Nothnick, Warren; Powers, Michael F.; Wong, Scott W.; Stephens, Edward B.

    2006-01-01

    The Vpu protein of human immunodeficiency virus type 1 has been shown to shunt the CD4 receptor molecule to the proteasome for degradation and to enhance virus release from infected cells. The exact mechanism by which the Vpu protein enhances virus release is currently unknown but some investigators have shown that this function is associated with the transmembrane domain and potential ion channel properties. In this study, we determined if the transmembrane domain of Vpu could be functionally substituted with that of the prototypical viroporin, the M2 protein of influenza A virus. We constructed chimeric vpu gene in which the transmembrane domain of Vpu was replaced with that of the M2 protein of influenza. This chimeric vpu gene was substituted for the vpu gene in the genome of a pathogenic simian human immunodeficiency virus, SHIV KU-1bMC33 . The resulting virus, SHIV M2 , synthesized a Vpu protein that had a slightly different M r compared to the parental SHIV KU-1bMC33 , reflecting the different sizes of the two Vpu proteins. The SHIV M2 was shown to replicate with slightly reduced kinetics when compared to the parental SHIV KU-1bMC33 but electron microscopy revealed that the site of maturation was similar to the parental virus SHIV KU1bMC33 . We show that the replication and spread of SHIV M2 could be blocked with the antiviral drug rimantadine, which is known to target the M2 ion channel. Our results indicate a dose dependent inhibition of SHIV M2 with 100 μM rimantadine resulting in a >95% decrease in p27 released into the culture medium. Rimantadine did not affect the replication of the parental SHIV KU-1bMC33 . Examination of SHIV M2 -infected cells treated with 50 μM rimantadine revealed numerous viral particles associated with the cell plasma membrane and within intracytoplasmic vesicles, which is similar to HIV-1 mutants lacking a functional vpu. To determine if SHIV M2 was as pathogenic as the parental SHIV KU-1bMC33 virus, two pig-tailed macaques

  10. Concomitant chemoradiotherapy with high dose rate brachytherapy ...

    African Journals Online (AJOL)

    Concomitant chemoradiotherapy with high dose rate brachytherapy as a definitive treatment modality for locally advanced cervical cancer. T Refaat, A Elsaid, N Lotfy, K Kiel, W Small Jr, P Nickers, E Lartigau ...

  11. Fiber optics in high dose radiation fields

    International Nuclear Information System (INIS)

    Partin, J.K.

    1985-01-01

    A review of the behavior of state-of-the-art optical fiber waveguides in high dose (greater than or equal to 10 5 rad), steady state radiation fields is presented. The influence on radiation-induced transmission loss due to experimental parameters such as dose rate, total dose, irradiation history, temperature, wavelength, and light intensity, for future work in high dose environments are given

  12. Progress in high-dose radiation dosimetry

    International Nuclear Information System (INIS)

    Ettinger, K.V.; Nam, J.W.; McLaughlin, W.L.; Chadwick, K.H.

    1981-01-01

    The last decade has witnessed a deluge of new high-dose dosimetry techniques and expanded applications of methods developed earlier. Many of the principal systems are calibrated by means of calorimetry, although production of heat is not always the final radiation effect of interest. Reference systems also include a number of chemical dose meters: ferrous sulphate, ferrous-cupric sulphate, and ceric sulphate acidic aqueous solutions. Requirements for stable and reliable transfer dose meters have led to further developments of several important high-dose systems: amino acids and saccharides analysed by ESR or lyoluminescence, thermoluminescent materials, radiochromic dyes and plastics, ceric-cerous solutions analysed by potentiometry, and ethanol-chlorobenzene solutions analysed by high-frequency oscillometry. A number of other prospective dose meters are also treated in this review. In addition, an IAEA programme of high-dose standardization and intercomparison for industrial radiation processing is described. (author)

  13. Intracranial meningiomas after high-dose irradiation

    International Nuclear Information System (INIS)

    Soffer, D.; Gomori, J.M.; Siegal, T.; Shalit, M.N.

    1989-01-01

    Three patients who presented with intracranial meningiomas 12, 15, and 20 years, respectively, after therapeutic high-dose irradiation of a primary brain tumor are described. Analysis of these cases and similar documented cases suggests that meningiomas after high-dose irradiation constitute a recognizable entity. Patients with such tumors received radiation therapy at a young age (mean age, 9.4 years). After a latent period of 2 to 47 years (mean, 19.8 years) they developed meningiomas at the site of irradiation, at a much younger age than patients with ''spontaneous'' meningiomas. Similar to the situation with meningiomas after low-dose irradiation, a relatively high proportion of meningiomas induced by high-dose irradiation tend to be malignant and biologically aggressive. A very young age at the time of irradiation seems to predispose to the induction of malignant meningiomas, rather than benign tumors. These unusual features provide indirect evidence that high-dose radiation may play a role in the pathogenesis of meningiomas.41 references

  14. Endorectal high dose rate brachytherapy quality assurance

    International Nuclear Information System (INIS)

    Devic, S.; Vuong, T.; Evans, M.; Podgorsak, E.

    2008-01-01

    We describe our quality assurance method for preoperative high dose rate (HDR) brachytherapy of endorectal tumours. Reproduction of the treatment planning dose distribution on a daily basis is crucial for treatment success. Due to the cylindrical symmetry, two types of adjustments are necessary: applicator rotation and dose distribution shift along the applicator axis. (author)

  15. High-dose irradiation of food

    International Nuclear Information System (INIS)

    Diehl, J.F.

    1999-01-01

    Studies performed on behalf of the International Project on Food Irradiation in the period from 1971 until 1980 resulted in the concluding statement that ''.the irradiation of any food commodity up to an overall average dose of 10 kGy presents no toxicological hazard; hence, toxicological testing of foods so treated is no longer required.'' Since then, licenses for food irradiation have been restricted to this maximum dose in any country applying this technology. Further testing programmes have been carried out investigating the wholesomeness or hazards of high-dose irradiation, but there has been little demand so far by the food industry for licensing of high-dose irradiation, as there is only a small range of products whose irradiation at higher doses offers advantages for given, intended use. These include eg. spices, dried herbs, meat products in flexible pouch packagings for astronauts, or patients with immune deficiencies. (orig./CB) [de

  16. High-dose erythropoietin for tissue protection

    DEFF Research Database (Denmark)

    Lund, Anton; Lundby, Carsten; Olsen, Niels Vidiendal

    2014-01-01

    BACKGROUND: The discovery of potential anti-apoptotic and cytoprotective effects of recombinant human erythropoietin (rHuEPO) has led to clinical trials investigating the use of high-dose, short-term rHuEPO therapy for tissue protection in conditions such as stroke and myocardial infarction....... Experimental studies have been favourable, but the clinical efficacy has yet to be validated. MATERIALS AND METHODS: We have reviewed clinical studies regarding the use of high-dose, short-term rHuEPO therapy for tissue protection in humans with the purpose to detail the safety and efficacy of r...... no effect of rHuEPO therapy on measures of tissue protection. Five trials including 1025 patients reported safety concerns in the form of increased mortality or adverse event rates. No studies reported reduced mortality. CONCLUSIONS: Evidence is sparse to support a tissue-protective benefit of r...

  17. HTLV-3/4 and simian foamy retroviruses in humans: discovery, epidemiology, cross-species transmission and molecular virology.

    Science.gov (United States)

    Gessain, Antoine; Rua, Réjane; Betsem, Edouard; Turpin, Jocelyn; Mahieux, Renaud

    2013-01-05

    Non-human primates are considered to be likely sources of viruses that can infect humans and thus pose a significant threat to human population. This is well illustrated by some retroviruses, as the simian immunodeficiency viruses and the simian T lymphotropic viruses, which have the ability to cross-species, adapt to a new host and sometimes spread. This leads to a pandemic situation for HIV-1 or an endemic one for HTLV-1. Here, we present the available data on the discovery, epidemiology, cross-species transmission and molecular virology of the recently discovered HTLV-3 and HTLV-4 deltaretroviruses, as well as the simian foamy retroviruses present in different human populations at risk, especially in central African hunters. We discuss also the natural history in humans of these retroviruses of zoonotic origin (magnitude and geographical distribution, possible inter-human transmission). In Central Africa, the increase of the bushmeat trade during the last decades has opened new possibilities for retroviral emergence in humans, especially in immuno-compromised persons. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. High dose rate endobronchial brachytherapy - treatment technique

    International Nuclear Information System (INIS)

    Carvalho, Heloisa de Andrade; Aisen, Salim; Haddad, Cecilia Maria Kalil; Nadalin, Wladimir; Pedreira Junior, Wilson Leite; Chavantes, Maria Cristina

    1998-01-01

    High dose rate endobronchial brachytherapy is efficient in symptom relief due to obstructive endobronchial malignancies. However, it's role in survival improvement for patients with lung cancer is not yet established. The use of this treatment in increasing, specially in the developing countries. The purpose of this paper is to present the treatment technique used in the Radiotherapy Department of the Hospital da Clinicas, University of Sao Paulo, based on an experience of 60 cases treated with 180 procedures. Some practical suggestions and rules adopted in the Department are described. The severe complications rate is 6.7%, demonstrating an adequate patient selection associated with the technique utilized. (author)

  19. Neuroprotective potential of high-dose biotin.

    Science.gov (United States)

    McCarty, Mark F; DiNicolantonio, James J

    2017-11-01

    A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS. But biotin's ability to boost cGMP synthesis in the brain may have broader neuroprotective potential. In many types of neurons and neural cells, cGMP exerts neurotrophic-mimetic effects - entailing activation of the PI3K-Akt and Ras-ERK pathways - that promote neuron survival and plasticity. Hippocampal long term potentiation requires nitric oxide synthesis, which in turn promotes an activating phosphorylation of CREB via a pathway involving cGMP and protein kinase G (PKG). In Alzheimer's disease (AD), amyloid beta suppresses this mechanism by inhibiting sGC activity; agents which exert a countervailing effect by boosting cGMP levels tend to restore effective long-term potentiation in rodent models of AD. Moreover, NO/cGMP suppresses amyloid beta production within the brain by inhibiting expression of amyloid precursor protein and BACE1. In conjunction with cGMP's ability to oppose neuron apoptosis, these effects suggest that high-dose biotin might have potential for the prevention and management of AD. cGMP also promotes neurogenesis, and may lessen stroke risk by impeding atherogenesis and hypertrophic remodeling in the cerebral vasculature. The neuroprotective potential of high-dose biotin likely could be boosted by concurrent administration of brain

  20. Immune reactivity after high-dose irradiation

    International Nuclear Information System (INIS)

    Gassmann, W.; Wottge, H.U.; von Kolzynski, M.; Mueller-Ruchholtz, W.

    1986-01-01

    Immune reactivity after total-body irradiation was investigated in rats using skin graft rejection as the indicator system. After sublethal irradiation with 10.5 Gy (approximately 50% lethality/6 weeks) the rejection of major histocompatibility complex allogeneic skin grafts was delayed significantly compared with nonirradiated control animals (28 versus 6.5 days). In contrast, skin grafts were rejected after 7.5 days in sublethally irradiated animals and 7 days in lethally irradiated animals if additional skin donor type alloantigens--namely, irradiated bone marrow cells--were given i.v. either simultaneously or with a delay of not more than 24 hr after the above conditioning regimen. These reactions were alloantigen-specific. They were observed in six different strain combinations with varying donors and recipients. Starting on day 2 after irradiation, i.v. injection of bone marrow gradually lost its effectivity and skin grafts were no longer rejected with uniform rapidity; skin donor marrow given on days 4 or 8 did not accelerate skin graft rejection at all. These data show that for approximately 1-2 days after high-dose total-body irradiation rats are still capable of starting a vigorous immune reaction against i.v.-injected alloantigens. The phenomenon of impaired rejection of skin grafted immediately after high-dose irradiation appears to result from the poor accessibility of skin graft alloantigens during the early postirradiation phase when vascularization of the grafted skin is insufficient

  1. High-dose vitamin C and cancer

    Directory of Open Access Journals (Sweden)

    Ahmet Unlu, M.D.

    2016-01-01

    Full Text Available Vitamin C (ascorbic acid, ascorbate is a basic compound that is of great importance with its role in various enzymatic reactions including the synthesis of collagen, as well as with its redox functions. Vitamin C has become the center of interest in cancer studies, in consequence of the facts that connective tissue changes and vitamin C deficiency were first alleged to be associated with cancer in the 1950s; and that high doses of vitamin C was asserted to be cytotoxic for cancer cells, later on. The results of the first study carried out in the 1970s were promising; but afterwards, the studies were ascertained to be faulty. Despite the positive results achieved from some laboratory and animal experiments, randomized clinical trials did not verify those findings, and no clear benefit of vitamin C for cancer treatment could be demonstrated. As for studies, where its use in combination with other cancer treatment regimens was assessed, conflicting results were obtained. Although intake of high doses of vitamin C is alleged to be harmless, based on that it is in the group of water soluble vitamins and is not stored in the body, there are many side effects and drug interactions reported in the literature. For now, it is better to abstain from this treatment, until the benefit of the treatment (if any is clearly demonstrated, considering the potential side effects and interactions.

  2. NIST high-dose calibration services

    International Nuclear Information System (INIS)

    Humphreys, J.C.

    1989-01-01

    There is a need for the standardization of high-dose measurements used in the radiation-processing industry in order to provide assured traceability to national standards. NIST provides dosimetry calibration services to this industry. One of these services involves administration of known absorbed doses of gamma rays to customer-supplied dosimeters. The dosimeters are packaged to provide electron equilibrium conditions and are irradiated in a standard 60 Co calibration facility; this provides a calibration of that batch of dosimeters. Another service consists of supplying to a customer calibrated transfer dosimeters for irradiation with the customer's radiation source. The irradiated transfer dosimeters are then returned to NIST for analysis; the results are reported to the customer, providing a calibration of the dose rate of the customer's source. (orig.)

  3. Onyx as radiation detector for high doses

    International Nuclear Information System (INIS)

    Teixeira, Maria Inês; Souza, Divanizia N.; Caldas, Linda V.E.

    2011-01-01

    A study of the thermoluminescent (TL) characteristics of white, black and stripped onyx samples is reported in this work. Onyx is a variety of chalcedony, a form of quartz. The onyx stone is considered nobler than marble. The irradiations were performed using a Gamma-Cell 220 system ( 60 Co). The TL emission curves presented two peaks around 150 °C and 210 °C for all samples. The dose–response curves showed a sublinear behavior between 0.5 Gy and 5 kGy, and the lower detection limit for the white onyx pellets was 1.5 mGy. The main dosimetric characteristics were studied, and the material showed good performance for high dose dosimetry.

  4. Nonlinear model of high-dose implantation

    International Nuclear Information System (INIS)

    Danilyuk, A.

    2001-01-01

    The models of high-dose implantation, using the distribution functions, are relatively simple. However, they must take into account the variation of the function of distribution of the implanted ions with increasing dose [1-4]. This variation takes place owing to the fact that the increase of the concentration of the implanted ions results in a change of the properties of the target. High-dose implantation is accompanied by sputtering, volume growth, diffusion, generation of defects, formation of new phases, etc. The variation of the distribution function is determined by many factors and is not known in advance. The variation within the framework of these models [1-4] is taken into account in advance by the introduction of intuitive assumptions on the basis of implicit considerations. Therefore, these attempts should be regarded as incorrect. The model prepared here makes it possible to take into account the sputtering of the target, volume growth and additional declaration on the implanted ions. Without any assumptions in relation to the variation of the distribution function with increasing dose. In our model it is assumed that the type of distribution function for small doses in a pure target substance is the same as in substances with implanted ions. A second assumption relates to the type of the distribution function valid for small doses in the given substances. These functions are determined as a result of a large number of theoretical and experimental investigations and are well-known at the present time. They include the symmetric and nonsymmetric Gauss distribution, the Pearson distribution, and others. We examine implantation with small doses of up to 10 14 - 10 15 cm -2 when the accurately known distribution is valid

  5. Ionization chamber for high dose measurements

    International Nuclear Information System (INIS)

    Rodrigues Junior, Ary de Araujo

    2005-01-01

    Industrial gamma irradiators facilities are designed for processing large amounts of products, which are exposed to large doses of gamma radiation. The irradiation, in industrial scale, is usually carried out in a dynamic form, where the products go through a 60 Co gamma source with activity of TBq to P Bq (k Ci to MCi). The dose is estimated as being directly proportional to the time that the products spend to go through the source. However, in some situations, mainly for research purposes or for validation of customer process following the ISO 11137 requirements, it is required to irradiate small samples in a static position with fractional deliver doses. The samples are put inside the irradiation room at a fixed distance from the source and the dose is usually determined using dosimeters. The dose is only known after the irradiation, by reading the dosimeter. Nevertheless, in the industrial irradiators, usually different kinds of products with different densities go through between the source and the static position samples. So, the dose rate varies in function of the product density. A suitable methodology would be to monitor the samples dose in real time, measuring the dose on line with a radiation detector, which would improve the dose accuracy and avoid the overdose. A cylindrical ionization chamber of 0.9 cm 3 has been developed for high-doses real-time monitoring, during the sample irradiation at a static position in a 60 Co gamma industrial plant. Nitrogen and argon gas at pressure of 10 exp 5 Pa (1 bar) was utilized to fill the ionization chamber, for which an appropriate configuration was determined to be used as a detector for high-dose measurements. To transmit the signal generated in the ionization chamber to the associated electronic and processing unit, a 20 m mineral insulated cable was welded to the ionization chamber. The signal to noise ratio produced by the detector was about 100. The dosimeter system was tested at a category I gamma

  6. Brachytherapy treatment with high dose rate

    International Nuclear Information System (INIS)

    Santana Rodriguez, Sergio Marcelino; Rodriguez Rodriguez, Lissi Lisbet; Ciscal Chiclana, Onelio Alberto

    2009-01-01

    Retrospectively analyze results and prognostic factors of cervical cancer patients treated with radio concomitant cisplatin-based chemotherapy, radiation therapy combined modality. Methods: From January 2003 to December 2007, 198 patients with invasive cervical cancer were treated at the Oncology Department of Hospital Robau Celestino Hernandez (brachytherapy performed at INOR). The most common age group was 31 to 40 years. The histology in squamous cell carcinoma accounted for 84.3% of cases. The treatment consisted of external pelvic irradiation and vaginal brachytherapy, high dose rate. Concomitant chemotherapy consisted of cisplatin 40 mg/m2 weekly with a maximum of 70 mg for 5 weeks. Results: 66.2% of patients completed 5 cycles of chemotherapy. The median overall survival was 39 months, overall survival, disease-free survival and survival free of locoregional recurrence at 5 years of 78%, 76% and 78.6% respectively .. We found that clinical stage, histological type (adenocarcinoma worst outcome) were statistically related to level of response. Conclusions: Treatment with external pelvic radiation, brachytherapy and concurrent weekly cisplatin in patients with stage IIIB cervical cancer is feasible in the Chilean public health system, well tolerated and results comparable to international literature. (Author)

  7. High dose rate brachytherapy for oral cancer

    International Nuclear Information System (INIS)

    Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Koizumi, Masahiko; Ogawa, Kazuhiko; Furukawa, Souhei

    2013-01-01

    Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer. (author)

  8. High dose rate brachytherapy for oral cancer.

    Science.gov (United States)

    Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Furukawa, Souhei; Koizumi, Masahiko; Ogawa, Kazuhiko

    2013-01-01

    Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.

  9. High dose gamma-ray standard

    International Nuclear Information System (INIS)

    Macrin, R.; Moraru, R.

    1999-01-01

    The high gamma-ray doses produced in a gamma irradiator are used, mainly, for radiation processing, i.e. sterilization of medical products, processing of food, modifications of polymers, irradiation of electronic devices, a.s.o. The used absorbed doses depend on the application and cover the range 10 Gy to 100 MGy. The regulations in our country require that the response of the dosimetry systems, used for the irradiation of food and medical products, be calibrated and traceable to the national standards. In order to be sure that the products receive the desired absorbed dose, appropriate dosimetric measurements must be performed, including the calibration of the dosemeters and their traceability to the national standards. The high dose gamma-ray measurements are predominantly based on the use of reference radiochemical dosemeters. Among them the ferrous sulfate can be used as reference dosemeter for low doses (up to 400 Gy) but due to its characteristics it deserves to be considered a standard dosemeter and to be used for transferring the conventional absorbed dose to other chemical dosemeters used for absorbed doses up to 100 MGy. The study of the ferrous sulfate dosemeter consisted in preparing many batches of solution by different operators in quality assurance conditions and in determining for all batches the linearity, the relative intrinsic error, the repeatability and the reproducibility. The principal results are the following: the linear regression coefficient: 0.999, the relative intrinsic error: max.6 %, the repeatability (for P* = 95 %): max.3 %, the reproducibility (P* = 95%): max.5 %. (authors)

  10. Performance of thermoluminescent materials for high dose dosimetry

    International Nuclear Information System (INIS)

    Texeira, Maria I.; Cecatti, Sonia G.P.; Caldas, Linda V.E.

    2008-01-01

    Cases involving high-doses of ionizing radiation are becoming increasingly common.The objective of this work was to characterize thermoluminescent materials for the dosimetry of workers exposed to high doses. Samples of TLD-200, TLD-400 and TLD-800 pellets from Thermo Electron Corporation were studied in gamma high-doses. Dose-response curves were obtained for doses between 100 mGy and 100 Gy. The reproducibility, the lower detection limits and dose-response curves were obtained for all three materials. The different kinds of detectors show usefulness for dosimetry of workers exposed accidentally to high doses. (author)

  11. Spatial analysis of feline immunodeficiency virus infection in cougars.

    Science.gov (United States)

    Wheeler, David C; Waller, Lance A; Biek, Roman

    2010-07-01

    The cougar (Puma concolor) is a large predatory feline found widely in the Americas that is susceptible to feline immunodeficiency virus (FIV), a fast-evolving lentivirus found in wild feline species that is analogous to simian immunodeficiency viruses in wild primates and belongs to the same family of viruses as human immunodeficiency virus. FIV infection in cougars can lead to a weakened immune system that creates opportunities for other infecting agents. FIV prevalence and lineages have been studied previously in several areas in the western United States, but typically without spatially explicit statistical techniques. To describe the distribution of FIV in a sample of cougars located in the northern Rocky Mountain region of North America, we first used kernel density ratio estimation to map the log relative risk of FIV. The risk surface showed a significant cluster of FIV in northwestern Montana. We also used Bayesian cluster models for genetic data to investigate the spatial structure of the feline immunodeficiency virus with virus genetic sequence data. A result of the models was two spatially distinct FIV lineages that aligned considerably with an interstate highway in Montana. Our results suggest that the use of spatial information and models adds novel insight when investigating an infectious animal disease. The results also suggest that the influence of landscape features likely plays an important role in the spatiotemporal spread of an infectious disease within wildlife populations.

  12. Molecular ecology and natural history of simian foamy virus infection in wild-living chimpanzees.

    Directory of Open Access Journals (Sweden)

    Weimin Liu

    2008-07-01

    Full Text Available Identifying microbial pathogens with zoonotic potential in wild-living primates can be important to human health, as evidenced by human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2 and Ebola virus. Simian foamy viruses (SFVs are ancient retroviruses that infect Old and New World monkeys and apes. Although not known to cause disease, these viruses are of public health interest because they have the potential to infect humans and thus provide a more general indication of zoonotic exposure risks. Surprisingly, no information exists concerning the prevalence, geographic distribution, and genetic diversity of SFVs in wild-living monkeys and apes. Here, we report the first comprehensive survey of SFVcpz infection in free-ranging chimpanzees (Pan troglodytes using newly developed, fecal-based assays. Chimpanzee fecal samples (n = 724 were collected at 25 field sites throughout equatorial Africa and tested for SFVcpz-specific antibodies (n = 706 or viral nucleic acids (n = 392. SFVcpz infection was documented at all field sites, with prevalence rates ranging from 44% to 100%. In two habituated communities, adult chimpanzees had significantly higher SFVcpz infection rates than infants and juveniles, indicating predominantly horizontal rather than vertical transmission routes. Some chimpanzees were co-infected with simian immunodeficiency virus (SIVcpz; however, there was no evidence that SFVcpz and SIVcpz were epidemiologically linked. SFVcpz nucleic acids were recovered from 177 fecal samples, all of which contained SFVcpz RNA and not DNA. Phylogenetic analysis of partial gag (616 bp, pol-RT (717 bp, and pol-IN (425 bp sequences identified a diverse group of viruses, which could be subdivided into four distinct SFVcpz lineages according to their chimpanzee subspecies of origin. Within these lineages, there was evidence of frequent superinfection and viral recombination. One chimpanzee was infected by a foamy virus from a Cercopithecus monkey

  13. Acute renal failure in high dose carboplatin chemotherapy

    NARCIS (Netherlands)

    Frenkel, J.; Kool, G.; de Kraker, J.

    1995-01-01

    Carboplatin has been reported to cause acute renal failure when administered in high doses to adult patients. We report a 4 1/2-year-old girl who was treated with high-dose carboplatin for metastatic parameningeal embryonal rhabdomyosarcoma. Acute renal failure developed followed by a slow partial

  14. Pharmacogenetics and Pharmacokinetics in high-dose alkylating chemotherapy

    NARCIS (Netherlands)

    Ekhart, G.C. (Corine)

    2008-01-01

    High-dose chemotherapy in combination with peripheral blood progenitor cell transplantation has been developed as a possible curative treatment modality in several solid tumours. A frequently used high-dose regimen in the Netherlands is the CTC regimen, which is a 4-day course of cyclophosphamide,

  15. Accelerated Irradiations for High Dose Microstructures in Fast Reactor Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Jiao, Zhijie [Univ. of Michigan, Ann Arbor, MI (United States)

    2017-03-31

    The objective of this project is to determine the extent to which high dose rate, self-ion irradiation can be used as an accelerated irradiation tool to understand microstructure evolution at high doses and temperatures relevant to advanced fast reactors. We will accomplish the goal by evaluating phase stability and swelling of F-M alloys relevant to SFR systems at very high dose by combining experiment and modeling in an effort to obtain a quantitative description of the processes at high and low damage rates.

  16. Immunogenicity of DNA vaccines encoding simian immunodeficiency virus antigen targeted to dendritic cells in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Matthias Tenbusch

    Full Text Available BACKGROUND: Targeting antigens encoded by DNA vaccines to dendritic cells (DCs in the presence of adjuvants enhances their immunogenicity and efficacy in mice. METHODOLOGY/PRINCIPAL FINDINGS: To explore the immunogenicity of this approach in non-human primates, we generated a single chain antibody to the antigen uptake receptor DEC-205 expressed on rhesus macaque DCs. DNA vaccines encoding this single chain antibody fused to the SIV capsid protein were delivered to six monkeys each by either intramuscular electroporation or conventional intramuscular injection co-injected or not with poly ICLC, a stabilized poly I: C analogue, as adjuvant. Antibodies to capsid were induced by the DC-targeting and non-targeting control DNA delivered by electroporation while conventional DNA immunization at a 10-fold higher dose of DNA failed to induce detectable humoral immune responses. Substantial cellular immune responses were also observed after DNA electroporation of both DNAs, but stronger responses were induced by the non-targeting vaccine. Conventional immunization with the DC-targeting DNA at a 10-fold higher dose did not give rise to substantial cellular immune responses, neither when co-injected with poly ICLC. CONCLUSIONS/SIGNIFICANCE: The study confirms the potent immunogenicity of DNA vaccines delivered by electroporation. Targeting the DNA via a single chain antibody to DEC-205 expressed by DCs, however, does not improve the immunogenicity of the antigens in non-human primates.

  17. Early depletion of proliferating B cells of germinal center in rapidly progressive simian immunodeficiency virus infection

    International Nuclear Information System (INIS)

    Zhang Zhiqiang; Casimiro, Danilo R.; Schleif, William A.; Chen, Minchun; Citron, Michael; Davies, Mary-Ellen; Burns, Janine; Liang, Xiaoping; Fu, Tong-Ming; Handt, Larry; Emini, Emilio A.; Shiver, John W.

    2007-01-01

    Lack of virus specific antibody response is commonly observed in both HIV-1-infected humans and SIV-infected monkeys with rapid disease progression. However, the mechanisms underlying this important observation still remain unclear. In a titration study of a SIVmac239 viral stock, three out of six animals with viral inoculation rapidly progressed to AIDS within 5 months. Unexpectedly, there was no obvious depletion of CD4 + T cells in both peripheral and lymph node (LN) compartments in these animals. Instead, progressive depletion of proliferating B cells and disruption of the follicular dendritic cell (FDC) network in germinal centers (GC) was evident in the samples collected at as early as 20 days after viral challenge. This coincided with undetectable, or weak and transient, virus-specific antibody responses over the course of infection. In situ hybridization of SIV RNA in the LN samples revealed a high frequency of SIV productively infected cells and large amounts of accumulated viral RNA in the GCs in these animals. Early severe depletion of GC proliferating B cells and disruption of the FDC network may thus result in an inability to mount a virus-specific antibody response in rapid progressors, which has been shown to contribute to accelerated disease progression of SIV infection

  18. Relative safety profiles of high dose statin regimens

    Directory of Open Access Journals (Sweden)

    Carlos Escobar

    2008-06-01

    Full Text Available Carlos Escobar, Rocio Echarri, Vivencio BarriosDepartment of Cardiology, Hospital Ramón y Cajal, Madrid, SpainAbstract: Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses.Keywords: statins, high doses, tolerability, liver, muscle

  19. Treatment of the prostate cancer with high dose rate brachytherapy

    International Nuclear Information System (INIS)

    Martinez, Alvaro; Torres Silva, Felipe

    2002-01-01

    The prostate cancer treatment in early stages is controversial. The high dose rate brachytherapy has been used like monotherapy or boost with external beam radiotherapy in advanced disease. This paper describes the technique and the advantages over other modalities

  20. High-dose dosimetry using natural silicate minerals

    International Nuclear Information System (INIS)

    Carmo, Lucas S. do; Mendes, Leticia; Watanabe, Shigueo; Rao, Gundu; Lucas, Natasha; Sato, Karina; Barbosa, Renata F.

    2015-01-01

    In the present study, certain natural silicate minerals such as aquamarine (AB), morganite (PB), goshenite (WB), white jadeite (JW), green jadeite (JG), pink tourmaline (PT) and two varieties of jadeite-like quartz, denoted here by JQ1 and JQ2, were investigated using the thermoluminescence technique to evaluate their potential for use as very-high- and high-dose dosimeters. These minerals respond to high doses of γ-rays of up to 1000 kGy and often to very high doses of up to 3000 kGy. The TL response of these minerals may be considered to be satisfactory for applications in high-dose dosimetry. Investigations of electron paramagnetic resonance and optically stimulated luminescence dosimetry are in progress. (author)

  1. High-dose dosimetry using natural silicate minerals

    Energy Technology Data Exchange (ETDEWEB)

    Carmo, Lucas S. do; Mendes, Leticia, E-mail: isatiro@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Watanabe, Shigueo; Rao, Gundu; Lucas, Natasha; Sato, Karina, E-mail: lacifid@if.usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Fisica. Departamento de Fisica Nuclear; Barbosa, Renata F., E-mail: profcelta@hotmail.com [Universidade Federal de Sao Paulo (UNIFESP), Santos, SP (Brazil). Departamento de Ciencias do Mar

    2015-07-01

    In the present study, certain natural silicate minerals such as aquamarine (AB), morganite (PB), goshenite (WB), white jadeite (JW), green jadeite (JG), pink tourmaline (PT) and two varieties of jadeite-like quartz, denoted here by JQ1 and JQ2, were investigated using the thermoluminescence technique to evaluate their potential for use as very-high- and high-dose dosimeters. These minerals respond to high doses of γ-rays of up to 1000 kGy and often to very high doses of up to 3000 kGy. The TL response of these minerals may be considered to be satisfactory for applications in high-dose dosimetry. Investigations of electron paramagnetic resonance and optically stimulated luminescence dosimetry are in progress. (author)

  2. Mechanism of feline immunodeficiency virus envelope glycoprotein-mediated fusion

    International Nuclear Information System (INIS)

    Garg, Himanshu; Fuller, Frederick J.; Tompkins, Wayne A.F.

    2004-01-01

    Feline immunodeficiency virus (FIV) shares remarkable homology to primate lentiviruses, human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). The process of lentiviral env glycoprotein-mediated fusion of membranes is essential for viral entry and syncytia formation. A detailed understanding of this phenomenon has helped identify new targets for antiviral drug development. Using a model based on syncytia formation between FIV env-expressing cells and a feline CD4+ T cell line we have studied the mechanism of FIV env-mediated fusion. Using this model we show that FIV env-mediated fusion mechanism and kinetics are similar to HIV env. Syncytia formation could be blocked by CXCR4 antagonist AMD3100, establishing the importance of this receptor in FIV gp120 binding. Interestingly, CXCR4 alone was not sufficient to allow fusion by a primary isolate of FIV, as env glycoprotein from FIV-NCSU 1 failed to induce syncytia in several feline cell lines expressing CXCR4. Syncytia formation could be inhibited at a post-CXCR4 binding step by synthetic peptide T1971, which inhibits interaction of heptad repeat regions of gp41 and formation of the hairpin structure. Finally, using site-directed mutagenesis, we also show that a conserved tryptophan-rich region in the membrane proximal ectodomain of gp41 is critical for fusion, possibly at steps post hairpin structure formation

  3. Implementation of high-dose chemical dosimetry for industrial facilities

    International Nuclear Information System (INIS)

    Conceicao, Cirilo Cezar Sant'Anna da

    2006-01-01

    The purpose of this work is the implementation of methodology for high dose measurements using chemical dosimeters in liquid phase, traceable to the international metrology system, and make available in the country, the standard of high-dose to industrial irradiation facilities and research irradiators, trough the quality program with comparative measurements and direct use of the standard dosimeters in routine. The use of these low cost dosimetry systems in industrial irradiation facilities, assists to the certification requirements and it can reduce the costs with dosimetry for approximately 20% of the total dosimetry costs, using these systems in routine measurements and validation process, largely substituting the imported PMMA dosimeters, among others. (author)

  4. Statistical behavior of high doses in medical radiodiagnosis

    International Nuclear Information System (INIS)

    Barboza, Adriana Elisa

    2014-01-01

    This work has as main purpose statistically estimating occupational exposure in medical diagnostic radiology in cases of high doses recorded in 2011 at national level. For statistical survey of this study, doses of 372 IOE's diagnostic radiology in different Brazilian states were evaluated. Data were extracted from the work of monograph (Research Methodology Of High Doses In Medical Radiodiagnostic) that contains the database's information Sector Management doses of IRD/CNEN-RJ, Brazil. The identification of these states allows the Sanitary Surveillance (VISA) responsible, becomes aware of events and work with programs to reduce these events. (author)

  5. Study of teflon pads as high doses dosemeters

    International Nuclear Information System (INIS)

    Teixeira, Maria Ines; Caldas, Linda V.E.

    2013-01-01

    The aim of this work is to study the Teflon, which is used as a binder in the manufacture of dosimetric tablets, for the feasibility of this material as high dose dosemeter. In this paper we used the technique of thermally stimulated luminescence (OSL) to characterize the dosimetric properties of Teflon. Teflon samples were exposed to different doses of radiation, using a source of gamma radiation ( 60 Co). It was obtained dose-response curve between 100 Gy to 50 kGy and reproducibility of OSL response. The preliminary results show that Teflon is a useful material to high dose dosimetry

  6. Use of glasses as radiation detectors for high doses

    International Nuclear Information System (INIS)

    Caldas, L.

    1989-08-01

    Glass samples were tested in relation to the possibility of use in high dose dosimetry in medical and industrial areas. The main characteristics were determined: detection threshold, reproducibility, response to gamma radiation of 137 Cs and 6 Co and thermal decay at ambient temperature, with the use of optical absorption and thermoluminesce techniques. (author) [pt

  7. Oval pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

    Hoogendijk, JE; Wokke, JHJ; de Visser, M

    To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Sis patients responded. Side effects

  8. Oral pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

    van der Meulen, M. F.; Hoogendijk, J. E.; Wokke, J. H.; de Visser, M.

    2000-01-01

    To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Six patients responded. Side effects

  9. Safety and tolerability of high doses of glucocorticoides

    Directory of Open Access Journals (Sweden)

    Rakić Branislava D.

    2016-01-01

    Full Text Available Introduction: Treatment of acute lymphoblastic leukemia includes the use of high doses of glucocorticoides (prednisone and dexamethasone, which significantly increase the success of therapy due to lymphocytolitic effect. The aim: The aim of the study was to determine tolerability of high doses of prednisone and dexamethasone in children with acute lymphoblastic leukemia and the structure and the intensity of adverse effects, occurred after application of these medicines. Subjects and methods: In a prospective study, we analyzed adverse effects of high doses of glucocorticoides in children suffering acute lymphoblastic leukemia treated in the Institute for Child and Youth Health Care of Vojvodina, since December 2010. until October 2014, were analyzed. This study included 18 patients, aged from 2 to 15 years. Results: Hyperglycemia appeared in 89% of patients treated with prednisone and in 61% of patients treated with dexamethasone. In order to control the high blood glucose level (above 10 mmol /L, in 11% of patients insulin was used. Hypertension appeared in 28% patients treated with prednisone and dexamethasone. Antihypertensives were needed for regulation in 17% patients. Hypopotassemia and hypocalcaemia were significantly more expressed after the use of prednisone in comparison to dexamethasone. In 11% of patients, the treatment with dexamethasone caused depressive behavior, followed by agitation. Conclusion: Adverse effects of dexamethasone and prednisone, administered in high doses in children with ALL were known, expected and reversible. Adverse reactions usually disappeared spontaneously or after short-term symptomatic therapy.

  10. Relevance of high-dose chemotherapy in solid tumours

    NARCIS (Netherlands)

    Nieboer, P; de Vries, EGE; Mulder, NH; van der Graaf, WTA

    Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with

  11. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  12. Unusual complication and successful high-dose chemotherapy ...

    African Journals Online (AJOL)

    ... treated with high-dose chemotherapy in our institution, complicated by unusual bilateral renal vein tumour thrombi and tumour lysis syndrome. We believe this unique case highlights the need for early recognition of current and potential complications on staging computed tomography imaging, as well as successful use of ...

  13. High-dose secondary calibration laboratory accreditation program

    Energy Technology Data Exchange (ETDEWEB)

    Humphreys, J.C. [National Institute of Standards and Technology, Gaithersburg, MD (United States)

    1993-12-31

    There is a need for high-dose secondary calibration laboratories to serve the multi-billion dollar radiation processing industry. This need is driven by the desires of industry for less costly calibrations and faster calibration-cycle response time. Services needed include calibration irradiations of routine processing dosimeters and the supply of reference standard transfer dosimeters for irradiation in the production processing facility. In order to provide measurement quality assurance and to demonstrate consistency with national standards, the high-dose secondary laboratories would be accredited by means of an expansion of an existing National Voluntary Laboratory Accreditation Program. A laboratory performance criteria document is under development to implement the new program.

  14. High-dose secondary calibration laboratory accreditation program

    International Nuclear Information System (INIS)

    Humphreys, J.C.

    1993-01-01

    There is a need for high-dose secondary calibration laboratories to serve the multi-billion dollar radiation processing industry. This need is driven by the desires of industry for less costly calibrations and faster calibration-cycle response time. Services needed include calibration irradiations of routine processing dosimeters and the supply of reference standard transfer dosimeters for irradiation in the production processing facility. In order to provide measurement quality assurance and to demonstrate consistency with national standards, the high-dose secondary laboratories would be accredited by means of an expansion of an existing National Voluntary Laboratory Accreditation Program. A laboratory performance criteria document is under development to implement the new program

  15. Anticoagulation and high dose liver radiation. A preliminary report

    International Nuclear Information System (INIS)

    Lightdale, C.J.; Wasser, J.; Coleman, M.; Brower, M.; Tefft, M.; Pasmantier, M.

    1979-01-01

    Two groups of patients were observed for evidence of acute radiation hepatitis during high dose radiation to the liver. The first group of 18 patients with metastatic liver disease received an average of 4,050 rad to the whole liver. Half received anticoagulation with warfarin. One patient on anticoagulation developed evidence of acute radiation hepatitis while 2 patients did so without anticoagulation. Eleven patients with Hodgkin's disease received 4,000 rad to the left lobe of the liver during extended field radiation. Four of these 11 patients were anticoagulated to therapeutic range. Only one of the fully anticoagulated patients showed changes on liver scan consistent with radiation hepatitis whereas three did so without anticoagulation. No serious sequelae from anticoagulation occurred in either group. These preliminary data suggest that anticoagulation may be safely administered with high dose hepatic radiation and that further trials with anticoagulation are warranted

  16. Radiotherapy and high-dose chemotherapy in advanced Ewing's tumors

    International Nuclear Information System (INIS)

    Pape, H.; Glag, M.; Gripp, S.; Wittkamp, M.; Schmitt, G.; Laws, H.J.; Kaik, B. van; Goebel, U.; Burdach, S.; Juergens, H.

    1999-01-01

    Background: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early ( [de

  17. Inactivation of human and simian rotaviruses by ozone

    Energy Technology Data Exchange (ETDEWEB)

    Vaughn, J.M.; Chen, Y.S.; Lindburg, K.; Morales, D.

    1987-09-01

    The inactivation of simian rotavirus Sa-11 and human rotavirus type 2 (Wa) by ozone was compared at 4/sup 0/C by using single-particle virus stocks. Although the human strain was clearly more sensitive, both virus types were rapidly inactivated by ozone concentrations of 0.25 mg/liter or greater at all pH levels tested. Comparison of the virucidal activity of ozone with that of chlorine in identical experiments indicated little significant difference in rotavirus-inactivating efficiencies when the disinfectants were used at concentrations of 0.25 mg/liter or greater.

  18. High-dose buprenorphine: perioperative precautions and management strategies.

    Science.gov (United States)

    Roberts, D M; Meyer-Witting, M

    2005-02-01

    Buprenorphine has been in clinical use in anaesthesia for several decades. Recently, the high-dose sublingual formulation (Subutex, Reckitt Benckiser, Slough, U.K.) has been increasingly used as maintenance therapy in opioid dependence, as an alternative to methadone and other pharmacological therapies. Buprenorphine has unique pharmacological properties making it well suited for use as a maintenance therapy in opioid dependence. However, these same properties may cause difficulty in the perioperative management of pain. Buprenorphine is a partial opioid agonist, attenuating the effects of supplemental illicit or therapeutic opioid agonists. As a result of its high receptor affinity, supplemental opioids do not readily displace buprenorphine from the opioid receptor in standard doses. High-dose buprenorphine has an extended duration of action that prolongs both of these effects. The perioperative management of patients stabilized on high-dose buprenorphine and undergoing surgery requires consideration of the likely analgesic requirements. Where possible the buprenorphine should be continued. Pain management should focus on maximizing non-opioid analgesia, local anaesthesia and non-pharmacological techniques. Where pain may not be adequately relieved by these methods, the addition of a full opioid agonist such as fentanyl or morphine at appropriate doses should be considered, accompanied by close monitoring in a high dependency unit. In situations where this regimen is unlikely to be effective, preoperative conversion to morphine or methadone may be an option. Where available, liaison with a hospital-based alcohol and drug service should always be considered.

  19. A novel theory of radiation damage at high doses

    International Nuclear Information System (INIS)

    Seeger, A.; Stuttgart Univ.

    1989-01-01

    Deviations of radiation damage (in the case of metals usually monitored by the residual electrical resistivity) from proportionality with the irradiation dose have so far been analysed almost exclusively in terms of extensions of models originally developed for small doses. The present theory considers the opposite limit i.e. the quasi-saturated state. It is argued that at high doses the Lueck-Sizmann effect may result in a self-organization of clusters of vacancies and self-interstitials, forming a heterogeneous froth. Possible structures of this froth and its effect on the electrical resistivity of metals are discussed. The model is shown to account for the dependence of the ''saturation resistivity'' on the nature of the irradiation as well as for several other hitherto poorly explained observations. Among them are the electrical-resistivity variation induced by high-dose irradiation with heavy ions, the amorphization of certain alloys by high-dose electron irradiation, and the occurrence of ordered arrays of stacking-fault tetrahedra after in-situ irradiations in high-voltage electron microscopes. (author)

  20. Radiophotoluminescence light scope for high-dose dosimetry

    International Nuclear Information System (INIS)

    Sato, Fuminobu; Zushi, Naoki; Sakiyama, Tomoki; Kato, Yushi; Murata, Isao; Shimizu, Kikuo; Yamamoto, Takayoshi; Iida, Toshiyuki

    2015-01-01

    A radiophotoluminescence (RPL) light scope is a remote-sensing technique for measuring in situ the radiation dose in an RPL detector placed at a distance. The RPL light scope is mainly composed of an ultraviolet (UV) pulse laser, telescopic lenses, a photomultiplier tube, and camera modules. In a performance test, some RPL detectors were placed at distances up to 30 m and were illuminated with a pulsed UV laser beam. The photoluminescence responses of the RPL detectors were analyzed using this scope. Their radiation doses were determined from the amplitude of the given component of the photoluminescence responses. The RPL readout could be repeated without fading, and its amplitude exhibited good linearity at a dose ranging from 0.1 to 60 Gy. Furthermore, a two-dimensional distribution of radiation dose was obtained by laser scanning on an RPL detector. It was confirmed that the RPL light scope was a useful remote-sensing tool for high-dose dosimetry. - Highlights: • A radiophotoluminescence (RPL) light scope was developed for high-dose dosimetry. • The RPL light scope has high sensitivity and accuracy in high-dose dosimetry. • Two-dimensional radiation dose distribution was obtained by the RPL light scope.

  1. Precision, high dose radiotherapy: helium ion treatment of uveal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Saunders, W.M.; Char, D.H.; Quivey, J.M.; Castro, J.R.; Chen, G.T.Y.; Collier, J.M.; Cartigny, A.; Blakely, E.A.; Lyman, J.T.; Zink, S.R.

    1985-02-01

    The authors report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) the authors have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons.

  2. Precision, high dose radiotherapy: helium ion treatment of uveal melanoma

    International Nuclear Information System (INIS)

    Saunders, W.M.; Char, D.H.; Quivey, J.M.

    1985-01-01

    The authors report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) the authors have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons

  3. Pyrimidine dimers block simian virus 40 replication forks

    International Nuclear Information System (INIS)

    Berger, C.A.; Edenberg, H.J.

    1986-01-01

    UV light produces lesions, predominantly pyrimidine dimers, which inhibit DNA replication in mammalian cells. The mechanism of inhibition is controversial: is synthesis of a daughter strand halted at a lesion while the replication fork moves on and reinitiates downstream, or is fork progression itself blocked for some time at the site of a lesion? We directly addressed this question by using electron microscopy to examine the distances of replication forks from the origin in unirradiated and UV-irradiated simian virus 40 chromosomes. If UV lesions block replication fork progression, the forks should be asymmetrically located in a large fraction of the irradiated molecules; if replication forks move rapidly past lesions, the forks should be symmetrically located. A large fraction of the simian virus 40 replication forks in irradiated molecules were asymmetrically located, demonstrating that UV lesions present at the frequency of pyrimidine dimers block replication forks. As a mechanism for this fork blockage, we propose that polymerization of the leading strand makes a significant contribution to the energetics of fork movement, so any lesion in the template for the leading strand which blocks polymerization should also block fork movement

  4. Intracistronic complementation in the simian virus 40 A gene.

    Science.gov (United States)

    Tornow, J; Cole, C N

    1983-01-01

    A set of eight simian virus 40 mutants was constructed with lesions in the A gene, which encodes the large tumor (T) antigen. These mutants have small deletions (3-20 base pairs) at either 0.497, 0.288, or 0.243 map units. Mutants having both in-phase and frameshift mutations at each site were isolated. Neither plaque formation nor replication of the mutant DNAs could be detected after transfection of monkey kidney cells. Another nonviable mutant, dlA2459, had a 14-base-pair deletion at 0.193 map unit and was positive for viral DNA replication. Each of the eight mutants were tested for ability to form plaques after cotransfection with dlA2459 DNA. The four mutants that had in-phase deletions were able to complement dlA2459. The other four, which had frameshift deletions, did not. No plaques were formed after cotransfection of cells with any other pair of group A mutants. This suggests that the defect in dlA2459 defines a distinct functional domain of simian virus 40 T antigen. Images PMID:6312452

  5. High dose vitamin K3 infusion in advanced hepatocellular carcinoma.

    Science.gov (United States)

    Sarin, Shiv K; Kumar, Manoj; Garg, Sanjay; Hissar, Syed; Pandey, Chandana; Sharma, Barjesh C

    2006-09-01

    The survival of patients with unresectable advanced hepatocellular carcinoma (HCC) with portal vein thrombosis is dismal. Current therapeutic options have limited efficacy. Vitamin K has been shown to have antitumor effect on HCC cells both in cell lines and patients with advanced HCC. The aim of this study was to assess the clinical efficacy of high dose vitamin K3 in the treatment of advanced HCC with portal vein thrombosis. Forty-two consecutive patients with advanced HCC (Stage C according to BCLC staging system) with portal vein thrombosis were randomized into two groups: (i) high dose vitamin K3 (n = 23); and (ii) placebo (n = 19). The vitamin K3 was administered by i.v. infusion of 50 mg/day with daily increase of dose by 50 mg for 6 days, followed by 20 mg i.m. twice daily for 2 weeks. Of the 23 patients treated with vitamin K, one (4.3%) achieved complete response and three (13%) partial response, for a total of four (17.4%) objective responders overall. The overall mean survival was 8.9 +/- 8.8 months (median: 6; range 1-37 months) in the vitamin K group and 6.8 +/- 5.3 months (median: 5; range 1.5-21 months) in the placebo group (P = 0.552). The mean duration of survival was longer in patients in the vitamin K group who achieved objective response (22.5 +/- 12.2; median: 21; range 11-37 months) as compared to patients not achieving objective response (6.1 +/- 4.6; median: 5; range 1-16 months) (P = 0.0.002). Portal vein thrombosis resolved with complete patency in one (4.35%) patient. Treatment with high dose vitamin K produces objective response in 17% patients with improved survival in patients achieving objective response; however, it does not affect the overall survival.

  6. Cooperative binding mitigates the high-dose hook effect.

    Science.gov (United States)

    Roy, Ranjita Dutta; Rosenmund, Christian; Stefan, Melanie I

    2017-08-14

    The high-dose hook effect (also called prozone effect) refers to the observation that if a multivalent protein acts as a linker between two parts of a protein complex, then increasing the amount of linker protein in the mixture does not always increase the amount of fully formed complex. On the contrary, at a high enough concentration range the amount of fully formed complex actually decreases. It has been observed that allosterically regulated proteins seem less susceptible to this effect. The aim of this study was two-fold: First, to investigate the mathematical basis of how allostery mitigates the prozone effect. And second, to explore the consequences of allostery and the high-dose hook effect using the example of calmodulin, a calcium-sensing protein that regulates the switch between long-term potentiation and long-term depression in neurons. We use a combinatorial model of a "perfect linker protein" (with infinite binding affinity) to mathematically describe the hook effect and its behaviour under allosteric conditions. We show that allosteric regulation does indeed mitigate the high-dose hook effect. We then turn to calmodulin as a real-life example of an allosteric protein. Using kinetic simulations, we show that calmodulin is indeed subject to a hook effect. We also show that this effect is stronger in the presence of the allosteric activator Ca 2+ /calmodulin-dependent kinase II (CaMKII), because it reduces the overall cooperativity of the calcium-calmodulin system. It follows that, surprisingly, there are conditions where increased amounts of allosteric activator actually decrease the activity of a protein. We show that cooperative binding can indeed act as a protective mechanism against the hook effect. This will have implications in vivo where the extent of cooperativity of a protein can be modulated, for instance, by allosteric activators or inhibitors. This can result in counterintuitive effects of decreased activity with increased concentrations of

  7. Radiation processing and high-dose dosimetry at ANSTO

    International Nuclear Information System (INIS)

    Gant, G.J.; Saunders, M.; Banos, C.; Mo, L.; Davies, J.; Evans, O.

    2001-01-01

    The Radiation Technology group at ANSTO is part of the Physics Division and provides services and advice in the areas of gamma irradiation and high-dose dosimetry. ANSTO's irradiation facilities are designed for maximum dose uniformity and provide a precision irradiation service unique in Australia. Radiation Technology makes and sells reference and transfer standard dosimeters which are purchased by users and suppliers of commercial irradiation services in Australia and the Asia-Pacific region. A calibration service is also provided for dosimeters purchased from other suppliers

  8. An evaluation of high-dose jobs for ALARA improvement

    International Nuclear Information System (INIS)

    Mun, J. H.; Kim, H. S.

    1997-01-01

    It is well known that about 70 percent of occupational dose have incurred from maintenance jobs at outage period. To reduce occupational dose, first, the high-dose jobs at the outage period should be identified and evaluated. For this, the database program is used, which contains the ORE data of reference plants, Kori Units 3 and 4. As a result, it is found that the jobs related to steam generator are the highest dose jobs in terms of collective ORE dose. From the analysis of the job procedures of those jobs, the ALARA improvements are also derived

  9. Australian high-dose-rate brachytherapy protocols for gynaecological malignancy

    International Nuclear Information System (INIS)

    MacLeod, C.; Dally, M.; Stevens, M.; Thornton, D.; Carruthers, S.; Jeal, P.

    2001-01-01

    There is no consensus over the optimal dose fractionation schedules for high-dose-rate (HDR) brachytherapy used for gynaecological malignancy. In Australian public hospital departments of radiation oncology, HDR brachytherapy for gynaecological cancer is being more commonly used. A survey of public departments that are using this technology, or that plan to introduce this technology, was performed. Their current protocols are presented. In general, protocols are similar biologically; however, the practical aspects such as the number of fractions given do vary and may reflect resource restrictions or, alternatively, differences in interpretations of the literature and of the best protocols by clinicians. Copyright (2001) Blackwell Science Pty Ltd

  10. Prehospital high-dose sublingual nitroglycerin rarely causes hypotension.

    Science.gov (United States)

    Clemency, Brian M; Thompson, Jeffrey J; Tundo, Gina N; Lindstrom, Heather A

    2013-10-01

    High-dose intravenous nitroglycerin is a common in-hospital treatment for respiratory distress due to congestive heart failure (CHF) with hypertension. Intravenous (IV) nitroglycerin administration is impractical in the prehospital setting. In 2011, a new regional Emergency Medical Services (EMS) protocol was introduced allowing advanced providers to treat CHF with high-dose oral nitroglycerin. The protocol calls for patients to be treated with two sublingual tabs (0.8 mg) when systolic blood pressure (SBP) was >160 mm Hg, or three sublingual tabs (1.2 mg) when SBP was >200 mm Hg, every five minutes as needed. Hypothesis/Problem To assess the protocol's safety, the incidence of hypotension following prehospital administration of multiple simultaneous nitroglycerin (MSN) tabs by EMS providers was studied. This study was a retrospective cohort study of patients from a single commercial EMS agency over a 6-month period. Records from patients with at least one administration of MSN were reviewed. For each administration, the first documented vital signs pre- and post-administration were compared. Administrations were excluded if pre- or post-administration vital signs were missing. One hundred case-patients had at least one MSN administration by an advanced provider during the study period. Twenty-five case-patients were excluded due to incomplete vital signs. Seventy-five case-patients with 95 individual MSN administrations were included for analysis. There were 65 administrations of two tabs, 29 administrations of three tabs, and one administration of four tabs. The mean change in SBP following MSN was -14.7 mm Hg (SD = 30.7; range, +59 to -132). Three administrations had documented systolic hypotension in the post-administration vital signs (97/71, 78/50 and 66/47). All three patients were over 65 years old, were administered two tabs, had documented improved respiratory status, and had repeat SBP of at least 100. The incidence of hypotension following MSN

  11. High-dose irradiated food: Current progress, applications, and prospects

    Science.gov (United States)

    Feliciano, Chitho P.

    2018-03-01

    Food irradiation as an established and mature technology has gained more attention in the food industry for ensuring food safety and quality. Primarily used for phytosanitary applications, its use has been expanded for developing various food products for varied purposes (e.g. ready-to-eat & ready-to-cook foods, hospital diets, etc.). This paper summarized and analyzed the recent progress and application of high-dose irradiation and discussed its prospects in the field of food product development, its safety and quality.

  12. Establishment of a dosimetric system for high doses using glasses

    International Nuclear Information System (INIS)

    Correa Quezada, Valeria de la Asuncion

    1997-01-01

    A routine dosimetric system was developed using commercial glass samples. The dosimetric characteristics of national and imported samples were studied: batch uniformity, response repeatability, reutilization, absorbed dose response, detection range, response stability as a function of absorbed dose, storage temperature and thermal treatments pre- and post-irradiation, using the optical absorption technique. As an application, the dosimetric system was tested in a flower irradiation process at IPEN. All the obtained results show the usefulness of the proposed system for high dose dosimetry. (author)

  13. The influence of high doses of radiation in citrine stones

    International Nuclear Information System (INIS)

    Teixeira, M. I.; Caldas, L. V. E.

    2014-08-01

    The possibility of using samples of Brazilian stones as quartz, amethyst, topaz, jasper, etc. for high-dose dosimetry has been studied in recent years at IPEN, using the techniques of optical absorption (Oa), thermoluminescent (Tl), optically stimulated luminescence (OSL) and resonance paramagnetic electron (EPR). In this work, the Tl properties of citrine samples were studied. They were exposed to different doses of gamma radiation ( 60 Co). The natural citrine stone was extracted from a mine in Minas Gerais state, Brazil; it is a tecto silicate ranked as one of three-dimensional structure, showing clear yellow to golden brown color. The natural citrine stone is classified as quartz (SiO 2 ), and it has a lower symmetry and more compact reticulum. The Tl emission curve showed two peaks at 160 grades C and 220 grades C. To remove the Tl peak (160 grades C) of the sintered citrine pellet glow curves, different thermal treatments were tested during several time intervals. The Tl dose-response curve between 50 Gy and 100 kGy, the reproducibility of Tl response and the lower detection dose were obtained. The results show that citrine may be useful as high-dose detectors. (Author)

  14. High-dose contrast-enhanced MRI in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Koudriavtseva, T. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Pozzilli, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Di Biasi, C. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Iannilli, M. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Trasimeni, G. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Gasperini, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Argentino, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Gualdi, G.F. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy)

    1996-05-01

    Contrast-enhanced MRI is effective for assessing disease activity in multiple sclerosis (MS) and may provide an outcome measure for testing the efficacy of treatment in clinical trials. To compare the sensitivity of high-dose gadolinium-HP-DO3A with that of a standard dose of gadolinium-DTPA, we studied 16 patients with relapsing-remitting MS in the acute phase of the disease. Each underwent two MRI examinations within at most 48 h. The initial MRI study was with a standard dose of gadolinium-DTPA (0.1 mmol/kg), and the second one an experimental dose of gadolinium-HP-DO3A (0.3 mmol/kg). No adverse effects were attributed to the contrast media. The high-dose study revealed more enhancing lesions than the standard-dose study (56 vs 38). This difference was found to be more relevant for infratentorial and small lesions. Furthermore, with the higher dose, there was a marked qualitative improvement in the visibility and delineation of the lesions. (orig.). With 4 figs., 2 tabs.

  15. TL response of citrine samples for high-dose dosimetry

    International Nuclear Information System (INIS)

    Teixeira, Maria Ines; Caldas, Linda V.E.

    2011-01-01

    The possibility of using samples of Brazilian stones as quartz, amethyst, topaz, etc. for high-dose dosimetry has been studied in recent years at IPEN, using the thermoluminescence technique (TL). In this work, the TL properties of citrine samples were studied. They were exposed to different doses of gamma radiation ( 60 Co). The natural citrine stone was extracted from a mine in Minas Gerais state, Brazil; it is a tectosilicate ranked as one of three-dimensional structure, showing clear yellow to golden brown color. The natural citrine stone is classified as quartz (SiO 2 ), and it has a lower symmetry and more compact reticulum. The citrine stone samples were powdered, and the selected grains were mixed with Teflon in the proportion 2 (Teflon):1 (Citrine). The mixture was pressed and sintered for production of Citrine -Teflon pellets of 50 mg. The TL emission curve showed two peaks at 160 deg C and 220 deg C. To remove the TL peak (160 deg C) of the sintered citrine pellet glow curves, different thermal treatments were tested during several time intervals. The TL dose-response curve between 50 Gy and 100 kGy, the reproducibility of TL response and the lower detection dose were obtained. The preliminary results show that citrine may be useful for high-dose dosimetry. (author)

  16. Spectroscopic gamma camera for use in high dose environments

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, Yuichiro, E-mail: yuichiro.ueno.bv@hitachi.com [Research and Development Group, Hitachi, Ltd., Hitachi-shi, Ibaraki-ken 319-1221 (Japan); Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi [Research and Development Group, Hitachi, Ltd., Hitachi-shi, Ibaraki-ken 319-1221 (Japan); Fujishima, Yasutake; Kometani, Yutaka [Hitachi Works, Hitachi-GE Nuclear Energy, Ltd., Hitachi-shi, Ibaraki-ken (Japan); Suzuki, Yasuhiko [Measuring Systems Engineering Dept., Hitachi Aloka Medical, Ltd., Ome-shi, Tokyo (Japan); Umegaki, Kikuo [Faculty of Engineering, Hokkaido University, Sapporo-shi, Hokkaido (Japan)

    2016-06-21

    We developed a pinhole gamma camera to measure distributions of radioactive material contaminants and to identify radionuclides in extraordinarily high dose regions (1000 mSv/h). The developed gamma camera is characterized by: (1) tolerance for high dose rate environments; (2) high spatial and spectral resolution for identifying unknown contaminating sources; and (3) good usability for being carried on a robot and remotely controlled. These are achieved by using a compact pixelated detector module with CdTe semiconductors, efficient shielding, and a fine resolution pinhole collimator. The gamma camera weighs less than 100 kg, and its field of view is an 8 m square in the case of a distance of 10 m and its image is divided into 256 (16×16) pixels. From the laboratory test, we found the energy resolution at the 662 keV photopeak was 2.3% FWHM, which is enough to identify the radionuclides. We found that the count rate per background dose rate was 220 cps h/mSv and the maximum count rate was 300 kcps, so the maximum dose rate of the environment where the gamma camera can be operated was calculated as 1400 mSv/h. We investigated the reactor building of Unit 1 at the Fukushima Dai-ichi Nuclear Power Plant using the gamma camera and could identify the unknown contaminating source in the dose rate environment that was as high as 659 mSv/h.

  17. High-dose contrast-enhanced MRI in multiple sclerosis

    International Nuclear Information System (INIS)

    Koudriavtseva, T.; Pozzilli, C.; Di Biasi, C.; Iannilli, M.; Trasimeni, G.; Gasperini, C.; Argentino, C.; Gualdi, G.F.

    1996-01-01

    Contrast-enhanced MRI is effective for assessing disease activity in multiple sclerosis (MS) and may provide an outcome measure for testing the efficacy of treatment in clinical trials. To compare the sensitivity of high-dose gadolinium-HP-DO3A with that of a standard dose of gadolinium-DTPA, we studied 16 patients with relapsing-remitting MS in the acute phase of the disease. Each underwent two MRI examinations within at most 48 h. The initial MRI study was with a standard dose of gadolinium-DTPA (0.1 mmol/kg), and the second one an experimental dose of gadolinium-HP-DO3A (0.3 mmol/kg). No adverse effects were attributed to the contrast media. The high-dose study revealed more enhancing lesions than the standard-dose study (56 vs 38). This difference was found to be more relevant for infratentorial and small lesions. Furthermore, with the higher dose, there was a marked qualitative improvement in the visibility and delineation of the lesions. (orig.). With 4 figs., 2 tabs

  18. Radiation safety program in a high dose rate brachytherapy facility

    International Nuclear Information System (INIS)

    Rodriguez, L.V.; Hermoso, T.M.; Solis, R.C.

    2001-01-01

    The use of remote afterloading equipment has been developed to improve radiation safety in the delivery of treatment in brachytherapy. Several accidents, however, have been reported involving high dose-rate brachytherapy system. These events, together with the desire to address the concerns of radiation workers, and the anticipated adoption of the International Basic Safety Standards for Protection Against Ionizing Radiation (IAEA, 1996), led to the development of the radiation safety program at the Department of Radiotherapy, Jose R. Reyes Memorial Medical Center and at the Division of Radiation Oncology, St. Luke's Medical Center. The radiation safety program covers five major aspects: quality control/quality assurance, radiation monitoring, preventive maintenance, administrative measures and quality audit. Measures for evaluation of effectiveness of the program include decreased unnecessary exposures of patients and staff, improved accuracy in treatment delivery and increased department efficiency due to the development of staff vigilance and decreased anxiety. The success in the implementation required the participation and cooperation of all the personnel involved in the procedures and strong management support. This paper will discuss the radiation safety program for a high dose rate brachytherapy facility developed at these two institutes which may serve as a guideline for other hospitals intending to install a similar facility. (author)

  19. ELDRS Characterization for a Very High Dose Mission

    Science.gov (United States)

    Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

    2010-01-01

    Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

  20. Methodology of high dose research in medical radiodiagnostic

    International Nuclear Information System (INIS)

    Barboza, Adriana E.; Martins, Cintia P. de S.

    2013-01-01

    This work has as main purpose to study occupational exposure in diagnostic radiology in medical cases of high doses recorded in 2011 at the national level . These doses were recorded by monitoring individual of the occupationally exposed individuals (OEI's). This monitoring of the doses received by ionizing radiation has as main objective to ensure that the principle of dose limitation is respected. In this study it were evaluated doses of 372 OEI's radiology in different Brazilian states. Doses were extracted from the database of Sector Management Doses of the Institute for Radioprotection and Dosimetry - IRD/CNEN-RJ, Brazil. The information from the database provide reports of doses from several states, which allows to quantify statistically, showing those with the highest doses in four areas: dose greater than or equal to 20 mSv apron and chest and dose greater than or equal to 100 mSv apron and chest. The identification of these states allows the respective Sanitary Surveillance (VISA), be aware of the events and make plans to reduce them. This study clarified the required procedures when there is a record of high dose emphasizing the importance of using protective radiological equipment, dosimeter and provide a safety environment work by maintaining work equipment. Proposes the ongoing training of professionals, emphasizing the relevance of the concepts of radiation protection and the use of the questionnaire with their investigative systematic sequence, which will allow quickly and efficiently the success the investigations

  1. Dosimetric properties of commercial glasses and sand for high doses

    International Nuclear Information System (INIS)

    Teixeira, Maria Ines

    2004-01-01

    Commercial glasses (transparent and colored) produced by Cebrace, Brazil, Sao Paulo, and sand samples of different Brazilian beaches were studied, due to their low cost and easy handling, to verify the possibility of their use in high dose dosimetry. The main dosimetric characteristics were determined using a densitometer, a spectrophotometer, a thermoluminescent (TL) reader and an electronic paramagnetic resonance system. The gamma irradiations were carried out using a Gamma-Cell 220 and a panoramic source ( 60 Co) of IPEN. An optical absorption band was observed at 420 nm in the glass samples. The TL glow curves presented peaks at 205 deg C, 135 deg C, 150 deg C and 145 deg C for the transparent, bronze, brown and green glass samples, respectively. All EPR spectra of the glasses showed Fe 3+ characteristic signals at g = 4.27 and 2.01. The gamma irradiated sand samples presented two peaks at 110 deg C and 170 deg C and an EPR signal at g= 1.999. However, these materials present a pronounced thermal fading at room temperature after irradiation. With the objective to minimize this thermal fading, both glass and sand samples were submitted to different pre- and post-irradiation thermal treatments. The glass and sand samples showed the possibility of utilization for high dose dosimetry and as Yes/No irradiation detectors. (author)

  2. Multifocal Electroretinography after High Dose Chloroquine Therapy for Malaria

    Directory of Open Access Journals (Sweden)

    Aline Correa de Carvalho

    2013-01-01

    Full Text Available Purpose: To investigate changes in multifocal electroretinography (mfERG parameters associated with high dose chloroquine therapy for treatment of malaria in the Amazonia region of Brazil. Methods: Forty-eight subjects who had received chloroquine treatment for single or multiple malaria infections with a cumulative dose ranging from 1,050 to 27,000mg were included. The control group consisted of 37 healthy aged-matched subjects. Data was collected on amplitude and implicit time of the N1, P1 and N2 waves in the central macular hexagon (R1 and in five concentric rings at different retinal eccentricities (R2-R6. Results: No significant difference was observed in any mfERG parameter between chloroquine treated patients and control subjects. A comparison with previous data obtained from patients with rheumatologic disorders in the same region of Brazil who had received larger cumulative doses of chloroquine and had displayed mfERG changes, indicated that retinal toxicity seems to be dependent on cumulative dose. Conclusion: Lack of mfERG changes in the current study suggests that intensive high dose chloroquine therapy for treatment of malaria is not associated with retinal toxicity.

  3. The influence of high doses of radiation in citrine stones

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, M. I. [Universidade Nove de Julho - UNINOVE, Rua Vergueiro 235/249, 01504-001 Sao Paulo (Brazil); Caldas, L. V. E., E-mail: miteixeira@ipen.br [Instituto de Pesquisas Energeticas e Nucleares / CNEN, Av. Lineu Prestes 2242, Cidade Universitaria, 05508-000 Sao Paulo (Brazil)

    2014-08-15

    The possibility of using samples of Brazilian stones as quartz, amethyst, topaz, jasper, etc. for high-dose dosimetry has been studied in recent years at IPEN, using the techniques of optical absorption (Oa), thermoluminescent (Tl), optically stimulated luminescence (OSL) and resonance paramagnetic electron (EPR). In this work, the Tl properties of citrine samples were studied. They were exposed to different doses of gamma radiation ({sup 60}Co). The natural citrine stone was extracted from a mine in Minas Gerais state, Brazil; it is a tecto silicate ranked as one of three-dimensional structure, showing clear yellow to golden brown color. The natural citrine stone is classified as quartz (SiO{sub 2}), and it has a lower symmetry and more compact reticulum. The Tl emission curve showed two peaks at 160 grades C and 220 grades C. To remove the Tl peak (160 grades C) of the sintered citrine pellet glow curves, different thermal treatments were tested during several time intervals. The Tl dose-response curve between 50 Gy and 100 kGy, the reproducibility of Tl response and the lower detection dose were obtained. The results show that citrine may be useful as high-dose detectors. (Author)

  4. Audits in high dose rate brachytherapy in Brazil

    International Nuclear Information System (INIS)

    Marechal, M.H.; Rosa, L.A.; Velasco, A.; Paiva, E. de; Goncalves, M.; Castelo, L.C.

    2002-01-01

    The lack of well established dosimetry protocols for HDR sources is a point of great concern regarding the uniformity of procedures within a particular country. The main objective of this paper is to report the results of an implementation of the audit program in dosimetry of high dose rate brachytherapy sources used by the radiation therapy centers in Brazil. In Brazil, among 169 radiotherapy centers, 35 have HDR brachytherapy systems. This program started in August 2001 and until now eight radiotherapy services were audited. The audit program consists of the visit in loco to each center and the evaluation of the intensity of the source with a well type chamber specially design for HDR 192 Ir sources. The measurements was carried out with a HDR1000PLUS Brachytherapy Well Type Chamber and a MAX 4000 Electrometer, both manufactured by Standard Imaging Inc. The chamber was calibrated in air kerma strength by the Accredited Dosimetry Calibration Laboratory, Department of Medical Physics, University of Wisconsin in the USA. The same chamber was calibrated in Brazil using a 192 lr high dose rate source whose intensity was determined by 60 Co gamma rays and 250 kV x rays interpolation methodology. The Nk of 60 Co and 250 kV x rays were provided by the Brazilian National Standard Laboratory for Ionizing Radiation (LMNRI)

  5. Stock selection of high-dose-irradiation-resistant materials for filter press under high-dose irradiation operation

    International Nuclear Information System (INIS)

    Ishiyama, Shintaro; Minami, Mamoru; Hara, Kouji; Yamashita, Manabu

    2015-01-01

    In a volume reduction process for the decontamination of contained soil, the performance degradation of a filter press is expected owing to material deterioration under high-dose irradiation. Eleven-stock selection of candidate materials including polymers, fibers and rubbers for the filter press was conducted to achieve a high performance of volume reduction of contaminated soil and the following results were derived. Crude rubber and nylon were selected as prime candidates for packing, diaphragm and filter plate materials. Polyethylene was also selected as a prime candidate for the filter cloth material. (author)

  6. High Doses Gamma Radiolysis of PVC: Mechanisms of Degradation

    International Nuclear Information System (INIS)

    Colombani, J.

    2006-01-01

    PVC radiolysis leads to the formation of various degradation products: radicals, gas, oxidized products or polyenes. In order to predict the formation of the degradation products with regard to irradiation and ageing parameters, it is important to improve the understanding of the radiolysis mechanisms of PVC. Thus, we used several analytical techniques (Electron Spin Resonance, Fourier Transform Infrared spectroscopy, Nuclear Magnetic Resonance, Size Exclusion Chromatography) to get information on PVC samples irradiated at high doses (up to 4MGy) under different conditions. Gamma irradiation induces the formation of various radicals into PVC. Older studies were generally focused on the effect of low dose and/or low temperature irradiations on PVC. We present here ESR signals of PVC irradiated at high doses and at room temperature. We show that peroxyl radicals are producted by radiolysis under aerobe conditions and that polyenyl radicals are formed under anaerobe conditions. PVC radiolysis induces gas production and especially hydrogen chloride. Production of hydrogen chloride is well known until 1 MGy. We have studied by FTIR, the evolution of the quantity of HCl produced until 4 MGy. We show that higher irradiation dose leads to the lower radiolytic yield of HCl (G(HCl)). Moreover, G(HCl) obtained in aerobe conditions is about fourfold as great as G(HCl) observed in anaerobe radiolysis. Propagation and termination reactions induce degradation products: polyene sequences and crosslinking reactions are observed under anaerobe conditions; oxidized products with addition of chain scissions are formed under aerobe conditions. Although the literature about PVC radiolysis is rich, the main reacting pathways are not well established. Moreover the high doses studies are almost non-existent. We show by FTIR that aerobe radiolysis induces formation of ketons and acids. NMR experiments confirme these results but also focuse on small acids formed (with 2, 3 or 4 carbons). The

  7. High-dose radioiodine therapy of Graves disease

    International Nuclear Information System (INIS)

    Solodky, V.; Fomin, D.; Pestritskaya, E.

    2015-01-01

    Full text of publication follows. Objectives: to estimate the effectiveness and safety of the disease treatment under different modes of applying RIT. Materials and methods: 67 patients with the thyrotoxicosis condition associated with Graves disease were researched. The patients were divided into 2 groups: a control group with 25 people (18 women and 7 men), who underwent a low-dose therapy of 150-500 MBq; and a main group of 42 people (32 women and 10 men), who underwent a high-dose therapy of 550 and 800 MBq. The volume of thyroid prior to the treatment made up 23.8 ± 20 ml in the main group and 30.2 ± 23 ml in the control one. The average age in the high-dose group was 44.6 ±23 years old and in the low-dose -47.2 ± 24 years old. In terms of the hormone level before the RIT, 52% of the main group patients experienced euthyroidism, while 48% - thyrotoxicosis. The corresponding indices in the control group were 42% and 58% respectively. The cessation of the thyreostatic therapy came on 5. to 21. day prior to the treatment, with the average of 14 ±7 days in both groups. The diagnosis of the disease was based on ultrasonography, planar scintigraphy, the hormone level and antibody titer. The performance was assessed through the attainment of hypo-thyrosis and the transition to a substitutive hormonal therapy with L-thyroxine in 6 months or more. The attainment of euthyroidism was seen as a partial effect due to a possibility of relapse. Results: in 6 months a positive result in the form of hypo-thyrosis was achieved for 39 patients in the main group, which accounted for 93%, and 3 patients (7%) experienced euthyroidism. No symptomatic thyrotoxicosis relapses were revealed. In the control group, hypo-thyrosis was achieved by 18 patients, which accounted for 72%; euthyroidism came up to 12%; 4 patients needed a refresher course of RIT, which made up 16% of the group. 93% of the main group patients tolerated the treatment favourably. 3 patients complained of the

  8. Routine quality control of high dose rate brachytherapy equipment

    International Nuclear Information System (INIS)

    Guzman Calcina, Carmen S.; Almeida, Adelaide de; Rocha, Jose R. Oliveira

    2001-01-01

    A Quality Assurance program should be installed also for High Dose Rate brachytherapy, in the order to achieve a correct dose administration to the patient and for the safety to those involved directly with the treatment. The work presented here has the following purposes: Analyze the types of equipment tests presented by the official protocols (TG40, TG56 e ARCAL XXX), evaluate the brachytherapy routine tests of protocols from various national and international radiotherapy services and compare the latter with those presented in the official protocols. As a result, we conclude the following: TG56 presents a higher number of tests when compared to the other official protocols and most of the tests presented by the analyzed services are present in TG56. A suggestion for a basic protocol is presented, emphasizing the periodicity and tolerance level of each of the tests. (author)

  9. Surface sputtering in high-dose Fe ion implanted Si

    International Nuclear Information System (INIS)

    Ishimaru, Manabu

    2007-01-01

    Microstructures and elemental distributions in high-dose Fe ion implanted Si were characterized by means of transmission electron microscopy and Rutherford backscattering spectroscopy. Single crystalline Si(0 0 1) substrates were implanted at 350 deg. C with 120 keV Fe ions to fluences ranging from 0.1 x 10 17 to 4.0 x 10 17 /cm 2 . Extensive damage induced by ion implantation was observed inside the substrate below 1.0 x 10 17 /cm 2 , while a continuous iron silicide layer was formed at 4.0 x 10 17 /cm 2 . It was found that the spatial distribution of Fe projectiles drastically changes at the fluence between 1.0 x 10 17 and 4.0 x 10 17 /cm 2 due to surface sputtering during implantation

  10. measurement of high dose radiation using yellow perspex dosimeter

    International Nuclear Information System (INIS)

    Thamrin, M Thoyib; Sofyan, Hasnel

    1996-01-01

    Measurement of high dose radiation using yellow perspex dosemeter has been carried out. Dose range used was between 0.1 to 3.0 kGy. Measurement of dose rate against Fricke dosemeter as a standard dose meter From the irradiation of Fricke dosemeter with time variation of 3,6,9,12,15 and 18 minute, it was obtained average dose rate of 955.57 Gy/hour, linear equation of dose was Y= 2.333+15.776 X with its correlation factor r = 0.9999. Measurement result using yellow perspex show that correlation between net optical density and radiation dose was not linear with its equation was ODc exp. [Bo + In(dose).Bi] Value of Bo = -0.215 and Bi=0.5020. From the experiment it was suggested that routine dosimeter (yellow perspex) should be calibrated formerly against standard dosemeters

  11. High Fidelity Ion Beam Simulation of High Dose Neutron Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Was, Gary; Wirth, Brian; Motta, Athur; Morgan, Dane; Kaoumi, Djamel; Hosemann, Peter; Odette, Robert

    2018-04-30

    Project Objective: The objective of this proposal is to demonstrate the capability to predict the evolution of microstructure and properties of structural materials in-reactor and at high doses, using ion irradiation as a surrogate for reactor irradiations. “Properties” includes both physical properties (irradiated microstructure) and the mechanical properties of the material. Demonstration of the capability to predict properties has two components. One is ion irradiation of a set of alloys to yield an irradiated microstructure and corresponding mechanical behavior that are substantially the same as results from neutron exposure in the appropriate reactor environment. Second is the capability to predict the irradiated microstructure and corresponding mechanical behavior on the basis of improved models, validated against both ion and reactor irradiations and verified against ion irradiations. Taken together, achievement of these objectives will yield an enhanced capability for simulating the behavior of materials in reactor irradiations

  12. High-dose erythropoietin in patients with progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Schreiber, Karen; Magyari, Melinda; Sellebjerg, Finn

    2017-01-01

    BACKGROUND: Erythropoietin (EPO) is a part of an endogenous neuroprotective system in the brain and may address pathophysiological mechanisms in progressive multiple sclerosis (MS). OBJECTIVE: To evaluate a treatment effect of EPO on progressive MS. METHODS: This was a single-center, randomized......, double-blind, placebo-controlled phase 2 trial, in which 52 patients with secondary or primary progressive MS were allocated to treatment with recombinant EPO (48,000 IU) or placebo, administered intravenously 17 times during 24 weeks. Patients had an Expanded Disability Status Score (EDSS) from 4 to 6......: This study provides class II evidence that treatment with high-dose EPO is not an effective treatment in patients with moderately advanced progressive MS....

  13. Safety handling manual for high dose rate remote afterloading system

    International Nuclear Information System (INIS)

    1999-01-01

    This manual is mainly for safety handling of 192 Ir-RALS (remote afterloading system) of high dose rate and followings were presented: Procedure and document format for the RALS therapy and for handling of its radiation source with the purpose of prevention of human errors and unexpected accidents, Procedure for preventing errors occurring in the treatment schedule and operation, and Procedure and format necessary for newly introducing the system into a facility. Consistency was intended in the description with the quality assurance guideline for therapy with small sealed radiation sources made by JASTRO (Japan Society for Therapeutic Radiology and Oncology). Use of the old type 60 Co-RALS was pointed out to be a serious problem remained and its safety handling procedure was also presented. (K.H.)

  14. Pharmacokinetics of high-dose intravenous melatonin in humans

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette Marie

    2016-01-01

    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60......, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments...... of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221...

  15. Calibration of {sup 192}Ir high dose rate brachytherapy sources

    Energy Technology Data Exchange (ETDEWEB)

    Marechal, M H [Instituto de Radioprotecao e Dozimetria, Rio de Jainero (Brazil); Almeida, C.E. de [Laboratorio de Ciencias Radiologicas, UERL, Rio de Janeiro (Brazil); Sibata, C H [Roswell Park Cancer Inst., Buffalo, NY (United States)

    1996-08-01

    A method for calibration of high dose rate sources used in afterloading brachytherapy systems is described. The calibration for {sup 192}Ir is determined by interpolating {sup 60}Co gamma-rays and 250 kV x-rays calibration factors. All measurements were done using the same build up caps as described by Goetsch et al and recommended by AAPM. The attenuation correction factors were determined to be 0.9903, 0.9928 and 0.9993 for {sup 192}Ir, {sup 60}Co and 250 kV x-ray, respectively. A wall + cap thickness of 0.421 g.cm{sup -2} is recommended for all measurements to ensure electronic equilibrium for {sup 60}Co and {sup 192}Ir gamma-ray beams. A mathematical formalism is described for determination of (N{sub x}){sub Ir}. (author). 5 refs, 1 fig.

  16. Assessments for high dose radionuclide therapy treatment planning

    International Nuclear Information System (INIS)

    Fisher, D.R.

    2003-01-01

    Advances in the biotechnology of cell specific targeting of cancer and the increased number of clinical trials involving treatment of cancer patients with radiolabelled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high dose radionuclide therapy procedures. Optimised radionuclide therapy for cancer treatment is based on the concept of absorbed dose to the dose limiting normal organ or tissue. The limiting normal tissue is often the red marrow, but it may sometimes be the lungs, liver, intestinal tract, or kidneys. Appropriate treatment planning requires assessment of radiation dose to several internal organs and tissues, and usually involves biodistribution studies in the patient using a tracer amount of radionuclide bound to the targeting agent and imaged at sequential timepoints using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organ tissues of concern, for the whole body and sometimes for selected tumours. Patient specific factors often require that dose estimates be customised for each patient. In the United States, the Food and Drug Administration regulates the experimental use of investigational new drugs and requires 'reasonable calculation of radiation absorbed dose to the whole body and to critical organs' using the methods prescribed by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high dose studies shows that some are conducted with minimal dosimetry, that the marrow dose is difficult to establish and is subject to large uncertainties. Despite the general availability of software, internal dosimetry methods often seem to be inconsistent from one clinical centre to another. (author)

  17. Basics of primary immunodeficiencies

    Directory of Open Access Journals (Sweden)

    Claudia Hernández-Martínez

    2016-05-01

    Full Text Available Primary immunodeficiencies (PID are a heterogeneous group of inherited disorders, the etiology are the defects in the development or function of the immune system. The principal PID manifestations are the infections in early age, malignancy and diseases of immune dysregulation as autoimmunity and allergy. PIDs are genetics disorders and most of them are inherited as autosomal recessive, also this group of diseases is more prevalent in males and in childhood. The antibody immunodeficiency is the PID more common in adults. The more frequent disorders are the infections in the respiratory tract, abscesses, candidiasis, diarrhea, BCGosis etc. Initial approach included a complete blood count and quantification of immunoglobulins. The delay in diagnosis could be explained due to a perception that the recurrent infections are normal process or think that they are exclusively of childhood. The early diagnosis of PID by primary care physicians is important to opportune treatment and better prognosis.

  18. High-dose MeV electron irradiation of Si-SiO2 structures implanted with high doses Si+

    Science.gov (United States)

    Kaschieva, S.; Angelov, Ch; Dmitriev, S. N.

    2018-03-01

    The influence was studied of 22-MeV electron irradiation on Si-SiO2 structures implanted with high-fluence Si+ ions. Our earlier works demonstrated that Si redistribution is observed in Si+-ion-implanted Si-SiO2 structures (after MeV electron irradiation) only in the case when ion implantation is carried out with a higher fluence (1016 cm-2). We focused our attention on the interaction of high-dose MeV electron irradiation (6.0×1016 cm-2) with n-Si-SiO2 structures implanted with Si+ ions (fluence 5.4×1016 cm-2 of the same order magnitude). The redistribution of both oxygen and silicon atoms in the implanted Si-SiO2 samples after MeV electron irradiation was studied by Rutherford back-scattering (RBS) spectroscopy in combination with a channeling technique (RBS/C). Our results demonstrated that the redistribution of oxygen and silicon atoms in the implanted samples reaches saturation after these high doses of MeV electron irradiation. The transformation of amorphous SiO2 surface into crystalline Si nanostructures (after MeV electron irradiation) was evidenced by atomic force microscopy (AFM). Silicon nanocrystals are formed on the SiO2 surface after MeV electron irradiation. The shape and number of the Si nanocrystals on the SiO2 surface depend on the MeV electron irradiation, while their size increases with the dose. The mean Si nanocrystals height is 16-20 nm after irradiation with MeV electrons at the dose of 6.0×1016 cm-2.

  19. Recurrent Infections May Signal Immunodeficiencies

    Science.gov (United States)

    American Academy of Allergy Asthma & Immunology Menu Search Main navigation Skip to content Conditions & Treatments Allergies Asthma Primary Immunodeficiency Disease Related Conditions Drug Guide Conditions Dictionary Just ...

  20. High dose rate brachytherapy for superficial cancer of the esophagus

    International Nuclear Information System (INIS)

    Maingon, Philippe; D'Hombres, Anne; Truc, Gilles; Barillot, Isabelle; Michiels, Christophe; Bedenne, Laurent; Horiot, Jean Claude

    2000-01-01

    Purpose: We analyzed our experience with external radiotherapy, combined modality treatment, or HDR brachytherapy alone to limited esophageal cancers. Methods and Materials: From 1991 to 1996, 25 patients with limited superficial esophagus carcinomas were treated by high dose rate brachytherapy. The mean age was 63 years (43-86 years). Five patients showed superficial local recurrence after external radiotherapy. Eleven patients without invasion of the basal membrane were staged as Tis. Fourteen patients with tumors involving the submucosa without spreading to the muscle were staged as T1. Treatment consisted of HDR brachytherapy alone in 13 patients, external radiotherapy and brachytherapy in 8 cases, and concomitant chemo- and radiotherapy in 4 cases. External beam radiation was administered to a total dose of 50 Gy using 2 Gy daily fractions in 5 weeks. In cases of HDR brachytherapy alone (13 patients), 6 applications were performed once a week. Results: The mean follow-up is 31 months (range 24-96 months). Twelve patients received 2 applications and 13 patients received 6 applications. Twelve patients experienced a failure (48%), 11/12 located in the esophagus, all of them in the treated volume. One patient presented an isolated distant metastasis. In the patients treated for superficial recurrence, 4/5 were locally controlled (80%) by brachytherapy alone. After brachytherapy alone, 8/13 patients were controlled (61%). The mean disease-free survival is 14 months (1-36 months). Overall survival is 76% at 1 year, 37% at 2 years, and 14% at 3 years. Overall survival for Tis patients is 24% vs. 20% for T1 (p 0.83). Overall survival for patients treated by HDR brachytherapy alone is 43%. One patient presented with a fistula with local failure after external radiotherapy and brachytherapy. Four stenosis were registered, two were diagnosed on barium swallowing without symptoms, and two required dilatations. Conclusion: High dose rate brachytherapy permits the treating

  1. Learning about Severe Combined Immunodeficiency (SCID)

    Science.gov (United States)

    ... immunodeficiency From The Journal of Allergy and Clinical Immunology Learning About Severe Combined Immunodeficiency (SCID) What is ... immunodeficiency From The Journal of Allergy and Clinical Immunology Get Email Updates Privacy Copyright Contact Accessibility Plug- ...

  2. High dose implantations of antimony for buried layer applications

    International Nuclear Information System (INIS)

    Gailliard, J.P.; Dupuy, M.; Garcia, M.; Roussin, J.C.

    1978-01-01

    Electrical and physical properties of high dose implantations of antimony in silicon have been studied for use in buried layer applications. The results have been obtained both on and oriented silicon wafers. Following implantations which lead to amorphization we perform an annealing at 600 0 C for 10 mn in order to recrystallize the layer. The observed electrical properties (μ, R) show that the concentration of electrically active antimony ions is greater than that predicted from the solubility of antimony in silicon. Further annealing (in the range 1050 0 - 1200 0 ) induces: firstly a precipitation of the Sb and secondly a diffusion and dissolution of the precipitates. There is a different evolution of the defects in the and silicon slices. T.E.M. reveals no defects in the wafers after one hour annealing at 1200 0 C, whereas defects and twins remain in wafers. Having obtained the evolution of R with time and temperature it is then determined the implantation and annealing conditions which lead to the low resistivity (R = 10) needed for buried layer applications. Results with very many industrially made devices are discussed

  3. Optimized dose distribution of a high dose rate vaginal cylinder

    International Nuclear Information System (INIS)

    Li Zuofeng; Liu, Chihray; Palta, Jatinder R.

    1998-01-01

    Purpose: To present a comparison of optimized dose distributions for a set of high-dose-rate (HDR) vaginal cylinders calculated by a commercial treatment-planning system with benchmark calculations using Monte-Carlo-calculated dosimetry data. Methods and Materials: Optimized dose distributions using both an isotropic and an anisotropic dose calculation model were obtained for a set of HDR vaginal cylinders. Mathematical optimization techniques available in the computer treatment-planning system were used to calculate dwell times and positions. These dose distributions were compared with benchmark calculations with TG43 formalism and using Monte-Carlo-calculated data. The same dwell times and positions were used for a quantitative comparison of dose calculated with three dose models. Results: The isotropic dose calculation model can result in discrepancies as high as 50%. The anisotropic dose calculation model compared better with benchmark calculations. The differences were more significant at the apex of the vaginal cylinder, which is typically used as the prescription point. Conclusion: Dose calculation models available in a computer treatment-planning system must be evaluated carefully to ensure their correct application. It should also be noted that when optimized dose distribution at a distance from the cylinder surface is calculated using an accurate dose calculation model, the vaginal mucosa dose becomes significantly higher, and therefore should be carefully monitored

  4. Shelf-stable food through high dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Placek, V. E-mail: pla@ujv.cz; Svobodova, V.; Bartonicek, B.; Rosmus, J.; Camra, M

    2004-10-01

    Irradiation of food with high doses (radappertization) is a way, how to prepare shelf-stable ready-to-eat food. The radappertization process requires that the food be heated at first to an internal temperature of at least 75 deg. C to inactivate autolytic enzyme, which could cause the spoilage during storage without refrigeration. In order to prevent radiation induced changes in sensory properties (off flavors, odors, undesirable color change, etc.) the food was vacuum packed and irradiated in frozen state at -30 deg. C or less to a minimum dose of 35 kGy. Such products have characteristics of fresh food prepared for eating even if they are stored for long time under tropical conditions. The wholesomeness (safety for consumption) has been confirmed during 40 years of testing. Within the NRI Rez 10 kinds of shelf-stable meat products have been prepared. The meat was cooked, vacuum packed in SiO{sub x}-containing pouch, freezed in liquid nitrogen and irradiated with electron beam accelerator. The microbial, chemical, and organoleptic properties have been tested.

  5. High-dose processing and application to Korean space foods

    Energy Technology Data Exchange (ETDEWEB)

    Song, Beom-Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Choi, Jong-il [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Kim, Jae-Hun [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Korea Astronaut Project Division, Korea Aerospace Research Institute, Daejeon 305-333 (Korea, Republic of); Byun, Myung-Woo [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Kang, Sang-Wook; Choi, Gi-Hyuk [Korea Astronaut Project Division, Korea Aerospace Research Institute, Daejeon 305-333 (Korea, Republic of); Lee, Ju-Woon [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: sjwlee@kaeri.re.kr

    2009-07-15

    Nutrition bar, Ramen (ready-to-cook noodle), and two Korean traditional foods (Kimchi, fermented vegetable; Sujeonggwa, cinnamon beverage) have been developed as space foods using high-dose gamma irradiation. Addition of calcium lactate and vitamin C, a mild heating, deep-freezing, and gamma irradiation at 25 kGy were conducted to prepare Kimchi as a ready-to-eat space food. Sterilization of Space Kimchi (SK) was confirmed by a microbiological test. The hardness of the Space Kimchi was lower than the untreated Kimchi (CON), but higher than the irradiated only Kimchi. Sensory attributes of the SK were similar to CON, and maintained during preservation at 35 {sup o}C for 30 days. The optimal doses for eliminating the contaminated microbes and maintaining the qualities of the Nutrition bars, Ramen, and Sujeonggwa were determined at 15, 10 and 6 kGy, respectively. All the Korean space food were certificated for use in space flight conditions of 30 days by the Russian Institute for Biomedical Problems.

  6. Characterization of Thymol blue Radiochromic dosimeters for high dose applications

    Directory of Open Access Journals (Sweden)

    Feras M. Aldweri

    2018-03-01

    Full Text Available Thymol blue (TB solutions and Thymol blue Polyvinyl Alcohol (TB-PVA films have been introduced as Radiochromic dosimeter for high dose applications. The dosimeters were irradiated with gamma ray (60Co source from 5 to 30 kGy for film, and from 0.150 kGy to 4 kGy for solution. The optical density of unirradiated and irradiated TB solution as well as TB-PVA film dosimeters were studied in terms of absorbance at 434 nm using UV/VIS spectrophotometer. The effects of scan temperature, light pre-gamma irradiation, dose rate, relative humidity and stability of the absorbance of solutions and films after irradiation were investigated. We found the dose sensitivity of TB solution and TB-PVA film dosimeters increases significantly with increases of the absorbed dose as well as with the increases of TB dye concentrations. The useful dose range of developed TB solutions and TB-PVA films dosimeters is in the range 0.125–1 kGy and of 5–20 kGy, respectively. Keywords: Dose sensitivity, Radio-chromic dosimeter, Thymol blue, Absorbance, Concentrations

  7. Shelf-stable food through high dose irradiation

    International Nuclear Information System (INIS)

    Placek, V.; Svobodova, V.; Bartonicek, B.; Rosmus, J.; Camra, M.

    2004-01-01

    Irradiation of food with high doses (radappertization) is a way, how to prepare shelf-stable ready-to-eat food. The radappertization process requires that the food be heated at first to an internal temperature of at least 75 deg. C to inactivate autolytic enzyme, which could cause the spoilage during storage without refrigeration. In order to prevent radiation induced changes in sensory properties (off flavors, odors, undesirable color change, etc.) the food was vacuum packed and irradiated in frozen state at -30 deg. C or less to a minimum dose of 35 kGy. Such products have characteristics of fresh food prepared for eating even if they are stored for long time under tropical conditions. The wholesomeness (safety for consumption) has been confirmed during 40 years of testing. Within the NRI Rez 10 kinds of shelf-stable meat products have been prepared. The meat was cooked, vacuum packed in SiO x -containing pouch, freezed in liquid nitrogen and irradiated with electron beam accelerator. The microbial, chemical, and organoleptic properties have been tested

  8. Ion exchange resins as high-dose radiation dosimeters

    International Nuclear Information System (INIS)

    Alian, A.; Dessouki, A.; El-Assay, N.B.

    1984-01-01

    This paper reports on the possibility of using various types of ion exchange resins as high-dose radiation dosimeters, by analysis of the decrease in exchange capacity with absorbed dose. The resins studied are Sojuzchim-export-Moscow Cation Exchanger KU-2 and Anion Exchanger AV-17 and Merck Cation Exchanger I, and Merck Anion Exchangers II and III. Over the dose range 1 to 100 kGy, the systems show linearity between log absorbed dose and decrease in resin ion exchange capacity. The slope of this response function differs for the different resins, depending on their ionic form and degree of cross-linking. The radiation sensitivity increases in the order KU-2; Exchanger I; AV-17; Exchanger II; Exchanger III. Merck resins with moisture content of 21% showed considerably higher radiation sensitivity than those with 2 to 3% moisture content. The mechanism of radiation-induced denaturing of the ion exchanger resins involves cleavage and decomposition of functional substituents, with crosslinking playing a stabilizing role, with water and its radiolytic products serving to inhibit radical recombination and interfering with the protection cage effect of crosslinking. (author)

  9. High dose rate brachytherapy for the palliation of malignant dysphagia

    International Nuclear Information System (INIS)

    Homs, Marjolein Y.V.; Eijkenboom, Wilhelmina M.H.; Coen, Veronique L.M.A.; Haringsma, Jelle; Blankenstein, Mark van; Kuipers, Ernst J.; Siersema, Peter D.

    2003-01-01

    Background and purpose: High dose rate (HDR) brachytherapy is a commonly used palliative treatment for esophageal carcinoma. We evaluated the outcome of HDR brachytherapy in patients with malignant dysphagia. Material and methods: A retrospective analysis over a 10-year period was performed of 149 patients treated with HDR brachytherapy, administered in one or two sessions, at a median dose of 15 Gy. Patients were evaluated for functional outcome, complications, recurrent dysphagia, and survival. Results: At 6 weeks after HDR brachytherapy, dysphagia scores had improved from a median of 3 to 2 (n=104; P<0.001), however, dysphagia had not improved in 51 (49%) patients. Procedure-related complications occurred in seven (5%) patients. Late complications, including fistula formation or bleeding, occurred in 11 (7%) patients. Twelve (8%) patients experienced minor retrosternal pain. Median survival of the patients was 160 days with a 1-year survival rate of 15%. Procedure-related mortality was 2%. At follow-up, 55 (37%) patients experienced recurrent dysphagia. In 34 (23%) patients a metal stent was placed to relieve persistent or recurrent dysphagia. Conclusion: HDR brachytherapy is a moderately effective treatment for the palliation of malignant dysphagia. The incidence of early major complications is low, however, persistent and recurrent dysphagia occur frequently, and require often additional treatment

  10. High dose tetrabromobisphenol A impairs hippocampal neurogenesis and memory retention.

    Science.gov (United States)

    Kim, Ah Hyun; Chun, Hye Jeong; Lee, Seulah; Kim, Hyung Sik; Lee, Jaewon

    2017-08-01

    Tetrabromobisphenol A (TBBPA) is a brominated flame retardant that is commonly used in commercial and household products, such as, computers, televisions, mobile phones, and electronic boards. TBBPA can accumulate in human body fluids, and it has been reported that TBBPA possesses endocrine disruptive activity. However, the neurotoxic effect of TBBPA on hippocampal neurogenesis has not yet been investigated. Accordingly, the present study was undertaken to evaluate the effect of TBBPA on adult hippocampal neurogenesis and cognitive function. Male C57BL/6 mice were orally administrated vehicle or TBBPA (20 mg/kg, 100 mg/kg, or 500 mg/kg daily) for two weeks. TBBPA was observed to significantly and dose-dependently reduce the survival of newly generated cells in the hippocampus but not to affect the proliferation of newly generated cells. Numbers of hippocampal BrdU and NeuN positive cells were dose-dependently reduced by TBBPA, indicating impaired neurogenesis in the hippocampus. Interestingly, glial activation without neuronal death was observed in hippocampi exposed to TBBPA. Furthermore, memory retention was found to be adversely affected by TBBPA exposure by a mechanism involving suppression of the BDNF-CREB signaling pathway. The study suggests high dose TBBPA disrupts hippocampal neurogenesis and induces associated memory deficits. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Dimethyl sulfoxyde diethyl fumarate solution for high dose dosimetry

    International Nuclear Information System (INIS)

    Al-Kassiri, H.; Kattan, M.; Daher, Y.

    2007-06-01

    Dosimetric characterization of diethyl fumarate DEF in dimethyl sulfoxyde DMSO solution has been studied spectrophotometrically for possible application at high dose radiation dosimetry in the range (0-225 kGy). The absorption spectra of irradiated solution showed broad absorption bands between (325-400 nm) with a shoulder at 332 nm. The absorption increases as the dose is increased. Absorbance at 332 nm were measured and plotted against absorbed dose. Linear relationship and good response were found between absorbed dose and absorbance of 20% DEF concentration in the range (0-225 kGy) at the wave length, and linearity up to 250 kGy of absorbance at 332 nm .Good dose rate independence was observed in the range (14-33 kGy/h). The effect of post irradiation storage in darkness and indirect daylight conditions were not found to influence the absorption up to 700 h after irradiation. The effect of irradiation temperature within the range (0 to 60 centigrade degree) on the dosimetry performance was discussed.(author)

  12. Radiation Parameters of High Dose Rate Iridium -192 Sources

    Science.gov (United States)

    Podgorsak, Matthew B.

    A lack of physical data for high dose rate (HDR) Ir-192 sources has necessitated the use of basic radiation parameters measured with low dose rate (LDR) Ir-192 seeds and ribbons in HDR dosimetry calculations. A rigorous examination of the radiation parameters of several HDR Ir-192 sources has shown that this extension of physical data from LDR to HDR Ir-192 may be inaccurate. Uncertainty in any of the basic radiation parameters used in dosimetry calculations compromises the accuracy of the calculated dose distribution and the subsequent dose delivery. Dose errors of up to 0.3%, 6%, and 2% can result from the use of currently accepted values for the half-life, exposure rate constant, and dose buildup effect, respectively. Since an accuracy of 5% in the delivered dose is essential to prevent severe complications or tumor regrowth, the use of basic physical constants with uncertainties approaching 6% is unacceptable. A systematic evaluation of the pertinent radiation parameters contributes to a reduction in the overall uncertainty in HDR Ir-192 dose delivery. Moreover, the results of the studies described in this thesis contribute significantly to the establishment of standardized numerical values to be used in HDR Ir-192 dosimetry calculations.

  13. High-dose processing and application to Korean space foods

    Science.gov (United States)

    Song, Beom-Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Kang, Sang-Wook; Choi, Gi-Hyuk; Lee, Ju-Woon

    2009-07-01

    Nutrition bar, Ramen (ready-to-cook noodle), and two Korean traditional foods ( Kimchi, fermented vegetable; Sujeonggwa, cinnamon beverage) have been developed as space foods using high-dose gamma irradiation. Addition of calcium lactate and vitamin C, a mild heating, deep-freezing, and gamma irradiation at 25 kGy were conducted to prepare Kimchi as a ready-to-eat space food. Sterilization of Space Kimchi (SK) was confirmed by a microbiological test. The hardness of the Space Kimchi was lower than the untreated Kimchi (CON), but higher than the irradiated only Kimchi. Sensory attributes of the SK were similar to CON, and maintained during preservation at 35 °C for 30 days. The optimal doses for eliminating the contaminated microbes and maintaining the qualities of the Nutrition bars, Ramen, and Sujeonggwa were determined at 15, 10 and 6 kGy, respectively. All the Korean space food were certificated for use in space flight conditions of 30 days by the Russian Institute for Biomedical Problems.

  14. Colon mucosal cells after high-dose fractional irradiation

    International Nuclear Information System (INIS)

    Zorc-Pleskovic, R.; Vraspir-Porenta, O.; Petrovic, D.; Zorc, M.; Pleskovic, L.

    2000-01-01

    The aim of this study was to investigate histological and stereological changes in cryptal enterocytes, mucosal lymphocytes and mast cells 10 days after irradiation. For experimental model, 24 Beagle dogs 1-2 years old were used. Twelve dogs were irradiated 20 days with 32 Gy over the whole pelvis and tail. Another 12 dogs represented a control group. For the detection of apoptosis, the TUNEL technique was used. Histological and stereological analyses were performed using a Wild sampling microscope M 1000. In the irradiated group, volume density (P < 0.01), numerical density (P < 0.05) and average volume of lymphocytes (P < 0.001) were significantly lower than in the nonirradiated group. Numerical areal density of mast cells in the irradiated group was also significantly lower (P < 0.05). Volume density (P < 0.001) and average volume of mast cells (P < 0.001) were significantly higher in the irradiated group. The results of our experiments show that irradiation causes injury and loss of lymphocytes and mast cells in the colon mucosa. Apoptosis was detected in enterocytes and lymphocytes in the irradiated group and in nonirradiated group in equal numbers (2.5 ± 0.3 vs. 2.3 ± 0.3; ns.), suggesting that 10 days after high-dose irradiation, the cell loss is not due to apoptosis. (author)

  15. Tungsten and carbon surface change under high dose plasma exposure

    International Nuclear Information System (INIS)

    Martynenko, Y.V.; Khripunov, B.I.; Petrov, V.B.

    2009-01-01

    Study of surface composition dynamics has been made on the LENTA linear plasma simulator. Experiments have been made on tungsten and carbon materials subjected to steady-state plasma exposure. The achieved ion doses on the surface were 10 21 ion cm -2 . WL 10 tungsten containing 1% of La2O3 oxide and titanium-doped graphite RG-T were studied. The following experimental conditions were varied in these experiments: energy of ions, surface temperature, working gas. Irradiations of tungsten WL 10 were executed in deuterium plasma at low ion energies (about 20 eV) and at 200 eV for temperatures below 340 K. Graphite RG-T was exposed at 1300 K. Elevated surface temperature (about 1050K) was also characteristic of experiments on tungsten sample under nitrogen plasma impact (simulated inter-ELMs condition). Surface microstructure modification has been observed and surface composition changes were found on the materials showing influence of high dose plasma irradiations on element redistribution in the near surface layers. (author)

  16. High dose progesterone effects the growth of early chick embryo

    International Nuclear Information System (INIS)

    Iqbal, I.; Qamar, K.

    2014-01-01

    Objective: To find out the effect of high dose progesterone on the development of early chick embryo. Study Design: Lab based randomized controlled trial. Place and Duration of study: This study was carried out in Army Medical College and Post Graduate Institute of Poultry Sciences, Rawalpindi from June 2010 - December 2010. Material and Methods: Forty five specific pathogen free, fertile, eggs of Fyoumi species of chick were selected at zero hour of incubation. They were incubated at 37.5oC and 75% relative humidity for 26 hrs until the embryos reached stage 8 of the development. Then on stage 8 the eggs were divided into three groups consisting of 15 eggs per group. The first group (GI) was incubated without any operation. The second (G2) and third groups (G3) were injected with two and twenty times more than physiologic does of progesterone respectively. After 48 hours of incvbation, all embryos were examined for their development under light microscopy. Results: All the embryos of G1 and G2 showed normal development according to their stage of development, while 4 out of 11 embryos of G3 were under developed and their survival rate was also less. Conclusion: Exogenous progesterone at levels twenty times above its physiologic range effects the development of chick embryos. Further studies are needed to explain the mechanisms of this effect. (author)

  17. Calibration of high-dose radiation facilities (Handbook)

    International Nuclear Information System (INIS)

    Gupta, B.L.; Bhat, R.M.

    1986-01-01

    In India at present several high intensity radiation sources are used. There are 135 teletheraphy machines and 65 high intensity cobalt-60 sources in the form of gamma chambers (2.5 Ci) and PANBIT (50 Ci). Several food irradiation facilities and a medical sterilization plant ISOMED are also in operation. The application of these high intensity sources involve a wide variation of dose from 10 Gy to 100 kGy. Accurate and reproducible radiation dosimetry is essential in the use of these sources. This handbook is especially compiled for calibration of high-dose radiation facilities. The first few chapters discuss such topics as interaction of radiation with matter, radiation chemistry, radiation processing, commonly used high intensity radiation sources and their special features, radiation units and dosimetry principles. In the chapters which follow, chemical dosimeters are discussed in detail. This discussion covers Fricke dosimeter, FBX dosimeter, ceric sulphate dosimeter, free radical dosimetry, coloured indicators for irrdiation verification. A final chapter is devoted to practical hints to be followed in calibration work. (author)

  18. High-dose processing and application to Korean space foods

    International Nuclear Information System (INIS)

    Song, Beom-Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Kang, Sang-Wook; Choi, Gi-Hyuk; Lee, Ju-Woon

    2009-01-01

    Nutrition bar, Ramen (ready-to-cook noodle), and two Korean traditional foods (Kimchi, fermented vegetable; Sujeonggwa, cinnamon beverage) have been developed as space foods using high-dose gamma irradiation. Addition of calcium lactate and vitamin C, a mild heating, deep-freezing, and gamma irradiation at 25 kGy were conducted to prepare Kimchi as a ready-to-eat space food. Sterilization of Space Kimchi (SK) was confirmed by a microbiological test. The hardness of the Space Kimchi was lower than the untreated Kimchi (CON), but higher than the irradiated only Kimchi. Sensory attributes of the SK were similar to CON, and maintained during preservation at 35 o C for 30 days. The optimal doses for eliminating the contaminated microbes and maintaining the qualities of the Nutrition bars, Ramen, and Sujeonggwa were determined at 15, 10 and 6 kGy, respectively. All the Korean space food were certificated for use in space flight conditions of 30 days by the Russian Institute for Biomedical Problems.

  19. Physics and quality assurance for high dose rate brachytherapy

    International Nuclear Information System (INIS)

    Anderson, Lowell L.

    1995-01-01

    Purpose: To review the physical aspects of high dose rate (HDR) brachytherapy, including commissioning and quality assurance, source calibration and dose distribution measurements, and treatment planning methods. Following the introduction of afterloading in brachytherapy, development efforts to make it 'remote' culminated in 1964 with the near-simultaneous appearance of remote afterloaders in five major medical centers. Four of these machines were 'high dose rate', three employing 60Co and one (the GammaMed) using a single, cable-mounted 192Ir source. Stepping-motor source control was added to the GammaMed in 1974, making it the precursor of modern remote afterloaders, which are now suitable for interstitial as well as intracavitary brachytherapy by virtue of small source-diameter and indexer-accessed multiple channels. Because the 192Ir sources currently used in HDR remote afterloaders are supplied at a nominal air-kerma strength of 11.4 cGy cm2 s-1 (10 Ci), are not collimated in clinical use, and emit a significant fraction (15%) of photons at energies greater than 600 keV, shielding and facility design must be undertaken as carefully and thoroughly as for external beam installations. Licensing requirements of regulatory agencies must be met with respect both to maximum permissible dose limits and to the existence and functionality of safety devices (door interlocks, radiation monitors, etc.). Commissioning and quality assurance procedures that must be documented for HDR remote afterloading relate to (1) machine, applicator, guide-tube, and facility functionality checks, (2) source calibration, (3) emergency response readiness, (4) planning software evaluation, and (5) independent checks of clinical dose calculations. Source calibration checks must be performed locally, either by in-air measurement of air kerma strength or with a well ionization chamber calibrated (by an accredited standards laboratory) against an in-air measurement of air kerma strength for the

  20. Human Immunodeficiency Virus Proteins Mimic Human T Cell Receptors Inducing Cross-Reactive Antibodies

    Directory of Open Access Journals (Sweden)

    Robert Root-Bernstein

    2017-10-01

    Full Text Available Human immunodeficiency virus (HIV hides from the immune system in part by mimicking host antigens, including human leukocyte antigens. It is demonstrated here that HIV also mimics the V-β-D-J-β of approximately seventy percent of about 600 randomly selected human T cell receptors (TCR. This degree of mimicry is greater than any other human pathogen, commensal or symbiotic organism studied. These data suggest that HIV may be evolving into a commensal organism just as simian immunodeficiency virus has done in some types of monkeys. The gp120 envelope protein, Nef protein and Pol protein are particularly similar to host TCR, camouflaging HIV from the immune system and creating serious barriers to the development of safe HIV vaccines. One consequence of HIV mimicry of host TCR is that antibodies against HIV proteins have a significant probability of recognizing the corresponding TCR as antigenic targets, explaining the widespread observation of lymphocytotoxic autoantibodies in acquired immunodeficiency syndrome (AIDS. Quantitative enzyme-linked immunoadsorption assays (ELISA demonstrated that every HIV antibody tested recognized at least one of twelve TCR, and as many as seven, with a binding constant in the 10−8 to 10−9 m range. HIV immunity also affects microbiome tolerance in ways that correlate with susceptibility to specific opportunistic infections.

  1. Seroprevalence and genomic divergence of circulating strains of feline immunodeficiency virus among Felidae and Hyaenidae species.

    Science.gov (United States)

    Troyer, Jennifer L; Pecon-Slattery, Jill; Roelke, Melody E; Johnson, Warren; VandeWoude, Sue; Vazquez-Salat, Nuria; Brown, Meredith; Frank, Laurence; Woodroffe, Rosie; Winterbach, Christiaan; Winterbach, Hanlie; Hemson, Graham; Bush, Mitch; Alexander, Kathleen A; Revilla, Eloy; O'Brien, Stephen J

    2005-07-01

    Feline immunodeficiency virus (FIV) infects numerous wild and domestic feline species and is closely related to human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Species-specific strains of FIV have been described for domestic cat (Felis catus), puma (Puma concolor), lion (Panthera leo), leopard (Panthera pardus), and Pallas' cat (Otocolobus manul). Here, we employ a three-antigen Western blot screening (domestic cat, puma, and lion FIV antigens) and PCR analysis to survey worldwide prevalence, distribution, and genomic differentiation of FIV based on 3,055 specimens from 35 Felidae and 3 Hyaenidae species. Although FIV infects a wide variety of host species, it is confirmed to be endemic in free-ranging populations of nine Felidae and one Hyaenidae species. These include the large African carnivores (lion, leopard, cheetah, and spotted hyena), where FIV is widely distributed in multiple populations; most of the South American felids (puma, jaguar, ocelot, margay, Geoffroy's cat, and tigrina), which maintain a lower FIV-positive level throughout their range; and two Asian species, the Pallas' cat, which has a species-specific strain of FIV, and the leopard cat, which has a domestic cat FIV strain in one population. Phylogenetic analysis of FIV proviral sequence demonstrates that most species for which FIV is endemic harbor monophyletic, genetically distinct species-specific FIV strains, suggesting that FIV transfer between cat species has occurred in the past but is quite infrequent today.

  2. Seroprevalence and Genomic Divergence of Circulating Strains of Feline Immunodeficiency Virus among Felidae and Hyaenidae Species†

    Science.gov (United States)

    Troyer, Jennifer L.; Pecon-Slattery, Jill; Roelke, Melody E.; Johnson, Warren; VandeWoude, Sue; Vazquez-Salat, Nuria; Brown, Meredith; Frank, Laurence; Woodroffe, Rosie; Winterbach, Christiaan; Winterbach, Hanlie; Hemson, Graham; Bush, Mitch; Alexander, Kathleen A.; Revilla, Eloy; O'Brien, Stephen J.

    2005-01-01

    Feline immunodeficiency virus (FIV) infects numerous wild and domestic feline species and is closely related to human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Species-specific strains of FIV have been described for domestic cat (Felis catus), puma (Puma concolor), lion (Panthera leo), leopard (Panthera pardus), and Pallas' cat (Otocolobus manul). Here, we employ a three-antigen Western blot screening (domestic cat, puma, and lion FIV antigens) and PCR analysis to survey worldwide prevalence, distribution, and genomic differentiation of FIV based on 3,055 specimens from 35 Felidae and 3 Hyaenidae species. Although FIV infects a wide variety of host species, it is confirmed to be endemic in free-ranging populations of nine Felidae and one Hyaenidae species. These include the large African carnivores (lion, leopard, cheetah, and spotted hyena), where FIV is widely distributed in multiple populations; most of the South American felids (puma, jaguar, ocelot, margay, Geoffroy's cat, and tigrina), which maintain a lower FIV-positive level throughout their range; and two Asian species, the Pallas' cat, which has a species-specific strain of FIV, and the leopard cat, which has a domestic cat FIV strain in one population. Phylogenetic analysis of FIV proviral sequence demonstrates that most species for which FIV is endemic harbor monophyletic, genetically distinct species-specific FIV strains, suggesting that FIV transfer between cat species has occurred in the past but is quite infrequent today. PMID:15956574

  3. Investigation of polymer composite for high dose dosimetry

    International Nuclear Information System (INIS)

    Pereira, E.L.M.; Batista, A.S.M.; Ribeiro, F.A.S.; Santos, A.P.; Faria, L.O.; Oliveira, A.H.

    2017-01-01

    Introduction: This paper presents the efficacy evaluation of PVDF and nanocomposites of the PVDF films for high gamma dosimetry. Our scope in this first part of our studies is the selection of the most promising film for future dosimetry trials, where the proportionality of response of the selected material will be investigated over a large range of doses and dose rates. Methods: Was prepared nanocomposites made by mixing Poly(vinylidene fluoride) (PVDF), zirconium oxide (ZrO 2 ) and multi-walled carbon nanotubes (MWCNTs) aiming to find dosimetric properties for applications in high dose dosimetry. The samples were irradiated with a Co-60 source at constant dose rate (16.7 kGy/h), with doses ranging from 100 to 2750 kGy. The UV-Vis and FTIR spectrophotometry have been used to monitor the appearing of C=C conjugated bonds and radio-oxidation of carbon (C=O). Results: FTIR spectrometry has that the absorbance intensities at 1715 cm -1 and 1730 cm -1 can be used for high dosimetry purposes for gamma doses ranging from 400 to 2750 kGy. In this range, it is possible to observe a linear relationship between Abs & Dose. Fading of signal was evaluated for one month and reproducibility in 2000 kGy dose. Conclusion: FTIR spectroscopic data revealed two optical absorption bands at 1715 cm -1 and 1730 cm -1 whose intensities are unambiguously related to gamma delivered dose ranging from 400 kGy to 2750 kGy. (author)

  4. Investigation of polymer composite for high dose dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, E.L.M.; Batista, A.S.M., E-mail: adriananuclear@yahoo.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Ribeiro, F.A.S.; Santos, A.P.; Faria, L.O.; Oliveira, A.H. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2017-07-01

    Introduction: This paper presents the efficacy evaluation of PVDF and nanocomposites of the PVDF films for high gamma dosimetry. Our scope in this first part of our studies is the selection of the most promising film for future dosimetry trials, where the proportionality of response of the selected material will be investigated over a large range of doses and dose rates. Methods: Was prepared nanocomposites made by mixing Poly(vinylidene fluoride) (PVDF), zirconium oxide (ZrO{sub 2}) and multi-walled carbon nanotubes (MWCNTs) aiming to find dosimetric properties for applications in high dose dosimetry. The samples were irradiated with a Co-60 source at constant dose rate (16.7 kGy/h), with doses ranging from 100 to 2750 kGy. The UV-Vis and FTIR spectrophotometry have been used to monitor the appearing of C=C conjugated bonds and radio-oxidation of carbon (C=O). Results: FTIR spectrometry has that the absorbance intensities at 1715 cm{sup -1} and 1730 cm{sup -1} can be used for high dosimetry purposes for gamma doses ranging from 400 to 2750 kGy. In this range, it is possible to observe a linear relationship between Abs & Dose. Fading of signal was evaluated for one month and reproducibility in 2000 kGy dose. Conclusion: FTIR spectroscopic data revealed two optical absorption bands at 1715 cm{sup -1} and 1730 cm{sup -1} whose intensities are unambiguously related to gamma delivered dose ranging from 400 kGy to 2750 kGy. (author)

  5. Urethral stricture following high dose rate brachytherapy for prostate cancer

    International Nuclear Information System (INIS)

    Sullivan, Lisa; Williams, Scott G.; Tai, Keen Hun; Foroudi, Farshad; Cleeve, L.; Duchesne, Gillian M.

    2009-01-01

    Purpose: To evaluate the incidence, timing, nature and outcome of urethral strictures following high dose rate brachytherapy (HDRB) for prostate carcinoma. Methods and materials: Data from 474 patients with clinically localised prostate cancer treated with HDRB were analysed. Ninety percent received HDRB as a boost to external beam radiotherapy (HDRBB) and the remainder as monotherapy (HDRBM). Urethral strictures were graded according to the Common Terminology Criteria for Adverse Events v3.0. Results: At a median follow-up of 41 months, 38 patients (8%) were diagnosed with a urethral stricture (6-year actuarial risk 12%). Stricture location was bulbo-membranous (BM) urethra in 92.1%. The overall actuarial rate of grade 2 or more BM urethral stricture was estimated at 10.8% (95% CI 7.0-14.9%), with a median time to diagnosis of 22 months (range 10-68 months). All strictures were initially managed with either dilatation (n = 15) or optical urethrotomy (n = 20). Second line therapy was required in 17 cases (49%), third line in three cases (9%) and 1 patient open urethroplasty (grade 3 toxicity). Predictive factors on multivariate analysis were prior trans-urethral resection of prostate (hazard ratio (HR) 2.81, 95% CI 1.15-6.85, p = 0.023); hypertension (HR 2.83, 95% CI 1.37-5.85, p = 0.005); and dose per fraction used in HDR (HR for 1 Gy increase per fraction 1.33, 95% CI 1.08-1.64, p = 0.008). Conclusions: BM urethral strictures are the most common late grade 2 or more urinary toxicity following HDR brachytherapy for prostate cancer. Most are manageable with minimally invasive procedures. Both clinical and dosimetric factors appear to influence the risk of stricture formation.

  6. Tolerance of the Brachial Plexus to High-Dose Reirradiation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Allen M., E-mail: achen5@kumc.edu; Yoshizaki, Taeko; Velez, Maria A.; Mikaeilian, Argin G.; Hsu, Sophia; Cao, Minsong

    2017-05-01

    Purpose: To study the tolerance of the brachial plexus to high doses of radiation exceeding historically accepted limits by analyzing human subjects treated with reirradiation for recurrent tumors of the head and neck. Methods and Materials: Data from 43 patients who were confirmed to have received overlapping dose to the brachial plexus after review of radiation treatment plans from the initial and reirradiation courses were used to model the tolerance of this normal tissue structure. A standardized instrument for symptoms of neuropathy believed to be related to brachial plexus injury was utilized to screen for toxicity. Cumulative dose was calculated by fusing the initial dose distributions onto the reirradiation plan, thereby creating a composite plan via deformable image registration. The median elapsed time from the initial course of radiation therapy to reirradiation was 24 months (range, 3-144 months). Results: The dominant complaints among patients with symptoms were ipsilateral pain (54%), numbness/tingling (31%), and motor weakness and/or difficulty with manual dexterity (15%). The cumulative maximum dose (Dmax) received by the brachial plexus ranged from 60.5 Gy to 150.1 Gy (median, 95.0 Gy). The cumulative mean (Dmean) dose ranged from 20.2 Gy to 111.5 Gy (median, 63.8 Gy). The 1-year freedom from brachial plexus–related neuropathy was 67% and 86% for subjects with a cumulative Dmax greater than and less than 95.0 Gy, respectively (P=.05). The 1-year complication-free rate was 66% and 87%, for those reirradiated within and after 2 years from the initial course, respectively (P=.06). Conclusion: The development of brachial plexus–related symptoms was less than expected owing to repair kinetics and to the relatively short survival of the subject population. Time-dose factors were demonstrated to be predictive of complications.

  7. "Time sequential high dose of Cytarabine in acute myelocytic leukemia "

    Directory of Open Access Journals (Sweden)

    Ghavamzadeh A

    2003-05-01

    Full Text Available Given preliminary evidence of timed, sequential chemotherapy of high dose cytosine arabinoside the current study was initiated to assess the side effects and efficacy of this regimen in patients with newly acute myelocytic leukemia (AML. Nineteen adults who referred to Hematology-Oncology and Bone Marrow Transplantation (BMT research center of Tehran University of Medical Sciences were enrolled in a trial from Aug 1999 to Nov 2000. All patients had a Karnofski classification above 60%. At this time induction therapy consisted of daunorubicin or idarubicin given at a dose of 60 mg/m² and 12 mg/m² IV respectively on days 1-3, and cytarabine (Ara-C 100 mg/m² intravenously by continuous infusion on days 1-7, followed by Ara-C 1000 mg/m² given on day 8-10 every 12 hours by IV infusion. Consolidation therapy started after 35th day. Of 19 fully evaluable patients, 10 patients achieved a complete remission, whereas 36.6% patients succumbed to death due to regeneration failure. The clinical data show that the overall survival rate from diagnosis 55.5% (95% CI, 30.8-78.5 at 6 months for the entire cohort of the patients. Disease free survival is also 50% (95% CI, 26-74. Mean duration of death due to treatment was 20 days (range 17-29 after beginning the regimen. Presenting WBC counts, French-American-British (FAB classification, sex and age were not useful prognostic variables. Fever, diarrhea, nausea and vomiting and GI hemorrhage were seen in 19, 6, 4, 7 patients respectively. It seems the 3+7+3 regimen is a promising approach for the AML patients regarding to high complete remission rate, but more supportive care should be considered. Furthermore any, benefit in long-term outcome can’t be determined regardless to the choice of post remission therapy (e.g., GCSF, appropriate antibiotics and etc.

  8. Replicative intermediates in UV-irradiated Simian virus 40

    International Nuclear Information System (INIS)

    Clark, J.M.; Hanawalt, P.C.

    1984-01-01

    The authors have used Simian virus 40 (SV40) as a probe to study the replication of UV-damaged DNA in mammalian cells. Viral DNA replication in infected monkey kidney cells was synchronized by incubating a mutant of SV40 (tsA58) temperature-sensitive for the initiation of DNA synthesis at the restrictive temperature and then adding aphidicolin to temporarily inhibit DNA synthesis at the permissive temperature while permitting pre-replicative events to occur. After removal of the drug, the infected cells were irradiated at 100 J/m 2 (254 nm) to produce 6-7 pyrimidine dimers per SV40 genome, and returned to the restrictive temperature to prevent reinitiation of replication from the SV40 origin. Replicative intermediates (RI) were labeled with [ 3 H]thymidine. The size distribution of daughter DNA strands in RI isolated shortly after irradiation was skewed towards lengths less than the interdimer spacing in parental DNA; this bias persisted for at least 1 h after irradiation, but disappeared within 3 h by which time the size of the newly-synthesized DNA exceeded the interdimer distance. Evidence was obtained for the generation at late times after irradiation, of Form I molecules in which the daughter DNA strand contain dimers. Thus DNA strand exchange as well as trans-dimer synthesis may be involved in the generation of supercoiled Form I DNA from 0V-damaged SV40 replicative intermediates. (Auth.)

  9. Evidence of simian retrovirus type D by polymerase chain reaction.

    Science.gov (United States)

    Hwa, Christian Z R; Tsai, Sheung Pun; Yee, JoAnn L; Van Rompay, Koen K; Roberts, Jeffrey A

    2017-06-01

    Over the past few years, there have been reports of finding Simian retrovirus type D (SRV) in macaque colonies where some animals were characterized as antibody positive but virus negative raising questions about how SRV was transmitted or whether there is a variant strain detected by antibody but not polymerase chain reaction (PCR) in current use. We developed a three-round nested PCR assay using degenerate primers targeting the pol gene to detect for SRV serotypes 1-5 and applied this newly validated PCR assay to test macaque DNA samples collected in China from 2010 to 2015. Using the nested PCR assay validated in this study, we found 0.15% of the samples archived on FTA ® cards were positive. The source of SRV infection identified within domestic colonies might have originated from imported macaques. The multiplex nested PCR assay developed here may supplement the current assays for SRV. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Physicochemical stability and inactivation of human and simian rotaviruses

    International Nuclear Information System (INIS)

    Meng, Z.D.; Birch, C.; Heath, R.; Gust, I.

    1987-01-01

    The effects of various physical and chemical treatments on the stability of a human serotype 1 rotavirus and simian agent 11 (SA11) were compared by using a fluorescence focus assay. The infectivity of both strains was retained after storage at room temperature for 14 days, 4 degree C for 22 days, and -20 degree C for 32 days; lyophilization; and treatment at pH 3 to 11. Both viruses were inactivated at pH 12, as was the human virus at pH 2, although this pH resulted in only partial inactivation of SA11. The human virus also appeared to be more sensitive than SA11 to the action of ether and chloroform. The infectivity of both viruses was lost after UV irradiation for 15 min and after treatment with 8% formaldehyde for 5 min, 70% (vol/vol) ethanol for 30 min, and 2% lysol, 2% phenol, and 1% H 2 O 2 for 1 h each

  11. Physicochemical stability and inactivation of human and simian rotaviruses

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Z.D.; Birch, C.; Heath, R.; Gust, I.

    1987-04-01

    The effects of various physical and chemical treatments on the stability of a human serotype 1 rotavirus and simian agent 11 (SA11) were compared by using a fluorescence focus assay. The infectivity of both strains was retained after storage at room temperature for 14 days, 4 degree C for 22 days, and -20 degree C for 32 days; lyophilization; and treatment at pH 3 to 11. Both viruses were inactivated at pH 12, as was the human virus at pH 2, although this pH resulted in only partial inactivation of SA11. The human virus also appeared to be more sensitive than SA11 to the action of ether and chloroform. The infectivity of both viruses was lost after UV irradiation for 15 min and after treatment with 8% formaldehyde for 5 min, 70% (vol/vol) ethanol for 30 min, and 2% lysol, 2% phenol, and 1% H/sub 2/O/sub 2/ for 1 h each.

  12. Inactivation of human and simian rotaviruses by chlorine dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu-Shiaw (Brookhaven National Lab., Upton, NY (USA)); Vaughn, J.M. (Univ. of New England College of Medicine, Biddeford, ME (USA))

    1990-05-01

    The inactivation of single-particle stocks of human (type 2, Wa) and simian (SA-11) rotaviruses by chlorine dioxide was investigated. Experiments were conducted at 4{degree}C in a standard phosphate-carbonate buffer. Both virus types were rapidly inactivated, within 20 s under alkaline conditions, when chlorine dioxide concentrations ranging from 0.05 to 0.2 mg/liter were used. Similar reductions of 10{sup 5}-fold in infectivity required additional exposure time of 120 s at 0.2 mg/liter for Wa and at 0.5 mg/liter for SA-11, respectively, at pH 6.0. The inactivation of both virus types was moderate a neutral pH, and the sensitivities to chlorine dioxide were similar. The observed enhancement of virucidal efficiency with increasing pH was contrary to earlier findings with chlorine- and ozone-treated rotavirus particles, where efficiencies decreased with increasing alkalinity. Comparison of 99.9% virus inactivation times revealed ozone to be the most effective virucidal agent among these three disinfectants.

  13. JST Thesaurus Headwords and Synonyms: simian virus 40 [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term simian virus 40 名詞 一般 * * * * SV4...0ウイルス SV40ウイルス エスブイヨンゼロウイルス Thesaurus2015 200906022865540531 C LS07 UNKNOWN_2 simian virus 4 0

  14. HIGH-DOSE RATE BRACHYTHERAPY IN CARCINOMA CERVIX STAGE IIIB

    Directory of Open Access Journals (Sweden)

    Sathya Maruthavanan

    2016-07-01

    Full Text Available INTRODUCTION Radiotherapy is the standard treatment in locally advanced (IIB-IVA and early inoperable cases. The current standard of practice with curable intent is concurrent chemoradiation in which intracavitary brachytherapy is an integral component of radiotherapy. This study aims at assessing the efficacy of HDR ICBT (High-dose rate intracavitary brachytherapy in terms local response, normal tissue reactions, and feasibility. METHODS AND MATERIALS A total of 20 patients of stage IIIB cancer of the uterine cervix were enrolled in the study and were planned to receive concurrent chemotherapy weekly along with EBRT (external beam radiotherapy to a dose of 50 Gy/25 Fr. Suitability for ICBT was assessed at 40 Gy/20 Fr. 6/20 patients were suitable at 40 Gy and received HDR ICBT with a dose of 5.5 Gy to point A in 4 sessions (5.5 Gy/4 Fr. The remaining 14/20 patients completed 50 Gy and received HDR ICBT with a dose of 6 Gy to point A in 3 sessions (6 Gy/3 Fr. RESULTS A total of 66 intracavitary applications were done and only one application required dose modification due to high bladder dose, the pelvic control rate was 85% (17/20. 10% (2/20 had stable disease and 5% (1/20 had progressive disease at one year of follow up. When toxicity was considered only 15% developed grade I and grade II rectal complications. Patient compliance and acceptability was 100%. Patients were very comfortable with the short treatment time as compared with patients on LDR ICBT (low-dose rate intracavitary brachytherapy treatment interviewed during the same period. CONCLUSION This study proves that HDR brachytherapy is efficacious and feasible in carcinoma of cervix stage IIIB. It also proves that good dose distribution can be achieved with HDR intracavitary facility by the use of dose optimization. The short treatment time in HDR ICBT makes it possible to maintain this optimised dose distribution throughout the treatment providing a gain in the therapeutic ratio and

  15. Immunogenicity and efficacy of immunodeficiency virus-like particles pseudotyped with the G protein of vesicular stomatitis virus

    International Nuclear Information System (INIS)

    Kuate, Seraphin; Stahl-Hennig, Christiane; Stoiber, Heribert; Nchinda, Godwin; Floto, Anja; Franz, Monika; Sauermann, Ulrike; Bredl, Simon; Deml, Ludwig; Ignatius, Ralf; Norley, Steve; Racz, Paul; Tenner-Racz, Klara; Steinman, Ralph M.; Wagner, Ralf; Uberla, Klaus

    2006-01-01

    Vaccination with exogenous antigens such as recombinant viral proteins, immunodeficiency virus-derived whole inactivated virus particles, or virus-like particles (VLP) has generally failed to provide sufficient protection in animal models for AIDS. Pseudotyping VLPs with the vesicular stomatitis virus G protein (VSV-G), which is known to mediate entry into dendritic cells, might allow more efficient stimulation of immune responses. Therefore, we pseudotyped noninfectious immunodeficiency virus-like particles with VSV-G and carried out a preliminary screen of their immunogenicity and vaccination efficacy. Incorporation of VSV-G into HIV-1 VLPs led to hundred-fold higher antibody titers to HIV-1 Gag and enhancement of T cell responses in mice. Repeated vaccination of rhesus monkeys for 65 weeks with VSV-G pseudotyped simian immunodeficiency virus (SIV)-like particles (VLP[G]) provided initial evidence for efficient suppression of viral load after mucosal challenge with the SIVmac239 virus. Challenge of monkeys after a 28 week vaccination regimen with VLP[G] led to a reduction in peak viremia, but persistent suppression of viral load was not achieved. Due to limitations in the number of animals available for this study, improved efficacy of VSV-G pseudotyped VLPs in nonhuman primates could not be demonstrated. However, mouse experiments revealed that pseudotyping of VLPs with fusion-competent VSV-G clearly improves their immunogenicity. Additional strategies, particularly adjuvants, should be considered to provide greater protection against a challenge with pathogenic immunodeficiency virus

  16. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver [Robert Koch-Institut, Berlin (Germany); Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D. [Paul-Ehrlich-Institut, Langen (Germany); Bannert, Norbert; Kurth, Reinhard [Robert Koch-Institut, Berlin (Germany); Norley, Stephen, E-mail: NorleyS@rki.de [Robert Koch-Institut, Berlin (Germany)

    2016-02-15

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  17. Characterization of a new simian immunodeficiency virus strain in a naturally infected Pan troglodytes troglodytes chimpanzee with AIDS related symptoms

    Directory of Open Access Journals (Sweden)

    Aghokeng Avelin F

    2011-01-01

    Full Text Available Abstract Background Data on the evolution of natural SIV infection in chimpanzees (SIVcpz and on the impact of SIV on local ape populations are only available for Eastern African chimpanzee subspecies (Pan troglodytes schweinfurthii, and no data exist for Central chimpanzees (Pan troglodytes troglodytes, the natural reservoir of the ancestors of HIV-1 in humans. Here, we report a case of naturally-acquired SIVcpz infection in a P.t.troglodytes chimpanzee with clinical and biological data and analysis of viral evolution over the course of infection. Results A male chimpanzee (Cam155, 1.5 years, was seized in southern Cameroon in November 2003 and screened SIV positive during quarantine. Clinical follow-up and biological analyses have been performed for 7 years and showed a significant decline of CD4 counts (1,380 cells/mm3 in 2004 vs 287 in 2009, a severe thrombocytopenia (130,000 cells/mm3 in 2004 vs 5,000 cells/mm3 in 2009, a weight loss of 21.8% from August 2009 to January 2010 (16 to 12.5 kg and frequent periods of infections with diverse pathogens. DNA from PBMC, leftover from clinical follow-up samples collected in 2004 and 2009, was used to amplify overlapping fragments and sequence two full-length SIVcpzPtt-Cam155 genomes. SIVcpzPtt-Cam155 was phylogenetically related to other SIVcpzPtt from Cameroon (SIVcpzPtt-Cam13 and Gabon (SIVcpzPtt-Gab1. Ten molecular clones 5 years apart, spanning the V1V4 gp120 env region (1,100 bp, were obtained. Analyses of the env region showed positive selection (dN-dS >0, intra-host length variation and extensive amino acid diversity between clones, greater in 2009. Over 5 years, N-glycosylation site frequency significantly increased (p Conclusions Here, we describe for the first time the clinical history and viral evolution of a naturally SIV infected P.t.troglodytes chimpanzee. The findings show an increasing viral diversity over time and suggest clinical progression to an AIDS-like disease, showing that SIVcpz can be pathogenic in its host, as previously described in P.t.schweinfurthii. Although studying the impact of SIV infection in wild apes is difficult, efforts should be made to better characterize the pathogenicity of the ancestors of HIV-1 in their natural host and to find out whether SIV infection also plays a role in ape population decline.

  18. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

    International Nuclear Information System (INIS)

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver; Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D.; Bannert, Norbert; Kurth, Reinhard; Norley, Stephen

    2016-01-01

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  19. Turnover rates of B cells, T cells, and NK cells in simian immunodeficiency virus-infected and uninfected rhesus macaques

    NARCIS (Netherlands)

    Boer, R.J. de; Mohri, H.; Ho, D.D.; Perelson, A.S.

    2003-01-01

    We determined average cellular turnover rates by fitting mathematical models to 5-bromo-2'-deoxyuridine measurements in SIV-infected and uninfected rhesus macaques. The daily turnover rates of CD4(+) T cells, CD4(-) T cells, CD20(+) B cells, and CD16(+) NK cells in normal uninfected rhesus macaques

  20. Relation between phylogeny of African green monkey CD4 genes and their respective simian immunodeficiency virus genes

    DEFF Research Database (Denmark)

    Fomsgaard, Anders; Müller-Trutwin, Michaela C.; Diop, Ousmane

    1997-01-01

    An apparent species-specific relatedness of SIVagm suggests a coevolution with their natural hosts. However, the exact species or subspecies classification of African green monkeys, AGM, is uncertain because current classification schemes rely on phenotype markers, while more definitive genetic d...

  1. High-dose continuous infusion beta-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections in immunocompromised patients.

    Science.gov (United States)

    Moriyama, Brad; Henning, Stacey A; Childs, Richard; Holland, Steven M; Anderson, Victoria L; Morris, John C; Wilson, Wyndham H; Drusano, George L; Walsh, Thomas J

    2010-05-01

    To report a case series of high-dose continuous infusion beta-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections. Continuous infusion ceftazidime or aztreonam was administered to achieve target drug concentrations at or above the minimum inhibitory concentration, when possible, in 3 patients with P. aeruginosa infections. The maximal calculated target drug concentration was 100 mg/L. In the first patient, with primary immunodeficiency, neutropenia, and aggressive cutaneous T-cell lymphoma/leukemia, continuous infusion ceftazidime (6.5-9.6 g/day) was used to successfully treat multidrug-resistant P. aeruginosa bacteremia. In the second patient, with leukocyte adhesion deficiency type 1, continuous infusion aztreonam (8.4 g/day) was used to successfully treat multidrug-resistant P. aeruginosa wound infections. In the third patient, with severe aplastic anemia, continuous infusion ceftazidime (7-16.8 g/day) was used to treat P. aeruginosa pneumonia and bacteremia. In each patient, bacteremia cleared, infected wounds healed, and pneumonia improved in response to continuous infusion ceftazidime or aztreonam. Treatment strategies for multidrug-resistant P. aeruginosa infections are limited. A novel treatment strategy, when no other options are available, is the continuous infusion of existing beta-lactam antibiotics to maximize their pharmacodynamic activity. High-dose continuous infusion ceftazidime or aztreonam was used for the successful treatment of resistant systemic P. aeruginosa infections in 3 chronically immunocompromised patients. Continuous infusion beta-lactam antibiotics are a potentially useful treatment strategy for resistant P. aeruginosa infections in immunocompromised patients.

  2. Human immunodeficiency virus endocrinopathy

    Directory of Open Access Journals (Sweden)

    Uma Sinha

    2011-01-01

    Full Text Available Human immunodeficiency virus (HIV endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients.

  3. Growth regulation of simian and human AIDS-related non-Hodgkin's lymphoma cell lines by TGF-β1 and IL-6

    Directory of Open Access Journals (Sweden)

    Levy Laura S

    2007-02-01

    Full Text Available Abstract Background AIDS-related non-Hodgkin's lymphoma (AIDS-NHL is the second most frequent cancer associated with AIDS, and is a frequent cause of death in HIV-infected individuals. Experimental analysis of AIDS-NHL has been facilitated by the availability of an excellent animal model, i.e., simian Acquired Immunodeficiency Syndrome (SAIDS in the rhesus macaque consequent to infection with simian immunodeficiency virus. A recent study of SAIDS-NHL demonstrated a lymphoma-derived cell line to be sensitive to the growth inhibitory effects of the ubiquitous cytokine, transforming growth factor-beta (TGF-beta. The authors concluded that TGF-beta acts as a negative growth regulator of the lymphoma-derived cell line and, potentially, as an inhibitory factor in the regulatory network of AIDS-related lymphomagenesis. The present study was conducted to assess whether other SAIDS-NHL and AIDS-NHL cell lines are similarly sensitive to the growth inhibitory effects of TGF-beta, and to test the hypothesis that interleukin-6 (IL-6 may represent a counteracting positive influence in their growth regulation. Methods Growth stimulation or inhibition in response to cytokine treatment was quantified using trypan blue exclusion or colorimetric MTT assay. Intracellular flow cytometry was used to analyze the activation of signaling pathways and to examine the expression of anti-apoptotic proteins and distinguishing hallmarks of AIDS-NHL subclass. Apoptosis was quantified by flow cytometric analysis of cell populations with sub-G1 DNA content and by measuring activated caspase-3. Results Results confirmed the sensitivity of LCL8664, an immunoblastic SAIDS-NHL cell line, to TGF-beta1-mediated growth inhibition, and further demonstrated the partial rescue by simultaneous treatment with IL-6. IL-6 was shown to activate STAT3, even in the presence of TGF-beta1, and thereby to activate proliferative and anti-apoptotic pathways. By comparison, human AIDS-NHL cell lines

  4. High dose rate 192Ir calibration: Indonesia experiences

    International Nuclear Information System (INIS)

    Nasukha; Tjiptanto, D.; Darmasyah, R.; Kurniawan, B.

    2002-01-01

    Indonesia with a population of more than 200 Million people which spread on about 5000 islands, up to now only has 23 radiotherapy centers and some not active anymore. As mention by Parkin et al that Cervix/Utery and breast cancer are the most estimated numbers of new cases of cancers in women for developing countries, stomach and lung cancers in men. Indonesia as a developing country is likely similar to other developing countries on numbers of new cases of cancers in women. But quite different in men, in Indonesia the most common cancers are nasopharynx and thyroid cancers. The use of lr-192 sources in high dose-rate (HDR) remotely afterloaded brachytherapy treatments have greatly increased in recent years and variety of such sources are commercially available. Nine radiotherapy centers in Indonesia installed Nucletron microSelectron HDR remote afterloader. Based on the data of CiptoMangunkusurno Hospital, Jakarta that the most common cancers are the cervix, breast, nasopharynx and thyroid cancers which of percentage are about 31%, 25 %, 13%, and 6 % respectively. It means that the use of HDR 192 Ir brachytherapy has to be an effective tool in the treatments. Two methods have been studied and applied to calibrate HDR 192 Ir brachytherapy in Indonesia, especially for Nucletron microSelectron HDR 192 lr remote afterloader brachytherapy. Calibration of HDR 192 Ir brachytherapy source has been done by Cavity lonization Chamber and with Well Type lonization Chamber. First, 0.6 cc of NE Farmer type dosimeter that was calibrated to 60 Co and 250 kV of x-rays in air kerma was used in this experiment. Position of measurement (detector and source) at the center of the room and about 1 meter from the floor. Eight variation of distances from 10 cm to 40 cms have been carried out measurement as recommended by IAEA-TECDOC-1079. Correction have been given for scatters, non-uniformity, and attenuation. To solve the problem of scatter correction factor was used Matlab programming

  5. High-dose-rate brachytherapy in uterine cervical carcinoma

    International Nuclear Information System (INIS)

    Patel, Firuza D.; Rai, Bhavana; Mallick, Indranil; Sharma, Suresh C.

    2005-01-01

    Purpose: High-dose-rate (HDR) brachytherapy is in wide use for curative treatment of cervical cancer. The American Brachytherapy Society has recommended that the individual fraction size be <7.5 Gy and the range of fractions should be four to eight; however, many fractionation schedules, varying from institution to institution, are in use. We use 9 Gy/fraction of HDR in two to five fractions in patients with carcinoma of the uterine cervix. We found that our results and toxicity were comparable to those reported in the literature and hereby present our experience with this fractionation schedule. Methods and Materials: A total of 121 patients with Stage I-III carcinoma of the uterine cervix were treated with HDR brachytherapy between 1996 and 2000. The total number of patients analyzed was 113. The median patient age was 53 years, and the histopathologic type was squamous cell carcinoma in 93% of patients. The patients were subdivided into Groups 1 and 2. In Group 1, 18 patients with Stage Ib-IIb disease, tumor size <4 cm, and preserved cervical anatomy underwent simultaneous external beam radiotherapy to the pelvis to a dose of 40 Gy in 20 fractions within 4 weeks with central shielding and HDR brachytherapy of 9 Gy/fraction, given weekly, and interdigitated with external beam radiotherapy. The 95 patients in Group 2, who had Stage IIb-IIIb disease underwent external beam radiotherapy to the pelvis to a dose of 46 Gy in 23 fractions within 4.5 weeks followed by two sessions of HDR intracavitary brachytherapy of 9 Gy each given 1 week apart. The follow-up range was 3-7 years (median, 36.4 months). Late toxicity was graded according to the Radiation Therapy Oncology Group criteria. Results: The 5-year actuarial local control and disease-free survival rate was 74.5% and 62.0%, respectively. The actuarial local control rate at 5 years was 100% for Stage I, 80% for Stage II, and 67.2% for Stage III patients. The 5-year actuarial disease-free survival rate was 88.8% for

  6. Association between simian virus 40 and non-Hodgkin lymphoma

    Science.gov (United States)

    Vilchez, Regis A.; Madden, Charles R.; Kozinetz, Claudia A.; Halvorson, Steven J.; White, Zoe S.; Jorgensen, Jeffrey L.; Finch, Chris J.; Butel, Janet S.

    2002-01-01

    BACKGROUND: Non-Hodgkin lymphoma has increased in frequency over the past 30 years, and is a common cancer in HIV-1-infected patients. Although no definite risk factors have emerged, a viral cause has been postulated. Polyomaviruses are known to infect human beings and to induce tumours in laboratory animals. We aimed to identify which one of the three polyomaviruses able to infect human beings (simian virus 40 [SV40], JC virus, and BK virus) was associated with non-Hodgkin lymphoma. METHODS: We analysed systemic non-Hodgkin lymphoma from 76 HIV-1-infected and 78 HIV-1-uninfected patients, and non-malignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumours; 54 colon and breast carcinoma samples served as cancer controls. We used PCR followed by Southern blot hybridisation and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. FINDINGS: Polyomavirus T antigen sequences, all of which were SV40-specific, were detected in 64 (42%) of 154 non-Hodgkin lymphomas, none of 186 non-malignant lymphoid samples, and none of 54 control cancers. This difference was similar for HIV-1-infected patients and HIV-1-uninfected patients alike. Few tumours were positive for both SV40 and Epstein-Barr virus. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B-cell and follicular-type lymphomas. INTERPRETATION: SV40 is significantly associated with some types of non-Hodgkin lymphoma. These results add lymphomas to the types of human cancers associated with SV40.

  7. Simian virus 40 vectors for pulmonary gene therapy

    Directory of Open Access Journals (Sweden)

    Oppenheim Ariella

    2007-10-01

    Full Text Available Abstract Background Sepsis remains the leading cause of death in critically ill patients. One of the primary organs affected by sepsis is the lung, presenting as the Acute Respiratory Distress Syndrome (ARDS. Organ damage in sepsis involves an alteration in gene expression, making gene transfer a potential therapeutic modality. This work examines the feasibility of applying simian virus 40 (SV40 vectors for pulmonary gene therapy. Methods Sepsis-induced ARDS was established by cecal ligation double puncture (2CLP. SV40 vectors carrying the luciferase reporter gene (SV/luc were administered intratracheally immediately after sepsis induction. Sham operated (SO as well as 2CLP rats given intratracheal PBS or adenovirus expressing luciferase served as controls. Luc transduction was evaluated by in vivo light detection, immunoassay and luciferase mRNA detection by RT-PCR in tissue harvested from septic rats. Vector abundance and distribution into alveolar cells was evaluated using immunostaining for the SV40 VP1 capsid protein as well as by double staining for VP1 and for the surfactant protein C (proSP-C. Immunostaining for T-lymphocytes was used to evaluate the cellular immune response induced by the vector. Results Luc expression measured by in vivo light detection correlated with immunoassay from lung tissue harvested from the same rats. Moreover, our results showed vector presence in type II alveolar cells. The vector did not induce significant cellular immune response. Conclusion In the present study we have demonstrated efficient uptake and expression of an SV40 vector in the lungs of animals with sepsis-induced ARDS. These vectors appear to be capable of in vivo transduction of alveolar type II cells and may thus become a future therapeutic tool.

  8. Genomic evidence that simian virus 2 and six other simian picornaviruses represent a new genus in Picornaviridae

    International Nuclear Information System (INIS)

    Oberste, M. Steven; Maher, Kaija; Pallansch, Mark A.

    2003-01-01

    Analysis of the VP1 capsid protein coding region of simian virus (SV) 2, SV16, SV18, SV42, SV44, SV45, and SV49 demonstrates that they are clearly distinct from members of the Enterovirus genus and from members of other existing picornavirus genera. To further characterize this group of viruses and to clarify their classification within the Picornaviridae, we have determined the complete genomic sequence of SV2 (8126 nucleotides). The genome was typical of members of Picornaviridae, encoding a single open reading frame. The putative polyprotein contained typical picornavirus protease cleavage sites, yielding mature proteins homologous to each of the known picornavirus proteins. SV2 contained an amino-terminal extension of the reading frame, which was analogous to the leader protein of members of the Aphthovirus, Cardiovirus, Erbovirus, Kobuvirus, and Teschovirus genera, but there was no significant amino acid homology with any of these known leader proteins. The 2A protein also aligned poorly with the 2A proteins of other picornaviruses. The deduced amino acid sequences of the SV2 structural and nonstructural proteins were related to but phylogenetically distinct from those of enteroviruses and human rhinoviruses. The major distinguishing features of SV2 were the presence of a type 2 internal ribosome entry site in the 5'-NTR, a putative leader protein encoded upstream of the structural proteins, and an unusually large 2A protein. On the basis of the molecular analysis, we propose that SV2, SV16, SV18, SV42, SV44, SV45, SV49, and porcine enterovirus 8 be classified as members of a new genus in Picornaviridae and that SV2 (strain 2383) be designated as the type strain

  9. The Role of High Dose Interleukin-2 in the Era of Targeted Therapy.

    Science.gov (United States)

    Gills, Jessie; Parker, William P; Pate, Scott; Niu, Sida; Van Veldhuizen, Peter; Mirza, Moben; Holzbeierlein, Jeffery M; Lee, Eugene K

    2017-09-01

    We assessed survival outcomes following high dose interleukin-2 in a contemporary cohort of patients during the era of targeted agents. We retrospectively reviewed the records of patients with metastatic renal cell carcinoma treated with high dose interleukin-2 between July 2007 and September 2014. Clinicopathological data were abstracted and patient response to therapy was based on RECIST (Response Evaluation Criteria In Solid Tumors), version 1.1 criteria. The Kaplan-Meier method was used to estimate progression-free and overall survival in the entire cohort, the response to high dose interleukin-2 in regard to previous targeted agent therapy and the response to the targeted agent in relation to the response to high dose interleukin-2. We identified 92 patients, of whom 87 had documentation of a response to high dose interleukin-2. Median overall survival was 34.4 months from the initiation of high dose interleukin-2 therapy in the entire cohort. Patients who received targeted therapy before high dose interleukin-2 had overall survival (median 34.4 and 30.0 months, p = 0.88) and progression-free survival (median 1.5 and 1.7 months, p = 0.8) similar to those in patients who received no prior therapy, respectively. Additionally, patients with a complete or partial response to high dose interleukin-2 had similar outcomes for subsequent targeted agents compared to patients whose best response was stable or progressive disease (median overall survival 30.1 vs 25.4 months, p = 0.4). Our data demonstrate that patient responses to high dose interleukin-2 and to targeted agents before and after receiving high dose interleukin-2 are independent. As such, carefully selected patients should be offered high dose interleukin-2 for the possibility of a complete and durable response without the fear of limiting the treatment benefit of targeted agents. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. The clinical pharmacology of alkylating agents in high-dose chemotherapy

    NARCIS (Netherlands)

    Huitema, A. D.; Smits, K. D.; Mathôt, R. A.; Schellens, J. H.; Rodenhuis, S.; Beijnen, J. H.

    2000-01-01

    Alkylating agents are widely used in high-dose chemotherapy regimens in combination with hematological support. Knowledge about the pharmacokinetics and pharmacodynamics of these agents administered in high doses is critical for the safe and efficient use of these regimens. The aim of this review is

  11. Risks Associated with High-Dose Lactobacillus rhamnosus in an Escherichia coli Model of Piglet Diarrhoea

    DEFF Research Database (Denmark)

    Li, Xiao-Qiong; Zhu, Yao-Hong; Zhang, Hong-Fu

    2012-01-01

    might be more effective than a high dose at ameliorating diarrhoea. There is a risk that high-dose L. rhamnosus pretreatment may negate the preventative effects, thus decreasing the prophylactic benefits against potential enteric pathogens. Our data suggest a safe threshold for preventative use...

  12. Split high-dose oral levothyroxine treatment as a successful therapy option in myxedema coma.

    Science.gov (United States)

    Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

    2017-10-01

    High-dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69-year-old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high-dose oral LT4 as a therapeutic option in myxedema coma.

  13. Consanguinity and primary immunodeficiencies.

    Science.gov (United States)

    Al-Herz, Waleed; Aldhekri, Hasan; Barbouche, Mohamed-Ridha; Rezaei, Nima

    2014-01-01

    Primary immunodeficiencies (PIDs) are a heterogeneous group of genetic disorders caused by defects in the immune system that predispose patients to infections, autoimmune diseases, lymphoproliferation and malignancies. Most PIDs are inherited in an autosomal recessive pattern; therefore, they are more common in areas with high rates of consanguineous marriage. Reports about PIDs from these areas have demonstrated a peculiar prevalence of more severe forms of diseases compared to other regions, and patients born to consanguineous parents have increased rates of morbidity and mortality compared to other patients. Individuals at high risk of having a child with a PID who wish to have a healthy child have limited options, these include prenatal diagnosis and pre-implantation genetic diagnosis. However, these options require a collaborative team of specialists and may not always be implemented due to geographic, religious, financial or social factors. The recent introduction of newborn-screening programs for a number of T and B lymphocyte deficiencies will facilitate early diagnosis and therapeutic interventions, which may include hematopoietic stem cell transplantation and intravenous immunoglobulin treatment. There is a need for the implementation of strategies to increase public awareness of the health risks associated with consanguineous marriage. It should be stressed that genetic counseling should be an important component of the care of patients with PIDs as well as their families. © 2014 S. Karger AG, Basel.

  14. Radiographic findings in immunodeficiency

    International Nuclear Information System (INIS)

    Obregon, R.; Lynch, D.A.; Cink, T.M.; Newell, J.D.; Kirkpatrick, C.

    1991-01-01

    This paper reviews the chest radiographs and high-resolution CT (HRCT) scans in patients with immunodeficiency disorders and define the role of HRCT. Thirty-three cases were retrospectively graded according to the consensus of two radiologists. Patients with HIV seropositivity and asthma were excluded. HRCT was performed in 12 cases with standard techniques. Diagnoses included common variable hypogammaglobulinemia (n = 19), X-linked agammaglobulinemia (n = 4), chronic mucocutaneous candidiasis (n = 4), and selective immunoglobulin g deficiencies (n = 2). Chest radiographs showed bronchiectasis in 11 of 33 cases with a predominant lower lobe distribution (82%). Nodules were present in six cases and mucus plugs in four cases. HRCT showed bronchiectasis in nine of 12 cases; in five of these nine cases, bronchiectasis was not apparent on chest radiographs. Other HRCT findings included segmental air trapping (four of 12), mucus plugs (three of 12), hazy consolidation (four of 12), nodules (five of 12), and bronchiolectasis (two of 12). Therapy was altered in seven of 12 cases in which HRCT was performed. Most pertinent to clinical management were the presence of a thymoma (n = 1) and severe focal of diffuse bronchiectasis

  15. Efficacy and tolerability of high-dose phenobarbital in children with focal seizures.

    Science.gov (United States)

    Okumura, Akihisa; Nakahara, Eri; Ikeno, Mitsuru; Abe, Shinpei; Igarashi, Ayuko; Nakazawa, Mika; Takasu, Michihiko; Shimizu, Toshiaki

    2016-04-01

    We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. We reviewed data on children (agedphenobarbital (>5 mg/kg/day to maintain a target serum level >40 μg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  16. Erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA

    International Nuclear Information System (INIS)

    Speight, E.L.; Farr, P.M.

    1994-01-01

    In PUVA treatment of psoriasis, clinical observation suggests that uninvolved skin is more susceptible to PUVA erythema than lesions of psoriasis. If this is the case, then the efficacy of PUVA treatment might be increased by using localized high-dose UVA restricted to lesional skin. We have therefore studied the erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA and, for comparison, the erythemal response to UVB. This study demonstrates that psoriasis may clear rapidly, without burning, using high-dose UVA. Availability of a suitable irradiation apparatus would allow rapid and effective PUVA treatment to be used for localized, resistant disease. (author)

  17. The skin in primary immunodeficiency disorders

    NARCIS (Netherlands)

    Sillevis Smitt, J. Henk; Wulffraat, Nico M.; Kuijpers, Taco W.

    2005-01-01

    Primary immunodeficiency disorders comprise serious and rare diseases, predominantly in children. The skin may be involved in a primary immunodeficiency and the cutaneous alterations such as infections, eczematous dermatitis, erythroderma, autoimmune dermatoses and vasculitis may be the basis for

  18. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline

    DEFF Research Database (Denmark)

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören

    2004-01-01

    OBJECTIVES: To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. METHODS: Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxi...

  19. Cancers related to immunodeficiencies : Update and perspectives

    NARCIS (Netherlands)

    Mortaz, Esmaeil; Tabarsi, Payam; Mansouri, Davod; Khosravi, Adnan; Garssen, Johan; Velayati, Aliakbar; Adcock, Ian M.

    2016-01-01

    The life span of patients with primary and secondary immunodeficiency is increasing due to recent improvements in therapeutic strategies. While the incidence of primary immunodeficiencies (PIDs) is 1:10,000 births, that of secondary immunodeficiencies are more common and are associated with

  20. High-dose zolpidem dependence - Psychostimulant effects? A case report and literature review

    Directory of Open Access Journals (Sweden)

    Abhijna Chandan Chattopadhyay

    2016-01-01

    Full Text Available Zolpidem, an imidazoline nonbenzodiazepine sedative drug, is used widely. Initial reports showed minimal abuse potential. However, multiple reports have appeared of dose escalation and abuse. Subjective effects of high-dose zolpidem are not known. In light of accumulating evidence of abuse potential, we hereby report a case of high-dose dependence and a review of relevant literature. A 33-year-old male presented with 5 years of daily use of 600–1700 mg of zolpidem tartrate. He reported subjective effects of euphoria, intense craving, and inability to stop use. Loss of receptor specificity, pharmacokinetic factors, and different receptor distributions can explain paradoxical stimulatory effects of high-dose zolpidem. Further studies are required to characterize subjective effects of high-dose zolpidem.

  1. Acute effects of high-dose furosemide on residual renal function in CAPD patients

    NARCIS (Netherlands)

    van Olden, Rudolf W.; Guchelaar, Henk-Jan; Struijk, Dirk G.; Krediet, Raymond T.; Arisz, Lambertus

    2003-01-01

    BACKGROUND: High doses of furosemide can increase urine volume in chronic peritoneal dialysis (CAPD) patients. However, no information is available about effects on urinary solute excretion in relation to residual glomerular filtration rate (GFR), urinary furosemide excretion, and peritoneal solute

  2. Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration

    OpenAIRE

    McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2011-01-01

    Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent (i.e., postnatal day (PND) 40) rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a “challenge” high-dose METH regimen when administered ...

  3. Safety aspects of preoperative high-dose glucocorticoid in primary total knee replacement

    DEFF Research Database (Denmark)

    Jørgensen, C C; Pitter, F T; Kehlet, H

    2017-01-01

    Background: Preoperative single high-dose glucocorticoid may have early outcome benefits in total hip arthroplasty (THA) and knee arthroplasty (TKA), but long-term safety aspects have not been evaluated. Methods: From October 2013, the departments reporting to the prospective Lundbeck Foundation....... Conclusions: In this detailed prospective cohort study, preoperative high-dose glucocorticoid administration was not associated with LOS >4 days, readmissions or infectious complications in TKA patients without contraindications....

  4. Evaluation of functioning of high dose rate brachytherapy at the Instituto Nacional do Cancer

    International Nuclear Information System (INIS)

    Guedes, Laura M.A.; Barreto, Rodrigo V.; Silva, Penha M.; Macedo, Afranio A.; Borges, Solange C.; Martinez, Valeria P.O.

    2001-01-01

    Quality control tests are very useful tools to assure the quality of patient's treatment. A daily control of the high dose rate micro selectron was performed based on the security parameters of the equipment and on the quickness of performance. The purpose of this report is to evaluate and to discuss the errors found during the first three years with the high dose rate brachytherapy, at the Instituto Nacional de Cancer. (author)

  5. High-dose Sulbactam Treatment for Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant

    Directory of Open Access Journals (Sweden)

    In Beom Jeong

    2016-11-01

    Full Text Available Background Several antibiotics can be used to treat ventilator-associated pneumonia caused by carbapenem-resistant A. baumannii (CRAB-VAP including high-dose sulbactam. However, the effectiveness of high-dose sulbactam therapy is not well known. We report our experience with high-dose sulbactam for treatment of CRAB-VAP. Methods Medical records of patients with CRAB-VAP who were given high-dose sulbactam between May 2013 and June 2015 were reviewed. Results Fifty-eight patients with CRAB-VAP were treated with high-dose sulbactam. The mean age was 72.0 ± 15.2 years, and the acute physiology and chronic health evaluation II (APACHE II score was 15.1 ± 5.10 at the time of CRAB-VAP diagnosis. Early clinical improvement was observed in 65.5% of patients, and 30-day mortality was 29.3%. Early clinical failure (odds ratio [OR]: 8.720, confidence interval [CI]: 1.346-56.484; p = 0.023 and APACHE II score ≥ 14 at CRAB-VAP diagnosis (OR: 10.934, CI: 1.047-114.148; p = 0.046 were associated with 30-day mortality. Conclusions High-dose sulbactam therapy may be effective for the treatment of CRAB-VAP. However, early clinical failure was observed in 35% of patients and was associated with poor outcome.

  6. Transperineal high-dose-rate interstitial radiation therapy in the management of gynecologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Itami, Jun; Hara, Ryuseke; Kozuka, Takuyou; Yamashita, Hideomi; Nakajima, Kaori; Shibata, Kouji; Abe, Yoshihisa; Fuse, Masashi; Ito, Masashi [International Medical Center of Japan, Tokyo (Japan). Dept. of Radiation Therapy and Oncology

    2003-11-01

    Background: High-dose-rate interstitial radiation therapy is a newly introduced modality, and its role in the management of gynecologic malignancies remains to be studied. Clinical experience in high-dose-rate interstitial radiation therapy was retrospectively investigated. Patients and Methods: Eight patients with primary and nine with recurrent gynecologic malignancies underwent high-dose-rate interstitial radiation therapy with/without external-beam irradiation. Fractional dose of the high-dose-rate interstitial radiation therapy ranged between 4 and 6 Gy with total doses of 15-54 Gy. Interstitial irradiation was performed twice daily with an interval of > 6 h. Results: 2-year local control rate was 75% for primary treatment and 47% for treatment of recurrence (p = 0.46). Maximum tumor size had a statistically significant impact on local control (p < 0.002). Grade 2 and 4 late complications were seen in five patients, and the incidence was significantly higher in patients with a larger volume enclosed by the prescribed fractional dose of high-dose-rate interstitial radiation therapy. The incidence of grade 2 and 4 complications at 18 months was 78% and 0% with a volume > 100 cm{sup 3} and {<=} 100 cm{sup 3}, respectively (p < 0.04). Conclusion: Although high-dose-rate interstitial radiation therapy is a promising modality, it must be applied cautiously to patients with bulky tumors because of the high incidence of serious complications. (orig.)

  7. Post-infection immunodeficiency virus control by neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Yamamoto

    Full Text Available BACKGROUND: Unlike most acute viral infections controlled with the appearance of virus-specific neutralizing antibodies (NAbs, primary HIV infections are not met with such potent and early antibody responses. This brings into question if or how the presence of potent antibodies can contribute to primary HIV control, but protective efficacies of antiviral antibodies in primary HIV infections have remained elusive; and, it has been speculated that even NAb induction could have only a limited suppressive effect on primary HIV replication once infection is established. Here, in an attempt to answer this question, we examined the effect of passive NAb immunization post-infection on primary viral replication in a macaque AIDS model. METHODS AND FINDINGS: The inoculums for passive immunization with simian immunodeficiency virus mac239 (SIVmac239-specific neutralizing activity were prepared by purifying polyclonal immunoglobulin G from pooled plasma of six SIVmac239-infected rhesus macaques with NAb induction in the chronic phase. Passive immunization of rhesus macaques with the NAbs at day 7 after SIVmac239 challenge resulted in significant reduction of set-point plasma viral loads and preservation of central memory CD4 T lymphocyte counts, despite the limited detection period of the administered NAb responses. Peripheral lymph node dendritic cell (DC-associated viral RNA loads showed a remarkable peak with the NAb administration, and DCs stimulated in vitro with NAb-preincubated SIV activated virus-specific CD4 T lymphocytes in an Fc-dependent manner, implying antibody-mediated virion uptake by DCs and enhanced T cell priming. CONCLUSIONS: Our results present evidence indicating that potent antibody induction post-infection can result in primary immunodeficiency virus control and suggest direct and indirect contribution of its absence to initial control failure in HIV infections. Although difficulty in achieving requisite neutralizing titers for

  8. Characterization of components released by alkali disruption of simian virus 40

    DEFF Research Database (Denmark)

    Christiansen, Gunna; Landers, T; Griffith, J

    1977-01-01

    Treatment of simian virus 40 (SV40) particles at pH 9.8 in the presence of 1 mM dithiothreitol for 5 min at 37 degrees C disrupted the virions into a 60S DNA-protein complex and DNA-free 7S protein particles. The DNA-protein complex contained approximately equal amounts of DNA and protein, and ap...

  9. A lion lentivirus related to feline immunodeficiency virus: epidemiologic and phylogenetic aspects.

    Science.gov (United States)

    Brown, E W; Yuhki, N; Packer, C; O'Brien, S J

    1994-09-01

    simian immunodeficiency virus without pathology in free-ranging African monkey species.

  10. High dose vitamin D may improve lower urinary tract symptoms in postmenopausal women.

    Science.gov (United States)

    Oberg, Johanna; Verelst, Margareta; Jorde, Rolf; Cashman, Kevin; Grimnes, Guri

    2017-10-01

    Lower urinary tract symptoms (LUTS) are common in postmenopausal women, and have been reported inversely associated with vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D) levels. The aim of this study was to investigate if high dose vitamin D supplementation would affect LUTS in comparison to standard dose. In a randomized controlled study including 297 postmenopausal women with low bone mineral density, the participants were allocated to receive capsules of 20 000IU of vitamin D 3 twice a week (high dose group) or similar looking placebo (standard dose group). In addition, all the participants received 1g of calcium and 800IU of vitamin D daily. A validated questionnaire regarding LUTS was filled in at baseline and after 12 months. At baseline, 76 women in the high dose group and 82 in the standard dose group reported any LUTS. Levels of serum 25(OH)D increased significantly more in the high dose group (from 64.7 to 164.1nmol/l compared to from 64.1 to 81.8nmol/l, p<0.01). No differences between the groups were seen regarding change in LUTS except for a statistically significant reduction in the reported severity of urine incontinence in the high dose group as compared to the standard dose group after one year (p<0.05). The results need confirmation in a study specifically designed for this purpose. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. High-dose gadolinium-enhanced MRI for diagnosis of meningeal metastases

    International Nuclear Information System (INIS)

    Kallmes, D.F.; Gray, L.; Glass, J.P.

    1998-01-01

    We compared high-dose (0.3 mmol/kg) and standard-dose (0.1 mmol/kg) gadolinium-enhanced MRI for diagnosis of meningeal metastases in 12 patients with suspected meningeal metastases. They were imaged with both standard-dose and high-dose gadolinium. All patients with abnormal meningeal enhancement underwent at least one lumbar puncture for cerebrospinal fluid (CSF) cytology, while patients with normal meningeal enhancement were followed clinically. All patients with negative CSF cytology also were followed clinically. A single observer reviewed all the images, with specific attention to the enhancement pattern of the meninges. Abnormal leptomeningeal enhancement was present in three cases, and abnormal pachymeningeal enhancement in three other patients. All of these patients had abnormal CSF analyses. In two of the three cases of abnormal leptomeningeal enhancement the disease was more evident on high-dose than on standard-dose imaging; in one case the abnormal enhancement was visible only on high-dose imaging. In one of the three cases with abnormal pachymeningeal enhancement, the disease was evident prospectively only with high-dose imaging. (orig.)

  12. Results in patients treated with high-dose-rate interstitial brachytherapy for oral tongue cancer

    International Nuclear Information System (INIS)

    Yamamoto, Michinori; Shirane, Makoto; Ueda, Tsutomu; Miyahara, Nobuyuki

    2006-01-01

    Eight patients were treated with high-dose-rate interstitial brachytherapy for oral tongue cancer between September 2000 and August 2004. The patient distribution was 1 T1, 5 T2, 1 T3, and 1 T4a. Patients received 50-60 Gy in 10 fractions over seven days with high-dose-rate brachytherapy. Six of the eight patients were treated with a combination of external beam radiotherapy (20-30 Gy) and interstitial brachytherapy. The two-year primary local control rate was 83% for initial case. High-dose-rate brachytherapy was performed safely even for an aged person, and was a useful treatment modality for oral tongue cancer. (author)

  13. High dose therapy with autologous stem cell support in malignant disorders

    International Nuclear Information System (INIS)

    Holte, H.; Kvaloey, S.O.; Engan, T.

    1996-01-01

    New biomedical knowledge may improve the diagnostic procedures and treatment provided by the Health Services, but at additional cost. In a social democratic health care system, the hospital budgets have no room for expensive, new procedures or treatments, unless these are funded through extra allocation from the central authorities. High dose therapy with autologous stem cell support in malignant disorders is an example of a new and promising, but rather expensive treatment, but its role in cancer therapy has yet to be established. The indications for testing high dose therapy with autologous stem cell support in various malignancies are discussed, with emphasis on the principles for deciding which categories of disease should have priority. The authors suggest some malignant disorder for which high dose therapy with stem cell support should be explored versus conventional treatment in randomized prospective trials. 8 refs., 1 tab

  14. Plasma Doping - Enabling Technology for High Dose Logic and Memory Applications

    International Nuclear Information System (INIS)

    Miller, T.; Godet, L.; Papasouliotis, G. D.; Singh, V.

    2008-01-01

    As logic and memory device dimensions shrink with each generation, there are more high dose implants at lower energies. Examples include dual poly gate (also referred to as counter-doped poly), elevated source drain and contact plug implants. Plasma Doping technology throughput and dopant profile benefits at these ultra high dose and lower energy conditions have been well established [1,2,3]. For the first time a production-worthy plasma doping implanter, the VIISta PLAD tool, has been developed with unique architecture suited for precise and repeatable dopant placement. Critical elements of the architecture include pulsed DC wafer bias, closed-loop dosimetry and a uniform low energy, high density plasma source. In this paper key performance metrics such as dose uniformity, dose repeatability and dopant profile control will be presented that demonstrate the production-worthiness of the VIISta PLAD tool for several high dose applications.

  15. Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial.

    Science.gov (United States)

    Strain, E C; Bigelow, G E; Liebson, I A; Stitzer, M L

    1999-03-17

    Methadone hydrochloride treatment is the most common pharmacological intervention for opioid dependence, and recent interest has focused on expanding methadone treatment availability beyond traditional specially licensed clinics. However, despite recommendations regarding effective dosing of methadone, controlled clinical trials of higher-dose methadone have not been conducted. To compare the relative clinical efficacy of moderate- vs high-dose methadone in the treatment of opioid dependence. A 40-week randomized, double-blind clinical trial starting in June 1992 and ending in October 1995. Outpatient substance abuse treatment research clinic at the Johns Hopkins University Bayview Campus, Baltimore, Md. One hundred ninety-two eligible clinic patients. Daily oral methadone hydrochloride in the dose range of 40 to 50 mg (n = 97) or 80 to 100 mg (n = 95), with concurrent substance abuse counseling. Opioid-positive urinalysis results and retention in treatment. By intent-to-treat analysis through week 30 patients in the high-dose group had significantly lower rates of opioid-positive urine samples compared with patients in the moderate-dose group (53.0% [95% confidence interval [CI], 46.9%-59.2%] vs 61.9% [95% CI, 55.9%-68.0%]; P = .047. These differences persisted during withdrawal from methadone. Through day 210 no significant difference was evident between dose groups in treatment retention (high-dose group mean retention, 159 days; moderate-dose group mean retention, 157 days). Nineteen (33%) of 57 patients in the high-dose group and 11 (20%) of 54 patients in the moderate-dose group completed detoxification. Both moderate- and high-dose methadone treatment resulted in decreased illicit opioid use during methadone maintenance and detoxification. The high-dose group had significantly greater decreases in illicit opioid use.

  16. Experimental research on fresh mussel meat irradiated by high-dose electron beam

    International Nuclear Information System (INIS)

    Xiao Lin; Lu Ruifeng; Hu Huachao; Wang Chaoqi; Liu Yanna

    2011-01-01

    The sterilization storage of fresh mussel irradiated high-dose electron beam was studied. From the subjective assessment by the weighted average of the test and other determined parameters, it can be concluded that the flavor of fresh mussel meat sealed canned food irradiated by high-dose electron beam has not been significant affected, and various micro-organisms can be killed effectively, which means that the irradiated fresh mussel meat can be preserved for long-term at room temperature. Therefore the method might resolve the problems induced by traditional frozen preservation methods. (authors)

  17. Statistical behavior of high doses in medical radiodiagnosis; Comportamento estatistico das altas doses em radiodiagnostico medico

    Energy Technology Data Exchange (ETDEWEB)

    Barboza, Adriana Elisa, E-mail: adrianaebarboza@gmail.com, E-mail: elisa@bolsista.ird.gov.br [Instituto de Radioprotecao e Dosimetria, (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2014-07-01

    This work has as main purpose statistically estimating occupational exposure in medical diagnostic radiology in cases of high doses recorded in 2011 at national level. For statistical survey of this study, doses of 372 IOE's diagnostic radiology in different Brazilian states were evaluated. Data were extracted from the work of monograph (Research Methodology Of High Doses In Medical Radiodiagnostic) that contains the database's information Sector Management doses of IRD/CNEN-RJ, Brazil. The identification of these states allows the Sanitary Surveillance (VISA) responsible, becomes aware of events and work with programs to reduce these events. (author)

  18. [High-dosed gestagen therapy of the metastatic mammary carcinoma (author's transl)].

    Science.gov (United States)

    Firusian, N; Becher, R

    1981-12-01

    Thirty patients with histologically proven metastatic mammary carcinoma were treated, after exhaustion of hormonal and cytostatic therapeutic means, with high-dosed medroxyprogesterone acetate (MPA) during a ten-day induction phase with 1000 mg MPAi.m. per day and then with 600 mg oral MPA per day. In eleven patients a complete or partial remission was achieved. The median period of remission comprised ten months. A positive relationship was found between the response to high-dosed MPA therapy and the length of free intervals. Side effects were tolerable.

  19. Analysis of volatile organic compounds and sensory characteristics of pork loin samples irradiated to high doses

    International Nuclear Information System (INIS)

    Hou Zhengchi; Sun Dakuan; Qin Zongying; Jin Jiang; Zhu Liandi; Yao Side; Sheng Kanglong

    2005-01-01

    Fresh pork loin samples, protein enzyme inactivated at (72 ± 3) degree C and vacuum packaged, were irradiated to up to 45 kGy at -20 degree C by 60 Co γ-rays. The irradiated samples were examined by various kinds of method to study high dose irradiation effects of sensory changes (meat color and off-odor), transverse shearing strength, weight loss in steam cooking, volatile organic compounds, and lipid oxidation. The results showed that the high dose irradiation produced no serious effects to the pork loin samples, and volunteer responses showed fine acceptability to the irradiated meat. (authors)

  20. Evaluation of glasses containing cadmium for high dose dosimetry by the thermoluminescence technique

    International Nuclear Information System (INIS)

    Carvalho, Gabriel Soares Marchiori de; Ferreira, Pamela Zati; Cunha, Diego Merigue da; Dantas, Noelio Oliveira; Silva, Anielle C.A.; Perini, Ana Paula; Neves, Lucio Pereira; Carrera, Betzabel Noemi Silva; Watanabe, Shigueo

    2016-01-01

    New glass matrices were evaluated for high dose dosimetry by the thermoluminescence technique. Their nominal composition are 20Li_2CO_3.10Al_2O_3.15CdO.55B_2O_3 and 20Li_2CO_3.10Al_2O_3.20CdO.50B_2O_3 (mol%). The glass matrices were irradiated with different doses: 50, 100, 200, 500, 700 and 900 Gy, and the thermoluminescence emission curves were obtained for each of these values. The results show a great potential of using these matrices in high dose dosimetry. (author)

  1. Salvage high-dose-rate brachytherapy for local prostate cancer recurrence after radical radiotherapy

    Directory of Open Access Journals (Sweden)

    V. A. Solodkiy

    2016-01-01

    Full Text Available Studies salvage interstitial radiation therapy for recurrent prostate cancer, launched at the end of the XX century. In recent years, more and more attention is paid to high-dose-rate brachytherapy (HDR-BT as a method of treating local recurrence.The purpose of research – preliminary clinical results of salvage high-dose-rate brachytherapy applied in cases of suspected local recurrence or of residual tumour after radiotherapy.Preliminary findings indicate the possibility of using HDR-BT, achieving local tumor control with low genitourinary toxicity.

  2. Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model

    Science.gov (United States)

    Kim, Jiae; Peachman, Kristina K.; Jobe, Ousman; Morrison, Elaine B.; Allam, Atef; Jagodzinski, Linda; Casares, Sofia A.; Rao, Mangala

    2017-01-01

    Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP) models for studying human immunodeficiency virus (HIV)-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several different types of humanized mice have been developed with varying levels of reconstitution of human CD45+ cells. In this study, we utilized humanized Rag1KO.IL2RγcKO.NOD mice expressing HLA class II (DR4) molecule (DRAG mice) infused with HLA-matched hematopoietic stem cells from umbilical cord blood to study early events after HIV-1 infection, since the mucosal tissues of these mice are highly enriched for human lymphocytes and express the receptors and coreceptors needed for HIV-1 entry. We examined the various tissues on days 4, 7, 14, and 21 after an intravaginal administration of a single dose of purified primary HIV-1. Plasma HIV-1 RNA was detected as early as day 7, with 100% of the animals becoming plasma RNA positive by day 21 post-infection. Single cells were isolated from lymph nodes, bone marrow, spleen, gut, female reproductive tissue, and brain and analyzed for gag RNA and strong stop DNA by quantitative (RT)-PCR. Our data demonstrated the presence of HIV-1 viral RNA and DNA in all of the tissues examined and that the virus was replication competent and spread rapidly. Bone marrow, gut, and lymph nodes were viral RNA positive by day 4 post-infection, while other tissues and plasma became positive typically between 7 and 14 days post-infection. Interestingly, the brain was the last tissue to become HIV-1 viral RNA and DNA positive by day 21 post-infection. These data support the notion that humanized DRAG mice could serve as an excellent model for studying the

  3. Tracking Human Immunodeficiency Virus-1 Infection in the Humanized DRAG Mouse Model

    Directory of Open Access Journals (Sweden)

    Jiae Kim

    2017-10-01

    Full Text Available Humanized mice are emerging as an alternative model system to well-established non-human primate (NHP models for studying human immunodeficiency virus (HIV-1 biology and pathogenesis. Although both NHP and humanized mice have their own strengths and could never truly reflect the complex human immune system and biology, there are several advantages of using the humanized mice in terms of using primary HIV-1 for infection instead of simian immunodeficiency virus or chimera simian/HIV. Several different types of humanized mice have been developed with varying levels of reconstitution of human CD45+ cells. In this study, we utilized humanized Rag1KO.IL2RγcKO.NOD mice expressing HLA class II (DR4 molecule (DRAG mice infused with HLA-matched hematopoietic stem cells from umbilical cord blood to study early events after HIV-1 infection, since the mucosal tissues of these mice are highly enriched for human lymphocytes and express the receptors and coreceptors needed for HIV-1 entry. We examined the various tissues on days 4, 7, 14, and 21 after an intravaginal administration of a single dose of purified primary HIV-1. Plasma HIV-1 RNA was detected as early as day 7, with 100% of the animals becoming plasma RNA positive by day 21 post-infection. Single cells were isolated from lymph nodes, bone marrow, spleen, gut, female reproductive tissue, and brain and analyzed for gag RNA and strong stop DNA by quantitative (RT-PCR. Our data demonstrated the presence of HIV-1 viral RNA and DNA in all of the tissues examined and that the virus was replication competent and spread rapidly. Bone marrow, gut, and lymph nodes were viral RNA positive by day 4 post-infection, while other tissues and plasma became positive typically between 7 and 14 days post-infection. Interestingly, the brain was the last tissue to become HIV-1 viral RNA and DNA positive by day 21 post-infection. These data support the notion that humanized DRAG mice could serve as an excellent model

  4. 78 FR 29755 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Science.gov (United States)

    2013-05-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0473] Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus Cure... an opportunity for public comment on human immunodeficiency virus (HIV) Patient-Focused Drug...

  5. 78 FR 46969 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Science.gov (United States)

    2013-08-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0473] Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus Cure... for the notice of public meeting entitled ``Human Immunodeficiency Virus (HIV) Patient-Focused Drug...

  6. Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer

    NARCIS (Netherlands)

    Rodenhuis, S.; Bontenbal, M.; Hoesel, Q.G.C.M. van; Smit, W.M.; Nooij, M.A.; Voest, E.E.; Wall, E. van der; Hupperets, P.; Tinteren, H. van; Peterse, J.L.; Vijver, M.J. van de; Vries, E.G.E. de

    2006-01-01

    Background: High-dose chemotherapy in the adjuvant treatment of breast cancer has been abandoned by many. Patients and methods: 885 patients with stage III primary breast cancer and four or more axillary lymph node metastases were randomised to receive either five courses of FEC (fluorouracil,

  7. Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer

    NARCIS (Netherlands)

    Rodenhuis, S; Bontenbal, M; van Hoesel, QGCM; Smit, WM; Nooij, MA; Voest, EE; van der Wall, E; Hupperets, P; van Tinteren, H; Peterse, JL; van de Vijver, MJ; de Vries, EGE

    Background: High-dose chemotherapy in the adjuvant treatment of breast cancer has been abandoned by many. Patients and methods: 885 patients with stage III primary breast cancer and four or more axillary lymph node metastases were randomised to receive either five courses of FEC (fluorouracil,

  8. Daily high doses of fluoxetine for weight loss and improvement in lifestyle before bariatric surgery

    NARCIS (Netherlands)

    Dolfing, JG; Wolffenbuttel, BHR; Oei, HI; ten Hoor-Aukerna, NM; Schweitzer, DH

    Background: The number of gastric restrictive bariatric operations is increasing each year, but about one-fifth of patients will become disappointed due to unsatisfactory weight reduction or annoying complications. We questioned whether weight reduction by taking high doses of fluoxetine improves

  9. Fertility of Tall Girls Treated with High-Dose Estrogen, a Dose-Response Relationship

    NARCIS (Netherlands)

    Hendriks, A. E. J.; Drop, S. L. S.; Laven, J. S. E.; Boot, A. M.

    Context: High-dose estrogen treatment to reduce final height of tall girls increases their risk for infertility in later life. Objective: The aim was to study the effect of estrogen dose on fertility outcome of these women. Design/Setting: We conducted a retrospective cohort study of university

  10. Differential sensitivity of long-sleep and short-sleep mice to high doses of cocaine.

    Science.gov (United States)

    de Fiebre, C M; Ruth, J A; Collins, A C

    1989-12-01

    The cocaine sensitivity of male and female long-sleep (LS) and short-sleep (SS) mice, which have been selectively bred for differential ethanol-induced "sleep-time," was examined in a battery of behavioral and physiological tests. Differences between these two mouse lines were subtle and were seen primarily at high doses. At high doses, SS mice were more sensitive than LS mice, particularly to cocaine-induced hypothermia; however, significant hypothermia was not seen except at doses which were very near to the seizure threshold. During a 60-min test of locomotor activity, LS mice showed greater stimulation of Y-maze activity by 20 mg/kg cocaine than SS mice. Consistent with the finding of subtle differences in sensitivity to low doses of cocaine. LS and SS mice did not differ in sensitivity to cocaine inhibition of synaptosomal uptake of [3H]-dopamine, [3H]-norepinephrine or [3H]-5-hydroxytryptamine. However, consistent with the finding of differential sensitivity to high doses of cocaine, SS mice were more sensitive to the seizure-producing effects of the cocaine and lidocaine, a local anesthetic. It is hypothesized that the differential sensitivity of these mouse lines to high doses of cocaine is due to differential sensitivity to cocaine's actions on systems that regulate local anesthetic effects. Selective breeding for differential duration of alcohol-induced "sleep-time" may have resulted in differential ion channel structure or function in these mice.

  11. Perennial soybean seeds coated with high doses of boron and zinc ...

    African Journals Online (AJOL)

    The objective of this work was to study combinations of high doses of boron (B) and zinc (Zn) in the recoating of perennial soybean seeds, in order to provide these nutrients to the future plants. The physical, physiological and nutritional characteristics of the coated seeds and initial development of plants in a greenhouse ...

  12. Early Angiographic Resolution of Cerebral Vasospasm with High Dose Intravenous Milrinone Therapy

    Directory of Open Access Journals (Sweden)

    F. A. Zeiler

    2015-01-01

    Full Text Available Background. Treatment of symptomatic delayed cerebral ischemia (DCI after subarachnoid hemorrhage (SAH is difficult. Recent studies suggest intravenous (IV high dose milrinone as a potential therapy. The timing to angiographic response with this is unclear. Methods. We reviewed the chart of one patient admitted for SAH who developed symptomatic DCI and was treated with high dose IV milrinone. Results. A 66-year-old female was admitted with a Hunt and Hess clinical grade 4, World Federation of Neurological Surgeons (WFNS clinical grade 4, and SAH secondary to a left anterior choroidal artery aneurysm which was clipped. After bleed day 6, the patient developed symptomatic DCI. We planned for angioplasty of the proximal segments. We administered high dose IV milrinone bolus followed by continuous infusion which led to clinical improvement prior to angiography. The angiogram performed 1.5 hours after milrinone administration displayed resolution of the CT angiogram and MRI based cerebral vasospasm such that further intra-arterial therapy was aborted. She completed 6 days of continuous IV milrinone therapy, was transferred to the ward, and subsequently rehabilitated. Conclusions. High dose IV milrinone therapy for symptomatic DCI after SAH can lead to rapid neurological improvement with dramatic early angiographic improvement of cerebral vasospasm.

  13. Quantitative MR changes in Gd-DTPA enhancement after high dose intravenous methylprednisolone in multiple sclerosis

    International Nuclear Information System (INIS)

    Barkhof, F.; Valk, J.; Hommes, O.R.; Scheltens, P.

    1991-01-01

    The purpose of this study was to investigate the effect of high dose intravenous methylprednisolone (MP) on gadolinium-DTPA enhancement in MS-lesions. By means of this the influence of MP on the permeability of the blood-brain barrier can be studied. (author). 19 refs.; 1 fig

  14. Irreversible neurological worsening following high-dose corticosteroids in advanced progressive multiple sclerosis

    NARCIS (Netherlands)

    Koch, M; De Keyser, J

    2006-01-01

    Background: A course of high-dose corticosteroids has been shown to hasten recovery from a relapse of multiple sclerosis (MS). Some patients with progressive MS ask for a course with corticosteroids outside a relapse, hoping to gain some functional improvement. Objective: To describe 4 patients with

  15. Cytoprotective responses in HaCaT keratinocytes exposed to high doses of curcumin

    NARCIS (Netherlands)

    Lundvig, D.M.S.; Pennings, S.W.C.; Brouwer, K.M.; Mtaya-Mlangwa, M.; Mugonzibwa, E.; Kuijpers-Jagtman, A.M.; Wagener, F.A.D.T.G.; Hoff, J.W. Von den

    2015-01-01

    Wound healing is a complex process that involves the well-coordinated interactions of different cell types. Topical application of high doses of curcumin, a plant-derived polyphenol, enhances both normal and diabetic cutaneous wound healing in rodents. For optimal tissue repair interactions between

  16. Absorption of high-dose enteral vitamin A in lowbirth- weight neonates

    African Journals Online (AJOL)

    A randomised, double-blind placebo-controlled trial was designed to detennine whether high-dose (25 000 IU) enteral vitamin A. to correct deficiency, would be absorbed and well tolerated in low-birth-weight (LBW) neonates. Thirty-five LBW infants (950 - 1 700 g; gestational age 27 - 36 weeks) were allocated to receive ...

  17. Severe encephalopathy after high-dose chemotherapy with autologous stem cell support for brain tumours

    NARCIS (Netherlands)

    van den Berkmortel, F.; Gidding, C.; de Kanter, M.; Punt, C. J. A.

    2006-01-01

    Recurrent medulloblastoma carries a poor prognosis. Long-term survival has been obtained with high-dose chemotherapy with autologous stem cell transplantation and secondary irradiation. A 21-year-old woman with recurrent medulloblastoma after previous chemotherapy and radiotherapy is presented. The

  18. Surface damage of 316 stainless steel irradiated with 4He+ to high doses

    International Nuclear Information System (INIS)

    Kaminsky, M.; Das, S.K.

    1978-01-01

    Surface blistering of niobium by implantation with helium ions in the 9 to 15 keV range was investigated. The apparent disappearance of blisters at sufficiently high doses was believed to be an equilibrium effect. To determine whether high temperature annealing causes the equilibrium condition, stainless steel-316 samples were irradiated at a constant 450 0 C. Results are presented

  19. Clinical approaches involving thrombopoietin to shorten the period of thrombocytopenia after high-dose chemotherapy

    NARCIS (Netherlands)

    Tijssen, Marloes R.; van der Schoot, C. Ellen; Voermans, Carlijn; Zwaginga, Jaap Jan

    2006-01-01

    High-dose chemotherapy followed by a peripheral blood stem cell transplant is successfully used for a wide variety of malignancies. A major drawback, however, is the delay in platelet recovery. Several clinical strategies using thrombopoietin (Tpo) have been developed in an attempt to speed up

  20. High-dose chemotherapy : studies on supportive care, quality of life and late effects of treatment

    NARCIS (Netherlands)

    Nieboer, Peter

    2008-01-01

    Drug resistance is a major problem in the treatment of malignancies. Based on steep dose-response relationship for certain chemotherapeutic drugs in vitro on tumor cell survival, high-dose chemotherapy was considered of interest for the treatment of malignancies. Introduction of autologous

  1. Hemolytic uremic syndrome after high dose chemotherapy with autologous stem cell support

    NARCIS (Netherlands)

    van der Lelie, H.; Baars, J. W.; Rodenhuis, S.; Van Dijk, M. A.; de Glas-Vos, C. W.; Thomas, B. L.; van Oers, R. H.; von dem Borne, A. E.

    1995-01-01

    BACKGROUND: Chemotherapy intensification may lead to new forms of toxicity such as hemolytic uremic syndrome. METHODS: Three patients are described who developed this complication 4 to 6 months after high dose chemotherapy followed by autologous stem cell support. The literature on this subject is

  2. Perioperative Interstitial High-Dose-Rate Brachytherapy for the Treatment of Recurrent Keloids

    DEFF Research Database (Denmark)

    Jiang, Ping; Baumann, René; Dunst, Jürgen

    2016-01-01

    PURPOSE: To prospectively evaluate high-dose-rate brachytherapy in the treatment of therapy-resistant keloids and report first results, with emphasis on feasibility and early treatment outcome. METHODS AND MATERIALS: From 2009 to 2014, 24 patients with 32 recurrent keloids were treated with immed...

  3. Influence of high doses of manganese, copper, zinc and boron on some legumes

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, G

    1973-01-01

    Macroscopic and microscopic examinations showed the following symptoms of an excess in trace elements: (1) High doses of manganese (50-150 ppm) cause dark patches (chloroplast accumulation) in young leaves, and necrosis of the leaf margin (MnO/sub 2/ accumulation) in older leaves. The roots become brown and die off. Roots newly formed in compensation are strikingly light-colored. (2) High doses of copper (5-40 ppm) cause iron deficiency chlorosis. A large number of side roots develop in quick succession as a result of damage to the root apex, so that a thick tangle of roots is formed. (3) High doses of zinc (50-150 ppm) bring about dark green, very brittle young leaves with very high ZnO content. The older leaves become red and then yellow. The roots remain stunted because of inhibited growth in length. (4) High doses of boron (30-90 ppm) cause a leaf necrosis which proceeds in the sequence tip, margin, lamina. The roots are not affected in any characteristic way. They become brown and die off.

  4. Determination of air kerma standard of high dose rate 192Ir brachytherapy source

    International Nuclear Information System (INIS)

    Pires, E.J.; Alves, C.F.E.; Leite, S.P.; Magalhaes, L.A.G.; David, M.G.; Almeida, C.E. de

    2015-01-01

    This paper presents the methodology developed by the Laboratorio de Ciencias Radiologicas and presently in use for determining of the air kerma standard of 192 Ir high dose rate sources to calibrate well-type chambers. Uncertainty analysis involving the measurements procedure are presented. (author)

  5. Hemolytic anemia following high dose intravenous immunoglobulin in patients with chronic neurological disorders

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Christiansen, I; Harbo, Thomas

    2014-01-01

    High dose intravenous immunoglobulin (IVIG) is an established treatment for various neuromuscular disorders. Recently, cases of hemolytic anemia following IVIG have been observed. The objective of this study was to determine the extent of anemia and hemolysis after IVIG and its relationship...

  6. High-dose therapy followed by bone marrow transplantation for relapsed follicular non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Schouten, IC; Raemaekers, JJM; Kluin-Nelemans, HC; vanKamp, H; Mellink, WAM; vantVeer, MB

    1996-01-01

    Purpose: To analyze whether, in addition to survival, and disease-free survival progression-free interval after transplantation would be longer than the last progression-free interval before transplantation, supporting the argument that high-dose therapy may change the biologic behavior of the

  7. Maternal high-dose folic acid during pregnancy and asthma medication in the offspring

    NARCIS (Netherlands)

    Zetstra-van der Woude, Priscilla A.; De Walle, Hermien E. K.; Hoek, Annemieke; Bos, H. Jens; Boezen, H. Marike; Koppelman, Gerhard H.; de Jong-van den Berg, Lolkje T. W.; Scholtens, Salome

    2014-01-01

    Purpose Low-dose folic acid supplementation (0.5 mg) taken during pregnancy has been associated with an increased risk for childhood asthma. The effect of high-dose folic acid (5 mg) advised to women at risk for having a child with neural tube defect has not been assessed so far. Our aim was to

  8. Occlusion-amblyopia following high dose oral levodopa combined with part time patching

    OpenAIRE

    Mihir Kothari

    2014-01-01

    Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  9. Occlusion-amblyopia following high dose oral levodopa combined with part time patching.

    Science.gov (United States)

    Kothari, Mihir

    2014-12-01

    Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  10. Occlusion-amblyopia following high dose oral levodopa combined with part time patching

    Directory of Open Access Journals (Sweden)

    Mihir Kothari

    2014-01-01

    Full Text Available Part time occlusion therapy is not reported to cause occlusion (reverse amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  11. High Dose Ascorbate Causes Both Genotoxic and Metabolic Stress in Glioma Cells

    Science.gov (United States)

    Castro, Maria Leticia; Carson, Georgia M.; McConnell, Melanie J.; Herst, Patries M.

    2017-01-01

    We have previously shown that exposure to high dose ascorbate causes double stranded breaks (DSBs) and a build-up in S-phase in glioblastoma (GBM) cell lines. Here we investigated whether or not this was due to genotoxic stress as well as metabolic stress generated by exposure to high dose ascorbate, radiation, ascorbate plus radiation and H2O2 in established and primary GBM cell lines. Genotoxic stress was measured as phosphorylation of the variant histone protein, H2AX, 8-oxo-7,8-dihydroguanine (8OH-dG) positive cells and cells with comet tails. Metabolic stress was measured as a decrease in NADH flux, mitochondrial membrane potential (by CMXRos), ATP levels (by ATP luminescence) and mitochondrial superoxide production (by mitoSOX). High dose ascorbate, ascorbate plus radiation, and H2O2 treatments induced both genotoxic and metabolic stress. Exposure to high dose ascorbate blocked DNA synthesis in both DNA damaged and undamaged cell of ascorbate sensitive GBM cell lines. H2O2 treatment blocked DNA synthesis in all cell lines with and without DNA damage. DNA synthesis arrest in cells with damaged DNA is likely due to both genotoxic and metabolic stress. However, arrest in DNA synthesis in cells with undamaged DNA is likely due to oxidative damage to components of the mitochondrial energy metabolism pathway. PMID:28737676

  12. Diagnosis of cerebral metastases by means of standard doses of Gadobutrol versus a high-dose protocol. Intraindividual evaluation of a phase-II high-dose study

    International Nuclear Information System (INIS)

    Vogl, T.J.; Friebe, C.E.; Balzer, T.; Mack, M.G.; Steiner, S.; Schedel, H.; Pegios, W.; Lanksch, W.; Banzer, D.; Felix, R.

    1995-01-01

    In a clinical phase-II study 20 patients who had been diagnosed as having brain metastases with CT or MRT were studied prospectively with Gadobutrol, a new nonionic, low osmolality contrast agent. Each patient received an initial injection of 0.1 mmol/kg body weight and an additional dose of 0.2 mmol/kg Gadobutrol 10 min later. Spinecho images were obtained before and after the two applications of Gadobutrol. Dynamic scanning (Turbo-FLASH) was performed for 3 min after each injection of the contrast agent. Both quantitative and qualitative data were intraindividually evaluated. The primary tumor was a bronchial carcinoma in 11 cases; in 9 other cases there were different primary tumors. Forty-eight hours after the use of Gadobutrol there were no adverse signs in the clinical examination, vital signs or blood and urine chemistry. Statistical analysis (Friedman test and Wilcoxon test) of the C/N ratios between tumor and white matter, percentage enhancement, and visual assessment rating revealed statistically significant superiority of high-dose Gadobutrol injection in comparison to the standard dose. The percentage enhancement increased on average from 104% after 0.1 mmol/kg to 162% after 0.3 mmol/kg Gadobutrol. Qualitative delineation and contrast of the lesions increased significantly. The use of high-dose Gadobutrol improved the detection of 36 additional lesions in 6 patients. (orig./VHE) [de

  13. Hypertonic saline solution and high-dose furosemide infusion in cardiorenal syndrome: our experience

    Directory of Open Access Journals (Sweden)

    Francesco Ventrella

    2013-03-01

    Full Text Available Introduction Heart failure is frequently complicated by renal failure, and this association is a negative prognostic factor. These patients sometimes present oligo-/anuria and resistance to high-dose furosemide, a condition referred to as the cardiorenal syndrome (CRS. Acute or chronic reductions in left ventricular function result in decreased blood flow, with reduction of renal perfusion and activation of several neurohormonal systems, which cause resistance to diuretic therapy. This condition often requires ultrafiltration, which is an effective, but invasive and expensive procedure. Infusions of hypertonic saline solution (HSS and high-dose furosemide can be an effective alternative. Materials and methods From November 2009 through May 2010, our team treated 20 patients with CRS and resistance to iv boluses of high-dose furosemide. These patients were treated with small-volume (150-250 mL infusions of HSS (NaCl 1.57 – 4.5%, depending on serum Na values and high-dose furosemide twice a day. The aim of this treatment is to modify renal hemodynamics and the water-saline balance in the kidney by counteracting the extracellular fluid accumulation and eliminating symptoms of congestion. Results In 18 patients (90%, urine output was restored and renal function improved during the first hours of treatment. Clinical improvement was evident from the first day of therapy, and there were no adverse events. Two patients (10% did not respond to the treatment: one (who had been in critical condition since admission died; the other required regular sessions of ultrafiltration. Conclusions HSS combined with high-dose furosemide is a safe, effective, low-cost approach to the treatment of CRS that is resistant to diuretic therapy.

  14. Review of high-dose intravenous vitamin C as an anticancer agent.

    Science.gov (United States)

    Wilson, Michelle K; Baguley, Bruce C; Wall, Clare; Jameson, Michael B; Findlay, Michael P

    2014-03-01

    In the 1970s, Pauling and Cameron reported increased survival of patients with advanced cancer treated with high-dose intravenous (IV) vitamin C (L-ascorbate, ascorbic acid). These studies were criticized for their retrospective nature and lack of standardization of key prognostic factors including performance status. Subsequently, several well-designed randomized controlled trials failed to demonstrate a significant survival benefit, although these trials used high-dose oral vitamin C. Marked differences are now recognized in the pharmacokinetics of vitamin C with oral and IV administration, opening the issue of therapeutic efficacy to question. In vitro evidence suggests that vitamin C functions at low concentrations as an antioxidant but may have pro-oxidant activity at high concentrations. The mechanism of its pro-oxidant action is not fully understood, and both intra- and extracellular mechanisms that generate hydrogen peroxide have been proposed. It remains to be proven whether vitamin C-induced reactive oxygen species occur in vivo and, if so, whether this will translate to a clinical benefit. Current clinical evidence for a therapeutic effect of high-dose IV vitamin C is ambiguous, being based on case series. The interpretation and validation of these studies is hindered by limited correlation of plasma vitamin C concentrations with response. The methodology exists to determine if there is a role for high-dose IV vitamin C in the treatment of cancer, but the limited understanding of its pharmacodynamic properties makes this challenging. Currently, the use of high-dose IV vitamin C cannot be recommended outside of a clinical trial. © 2014 Wiley Publishing Asia Pty Ltd.

  15. High Dose Oral Calcium Treatment in Patients with Vitamin D-dependent Rickets Type II

    Directory of Open Access Journals (Sweden)

    R Vakili

    2017-02-01

    Full Text Available BACKGROUND AND OBJECTIVE: Vitamin D-dependent rickets type II (VDDR2 is a rare genetic disorder caused by mutations in vitamin D receptor (VDR and leads to resistance to biological effects of calcitriol. Based on the type of mutation, this disease is resistant to calcitriol even at high doses of calcitriol and successful treatment of these patients requires hypocalcemic modification through administration of high doses of calcium and bypassing the intestinal defect in VDR signaling. In addition to the need for frequent hospitalization and high costs, intravenous administration of calcium is associated with complications and problems such as arrhythmia and sepsis, venous catheter infection and hypercalciuria. This study aims to report the positive treatment effects of high doses of oral calcium in 4 patients with vitamin D-dependent rickets type II. CASE REPORT: In this study, 4 patients with vitamin D-dependent rickets type II, diagnosed based on clinical and biochemical symptoms of rickets with alopecia, underwent therapy using high doses of oral calcium (300 mg/kg/day in pediatric endocrinology and metabolism center of Imam Reza hospital. After a short period, increased growth rate in height, strength and elasticity of muscles was observed in addition to biochemical improvements without serious side effects and even one patient started walking independently within the first week of therapy for the first time. Patients were regularly followed up in terms of height and weight, growth rate and biochemical factors including calcium, phosphorus and alkaline phosphatase every 3 months for one year. CONCLUSION: Regardless of the type of mutation in vitamin D receptor, it is suggested that a 3-6 months trial of high dose oral calcium be started in each patient with vitamin D-dependent rickets type II, particularly for patients whose disease was diagnosed at lower ages.

  16. Treatment of carcinoma of uterine cervix with high-dose-rate intracavitary irradiation using Ralstron

    International Nuclear Information System (INIS)

    Suh, C.O.; Kim, G.E.; Loh, J.J.K.

    1988-01-01

    From May 1979 through December 1981, a total of 530 patients with carcinoma of the uterine cervix were treated with radiation therapy with curative intent. Of the 530 patients, 365 were treated with a high-dose-rate remote-controlled afterloading system (RALS) using a cobalt source, and 165 patients received a low dose rate using a radium source. External pelvic irradiation with a total of 40-50 Gy to the whole pelvis followed by intracavitary radiation (ICR) with a total dose of 30-39 Gy in ten to 13 fractions to point A was the treatment protocol. ICR was given three times a week with a dose of 3 Gy per fraction. Five-year actuarial survival rate with high-dose-rate ICR by stage was as follows: stage I:82.7% (N = 19) stage II:69.6% (N = 184), and stage III:52.2% (N = 156). The above results were comparable with those with conventional low-dose-rate ICR treatment, and late complications were far less. The application of high-dose-rate ICR was technically simple and easily performed on an outpatient basis without anesthesia, and the patients tolerated it very well. Radiation exposure to personnel was virtually none as compared with that of low-dose-rate ICR. Within a given period of time, more patients can be treated with high-dose-rate ICR because of the short treatment time. The authors therefore conclude that high-dose-rate ICR is suitable for a cancer center where a large number of patients are to be treated

  17. High-dose anti-histamine use and risk factors in children with urticaria.

    Science.gov (United States)

    Uysal, Pınar; Avcil, Sibelnur; Erge, Duygu

    2016-12-01

    The drugs of choice in the treatment of urticaria in children are H1-antihistamines. The aim of the study was to evaluate children with urticaria and define risk factors for requirement of high-dose H1-antihistamines in children with urticaria. The medical data of children who were diagnosed as having urticaria admitted to our outpatient clinic between January 2014 and January 2016 were searched. The medical histories, concomitant atopic diseases, parental atopy histories, medications, treatment responses, blood eosinophil and basophil counts, and serum total IgE levels were recorded. In addition, the urticaria activity score for seven days, autoimmune antibody tests, and skin prick test results were evaluated in children with chronic urticaria. The numbers of the children with acute and chronic urticaria were 138 and 92, respectively. The age of the children with chronic urticaria was higher than that of those with acute urticaria (p0.05). There was a negative correlation between blood eosinophil count and the UAS7 score in children with chronic urticaria (r=-0.276, p=0.011). Chronic urticaria and requirement of high dose H1-antihistamines were significant in children aged ≥10 years (p<0.001, p=0.015). High UAS7 score (OR: 1.09; CI 95%: [1.03-1.15]) and basopenia (OR: 6.77; CI 95%: [2.01-22.75]) were associated with the requirement of high-dose H1-AH in children with chronic urticaria. The requirement of high-dose H1-antihistamines was higher with children's increasing age. Disease severity and basopenia were risk factors for the requirement of high-dose H1-antihistamines.

  18. Braquiterapia de alta taxa de dose no Brasil High-dose rate brachytherapy in Brazil

    Directory of Open Access Journals (Sweden)

    Sérgio Carlos Barros Esteves

    2004-10-01

    Full Text Available A braquiterapia de alta taxa de dose foi introduzida em nosso meio em janeiro de 1991. Desde então, houve uma mudança significativa na abordagem das neoplasias malignas em relação às vantagens do novo método, e também resolução da demanda reprimida de braquiterapia para as neoplasias ginecológicas. Nos primeiros dez anos de atividade, o Brasil tratou, em 31 serviços, 26.436 pacientes com braquiterapia, sendo mais de 50% das pacientes portadoras de neoplasias do colo uterino. Este estudo mostra o número e o perfil de pacientes tratados com esse método e a sua distribuição no território nacional, deixando explícito o benefício da braquiterapia de alta taxa de dose para o Brasil.High-dose rate brachytherapy was first introduced in Brazil in January 1991. Significant changes in the management of malignant neoplasms were observed since utilization of high-dose rate brachytherapy. The high number of gynecological patients awaiting for brachytherapy also decreased during this period. In the first ten years 26,436 patients were treated with high-dose rate brachytherapy. More than 50% of these patients presented neoplasms of the uterine cervix. In this study we present the number and profile of the patients treated with high-dose rate brachytherapy as well as the distribution of these patients in the Brazilian territory, proving the benefit of the use of high-dose rate brachytherapy in Brazil.

  19. Impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat

    Directory of Open Access Journals (Sweden)

    Jan Muhammad Shah

    2016-10-01

    Full Text Available Aim: The aim of this study was to evaluate the impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat species. Materials and Methods: Six mature, healthy goats (combine breed and sex with average weight 25 kg were selected for this study. The therapeutic (20 mg/kg b.w. and high doses (40 and 60 mg of florfenicol were administered for 3 days with 24 h interval. Blood samples were collected at 0, 24, 48, 72, 96, and 120 h following the each administered dose. Results: The results showed that the therapeutic dose of florfenicol produced nonsignificant effect on serum urea, creatinine, total protein (TP, alkaline phosphatase (ALP, gamma-glutamyl transferase (GGT and bilirubin on all timings, and increased (p<0.05 the serum glutamic oxaloacetic transaminase (SGOT and serum glutamate-pyruvate transaminase (SGPT levels for 48 h. Whereas the high doses of florfenicol (40 and 60 mg significantly altered the kidney and liver functional indicators in the blood. In contrast with control, the serum urea level was (p<0.01 increased at all timing points. Creatinine values were altered (p<0.01, <0.05 in increasing manner from 24 to 96 h. The high dose of 40 mg decreased the TP (p<0.05 for 72 h and 60 mg persisted same effect (p<0.01 up to 120 h. The indices of ALP, GGT, SGOT, and SGPT were raised (p<0.01, <0.05 at all timings. The bilirubin indexes also (p<0.05 elevated from 48 to 72. Conclusion: It was concluded that the high doses of florfenicol produced reversible dose-dependent effects on functional indicators of kidney and liver such as urea, creatinine, TP, ALP, SGOT, SGPT, GGT, and bilirubin.

  20. Reactivation of herpes simplex virus in a cell line inducible for simian virus 40 synthesis

    International Nuclear Information System (INIS)

    Zamansky, G.B.; Kleinman, L.F.; Black, P.H.; Kaplan, J.C.

    1980-01-01

    The reactivation of UV-irradiated herpes simplex virus (HSV) was investigated in irradiated and unirradiated transformed hamster cells in which infectious simian virus 40(SV40) can be induced. Reactivation was enhanced when the cells were treated with UV light or mitomycin C prior to infection with HSV. The UV dose-response curve of this enhanced reactivation was strikingly similar to that found for induction of SV40 virus synthesis in cells treated under identical conditions. This is the first time that two SOS functions described in bacteria have been demonstrated in a single mammalian cell line. (orig.)

  1. Efficacy and Safety of Single and Double Doses of Ivermectin versus 7-Day High Dose Albendazole for Chronic Strongyloidiasis

    Science.gov (United States)

    Suputtamongkol, Yupin; Premasathian, Nalinee; Bhumimuang, Kid; Waywa, Duangdao; Nilganuwong, Surasak; Karuphong, Ekkapun; Anekthananon, Thanomsak; Wanachiwanawin, Darawan; Silpasakorn, Saowaluk

    2011-01-01

    , and double doses of oral ivermectin respectively (P = 0.006) in modified intention to treat analysis. No serious adverse event associated with treatment was found in any of the groups. Conclusion/Significance This study confirms that both a single, and a double dose of oral ivermectin taken two weeks apart, is more effective than a 7-day course of high dose albendazole for patients with chronic infection due to S. stercoralis. Double dose of ivermectin, taken two weeks apart, might be more effective than a single dose in patients with concomitant illness. Trial Registration ClinicalTrials.gov NCT00765024 PMID:21572981

  2. Approach to a child with primary immunodeficiency

    Directory of Open Access Journals (Sweden)

    Özge Yılmaz

    2010-09-01

    Full Text Available Primary immunodeficiencies are clinically and epidemiologically important, despite their low prevalence, due to the associated risk of high morbidity and mortality. Most commonly encountered primary immunodeficiencies include humoral immune system deficiencies, cellular immune system defects, combined immunodeficiencies, phagocyte system defects, complement system defects. Classical clinical findings of immunodeficiencies include recurrent, severe infections which do not respond to treatment or which progress with complications as well as tendency to develop infections with low virulence microorganisms. Moreover, they may present with autoimmunity, autoinflammatory or hemaphagocytic syndromes. Congenital diseases usually start in early childhood and lead to morbidity and mortality. Therefore, early diagnosis may be life saving and allow increasing quality of life, genetic counseling or prenatal diagnosis. Considering primary immunodeficiencies more frequently in differential diagnosis and early immunological evaluation would lead to early diagnosis of these patients and allow them to reach early treatment or preventive measures.

  3. Lymphocytes B and primary immunodeficiencies

    Directory of Open Access Journals (Sweden)

    Gabriela López-Herrera

    2016-03-01

    Full Text Available Primary antibody deficiencies represent the most frequent genetic diseases of the immune system and the first to be recognized along immunology history. The antibodies were recognized as part of the humoral immune system long ago, and after immunoglobulin discovery, the first antibody immunodeficiency were recognized and named as “agammaglobulinemia”, followed by the common variable immunodeficiency and the hyper-IgM syndrome. The following discoveries in immunology history made possible the understanding of these pathologies, for example: the discoveries of B cells, pre-B cells, the signaling pathway directed by the antigen receptor and many other cellular and molecular mechanisms. Primary antibody deficiencies have been studied for a long time and the discoveries of new syndromes have been helpful in the understanding of immunological mechanisms that take place in our organism. Then, this manuscript pretends to review the relevant findings in the history of immunology, focused on the B cells and the connection with the description of representative clinical entities of primary antibody deficiencies. The aim of this manuscript is to show to the reader that the generation of scientific knowledge has a direct application in the understanding of the molecular mechanisms that are affected in these diseases.

  4. Evidence for a Euro-American origin of human immunodeficiency virus (HIV).

    Science.gov (United States)

    Katner, H P; Pankey, G A

    1987-10-01

    Recent reports of the nonspecificity of the enzyme-linked immunosorbent assay (ELISA) test in African populations, significant genomic differences between simian T-cell lymphotropic virus and human immunodeficiency virus (HIV), and the early appearance of clinical acquired immunodeficiency syndroME (AIDS) in the US and Europe are powerful arguments against the assumption that AIDS originated in Africa. The authors postulate that HIV infection has been endemic in the Euro-American population at least since the beginning of the 20th century and that sociocultural changes led to the introduction of the virus into Africa. A search of the literature reveals 28 cases of disseminated Kaposi's sarcoma in the pre-epidemic 1902-66 period. In none of these cases are notations made on intravenous drug abuse, homosexuality, or other risk factors for AIDS. The majority of cases involved men, however. It is pointed out that, in a population where the incidence of a virus such as HIV is low, the number of sexual partners is limited, and intravenous drug abuse is nonexistent, an infection with as long a latency period as HIV may not only be expressed sporadically, but would probably not be recognized as a transmissible infection. On the other hand, the significant changes in these social factors that occurred as a result of the sexual revolution of the late 1960s and early 1970s would be expected to increase the spread of infection and clinical disease so that recognition would be achieved. During the past decade, there have been marked increases in the number of sexually transmitted infections in the homosexual male population. The efficiency of anal intercourse as a mode of transmission probably accounts for the fact that HIV infection first expressed itself in this population.

  5. Dramatic response to high-dose icotinib in a lung adenocarcinoma patient after erlotinib failure.

    Science.gov (United States)

    Guan, Yin; Zhao, Hong; Meng, Jing; Yan, Xiang; Jiao, ShunChang

    2014-02-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) retreatment is rarely administered for non-small cell lung cancer (NSCLC) patients who did not respond to previous TKI treatment. A high dose of TKI may overcome resistance to the standard dose of TKI and have different effectiveness toward cancer compared with the standard dose of TKI. This manuscript describes a dramatic and durable response to high-dose icotinib in a NSCLC patient who did not respond to a previous standard dose of erlotinib. The treatment extended the life of the patient for one additional year. A higher dose of icotinib deserves further study not only for patients whose therapy failed with the standard dose of TKI but also for newly diagnosed NSCLC patients with a sensitive mutation. Serial mutation testing during disease development is necessary for analysis and evaluation of EGFR TKI treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Heavy ion time-of-flight ERDA of high dose metal implanted germanium

    Energy Technology Data Exchange (ETDEWEB)

    Dytlewski, N.; Evans, P.J.; Noorman, J.T. [Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW (Australia); Wielunski, L.S. [Commonwealth Scientific and Industrial Research Organisation (CSIRO), Lindfield, NSW (Australia). Div. of Applied Physics; Bunder, J. [New South Wales Univ., Wollongong, NSW (Australia). Wollongong Univ. Coll

    1996-12-31

    With the thick Ge substrates used in ion implantation, RBS can have difficulty in resolving the mass-depth ambiguities when analysing materials composed of mixtures of elements with nearly equal masses. Additional, and complimentary techniques are thus required. This paper reports the use of heavy ion time-of-flight elastic recoil detection analysis (ToF- ERDA), and conventional RBS in the analysis of Ge(100) implanted with high dose Ti and Cu ions from a MEWA ion source . Heavy ion ToF ERDA has been used to resolve, and profile the implanted transition metal species, and also to study any oxygen incorporation into the sample resulting from the implantation, or subsequential reactions with air or moisture. This work is part of a study on high dose metal ion implantation of medium atomic weight semiconductor materials. 13 refs., 6 figs.

  7. Heavy ion time-of-flight ERDA of high dose metal implanted germanium

    Energy Technology Data Exchange (ETDEWEB)

    Dytlewski, N; Evans, P J; Noorman, J T [Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW (Australia); Wielunski, L S [Commonwealth Scientific and Industrial Research Organisation (CSIRO), Lindfield, NSW (Australia). Div. of Applied Physics; Bunder, J [New South Wales Univ., Wollongong, NSW (Australia). Wollongong Univ. Coll

    1997-12-31

    With the thick Ge substrates used in ion implantation, RBS can have difficulty in resolving the mass-depth ambiguities when analysing materials composed of mixtures of elements with nearly equal masses. Additional, and complimentary techniques are thus required. This paper reports the use of heavy ion time-of-flight elastic recoil detection analysis (ToF- ERDA), and conventional RBS in the analysis of Ge(100) implanted with high dose Ti and Cu ions from a MEWA ion source . Heavy ion ToF ERDA has been used to resolve, and profile the implanted transition metal species, and also to study any oxygen incorporation into the sample resulting from the implantation, or subsequential reactions with air or moisture. This work is part of a study on high dose metal ion implantation of medium atomic weight semiconductor materials. 13 refs., 6 figs.

  8. High dose rate intracavitary afterloading irradiation in malignant inoperable obturation of bile ducts

    Energy Technology Data Exchange (ETDEWEB)

    Itami, J.; Saegusa, K.; Mamiya, T.; Miyoshi, T.; Arimizu, N.; Tsuchiya, Y.; Ohto, M.

    1986-02-01

    After decompression of the bile duct with PTCD, seven patients with carcinomas of the bile ducts were submitted to an intracavitary Ir-afterloading irradiation performed according to the high-dose-rate method with a Buchler device. Most of the patients were irradiated with 30 Gy in two fractions. Five patients were also exposed to percutaneous radiation with 40 to 50 Gy. Local control was achieved in six patients. One patient developed a locoregional recurrence which was possibly due to a so-called 'geographic miss'. In one patient a benign fibrotic stenosis of the bile duct was found at the site of most intensive irradiation. Intracavitary irradiation is very important in the treatment of malignant of bile ducts. However, there is an urgent need of research with regard to the combined method with percutaneous irradiation and to the optimum fractionation of intracavitary high dose rate irradiation.

  9. Evaluation of glasses containing cadmium for high dose dosimetry by the thermoluminescence technique

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, Gabriel Soares Marchiori de; Ferreira, Pamela Zati; Cunha, Diego Merigue da; Dantas, Noelio Oliveira; Silva, Anielle C.A.; Perini, Ana Paula; Neves, Lucio Pereira, E-mail: lucio.neves@ufu.br [Universidade Federal de Uberlandia (INFIS/UFU), MG (Brazil). Instituto de Fisica; Caldas, Linda V.E. [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil); Carrera, Betzabel Noemi Silva; Watanabe, Shigueo [Universidade de Sao Paulo (IF/USP), SP (Brazil). Instituto de Fisica

    2016-07-01

    New glass matrices were evaluated for high dose dosimetry by the thermoluminescence technique. Their nominal composition are 20Li{sub 2}CO{sub 3}.10Al{sub 2}O{sub 3}.15CdO.55B{sub 2}O{sub 3} and 20Li{sub 2}CO{sub 3}.10Al{sub 2}O{sub 3}.20CdO.50B{sub 2}O{sub 3} (mol%). The glass matrices were irradiated with different doses: 50, 100, 200, 500, 700 and 900 Gy, and the thermoluminescence emission curves were obtained for each of these values. The results show a great potential of using these matrices in high dose dosimetry. (author)

  10. Study of a new glass matrix by thermoluminescent technique for high-dose dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Pamela Z.; Carvalho, Gabriel S. Marchiori de; Cunha, Diego M. da; Dantas, Noelio O.; Silva, Anielle C.A.; Neves, Lucio P.; Perini, Ana P., E-mail: anapaula.perini@ufu.br [Universidade Federal de Uberlandia (UFU), MG (Brazil). Instituto de Fisica; Linda, V.E. Caldas [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Carrera, Betzabel N.S.; Watanabe, Shigueo [Universidade de Sao Paulo (IF/USP), Sao Paulo, SP (Brazil). Instituto de Fisica

    2016-07-01

    The thermoluminescence technique is widely used for both personal and for high-dose dosimetry. In this work, the thermoluminescence technique was utilized to study a new glass matrix, with nominal composition of 20Li{sub 2}CO{sub 3}.10Al{sub 2}O{sub 3}.30BaO.40B{sub 2}O{sub 3} (mol%), irradiated with different doses in a {sup 60}Co source. The glow curves and the dose-response curve were obtained for radiation doses of 10, 50, 100, 200 e 700 Gy. The results showed that this new glass matrix has potential use in high-dose dosimetry. (author)

  11. Practice for characterization and performance of a high-dose radiation dosimetry calibration laboratory

    International Nuclear Information System (INIS)

    2003-01-01

    This practice addresses the specific requirements for laboratories engaged in dosimetry calibrations involving ionizing radiation, namely, gamma-radiation, electron beams or X-radiation (bremsstrahlung) beams. It specifically describes the requirements for the characterization and performance criteria to be met by a high-dose radiation dosimetry calibration laboratory. The absorbed-dose range is typically between 10 and 10 5 Gy. This practice addresses criteria for laboratories seeking accreditation for performing high-dose dosimetry calibrations, and is a supplement to the general requirements described in ISO/IEC 17025. By meeting these criteria and those in ISO/IEC 17025, the laboratory may be accredited by a recognized accreditation organization. Adherence to these criteria will help to ensure high standards of performance and instill confidence regarding the competency of the accredited laboratory with respect to the services it offers

  12. Synergies Between ' and Cavity Formation in HT-9 Following High Dose Neutron Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Parish, Chad M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Saleh, Tarik A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Eftink, Benjamin P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-06-01

    Candidate cladding materials for advanced nuclear power reactors including fast reactor designs require materials capable of withstanding high dose neutron irradiation at elevated temperatures. One candidate material, HT-9, through various research programs have demonstrated the ability to withstand significant swelling and other radiation-induced degradation mechanisms in the high dose regime (>50 displacements per atom, dpa) at elevated temperatures (>300 C). Here, high efficiency multi-dimensional scanning transmission electron microscopy (STEM) acquisition with the aid of a three-dimensional (3D) reconstruction and modeling technique is used to probe the microstructural features that contribute to the exceptional swelling resistance of HT-9. In particular, the synergies between ' and fine-scale and moderate-scale cavity formation is investigated.

  13. CT of multiple sclerosis: reassessment of delayed scanning with high doses of contrast material

    International Nuclear Information System (INIS)

    Spiegel, S.M.; Vinuela, F.; Fox, A.J.; Pelz, D.M.

    1985-01-01

    A prospective study involving 87 patients was carried out to evaluate the necessity for a high dose of contrast material in addition to delayed computed tomographic (CT) scanning for optimal detection of the lesions of multiple sclerosis in the brain. In patients with either clinically definite multiple sclerosis or laboratory-supported definite multiple sclerosis, CT scans were obtained with a uniform protocol. Lesions consistent with multiple sclerosis were demonstrated on the second scan in 54 patients. In 36 of these 54 patients, the high-dose delayed scan added information. These results are quite similar to those of a previous study from this institution using different patients, in whom the second scan was obtained immediately after the bolus injection of contrast material containing 40 g of organically bound iodine. The lack of real difference in the results of the two studies indicate that the increased dose, not just the delay in scanning, is necessary for a proper study

  14. Gene expression profiles following high-dose exposure to gamma radiation in salmonella enterica serovar typhimurium

    International Nuclear Information System (INIS)

    Lim, Sang Yong; Jung, Sun Wook; Joe, Min Ho; Kim, Dong Ho

    2008-01-01

    Microarrays can measure the expression of thousands of genes to identify the changes in expression between different biological states. To survey the change of whole Salmonella genes after a relatively high dose of gamma radiation (1 kGy), transcriptome dynamics were examined in the cells by using DNA microarrays. At least 75 genes were induced and 89 genes were reduced two-fold or more after irradiation. Several genes located in pSLT plasmid, cyo operon, and Gifsy prophage were induced along with many genes encoding uncharacterized proteins.While, the expression of genes involved in the virulence of Salmonella as well as metabolic functions were decreased. Although the radiation response as a whole could not be illustrated by using DNA microarrays, the data suggest that the response to high dose of irradiation might be more complex than the SOS response

  15. No seasonal accumulation of resistant P. falciparum when high-dose chloroquine is used

    DEFF Research Database (Denmark)

    Ursing, Johan; Kofoed, Poul-Erik; Rodrigues, Amabelia

    2009-01-01

    increase of pfcrt 76T if the high doses of CQ commonly used are effective. METHODS AND FINDINGS: P. falciparum parasite density, age, sex, the proportion of chloroquine resistance associated haplotypes pfcrt 76T and P. falciparum multidrug resistance gene 1 86Y were assessed in 988 samples collected from...... to become the dominant P.falciparum type in Guinea-Bissau. This is most likely due to the efficacy of high-dose chloroquine as used in Guinea-Bissau, combined with a loss of fitness associated with pfcrt 76T.......BACKGROUND: Potentially chloroquine resistant P. falciparum, identified by the 76T haplotype in the chloroquine resistance transporter (pfcrt 76T), are highly prevalent throughout Africa. In Guinea-Bissau, normal and double dose chloroquine have respective efficacies of 34% and 78% against P...

  16. The radiosensitizing effect of doranidazole on human colorectal cancer cells exposed to high doses of irradiation

    International Nuclear Information System (INIS)

    Zhang, Li; Gong, Aimin; Ji, Jun; Wu, Yuanyuan; Zhu, Xiaoyu; Lv, Suqing; Lv, Hongzhu; Sun, Xizhuo

    2007-01-01

    This paper investigates the effects of a new radiosensitizer, doranidazole, and enhancing irradiation on colorectal cancer cells. The radiosensitizing effect of doranidazole was determined using colony formation and propidium iodide (PI) assays to measure cell growth inhibition and the cell killing effect of human colorectal cancer cell lines exposed to high doses of γ-ray irradiation under hypoxic conditions in vitro. Fluorescence staining and cell migration assays were also used to assess the radiosensitizing effect. Cell proliferation evaluated by clonogenic survival curves was significantly inhibited by 5 mmol/L doranidazole, particularly at doses ranging from 10 to 30 Gy of irradiation. The radiosensitizing effect of doranidazole on colorectal cancer cells occurs in a time- and dose-dependent manner. Doranidazole also inhibited the mobility of cell invasion and migration. Doranidazole can enhance the killing effect and the cell growth inhibition of colorectal cancer after high-dose irradiation in a time and dose-dependent manner

  17. Gene expression profiles following high-dose exposure to gamma radiation in salmonella enterica serovar typhimurium

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Yong; Jung, Sun Wook; Joe, Min Ho; Kim, Dong Ho [Radiation Research Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2008-08-15

    Microarrays can measure the expression of thousands of genes to identify the changes in expression between different biological states. To survey the change of whole Salmonella genes after a relatively high dose of gamma radiation (1 kGy), transcriptome dynamics were examined in the cells by using DNA microarrays. At least 75 genes were induced and 89 genes were reduced two-fold or more after irradiation. Several genes located in pSLT plasmid, cyo operon, and Gifsy prophage were induced along with many genes encoding uncharacterized proteins.While, the expression of genes involved in the virulence of Salmonella as well as metabolic functions were decreased. Although the radiation response as a whole could not be illustrated by using DNA microarrays, the data suggest that the response to high dose of irradiation might be more complex than the SOS response.

  18. High-dose therapy improved the bone remodelling compartment canopy and bone formation in multiple myeloma

    DEFF Research Database (Denmark)

    Hinge, Maja; Delaissé, Jean-Marie; Plesner, Torben

    2015-01-01

    transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed......Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling....... Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell...

  19. Human immunodeficiency virus long terminal repeat responds to T-cell activation signals

    International Nuclear Information System (INIS)

    Tong-Starksen, S.E.; Luciw, P.A.; Peterlin, B.M.

    1987-01-01

    Human immunodeficiency virus (HIV), the causative agent of AIDS, infects and kills lymphoid cells bearing the CD4 antigen. In an infected cell, a number of cellular as well as HIV-encoded gene products determine the levels of viral gene expression and HIV replication. Efficient HIV replication occurs in activated T cells. Utilizing transient expression assays, the authors show that gene expression directed by the HIV long terminal repeat (LTR) increases in response to T-cell activation signals. The effects of T-cell activation and of the HIV-encoded trans-activator (TAT) are multiplicative. Analysis of mutations and deletions in the HIV LTR reveals that the region responding to T-cell activation signals is located at positions -105 to -80. These sequences are composed of two direct repeats, which are homologous to the core transcriptional enhancer elements in the simian virus 40 genome. The studies reveal that these elements function as the HIV enhancer. By acting directly on the HIV LTR, T-cell activation may play an important role in HIV gene expression and in the activation of latent HIV

  20. A photocurrent compensation method of bipolar transistors under high dose rate radiation and its experimental research

    International Nuclear Information System (INIS)

    Yin Xuesong; Liu Zhongli; Li Chunji; Yu Fang

    2005-01-01

    Experiment using discrete bipolar transistors has been performed to verify the effect of the photocurrent compensation method. The theory of the dose rate effects of bipolar transistors and the photocurrent compensation method are introduced. The comparison between the response of hardened and unhardened circuits under high dose rate radiation is discussed. The experimental results show instructiveness to the hardness of bipolar integrated circuits under transient radiation. (authors)

  1. High dose radiation damage in nuclear energy structural materials investigated by heavy ion irradiation simulation

    International Nuclear Information System (INIS)

    Zheng Yongnan; Xu Yongjun; Yuan Daqing

    2014-01-01

    Structural materials in ITER, ADS and fast reactor suffer high dose irradiations of neutrons and/or protons, that leads to severe displacement damage up to lOO dpa per year. Investigation of radiation damage induced by such a high dose irradiation has attracted great attention along with the development of nuclear energy facilities of new generation. However, it is deeply hampered for the lacking of high dose neutron and proton sources. Irradiation simulation of heavy ions produced by accelerators opens up an effective way for laboratory investigation of high dose irradiation induced radiation damage encountered in the ITER, ADS, etc. Radiation damage is caused mainly by atomic displacement in materials. The displacement rate of heavy ions is about lO 3 ∼10 7 orders higher than those of neutrons and protons. High displacement rate of heavy ions significantly reduces the irradiation time. The heavy ion irradiation simulation technique (HIIS) technique has been developed at China Institute of Atomic Energy and a series of the HIIS experiments have been performed to investigate radiation damage in stainless steels, tungsten and tantalum at irradiation temperatures from room temperature to 800 ℃ and in the irradiation dose region up to 100 dpa. The experimental results show that he radiation swelling peak for the modified stainless steel appears in the temperature region around 580 ℃ and the radiation damage is more sensitive to the temperature, the size of the radiation induced vacancy cluster or void increase with the increasing of the irradiation dose, and among the three materials the home-made modified stainless steel has the best radiation resistant property. (authors)

  2. Persistent DNA damage after high dose in vivo gamma exposure of minipig skin.

    Directory of Open Access Journals (Sweden)

    Emad A Ahmed

    Full Text Available Exposure to high doses of ionizing radiation (IR can lead to localized radiation injury of the skin and exposed cells suffer dsDNA breaks that may elicit cell death or stochastic changes. Little is known about the DNA damage response after high-dose exposure of the skin. Here, we investigate the cellular and DNA damage response in acutely irradiated minipig skin.IR-induced DNA damage, repair and cellular survival were studied in 15 cm(2 of minipig skin exposed in vivo to ~50 Co-60 γ rays. Skin biopsies of control and 4 h up to 96 days post exposure were investigated for radiation-induced foci (RIF formation using γ-H2AX, 53BP1, and active ATM-p immunofluorescence. High-dose IR induced massive γ-H2AX phosphorylation and high 53BP1 RIF numbers 4 h, 20 h after IR. As time progressed RIF numbers dropped to a low of 3-fold elevated at all subsequent time points. Replicating basal cells (Ki67+ were reduced 3 days post IR followed by increased proliferation and recovery of epidermal cellularity after 28 days.Acute high dose irradiation of minipig epidermis impaired stem cell replication and induced elevated apoptosis from 3 days onward. DNA repair cleared the high numbers of DBSs in skin cells, while RIFs that persisted in <1% cells marked complex and potentially lethal DNA damage up to several weeks after exposure. An elevated frequency of keratinocytes with persistent RIFs may thus serve as indicator of previous acute radiation exposure, which may be useful in the follow up of nuclear or radiological accident scenarios.

  3. High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection

    Science.gov (United States)

    2010-06-01

    host defense against a wide range of viral and other pathogens. MBL is a C-type lectin that recognizes hexose sugars including man- nose, glucose...should be evaluatedmore broadly as an immunotherapeutic agent for a wide spectrum of glycosylated pathogens. MATERIALS AND METHODS Production and... coagulation mod- ulators, antisense technologies, therapeutic antibodies and Table 1. Pharmacokinetic Parameters of Low- vs High-Dose Recombinant Human

  4. Biological dose estimation for accidental supra-high dose gamma-ray exposure

    International Nuclear Information System (INIS)

    Chen, Y.; Yan, X.K.; Du, J.; Wang, Z.D.; Zhang, X.Q.; Zeng, F.G.; Zhou, P.K.

    2011-01-01

    To correctly estimate the biological dose of victims accidentally exposed to a very high dose of 60 Co gamma-ray, a new dose-effect curve of chromosomal dicentrics/multicentrics and rings in the supra-high dose range was established. Peripheral blood from two healthy men was irradiated in vitro with doses of 60 Co gamma-rays ranging from 6 to 22 Gy at a dose rate of 2.0 Gy/min. Lymphocytes were concentrated, cultured and harvested at 52 h, 68 h and 72 h. The numbers of dic + r were counted. The dose-effect curves were established and validated using comparisons with doses from the Tokai-mura accident and were then applied to two victims of supra-high dose exposure accident. The results indicated that there were no significant differences in chromosome aberration frequency among the different culture times from 52 h to 72 h. The 6-22 Gy dose-effect curve was fitted to a linear quadratic model Y = -2.269 + 0.776D - 7.868 x l0 -3 D 2 . Using this mathematic model, the dose estimates were similar to data from Tokai-mura which were estimated by PCC ring. Whole body average doses of 9.7 Gy and 18.1 Gy for two victims in the Jining accident were satisfactorily given. We established and successfully applied a new dose-effect curve of chromosomal dicentrics plus ring (dic + r) after 6-22 Gy γ-irradiation from a supra-high dose 60 Co gamma-ray accident.

  5. Quality control of 192Ir high dose rate after loading brachytherapy dose veracity

    International Nuclear Information System (INIS)

    Feng Zhongsu; Xu Xiao; Liu Fen

    2008-01-01

    Recently, 192 Ir high dose rate (HDR) afterloading are widely used in brachytherapy. The advantage of using HDR systems over low dose rate systems are shorter treatment time and higher fraction dose. To guarantee the veracity of the delivery dose, several quality control methods are deseribed in this work. With these we can improve the position precision, time precision and dose precision of the brachytherapy. (authors)

  6. Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy.

    Science.gov (United States)

    Leung, Loh-Shan B; Neal, Joel W; Wakelee, Heather A; Sequist, Lecia V; Marmor, Michael F

    2015-10-01

    To report rapid onset of retinal toxicity in a series of patients followed on high-dose (1000 mg daily) hydroxychloroquine during an oncologic clinical trial studying hydroxychloroquine with erlotinib for non-small cell lung cancer. Retrospective observational case series. Ophthalmic surveillance was performed on patients in a multicenter clinical trial testing high-dose (1000 mg daily) hydroxychloroquine for advanced non-small cell lung cancer. The US Food & Drug Administration-recommended screening protocol included only visual acuity testing, dilated fundus examination, Amsler grid testing, and color vision testing. In patients seen at Stanford, additional sensitive screening procedures were added at the discretion of the retinal physician: high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, Humphrey visual field (HVF) testing, and multifocal electroretinography (mfERG). Out of the 7 patients having exposure of at least 6 months, 2 developed retinal toxicity (at 11 and 17 months of exposure). Damage was identified by OCT imaging, mfERG testing, and, in 1 case, visual field testing. Fundus autofluorescence imaging remained normal. Neither patient had symptomatic visual acuity loss. These cases show that high doses of hydroxychloroquine can initiate the development of retinal toxicity within 1-2 years. Although synergy with erlotinib is theoretically possible, there are no prior reports of erlotinib-associated retinal toxicity despite over a decade of use in oncology. These results also suggest that sensitive retinal screening tests should be added to ongoing and future clinical trials involving high-dose hydroxychloroquine to improve safety monitoring and preservation of vision. Published by Elsevier Inc.

  7. Controversies in external beam and high dose rate brachytherapy of oesophageal cancer

    International Nuclear Information System (INIS)

    Sur, R.K.; Levin, V.C.; Malas, Simon; Donde, Bernard

    1994-01-01

    Various controversies in the treatment of oesophageal carcinoma with external beam radiotherapy and high dose rate intracavitary irradiation have been reviewed. Conflicting results from different parts of the world has made it difficult to optimize the radiation dose that may give the best results. More studies and longer follow-up are needed before a definite conclusion can be made on the optimization of dose. (author). 18 refs., 2 tabs

  8. Non-linear failure analysis of HCPB blanket for DEMO taking into account high dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Aktaa, J., E-mail: jarir.aktaa@kit.edu [Karlsruhe Institute of Technology (KIT), Institute for Applied Materials, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany); Kecskés, S.; Pereslavtsev, P.; Fischer, U.; Boccaccini, L.V. [Karlsruhe Institute of Technology (KIT), Institute for Neutron Physics and Reactor Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany)

    2014-10-15

    Highlights: • First non-linear structural analysis for the European Helium Cooled Pebble Bed Blanket Module taking into account high dose irradiation. • Most critical areas were identified and analyzed with regard to the effect of irradiation on predicted damage at these areas. • Despite the extensive computing time 100 cycles were simulated by using the sub-modelling technique investigating damage at most critical area. • The results show a positive effect of irradiation on calculated damage which is mainly attributed to the irradiation induced hardening. - Abstract: For the European helium cooled pebble bed (HCPB) blanket of DEMO the reduced activation ferritic martensitic steel EUROFER has been selected as structural material. During operation the HCPB blanket will be subjected to complex thermo-mechanical loadings and high irradiation doses. Taking into account the material and structural behaviour under these conditions is a precondition for a reliable blanket design. For considering high dose irradiation in structural analysis of the DEMO blanket, the coupled deformation damage model, extended recently taking into account the influence of high dose irradiation on the material behaviour of EUROFER and implemented in the finite element code ABAQUS, has been used. Non-linear finite element (FE) simulations of the DEMO HCPB blanket have been performed considering the design of the HCPB Test Blanket Module (TBM) as reference and the thermal and mechanical boundary conditions of previous analyses. The irradiation dose rate required at each position in the structure as an additional loading parameter is estimated by extrapolating the results available for the TBM in ITER scaling the value calculated in neutronics and activation analysis for ITER boundary conditions to the DEMO boundary conditions. The results of the FE simulations are evaluated considering damage at most critical highly loaded areas of the structure and discussed with regard to the impact of

  9. Charge collection efficiency in ionization chambers exposed to electron beams with high dose per pulse

    Energy Technology Data Exchange (ETDEWEB)

    Laitano, R F [Istituto Nazionale di Metrologia delle Radiazioni Ionizzanti, ENEA Centro Ricerche Casaccia, c.p. 2400 Rome (Italy); Guerra, A S [Istituto Nazionale di Metrologia delle Radiazioni Ionizzanti, ENEA Centro Ricerche Casaccia, c.p. 2400 Rome (Italy); Pimpinella, M [Istituto Nazionale di Metrologia delle Radiazioni Ionizzanti, ENEA Centro Ricerche Casaccia, c.p. 2400 Rome (Italy); Caporali, C [Istituto Nazionale di Metrologia delle Radiazioni Ionizzanti, ENEA Centro Ricerche Casaccia, c.p. 2400 Rome (Italy); Petrucci, A [A.C.O. S. Filippo Neri, U.O. Fisica Sanitaria, Rome (Italy)

    2006-12-21

    The correction for charge recombination was determined for different plane-parallel ionization chambers exposed to clinical electron beams with low and high dose per pulse, respectively. The electron energy was nearly the same (about 7 and 9 MeV) for any of the beams used. Boag's two-voltage analysis (TVA) was used to determine the correction for ion losses, k{sub s}, relevant to each chamber considered. The presence of free electrons in the air of the chamber cavity was accounted for in determining k{sub s} by TVA. The determination of k{sub s} was made on the basis of the models for ion recombination proposed in past years by Boag, Hochhaeuser and Balk to account for the presence of free electrons. The absorbed dose measurements in both low-dose-per-pulse (less than 0.3 mGy per pulse) and high-dose-per-pulse (20-120 mGy per pulse range) electron beams were compared with ferrous sulphate chemical dosimetry, a method independent of the dose per pulse. The results of the comparison support the conclusion that one of the models is more adequate to correct for ion recombination, even in high-dose-per-pulse conditions, provided that the fraction of free electrons is properly assessed. In this respect the drift velocity and the time constant for attachment of electrons in the air of the chamber cavity are rather critical parameters because of their dependence on chamber dimensions and operational conditions. Finally, a determination of the factor k{sub s} was also made by zero extrapolation of the 1/Q versus 1/V saturation curves, leading to the conclusion that this method does not provide consistent results in high-dose-per-pulse beams.

  10. Radiation proctitis after the high dose rate brachytherapy for prostate cancer

    International Nuclear Information System (INIS)

    Kitano, Masashi; Katsumata, Tomoe; Satoh, Takefumi

    2006-01-01

    We reviewed the medical records of 12 patients treated for rectal bleeding after high-dose rate brachytherapy for prostate cancer. All patients developed grade 2 proctitis according to the Common Terminology Criteria for Adverse Events (CTCAC) and no patients needed blood transfusion. The patients were treated with argon plasma coagulation (APC) and/or steroid suppositories. The bleeding stopped or improved in 11 patients. Although re-bleeding was noticed in 7 patients the same treatment was effective in 5 patients. (author)

  11. Non-linear failure analysis of HCPB blanket for DEMO taking into account high dose irradiation

    International Nuclear Information System (INIS)

    Aktaa, J.; Kecskés, S.; Pereslavtsev, P.; Fischer, U.; Boccaccini, L.V.

    2014-01-01

    Highlights: • First non-linear structural analysis for the European Helium Cooled Pebble Bed Blanket Module taking into account high dose irradiation. • Most critical areas were identified and analyzed with regard to the effect of irradiation on predicted damage at these areas. • Despite the extensive computing time 100 cycles were simulated by using the sub-modelling technique investigating damage at most critical area. • The results show a positive effect of irradiation on calculated damage which is mainly attributed to the irradiation induced hardening. - Abstract: For the European helium cooled pebble bed (HCPB) blanket of DEMO the reduced activation ferritic martensitic steel EUROFER has been selected as structural material. During operation the HCPB blanket will be subjected to complex thermo-mechanical loadings and high irradiation doses. Taking into account the material and structural behaviour under these conditions is a precondition for a reliable blanket design. For considering high dose irradiation in structural analysis of the DEMO blanket, the coupled deformation damage model, extended recently taking into account the influence of high dose irradiation on the material behaviour of EUROFER and implemented in the finite element code ABAQUS, has been used. Non-linear finite element (FE) simulations of the DEMO HCPB blanket have been performed considering the design of the HCPB Test Blanket Module (TBM) as reference and the thermal and mechanical boundary conditions of previous analyses. The irradiation dose rate required at each position in the structure as an additional loading parameter is estimated by extrapolating the results available for the TBM in ITER scaling the value calculated in neutronics and activation analysis for ITER boundary conditions to the DEMO boundary conditions. The results of the FE simulations are evaluated considering damage at most critical highly loaded areas of the structure and discussed with regard to the impact of

  12. Influence of high dose irradiation on core structural and fuel materials in advanced reactors

    International Nuclear Information System (INIS)

    1998-08-01

    The IAEA International Working Group on Fast Reactors (IWGFR) periodically organizes meeting to discuss and review important aspects of fast reactor technology. The fifth meeting held in Obninsk, Russian Federation, 16-19 June 1997, was devoted to the influence of high dose irradiation on the mechanical properties of reactor core structural and fuel materials. The proceedings includes the papers submitted at this meeting each with a separate abstract

  13. Salvage high-dose-rate interstitial brachytherapy for locally recurrent rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pellizzon, Antonio Cassio Assis, E-mail: acapellizzon@hcancer.org.br [A.C. Camargo Cancer Center, Sao Paulo, SP (Brazil). Departamento de Radioterapia

    2016-05-15

    For tumors of the lower third of the rectum, the only safe surgical procedure is abdominal-perineal resection. High-dose-rate interstitial brachytherapy is a promising treatment for local recurrence of previously irradiated lower rectal cancer, due to the extremely high concentrated dose delivered to the tumor and the sparing of normal tissue, when compared with a course of external beam radiation therapy. (author)

  14. Management of hilar bile duct carcinoma with high-dose radiotherapy and expandable metallic stent placement

    International Nuclear Information System (INIS)

    Saito, Hiroya; Takamura, Akio

    2000-01-01

    This article describes our experience with high-dose radiotherapy in combination with the placement of expandable metallic stents (EMS) in the management of hilar bile duct carcinoma. Between 1988 and 1999, 107 consecutive patients with hilar bile duct carcinoma were treated with EMS placement either alone or in combination with high-dose radiotherapy. External beam radiotherapy (EBRT) was indicated in 101 patients, and in 86 this was combined with intraluminal 192 Ir irradiation (ILRT, 59-98 Gy) EMS were placed after the completion of radiotherapy. The 1-, 2-, 3-, and 5-year actuarial survival rates for the radiotherapy group were 66.4%, 23.4%, 15.6%, 7.8%, respectively, and the 1- and 2-year actuarial survival rates for the nonradiotherapy group were 66.4% and 0%, respectively. The placement of EMS was useful for the early establishment of an internal bile passage in radically irradiated patients and the 1-, 2-, 3-, and 5-year actuarial patency rates for the radiotherapy group were 56.3%, 45.3%, 35.2%, and 23.4%, respectively, and the 1- and 2-year actuarial patency rates for the non radiotherapy group were 50.0% and 0% respectively. High-dose radiotherapy, consisting of ILRT and EBRT, appears to be feasible in the management of hilar bile duct carcinoma, and it offers a survival advantage for patients no suited for surgical resection. The placement of EMS assists the internal bile flow and lengthens survival after high-dose radiotherapy. (author)

  15. Treating tuberculosis with high doses of anti-TB drugs: mechanisms and outcomes.

    Science.gov (United States)

    Xu, Yuhui; Wu, Jianan; Liao, Sha; Sun, Zhaogang

    2017-10-03

    Tuberculosis (TB) is considered as one of the most serious threats to public health in many parts of the world. The threat is even more severe in the developing countries where there is a lack of advanced medical amenities and contemporary anti-TB drugs. In such situations, dosage optimization of existing medication regimens seems to be the only viable option. Therapeutic drug monitoring study results suggest that high-dose treatment regimens can compensate the low serum concentration of anti-TB drugs and shorten the therapy duration. The article presents a critical review on the possible changes that occur in the host and the pathogen upon the administration of standard and high-dose regimens. Some of the most common factors that are responsible for low anti-TB drug concentrations in the serum are differences in hosts' body weight, metabolic processing of the drug, malabsorption and/or drug-drug interaction. Furthermore, failure to reach the cavitary pulmonary and extrapulmonary tissues also contributes to the therapeutic inefficiency of the drugs. In such conditions, administration of higher doses can help in compensating the pathogenic outcomes of enhancement of the pathogen's physical barriers, efflux pumps and genetic mutations. The present article also presents a summary of the recorded treatment outcomes of clinical trials that were conducted to test the efficacy of administration of high dose of anti-tuberculosis drugs. This review will help physicians across the globe to understand the underlying pathophysiological changes (including side effects) that dictate the clinical outcomes in patients administered with standard and/or high dose anti-TB drugs.

  16. Epithelial regeneration of transposed intestine after high doses of X irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Both, N.J. de; Vermey, M [Erasmus Universiteit, Rotterdam (Netherlands)

    1976-01-01

    The regeneration capacities of normal and transposed small bowel epithelium were compared in rats after applying high doses of x irradiation. It has been shown that the potency of the mucosa to regenerate was much higher than assumed and that the mucosa could regenerate after single doses varying from 2000 to 5000 R. Even in the villus epithelium and in flat epithelium covering infiltrates of the lamina propria cells survived, which were still able to resume proliferative activity several days after irradiation.

  17. Polybutadiene and Styrene-Butadiene rubbers for high-dose dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Lucas N. [Instituto Federal de Educacao, Ciencia e Tecnologia de Goias-IFG,Campus Goiania, Goiania -GO (Brazil); Instituto de Pesquisas Energeticas e Nucleares -IPEN, Sao Paulo-SP (Brazil); Vieira, Silvio L. [Instituto de Fisica, Universidade Federal de Goias-UFG, Campus Samambaia, Goiania-GO (Brazil); Schimidt, Fernando [Instituto Federal de Educacao, Ciencia e Tecnologia de Goias-IFG,Campus Inhumas, Inhumas-GO (Brazil); Antonio, Patricia L.; Caldas, Linda V.E. [Instituto de Pesquisas Energeticas e Nucleares -IPEN, Sao Paulo-SP (Brazil)

    2015-07-01

    Polybutadiene and Styrene-Butadiene are synthetical rubbers used widely for pneumatic tires manufacturing. In this research, the dosimeter characteristics of those rubbers were studied for application in high-dose dosimetry. The rubber samples were irradiated with doses of 10 Gy up to 10 kGy, using a {sup 60}Co Gamma Cell-220 system (dose rate of 1.089 kGy/h) and their readings were taken on a Fourier Transform Infrared Spectroscopy-FTIR system (model Frontier/Perkin Elmer). The ratios of two absorbance peaks were taken for each kind of rubber spectrum, Polybutadiene (1306/1130 cm{sup -1}) and Styrene-Butadiene (1449/1306 cm{sup -1}). The ratio calculated was used as the response to the irradiation, and is not uniform across the sample. From the results, it can be concluded for both rubbers: a) the dose-response curves may be useful for high-dose dosimetry (greater than 250 Gy); b) their response for reproducibility presented standard deviations lower than 2.5%; c) the relative sensitivity was higher for Styrene-Butadiene (1.86 kGy{sup -1}) than for Polybutadiene (1.81 kGy{sup -1}), d) for doses of 10 kGy to 200 kGy, there was no variation in the dosimetric response. Both types of rubber samples showed usefulness as high-dose dosimeters. (authors)

  18. Cosmetic results in early stage breast cancer patients with high-dose brachytherapy after conservative surgery

    International Nuclear Information System (INIS)

    Torres, Felipe; Pineda, Beatriz E

    2004-01-01

    Purpose: to reveal cosmetic results in patients at early stages of low risk breast cancer treated with partial accelerated radiotherapy using high dose rate brachytherapy. Methods and materials: from March 2001 to July 2003,14 stages l and ll breast cancer patients were treated at the Colombian national cancer institute in Bogota with conservative surgery and radiotherapy upon the tumor bed (partial accelerated radiotherapy), using interstitial implants with iridium 192 (high dose rate brachytherapy) with a dose of 32 Gys, over 4 days, at 8 fractions twice a day. Results: with an average follow up of 17.7 months, good cosmetic results were found among 71.4 % of patients and excellent results among 14.3% of patients, furthermore none of the patients neither local nor regional or distant relapses. Conclusion: among patients who suffer from breast cancer at early stages, it showed is possible to apply partial accelerated radiotherapy upon the tumor bed with high doses over 4 days with good to excellent cosmetic results

  19. Development of computerized dose planning system and applicator for high dose rate remote afterloading irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, T. J. [Keimyung Univ., Taegu (Korea); Kim, S. W. [Fatima Hospital, Taegu (Korea); Kim, O. B.; Lee, H. J.; Won, C. H. [Keimyung Univ., Taegu (Korea); Yoon, S. M. [Dong-a Univ., Pusan (Korea)

    2000-04-01

    To design and fabricate of the high dose rate source and applicators which are tandem, ovoids and colpostat for OB/Gyn brachytherapy includes the computerized dose planning system. Designed the high dose rate Ir-192 source with nuclide atomic power irradiation and investigated the dose characteristics of fabricated brachysource. We performed the effect of self-absorption and determining the gamma constant and output factor and determined the apparent activity of designed source. he automated computer planning system provided the 2D distribution and 3D includes analysis programs. Created the high dose rate source Ir-192, 10 Ci(370GBq). The effective attenuation factor from the self-absorption and source wall was examined to 0.55 of the activity of bare source and this factor is useful for determination of the apparent activity and gamma constant 4.69 Rcm{sup 2}/mCi-hr. Fabricated the colpostat was investigated the dose distributions of frontal, axial and sagittal plane in intra-cavitary radiation therapy for cervical cancer. The reduce dose at bladder and rectum area was found about 20 % of original dose. The computerized brachytherapy planning system provides the 2-dimensional isodose and 3-D include the dose-volume histogram(DVH) with graphic-user-interface mode. emoted afterloading device was built for experiment of created Ir-192 source with film dosimetry within {+-}1 mm discrepancy. 34 refs., 25 figs., 11 tabs. (Author)

  20. High-dose calcium stimulation test in a case of insulinoma masquerading as hysteria.

    Science.gov (United States)

    Nakamura, Yoshio; Doi, Ryuichiro; Kohno, Yasuhiro; Shimono, Dai; Kuwamura, Naomitsu; Inoue, Koichi; Koshiyama, Hiroyuki; Imamura, Masayuki

    2002-11-01

    It is reported that some cases with insulinoma present with neuropsychiatric symptoms and are often misdiagnosed as psychosis. Here we report a case of insulinoma masquerading as hysteria, whose final diagnosis could be made using high-dose calcium stimulation test. A 28-yr-old woman was referred presenting with substupor, mutism, mannerism, restlessness, and incoherence. Laboratory examinations revealed hypoglycemia (33 mg/dL) and detectable insulin levels (9.7 microU/mL), suggesting the diagnosis of insulinoma. However, neither imaging studies nor selective arterial calcium injection (SACI) test with a conventional dose of calcium (0.025 mEq/kg) indicated the tumor. High-dose calcium injection (0.05 mEq/kg) evoked insulin secretion when injected into superior mesenteric artery. A solitary tumor in the head of the pancreas was resected, and her plasma glucose returned to normal. Postoperatively, iv injection of secretin resulted in a normal response of insulin, which was not found preoperatively. This case suggests the usefulness of the SACI test with high-dose of calcium in the case of insulinoma when the standard dose fails to detect such a tumor.

  1. Base of skull and cervical spine chordomas in children treated by high-dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Benk, Veronique; Liebsch, Norbert J; Munzenrider, John E; Efird, John; McManus, Patricia; Suit, Herman

    1995-02-01

    Purpose: To evaluate the outcome of children with base of skull or cervical spine chordomas treated by high dose irradiation. Methods and Materials: Eighteen children, 4 to 18 years of age, with base of skull or cervical spine chordomas, received fractionated high-dose postoperative radiation using mixed photon and 160 MeV proton beams. The median tumor dose was 69 Cobalt Gray-equivalent (CGE) with a 1.8 CGE daily fraction. Results: The median follow-up was 72 months. The 5-year actuarial survival was 68% and the 5-year disease-free survival (DFS) was 63%. The only significant prognostic factor was the location: patients with cervical spine chordomas had a worse survival than those with base of skull lesions (p = 0.008). The incidence of treatment-related morbidity was acceptable: two patients developed a growth hormone deficit corrected by hormone replacement, one temporal lobe necrosis, and one fibrosis of the temporalis muscle, improved by surgery. Conclusion: Chordomas in children behave similarly to those in adults: children can receive the same high-dose irradiation as adults with acceptable morbidity.

  2. The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

    Science.gov (United States)

    Schlienz, Nicolas J; Lee, Dustin C; Stitzer, Maxine L; Vandrey, Ryan

    2018-06-01

    There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine.

    Science.gov (United States)

    Babaei-Jadidi, Roya; Karachalias, Nikolaos; Ahmed, Naila; Battah, Sinan; Thornalley, Paul J

    2003-08-01

    Accumulation of triosephosphates arising from high cytosolic glucose concentrations in hyperglycemia is the trigger for biochemical dysfunction leading to the development of diabetic nephropathy-a common complication of diabetes associated with a high risk of cardiovascular disease and mortality. Here we report that stimulation of the reductive pentosephosphate pathway by high-dose therapy with thiamine and the thiamine monophosphate derivative benfotiamine countered the accumulation of triosephosphates in experimental diabetes and inhibited the development of incipient nephropathy. High-dose thiamine and benfotiamine therapy increased transketolase expression in renal glomeruli, increased the conversion of triosephosphates to ribose-5-phosphate, and strongly inhibited the development of microalbuminuria. This was associated with decreased activation of protein kinase C and decreased protein glycation and oxidative stress-three major pathways of biochemical dysfunction in hyperglycemia. Benfotiamine also inhibited diabetes-induced hyperfiltration. This was achieved without change in elevated plasma glucose concentration and glycated hemoglobin in the diabetic state. High-dose thiamine and benfotiamine therapy is a potential novel strategy for the prevention of clinical diabetic nephropathy.

  4. Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?

    Science.gov (United States)

    Day, Troy; Read, Andrew F.

    2016-01-01

    High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients. PMID:26820986

  5. Rectal dose assessment in patients submitted to high-dose-rate brachytherapy for uterine cervix cancer

    International Nuclear Information System (INIS)

    Oliveira, Jetro Pereira de; Batista, Delano Valdivino Santos; Bardella, Lucia Helena; Carvalho, Arnaldo Rangel

    2009-01-01

    Objective: The present study was aimed at developing a thermoluminescent dosimetric system capable of assessing the doses delivered to the rectum of patients submitted to high-dose-rate brachytherapy for uterine cervix cancer. Materials and methods: LiF:Mg,Ti,Na powder was the thermoluminescent material utilized for evaluating the rectal dose. The powder was divided into small portions (34 mg) which were accommodated in a capillary tube. This tube was placed into a rectal probe that was introduced into the patient's rectum. Results: The doses delivered to the rectum of six patients submitted to high-dose-rate brachytherapy for uterine cervix cancer evaluated by means of thermoluminescent dosimeters presented a good agreement with the planned values based on two orthogonal (anteroposterior and lateral) radiographic images of the patients. Conclusion: The thermoluminescent dosimetric system developed in the present study is simple and easy to be utilized as compared to other rectal dosimetry methods. The system has shown to be effective in the evaluation of rectal doses in patients submitted to high-dose-rate brachytherapy for uterine cervix cancer. (author)

  6. False-positive buprenorphine EIA urine toxicology results due to high dose morphine: a case report.

    Science.gov (United States)

    Tenore, Peter L

    2012-01-01

    In monitoring a patient with chronic pain who was taking high-dose morphine and oxycodone with weekly urine enzymatic immunoassay (EIA) toxicology testing, the authors noted consistent positives for buprenorphine. The patient was not taking buprenorphine, and gas chromatography/mass spectroscopy (GCMS) testing on multiple samples revealed no buprenorphine, indicating a case of false-positive buprenorphine EIAs in a high-dose opiate case. The authors discontinued oxycodone for a period of time and then discontinued morphine. Urine monitoring with EIAs and GCMS revealed false-positive buprenorphine EIAs, which remained only when the patient was taking morphine. When taking only oxycodone and no morphine, urine samples became buprenorphine negative. When morphine was reintroduced, false-positive buprenorphine results resumed. Medical practitioners should be aware that high-dose morphine (with morphine urine levels turning positive within the 15,000 to 28,000 mg/mL range) may produce false-positive buprenorphine EIAs with standard urine EIA toxicology testing.

  7. Extra-high doses detected in the enamel of human teeth in the Techa riverside region

    Energy Technology Data Exchange (ETDEWEB)

    Shishkina, E.A., E-mail: ElenaA.Shishkina@gmail.com [Urals Research Center for Radiation Medicine, 68A, Vorovsky Str., 454076 Chelyabinsk (Russian Federation); Degteva, M.O.; Tolstykh, E.I.; Volchkova, A. [Urals Research Center for Radiation Medicine, 68A, Vorovsky Str., 454076 Chelyabinsk (Russian Federation); Ivanov, D.V. [Institute of Metal Physics, Russian Academy of Sciences, 18 S. Kovalevsky Str, 620041 Yekaterinburg (Russian Federation); Wieser, A. [Helmholtz Zentrum Muenchen, German Research Centre for Environmental Health, D-85764 Neuherberg (Germany); Della Monaca, S. [Istituto Superiore di Sanita, 00161 Rome (Italy); Istituto Regina Elena, 00144 Rome (Italy); Fattibene, P. [Istituto Superiore di Sanita, 00161 Rome (Italy); Istituto Nazionale di Fisica Nucleare, 00161 Rome (Italy)

    2011-09-15

    During the long-term study of tooth enamel by EPR dosimetry for population exposed to radiation due to contamination of the Techa River, it was found out that for some of the tooth donors the dose accumulated in tooth enamel could be as high as several tens of Gy. Such doses were absorbed only in tooth enamel and they should not be associated with exposures to other organs or the whole body. The nature of such doses was discussed in a number of previous papers where it was shown that the source of such doses is {sup 90}Sr incorporated in the calcified dental tissues. However, among specialists in radiation dosimetry who were not involved in the biokinetic studies, the nature and dosimetric significance of extra-high doses in tooth enamel are still raising questions. The aim of the current paper is to summarize the accumulated information on extra-high doses in the teeth of the Techa riverside residents, describe the dose levels observed, explain the nature of extra-high doses in the enamel and discuss their informative value. The paper includes an overview of already published findings and an analysis of information collected in the data bank of the Urals Research Center for Radiation Medicine (URCRM), Chelyabinsk, Russia, which has not been published before.

  8. Base of skull and cervical spine chordomas in children treated by high-dose irradiation

    International Nuclear Information System (INIS)

    Benk, Veronique; Liebsch, Norbert J.; Munzenrider, John E.; Efird, John; McManus, Patricia; Suit, Herman

    1995-01-01

    Purpose: To evaluate the outcome of children with base of skull or cervical spine chordomas treated by high dose irradiation. Methods and Materials: Eighteen children, 4 to 18 years of age, with base of skull or cervical spine chordomas, received fractionated high-dose postoperative radiation using mixed photon and 160 MeV proton beams. The median tumor dose was 69 Cobalt Gray-equivalent (CGE) with a 1.8 CGE daily fraction. Results: The median follow-up was 72 months. The 5-year actuarial survival was 68% and the 5-year disease-free survival (DFS) was 63%. The only significant prognostic factor was the location: patients with cervical spine chordomas had a worse survival than those with base of skull lesions (p = 0.008). The incidence of treatment-related morbidity was acceptable: two patients developed a growth hormone deficit corrected by hormone replacement, one temporal lobe necrosis, and one fibrosis of the temporalis muscle, improved by surgery. Conclusion: Chordomas in children behave similarly to those in adults: children can receive the same high-dose irradiation as adults with acceptable morbidity

  9. High dose per fraction dosimetry of small fields with Gafchromic EBT2 film

    International Nuclear Information System (INIS)

    Hardcastle, Nicholas; Basavatia, Amar; Bayliss, Adam; Tome, Wolfgang A.

    2011-01-01

    Purpose: Small field dosimetry is prone to uncertainties due to the lack of electronic equilibrium and the use of the correct detector size relative to the field size measured. It also exhibits higher sensitivity to setup errors as well as large variation in output with field size and shape. Radiochromic film is an attractive method for reference dosimetry in small fields due to its ability to provide 2D dose measurements while having minimal impact on the dose distribution. Gafchromic EBT2 has a dose range of up to 40 Gy; therefore, it could potentially be useful for high dose reference dosimetry with high spatial resolution. This is a requirement in stereotactic radiosurgery deliveries, which deliver high doses per fraction to small targets. Methods: Targets of 4 mm and 12 mm diameters were treated to a minimum peripheral dose of 21 Gy prescribed to 80% of the maximum dose in one fraction. Target doses were measured with EBT2 film (both targets) and an ion chamber (12 mm target only). Measured doses were compared with planned dose distributions using profiles through the target and minimum peripheral dose coverage. Results: The measured target doses and isodose coverage agreed with the planned dose within ±1 standard deviation of three measurements, which were 2.13% and 2.5% for the 4 mm and 12 mm targets, respectively. Conclusions: EBT2 film is a feasible dosimeter for high dose per fraction reference 2D dosimetry.

  10. High-dose ascorbic acid decreases cholesterolemic factors of an atherogenic diet in guinea pigs.

    Science.gov (United States)

    Filis, Konstantinos; Anastassopoulou, Aikaterini; Sigala, Fragiska; Theodorou, Dimitrios; Manouras, Andreas; Leandros, Emanouel; Sigalas, Panagiotis; Hepp, Wolfgang; Bramis, John

    2007-03-01

    The study evaluates the effect of a high supplemental dose of ascorbic acid (AA) on plasma concentrations of total cholesterol (TC), triglycerides (TG), total lipids (TL), and lipoprotein fractions high-density, very-low-density-, and low-density lipoprotein (HDL, VLDL, LDL) in guinea pigs fed with atherogenic diet. Group I consisted of 5 normally fed guinea pigs plus a low dose of AA (1 mg/100 g/day), group II consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a low dose of AA (1 mg/100 g/day), and group III consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a high dose of AA (30 mg/100 g/day). Cholesterolemic factors concentrations were determined after nine weeks. Concentrations of TC, TG, TL, LDL, and VLDL were increased in group II compared to group I (p < 0.01 for all differences). Supplementation with a high dose of AA resulted in decreased concentrations of TC (p < 0.01), TG (p < 0.01), TL (p < 0.01), and LDL (p < 0.01) in group III compared to group II. Additionally, concentration of HDL was increased in group III compared to group II (p < 0.01). High-dose AA supplementation to an atherogenic diet decreases concentrations of TC, TG, TL, and LDL and increases concentration of HDL compared to low-dose AA.

  11. Image-Guided Stereotactic Radiosurgery Using a Specially Designed High-Dose-Rate Linac

    International Nuclear Information System (INIS)

    Bayouth, John E.; Kaiser, Heather S.; Smith, Mark C.; Pennington, Edward C.; Anderson, Kathleen M. C.; Ryken, Timothy C.; Buatti, John M.

    2007-01-01

    Stereotactic radiosurgery and image-guided radiotherapy (IGRT) place enhanced demands on treatment delivery machines. In this study, we describe a high-dose-rate output accelerator as a part of our stereotactic IGRT delivery system. The linac is a Siemens Oncor without a flattening filter, and enables dose rates to reach 1000 monitor units (MUs) per minute. Even at this high-dose-rate, the linac dosimetry system remains robust; constancy, linearity, and beam energy remain within 1% for 3 to 1000 MU. Dose profiles for larger field sizes are not flat, but they are radially symmetric and, as such, able to be modeled by a treatment planning system. Target localization is performed via optical guidance utilizing a 3-dimensional (3D) ultrasound probe coupled to an array of 4 infrared light-emitting diodes. These diodes are identified by a fixed infrared camera system that determines diode position and, by extension, all objects imaged in the room coordinate system. This system provides sub-millimeter localization accuracy for cranial applications and better than 1.5 mm for extracranial applications. Because stereotactic IGRT can require significantly longer times for treatment delivery, the advantages of the high-dose-rate design and its direct impact on IGRT are discussed

  12. Myocardial protection induced by fentanyl in pigs exposed to high-dose adrenaline.

    Science.gov (United States)

    da Luz, Vinicius Fernando; Otsuki, Denise Aya; Gonzalez, Maria Margarita Castro; Negri, Elnara Marcia; Caldini, Elia Garcia; Damaceno-Rodrigues, Nilsa Regina; Malbouisson, Luiz Marcelo Sá; Viana, Bruno Gonçalves; Vane, Matheus Fachini; Carmona, Maria Jose Carvalho

    2015-10-01

    The use of high doses of adrenaline is common in critical patients, especially during cardiac arrest. During these situations, myocardial dysfunction can be a result of multiple factors, including adrenaline use. In addition, opioids have been shown to have anti-arrhythmic and anti-ischemic mechanisms that may confer cardiac protection. This study aimed to evaluate the effects of fentanyl on myocardial function in pigs exposed to high-dose adrenaline. After institutional ethics committee approval, 26 pigs were randomly allocated to receive either 20 μg/kg fentanyl (n = 10; fentanyl group) administered 5 min before five doses of adrenaline (20 μg/kg), equivalent-volume saline (n = 10; saline group) using the same adrenaline dosing protocol, or neither fentanyl nor adrenaline (n = 6; sham group). The fentanyl group showed lower levels of troponin at the end of the sixth hour compared with the saline group (1.91 ± 1.47 vs 5.44 ± 5.35 ng/mL, P = 0.019). Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. The conclusion was reached that fentanyl attenuates myocardial injury caused by high-dose adrenaline without blunting the hemodynamic effect of adrenaline. © 2015 Wiley Publishing Asia Pty Ltd.

  13. Feline immunodeficiency virus OrfA alters gene expression of splicing factors and proteasome-ubiquitination proteins

    International Nuclear Information System (INIS)

    Sundstrom, Magnus; Chatterji, Udayan; Schaffer, Lana; Rozieres, Sohela de; Elder, John H.

    2008-01-01

    Expression of the feline immunodeficiency virus (FIV) accessory protein OrfA (or Orf2) is critical for efficient viral replication in lymphocytes, both in vitro and in vivo. OrfA has been reported to exhibit functions in common with the human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) accessory proteins Vpr and Tat, although the function of OrfA has not been fully explained. Here, we use microarray analysis to characterize how OrfA modulates the gene expression profile of T-lymphocytes. The primary IL-2-dependent T-cell line 104-C1 was transduced to express OrfA. Functional expression of OrfA was demonstrated by trans complementation of the OrfA-defective clone, FIV-34TF10. OrfA-expressing cells had a slightly reduced cell proliferation rate but did not exhibit any significant alteration in cell cycle distribution. Reverse-transcribed RNA from cells expressing green fluorescent protein (GFP) or GFP + OrfA were hybridized to Affymetrix HU133 Plus 2.0 microarray chips representing more than 47,000 genome-wide transcripts. By using two statistical approaches, 461 (Rank Products) and 277 (ANOVA) genes were identified as modulated by OrfA expression. The functional relevance of the differentially expressed genes was explored by Ingenuity Pathway Analysis. The analyses revealed alterations in genes critical for RNA post-transcriptional modifications and protein ubiquitination as the two most significant functional outcomes of OrfA expression. In these two groups, several subunits of the spliceosome, cellular splicing factors and family members of the proteasome-ubiquitination system were identified. These findings provide novel information on the versatile function of OrfA during FIV infection and indicate a fine-tuning mechanism of the cellular environment by OrfA to facilitate efficient FIV replication

  14. Cutaneous manifestations of primary immunodeficiency

    Directory of Open Access Journals (Sweden)

    Safa Abdelhakim

    2017-01-01

    Full Text Available Primary immunodeficiency diseases (PIDs are a group of rare, chronic disorders with deficient or malfunctioning immune system. It commonly affects the hematopoietic system, with skin the second most affected organ. Skin involvement is observed in half of pediatric PID cases and often precedes the final diagnosis. Skin infections and eczemas are the two most common manifestations in PID.[1] Skin manifestations associated with PIDs can be of infectious and noninfectious causes. Common noninfectious causes are eczema, erythroderma, cutaneous granulomas, dysplasia, vasculitis, and telangiectasia. It is important to be aware of skin manifestations in pediatric patients as early detection of PID may aid in the management of serious immunologic conditions and prevent associated morbidity and mortality.

  15. Cancer as secondary immunodeficiency. Review

    Directory of Open Access Journals (Sweden)

    María Eugenia Vargas-Camaño

    2016-05-01

    Full Text Available The secondary immunodeficiency’s, previously presented in immunocompetent individuals. The lack of primary or secondary response to the presence of a foreign antigen, in the case of infections is a sentinel data in the diagnosis of immunodeficiency (can be primary or secondary, in the case of a self antigen may generate the presence of Cancer. Cancer has shown an increase in the prevalence and incidence globally. Most current medical treatments in cancer are focused primarily on immunomodulatory actions (immunosuppression / immune stimulation or both. Knowledge of key concepts from the perspective of innate and acquired immunity lead to cancer development, engaging immune surveillance and escape mechanisms of this that contribute to better understand the origin, behavior and treatment of neoplasm’s. These treatments can cause immunological disorders such as allergy, anaphylaxis, lack of response immunogenicity care fields specialist in Allergy and Clinical Immunology.

  16. Strategies for B-cell receptor repertoire analysis in Primary Immunodeficiencies:From severe combined immunodeficiency to common variable immunodeficiency

    Directory of Open Access Journals (Sweden)

    Hanna eIJspeert

    2015-04-01

    Full Text Available The antigen receptor repertoires of B and T cells form the basis of the adaptive immune response. The repertoires should be sufficiently diverse to recognize all possible pathogens. However, careful selection is needed to prevent responses to self or harmless antigens. Limited antigen receptor repertoire diversity leads to immunodeficiency, whereas unselected or misdirected repertoires can result in autoimmunity. The antigen receptor repertoire harbors information about abnormalities in many immunological disorders. Recent developments in next generation sequencing allow the analysis of the antigen receptor repertoire in much greater detail than ever before. Analyzing the antigen receptor repertoire in patients with mutations in genes responsible for the generation of the antigen receptor repertoire will give new insights into repertoire formation and selection. In this perspective we describe strategies and considerations for analysis of the naive and antigen selected B-cell repertoires in primary immunodeficiency (PID patients with a focus on severe combined immunodeficiency (SCID and common variable immunodeficiency (CVID.

  17. High-dose Extended-Field Irradiation and High-Dose-Rate Brachytherapy With Concurrent Chemotherapy for Cervical Cancer With Positive Para-Aortic Lymph Nodes

    International Nuclear Information System (INIS)

    Kim, Young Seok; Kim, Jong Hoon; Ahn, Seung Do; Lee, Sang-wook; Shin, Seong Soo; Nam, Joo-Hyun; Kim, Young-Tak; Kim, Yong-Man; Kim, Jong-Hyeok; Choi, Eun Kyung

    2009-01-01

    Purpose: To determine the efficacy and toxicity of extended-field radiotherapy (RT) with concurrent platinum-based chemotherapy in patients with uterine cervical carcinoma and positive para-aortic nodes. Methods and Materials: We retrospectively reviewed the results for 33 women with Stage IB-IVB cervical cancer. Each patient had received 59.4 Gy, including a three-dimensional conformal boost to the para-aortic lymph nodes and 41.4-50.4 Gy of external beam radiotherapy to the pelvis. Each patient also underwent six or seven applications of high-dose-rate brachytherapy (median, 5 Gy to point A at each session). Results: The median follow-up period of surviving patients was 39 months. The most common acute toxicity was hematologic, observed in 23 women. Severe acute and late gastrointestinal toxicity was observed in 3 and 4 patients, respectively. More than three-quarters of patients showed a complete response, encompassing the primary mass, metastatic pelvic, and para-aortic lymph nodes. Of the 33 women, 15 had no evidence of disease, 6 had persistent disease, 4 developed in-field failures, and 6 developed distant failures. The 5-year overall and disease-free survival rate was 47% and 42%, respectively. Conclusion: Concurrent chemoradiotherapy with extended-field radiotherapy is feasible in women with uterine cervical carcinoma and positive para-aortic lymph nodes, with acceptable late morbidity and a high survival rate, although it was accompanied by substantial acute toxicity.

  18. Replication of simian virus 40 in simian virus 40-transformed hamster kidney cells induced by mitomycin C or 60Co γ irradiation

    International Nuclear Information System (INIS)

    Rakusanova, T.; Smales, W.P.; Kaplan, J.C.; Black, P.H.

    1978-01-01

    Several clones of simian virus 40 (SV40)-transformed hamster kidney cells, which are heterogeneous for induction of infectious SV40, have been studied. SV40 yields are low after induction with 60 Co γ irradiation or mitomycin C. In order to clarify the mechanism(s) by which virus is produced in induced cells, we analyzed the replication of viral DNA and production of virion (V) antigen and infectious virus after induction in various clones as well as in lytically infected permissive cells. Cells replicating SV40 DNA or synthesizing V antigen were visualized by in situ hybridization and immunofluorescence techniques, respectively. Only some cells in induced cultures were found to produce SV40 and those which did were less efficient than lytically infected monkey cells. Mitomycin C or 60 Co γ irradiation acted by inducing more cells to replicate virus rather than by increasing the amount of SV40 released from individual cells. A greater proportion of cells could be induced to replicate SV40 DNA than to synthesize V antigen in all induced clones studied. Also, SV40 DNA replication was induced at lower doses of γ irradiation than the production of either V antigen or infectious virus suggesting that synthesis of late virus protein is more restricted in induced cells than is replication of SV40 DNA. These findings indicate that one of the effects of induction treatments on SV40-transformed hamster cells is an enhancement of the cells' capacity to support SV40 replication

  19. Ethnopharmacology of human immunodeficiency virus in South ...

    African Journals Online (AJOL)

    Administrator

    2006-10-02

    Oct 2, 2006 ... This mini-review takes a look at the evaluations of South African medicinal plants to determine ... Key words: Human immunodeficiency virus, Medicinal plants, South Africa. ... The greatest degree of antiviral activity against.

  20. Screening for Human Immunodeficiency Virus (HIV)

    Science.gov (United States)

    ... with antiretroviral therapy (ART). Starting ART early—before symptoms appear—greatly reduces the risk of developing acquired immunodeficiency syndrome (AIDS, the final stage of HIV infection), having AIDS-related complications, or dying of ...

  1. Human immunodeficiency virus (HIV) infection in tuberculosis ...

    African Journals Online (AJOL)

    Human immunodeficiency virus (HIV) infection in tuberculosis patients in Addis ... METHODS: A cross-sectional survey whereby blood sample was collected ... of co-infection appeared to have increased compared to previous studies, 6.6%, ...

  2. Calibration procedure for thermoluminescent dosemeters in water absorbed doses for Iridium-192 high dose rate sources

    International Nuclear Information System (INIS)

    Reyes Cac, Franky Eduardo

    2004-10-01

    Thermoluminescent dosimeters are used in brachytherapy services quality assurance programs, with the aim of guaranteeing the correct radiation dose supplied to cancer patients, as well as with the purpose of evaluating new clinical procedures. This work describes a methodology for thermoluminescent dosimeters calibration in terms of absorbed dose to water for 192 Ir high dose rate sources. The reference dose used is measured with an ionization chamber previously calibrated for 192 Ir energy quality, applying the methodology proposed by Toelli. This methodology aims to standardizing the procedure, in a similar form to that used for external radiotherapy. The work evolves the adaptation of the TRS-277 Code of the International Atomic Energy Agency, for small and big cavities, through the introduction for non-uniform experimental factor, for the absorbed dose in the neighborhood of small brachytherapy sources. In order to simulate a water medium around the source during the experimental work, an acrylic phantom was used. It guarantees the reproducibility of the ionization chamber and the thermoluminescent dosimeter's location in relation to the radiation source. The values obtained with the ionization chamber and the thermoluminescent dosimeters, exposed to a 192 Ir high dose rate source, were compared and correction factors for different source-detector distances were determined for the thermoluminescent dosimeters. A numeric function was generated relating the correction factors and the source-detector distance. These correction factors are in fact the thermoluminescent dosimeter calibration factors for the 192 Ir source considered. As a possible application of this calibration methodology for thermoluminescent dosimeters, a practical range of source-detector distances is proposed for quality control of 192 Ir high dose rate sources. (author)

  3. Development of radiation fusion technology with food technology by the application of high dose irradiation

    International Nuclear Information System (INIS)

    Lee, Juwoon; Kim, Jaehun; Choi, Jongil

    2012-04-01

    This study was performed to achieve stable food supply and food safety with radiation fusion technology as a preparation for food weaponization. Results at current stage are following: First, for the development of radiation and food engineering fusion technology using high dose irradiation, the effects of high dose irradiation on food components were evaluated. The combination treatment of irradiation with food engineering was developed. Irradiation condition to destroy radiation resistant foodborne bacteria were determined. Second, for the development of E-beam irradiation technology, the effects of radiation sources on food compounds, processing conditions, and food quality of final products were compared. Food processing conditions for agricultural/aquatic products with different radiation sources was developed and the domination of E-beam irradiation foods were determined. The physical marker for E-beam irradiated foods or not was developed. Third, for the fundamental researches to develop purposed foods to extreme environmental, ready-to-eat foods were developed using high dose irradiation. Food processing for export strategy foods such as process ginseng were developed. Food processing with irradiation to destroy mycotoxin and to inhibit production of mycotoxin was developed. Mathematical models to predict necessary irradiation doses and radiation sources were developed and validated. Through the fundamental researches, the legislation for irradiation approval on meat products, sea foods and dried sea foods, and use of E-beam was introduced. Results from this research project, the followings are expected. Improvement of customer acceptance and activation of irradiation technology by the use of various irradiation rays. Increase of indirect food productivity, and decrease of SOC and improvement of public health by prevention of foodborne outbreaks. Build of SPS/TBT system against imported products and acceleration of domestic product export. Systemized

  4. Development of Radiation Fusion Technology with Food Technology by the Application of High Dose Irradiation

    International Nuclear Information System (INIS)

    Kim, Ju Won; Kim, Jae Hun; Choi, Jong Il

    2010-04-01

    This study was studied to achieve stable food supply and food safety with radiation fusion technology as a preparation for food weaponization. Results at current stage are following: First, for the development of radiation and food engineering fusion technology using high dose irradiation, the effects of high dose irradiation on food components were evaluated. The combination treatment of irradiation with food engineering were developed. Irradiation condition to destroy radiation resistant food borne bacteria were determined. Second, for the development of E-beam irradiation technology, the effects of radiation sources on food compounds, processing conditions, and food quality of final products were compared. Food processing conditions for agricultural/aquatic products with different radiation sources were developed and the domination of E-beam irradiation foods were determined. The physical marker for E-beam irradiated foods or not were developed. Third, for the fundamental researches to develop purposed foods to extreme environmental, ready-to-eat foods were developed using high dose irradiation. Food processing for export strategy foods such as process ginseng were developed. Food processing with irradiation to destroy mycotoxin and to inhibit production of mycotoxin were developed. Mathematical models to predict necessary irradiation doses and radiation sources were developed and validated. Through the fundamental researches, the legislation for irradiation approval on meat products, sea foods and dried sea foods, and use of E-beam were introduced. Results from this research project, the followings are expected. (1) Improvement of customer acceptance and activation of irradiation technology by the use of various irradiation rays. (2) Increase of indirect food productivity, and decrease of SOC and improvement of public health by prevention of food borne outbreaks. (3) Build of SPS/TBT system against imported products and acceleration of domestic product export

  5. Does perioperative high-dose prednisolone have clinical benefits for generalized myasthenia gravis?

    Science.gov (United States)

    Sekine, Yasuo; Kawaguchi, Naoki; Hamada, Chikuma; Sekiguchi, Hiromi; Yasufuku, Kazuhiro; Iyoda, Akira; Shibuya, Kiyoshi; Fujisawa, Takehiko

    2006-06-01

    The purpose of this study was to clarify the clinical benefits of perioperative administration of high-dose prednisolone (PSL) combined with extended thymectomy on the long-term outcomes of 116 consecutive patients with generalized myasthenia gravis (MG). A retrospective review was conducted on 116 patients diagnosed with generalized MG who received alternate-day oral administration of high-dose PSL (100 mg/alternate days) and had undergone transsternal extended thymectomy. Incidences of postoperative myasthenic crisis, adverse effects of steroid, long-term outcomes, such as complete stable remission (CSR), pharmacologic remission (PR) or improvement (Imp), and disease recurrence after CSR were evaluated. Six patients (5.2%) experienced post-thymectomy myasthenic crisis. Crude cumulative CSR and PR + CSR rates were 44.8 and 62.7%, respectively. Life table analysis showed that 41.8, 52.8 and 63.4% of the patients were in CSR at 3, 5 and 10 years, respectively. Multivariate analysis revealed that age and pretreatment classification according to the Myasthenia Gravis Foundation of America (MGFA) criteria tended to be independent predictors of CSR. There were 6.9% with compressive vertebral fracture, 13.8% with cataract, and 5.2% with steroid-induced diabetes. Life table analysis revealed that recurrence rates after CSR were 36.8 and 46.0% at 3 and 5 years, respectively. Patients with thymoma had a significantly higher rate of recurrence than those without thymoma (p = 0.001). Alternate-day administration of high-dose prednisolone reduced the risk of post-thymectomy myasthenic crisis. Presence of thymoma was a risk factor for MG recurrence after CSR.

  6. Development of Radiation Fusion Technology with Food Technology by the Application of High Dose Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ju Won; Kim, Jae Hun; Choi, Jong Il

    2010-04-15

    This study was studied to achieve stable food supply and food safety with radiation fusion technology as a preparation for food weaponization. Results at current stage are following: First, for the development of radiation and food engineering fusion technology using high dose irradiation, the effects of high dose irradiation on food components were evaluated. The combination treatment of irradiation with food engineering were developed. Irradiation condition to destroy radiation resistant food borne bacteria were determined. Second, for the development of E-beam irradiation technology, the effects of radiation sources on food compounds, processing conditions, and food quality of final products were compared. Food processing conditions for agricultural/aquatic products with different radiation sources were developed and the domination of E-beam irradiation foods were determined. The physical marker for E-beam irradiated foods or not were developed. Third, for the fundamental researches to develop purposed foods to extreme environmental, ready-to-eat foods were developed using high dose irradiation. Food processing for export strategy foods such as process ginseng were developed. Food processing with irradiation to destroy mycotoxin and to inhibit production of mycotoxin were developed. Mathematical models to predict necessary irradiation doses and radiation sources were developed and validated. Through the fundamental researches, the legislation for irradiation approval on meat products, sea foods and dried sea foods, and use of E-beam were introduced. Results from this research project, the followings are expected. (1) Improvement of customer acceptance and activation of irradiation technology by the use of various irradiation rays. (2) Increase of indirect food productivity, and decrease of SOC and improvement of public health by prevention of food borne outbreaks. (3) Build of SPS/TBT system against imported products and acceleration of domestic product export

  7. Development of radiation fusion technology with food technology by the application of high dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Juwoon; Kim, Jaehun; Choi, Jongil; and others

    2012-04-15

    This study was performed to achieve stable food supply and food safety with radiation fusion technology as a preparation for food weaponization. Results at current stage are following: First, for the development of radiation and food engineering fusion technology using high dose irradiation, the effects of high dose irradiation on food components were evaluated. The combination treatment of irradiation with food engineering was developed. Irradiation condition to destroy radiation resistant foodborne bacteria were determined. Second, for the development of E-beam irradiation technology, the effects of radiation sources on food compounds, processing conditions, and food quality of final products were compared. Food processing conditions for agricultural/aquatic products with different radiation sources was developed and the domination of E-beam irradiation foods were determined. The physical marker for E-beam irradiated foods or not was developed. Third, for the fundamental researches to develop purposed foods to extreme environmental, ready-to-eat foods were developed using high dose irradiation. Food processing for export strategy foods such as process ginseng were developed. Food processing with irradiation to destroy mycotoxin and to inhibit production of mycotoxin was developed. Mathematical models to predict necessary irradiation doses and radiation sources were developed and validated. Through the fundamental researches, the legislation for irradiation approval on meat products, sea foods and dried sea foods, and use of E-beam was introduced. Results from this research project, the followings are expected. Improvement of customer acceptance and activation of irradiation technology by the use of various irradiation rays. Increase of indirect food productivity, and decrease of SOC and improvement of public health by prevention of foodborne outbreaks. Build of SPS/TBT system against imported products and acceleration of domestic product export. Systemized

  8. The biochemical changes of bone collagen after high-dose irradiation

    International Nuclear Information System (INIS)

    Tajiri, Ken

    1980-01-01

    In our clinic, patients with malignant bone tumors have been treated by high-dose irradiation therapy, 10,000-20,000 rads, for primary lesions. In order to study the biochemical changes of normal bone around tumor tissue, especially bone collagen, after high-dose irradiation, the author performed the following experiments. The right knee joint of rabbits was irradiated with either 6,000, 10,000, or 15,000 rads by 60 Co-γ ray. The cortical bone of the right tibial metaphysis was used for analyses and compared with the left tibia of the same rabbit. These studies were followed for one year after the final irradiation. The calcium, phosphorous and collagen contents of irradiated bone were remarkably changed. These data indicate that collagen biosynthesis of irradiated bone was decreased and the calcification was disturbed. An increase in the amount of total soluble collagen and a decrease in the amount of hydroxylysine bound sugar were observed. The ratio of β to α chains of the collagen molecule was also changed by the irradiation. The amount of reducible cross-links per hydroxyproline residue was strikingly increased three months after the final irradiation. These changes were remarkable especially in the 10,000 and 15,000 rads irradiated group and found to be recovered approximately six months to one year after the final irradiation. These findings indicate that high-dose irradiation reduces the stability of bone collagen both with the destruction of sugar bonds of hydroxylysine residues and the replacement of matured collagen matrix to immatured one which contain mostly labile reducible cross-links. (author)

  9. Successfully Managing Impending Skin Necrosis following Hyaluronic Acid Filler Injection, using High-Dose Pulsed Hyaluronidase

    Directory of Open Access Journals (Sweden)

    Kwok Thye David Loh, MBBS

    2018-02-01

    Full Text Available Summary:. Facial fillers are becoming increasingly popular as aesthetic procedures to temporarily reduce the depth of wrinkles or to contour faces. However, even in the hands of very experienced injectors, there is always a small possibility of vascular complications like intra-arterial injection of filler substance. We present a case report of a patient who developed features of vascular obstruction in right infraorbital artery and tell-tale signs of impending skin necrosis, after hyaluronic acid filler injection by an experienced injector. The diagnosis of a vascular complication was made quickly with the help of clinical features like blanching, livedo reticularis, and poor capillary refill. Patient was treated promptly with “high-dose pulsed hyaluronidase protocol” comprising three 1,000-unit pulses of hyaluronidase, administered hourly. There was no further increase in size of the involved area after the first dose of hyaluronidase. All of the involved area, along with 1 cm overlapping in uninvolved skin area, was injected during each injection pulse, using a combination of cannula and needle. Complete reperfusion and good capillary filling were achieved after completion of 3 pulses, and these were taken as the end-point of high-dose pulsed hyaluronidase treatment. Immediate skin changes after filler injections, as well as after hyaluronidase injections and during the 3-week recovery period, were documented with photographs and clinical notes. Involved skin was found to have been fully recovered from this vascular episode, thus indicating that complete recovery of the ischemic skin changes secondary to possible intra-arterial injection could be achieved using high-dose pulsed hyaluronidase protocol.

  10. Effects of high dose coffee intake on aerobic power in dragon female athletes

    Directory of Open Access Journals (Sweden)

    Shabani Ramin

    2016-08-01

    Full Text Available Background : There are few studies that consider the effect of high doses of caffeine on aerobic power (VO2max. Also, to date, no study examined the effect of coffee intake on dragon boat paddler specifically on women. The purpose of this study was to investigate the effect of espresso coffee on improvement of aerobic power of dragon boat paddler. Material : Twenty women athletes of Guilan dragon bout team members of Malavan club of port city of Anzali (mean ±SD age, 23.60± 3.49 years; BMI,23.77±1.88kg/m2; body fat, 30.32±4.65% were recruited to this study, after they completed a primary test without consuming any coffee, they consumed 6mg/kg of coffee (espresso or decaffeinated and following that they completed two experimental trials. A randomized, double-blind, repeated-measures, design was employed whereby paddlers complete a 2000m paddling dragon boat ergo-meter. Results : Coffee could improve VO2max (Without coffee =74.40± QUOTE 4.99, Espresso coffee =90.10± QUOTE 6.19, Decaffeinated coffee =91.00± QUOTE 5.67, P≤ QUOTE 0.05. VO2max amount after exercise were significantly higher for both espresso coffee and decaffeinated coffee, when compared with without coffee condition. No significant differences were observed between espresso coffee and decaffeinated coffee (P≤ QUOTE 0.05. Conclusion : The present study shows that both high doses of caffeine (espresso coffee and decaffeinated coffee can enhance VO2max during aerobic exercise including 2000m dragon boat paddling. It seems that some compounds except caffeine in decaffeinated coffee can act improve VO2max. Further studies needed for considering the effect of high doses of coffee on endurance exercises. Also in other age ranges of women athletes and other sport athletes.

  11. Pre-installation empirical testing of room shielding for high dose rate remote afterloaders

    International Nuclear Information System (INIS)

    Klein, E.E.; Grigsby, P.W.; Williamson, J.F.; Meigooni, A.S.

    1993-01-01

    PURPOSE: Many facilities are acquiring high dose rate remote afterloading units. It is economical that these units be placed in existing shielded teletherapy rooms. Scatter-radiation barriers marginally protect uncontrolled areas from a high dose rate source especially in a room that houses a non-dynamic Cobalt-60 unit. In addition the exact thickness and material composition of the barriers are unknown and therefore, a calculation technique may give misleading results. Also, it would be impossible to evaluate an entire wall barrier by taking isolated core samples in order to assist in the calculations. A quick and inexpensive measurement of dose equivalent using a rented high activity 192Ir source evaluates the barriers and locates shielding deficiencies. METHODS AND MATERIALS: We performed transmission calculations for primary and scattered radiation based on National Council on Radiation Protection and Measurements Reports 49 and 51, respectively. We then rented a high activity 21.7 Ci (8.03 x 10(11) Bq) Ir-192 source to assess our existing teletherapy room shielding for adequacy and voids. This source was placed at the proposed location for clinical high dose rate treatment and measurements were performed. RESULTS: No deficiencies were found in controlled areas surrounding the room, but large differences were found between the calculated and measured values. Our survey located a region in the uncontrolled area above the room requiring augmented shielding which was not predicted by the calculations. A canopy shield was designed to potentially augment the shielding in the ceiling direction. CONCLUSION: Pre-installation testing by measurement is an invaluable method for locating shielding deficiencies and avoiding unnecessary enhancement of shielding particularly when there is lack of information of the inherent shielding

  12. Efficacy and Tolerability of High-Dose Escitalopram in Posttraumatic Stress Disorder.

    Science.gov (United States)

    Qi, Wei; Gevonden, Martin; Shalev, Arieh

    2017-02-01

    Open-label trials suggest that escitalopram (up to 20 mg/d) is an effective treatment for some, but not all posttraumatic stress disorder (PTSD) patients. Higher doses of escitalopram effectively reduced major depression symptoms in patients who had not responded to regular doses. The current study examines the efficacy, tolerability, and adherence to high-dose escitalopram in PTSD. Forty-five PTSD patients received 12 weeks of gradually increasing doses of escitalopram reaching 40 mg daily at 4 weeks. Among those, 12 participants received regular doses of antidepressants at study onset including escitalopram (n = 7). The Clinician-Administered PTSD Scale (CAPS) evaluated PTSD symptoms severity before treatment, at 3 months (upon treatment termination), and at 6 months (maintenance effect). A 20% reduction in CAPS scores was deemed clinically significant. Adverse events and medication adherence were monitored at each clinical session. Linear mixed-models analysis showed a significant reduction of mean CAPS scores (11.5 ± 18.1 points) at 3 months and maintenance of gains by 6 months (F2,34.56 = 8.15, P = 0.001). Eleven participants (34.3%) showed clinically significant improvement at 3 months. Only 9 participants (20%) left the study. There were no serious adverse events and few mild ones with only 2 adverse events (diarrhea, 11.1%; drowsiness, 11.1%) reported by more than 10% of participants. High doses of escitalopram are tolerable and well adhered to in PTSD. Their beneficial effect at a group level is due to a particularly good response in a subset of patients.Variability in prior pharmacological treatment precludes a definite attribution of the results to high doses of escitalopram.

  13. High-Dose Citalopram and Escitalopram and the Risk of Out-of-Hospital Death.

    Science.gov (United States)

    Ray, Wayne A; Chung, Cecilia P; Murray, Katherine T; Hall, Kathi; Stein, C Michael

    2017-02-01

    Studies demonstrating that higher doses of citalopram (> 40 mg) and escitalopram (> 20 mg) prolong the corrected QT interval prompted regulatory agency warnings, which are controversial, given the absence of confirmatory clinical outcome studies. We compared the risk of potential arrhythmia-related deaths for high doses of these selective serotonin reuptake inhibitors (SSRIs) to that for equivalent doses of fluoxetine, paroxetine, and sertraline. The Tennessee Medicaid retrospective cohort study included 54,220 persons 30-74 years of age without cancer or other life-threatening illness who were prescribed high-dose SSRIs from 1998 through 2011. The mean age was 47 years, and 76% were female. Demographic characteristics and comorbidity for individual SSRIs were comparable. Because arrhythmia-related deaths are typically sudden and occur outside the hospital, we analyzed out-of-hospital sudden unexpected death as well as sudden cardiac deaths, a more specific indicator of proarrhythmic effects. The adjusted risk of sudden unexpected death for citalopram did not differ significantly from that for the other SSRIs. The respective hazard ratios (HRs) for citalopram versus escitalopram, fluoxetine, paroxetine, and sertraline were 0.84 (95% CI, 0.40-1.75), 1.24 (95% CI, 0.75-2.05), 0.75 (95% CI, 0.45-1.24), and 1.53 (95% CI, 0.91-2.55). There were no significant differences for sudden cardiac death or all study deaths, nor were there significant differences among high-risk patients (≥ 60 years of age, upper quartile baseline cardiovascular risk). Escitalopram users had no significantly increased risk for any study end point. We found no evidence that risk of sudden unexpected death, sudden cardiac death, or total mortality for high-dose citalopram and escitalopram differed significantly from that for comparable doses of fluoxetine, paroxetine, and sertraline. © Copyright 2016 Physicians Postgraduate Press, Inc.

  14. Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.

    Science.gov (United States)

    Martinez, Alvaro A; Gustafson, Gary; Gonzalez, José; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

    2002-06-01

    To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose 93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

  15. High-dose alcohol intoxication differentially modulates cognitive subprocesses involved in response inhibition.

    Science.gov (United States)

    Stock, Ann-Kathrin; Schulz, Tom; Lenhardt, Martin; Blaszkewicz, Meinolf; Beste, Christian

    2016-01-01

    Aside from well-known physiological effects, high-dose alcohol intoxication (a.k.a. binge drinking) can lead to aversive social and legal consequences because response inhibition is usually compromised under the influence of alcohol. Although the behavioral aspects of this phenomenon were reported on extensively, the underlying neurophysiological mechanisms mediating this disinhibition are unclear. To close this gap, we used both behavioral and neurophysiological measures (event-related potentials, ERPs) to investigate which subprocesses of response inhibition are altered under the influence of high-dose alcohol intoxication. Using a within-subject design, we asked young healthy participants (n = 27) to complete a GO/NOGO task once sober and once intoxicated (approximately 1.2‰). During intoxication, high-dose alcohol effects were highest in a condition where the participants could not rely on automated stimulus-response mapping processes during response inhibition. In this context, the NOGO-P3 (ERP), that likely depends on dopaminergic signaling within mesocorticolimbic pathways and is thought to reflect motor inhibition and/or the evaluation of inhibitory processes, was altered in the intoxicated state. In contrast to this, the N2 component, which largely depends on nigrostriatal dopamine pathways and is thought to reflect inhibition on a pre-motor level, was not altered. Based on these results, we demonstrate that alcohol-induced changes of dopaminergic neurotransmission do not exert a global effect on response inhibition. Instead, changes are highly subprocess-specific and seem to mainly target mesocorticolimbic pathways that contribute to motor inhibition and the evaluation of such. © 2014 Society for the Study of Addiction.

  16. Acute cognitive effects of high doses of dextromethorphan relative to triazolam in humans

    Science.gov (United States)

    Carter, Lawrence P.; Reissig, Chad J.; Johnson, Matthew W.; Klinedinst, Margaret A.; Griffiths, Roland R.

    2012-01-01

    BACKGROUND Although concerns surrounding high-dose dextromethorphan (DXM) abuse have recently increased, few studies have examined the acute cognitive effects of high doses of DXM. The aim of this study was to compare the cognitive effects of DXM with those of triazolam and placebo. METHODS Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg /70 kg), and placebo were administered p.o. to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Effects on cognitive performance were examined at baseline and after drug administration for up to 6 hours. RESULTS Both triazolam and DXM produced acute impairments in attention, working memory, episodic memory, and metacognition. Impairments observed following doses of 100-300 mg/70 kg DXM were generally smaller in magnitude than those observed after 0.5 mg/70 kg triazolam. Doses of DXM that impaired performance to the same extent as triazolam were in excess of 10-30 times the therapeutic dose of DXM. CONCLUSION The magnitude of the doses required for these effects and the absence of effects on some tasks within the 100-300 mg/70 kg dose range of DXM, speak to the relatively broad therapeutic window of over-the-counter DXM preparations when used appropriately. However, the administration of supratherapeutic doses of DXM resulted in acute cognitive impairments on all tasks that were examined. These findings are likely relevant to cases of high-dose DXM abuse. PMID:22989498

  17. High doses of biotin in chronic progressive multiple sclerosis: a pilot study.

    Science.gov (United States)

    Sedel, Frédéric; Papeix, Caroline; Bellanger, Agnès; Touitou, Valérie; Lebrun-Frenay, Christine; Galanaud, Damien; Gout, Olivier; Lyon-Caen, Olivier; Tourbah, Ayman

    2015-03-01

    No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis. The aim of this pilot study is to assess the clinical efficacy and safety of high doses of biotin in patients suffering from progressive MS. Uncontrolled, non-blinded proof of concept study 23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100-300mg/day) from 2 to 36 months (mean=9.2 months). Judgement criteria varied according to clinical presentations and included quantitative and qualitative measures. In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two patients exhibited progressive reappearance of P100 waves, with normalization of latencies in one case. Proton magnetic resonance spectroscopy (H-MRS) in one case showed a progressive normalization of the Choline/Creatine ratio. One patient with left homonymous hemianopia kept on improving from 2 to 16 months following treatment׳s onset. Sixteen patients out of 18 (89%) with prominent spinal cord involvement were considered as improved as confirmed by blinded review of videotaped clinical examination in 9 cases. In all cases improvement was delayed from 2 to 8 months following treatment׳s onset. These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. Two double-blind placebo-controlled trials are on going. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Surface applicators for high dose rate brachytherapy in AIDS-related kaposi's sarcoma

    International Nuclear Information System (INIS)

    Evans, Michael D.C.; Yassa, Mariam; Podgorsak, Ervin B.; Roman, Ted N.; Schreiner, L. John; Souhami, Luis

    1997-01-01

    Purpose: The development of commercially available surface applicators using high dose rate remote afterloading devices has enabled radiotherapy centers to treat selected superficial lesions using a remote afterloading brachytherapy unit. The dosimetric parameters of these applicators, the clinical implementation of this technique, and a review of the initial patient treatment regimes are presented. Methods and Materials: A set of six fixed-diameter (1, 2, and 3 cm), tungsten/steel surface applicators is available for use with a single stepping-source (Ir-192, 370 GBq) high dose rate afterloader. The source can be positioned either in a parallel or perpendicular orientation to the treatment plane at the center of a conical aperture that sits at an SSD of approximately 15 mm and is used with a 1-mm thick removable plastic cap. The surface dose rates, percent depth dose, and off-axis ratios were measured. A custom-built, ceiling-mounted immobilization device secures the applicator on the surface of the patient's lesion during treatment. Results: Between November 1994, and September 1996, 16 AIDS-related Kaposi's sarcoma patients having a total of 120 lesions have been treated with palliative intent. Treatment sites were distributed between the head and neck, extremity, and torso. Doses ranged from 8 to 20 Gy, with a median dose of 10 Gy delivered in a single fraction. Treatments were well tolerated with minimal skin reaction, except for patients with lesions treated to 20 Gy who developed moderate/severe desquamation. Conclusion: Radiotherapy centers equipped with a high dose rate remote afterloading unit may treat small selected surface lesions with commercially available surface applicators. These surface applicators must be used with a protective cap to eliminate electron contamination. The optimal surface dose appears to be either 10 or 15 Gy depending upon the height of the lesion

  19. Induction of regulatory T cells by high-dose gp96 suppresses murine liver immune hyperactivation.

    Directory of Open Access Journals (Sweden)

    Xinghui Li

    Full Text Available Immunization with high-dose heat shock protein gp96, an endoplasmic reticulum counterpart of the Hsp90 family, significantly enhances regulatory T cell (Treg frequency and suppressive function. Here, we examined the potential role and mechanism of gp96 in regulating immune-mediated hepatic injury in mice. High-dose gp96 immunization elicited rapid and long-lasting protection of mice against concanavalin A (Con A-and anti-CD137-induced liver injury, as evidenced by decreased alanine aminotransaminase (ALT levels, hepatic necrosis, serum pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6, and number of IFN-γ (+ CD4(+ and IFN-γ (+ CD8(+ T cells in the spleen and liver. In contrast, CD4(+CD25(+Foxp3(+ Treg frequency and suppressive function were both increased, and the protective effect of gp96 could be generated by adoptive transfer of Treg cells from gp96-immunized mice. In vitro co-culture experiments demonstrated that gp96 stimulation enhanced Treg proliferation and suppressive function, and up-regulation of Foxp3, IL-10, and TGF-β1 induced by gp96 was dependent on TLR2- and TLR4-mediated NF-κB activation. Our work shows that activation of Tregs by high-dose gp96 immunization protects against Con A- and anti-CD137-induced T cell-hepatitis and provides therapeutic potential for the development of a gp96-based anti-immune hyperactivation vaccine against immune-mediated liver destruction.

  20. The Effect of High Dose Radioiodine Therapy on Formation of Radiation Retinopathy During Thyroid Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tülay Kaçar Güvel

    2014-10-01

    Full Text Available Objective: Non-thyroidal complication of high-dose radioiodine therapy for thyroid carcinoma might cause salivary and lacrimal gland dysfunction, which may be transient or permanent in a dose-dependent manner. However, radiation retinopathy complicating 131I therapy, has not been previously well characterized. The aim of this study was to evaluate the extent of retinal damage among patients who had received high doses of radioiodine treatment. Methods: Forty eyes of 20 patients (3 male, 17 female who received 250-1000 mCi during 131I therapy and on ophthalmological follow up for a year after the last treatment were included in the study. Mean age of the study group was 50 years (range 25-70 years. In ophthalmologic examination, visual acuity was measured in order to determine visual loss. Intraocular pressure was measured in all the patients. Then lens examination was carried out with slit lamp biomicroscopy in order to investigate cataract or partial lens opacities. Fundus observation was carried out through the dilated pupil with slit lamp biomicroscopy using 90 D noncontact lens. Result: The best corrected visual aquity with Snellen chart was found as 1.0 in 36 eyes (90% and between 0.6 and 0.9 (10% in 4 eyes (10%. At the biomicroscopic fundus examination, retinal hemorrhage consistent with radiation retinopathy, microaneurysm, microinfarction, edema or exudation, vitreus hemorrhage, partial or total optical disc pallor indicating papillopathy in the optic disc were not observed in any of the eyes. Conclusion: This result indicates that there is not any significant correlation between repeated high-dose radioiodine therapy and radiation retinopathy in differentiated thyroid carcinomas. Even though there is not a significant restriction in use of higher doses of radioiodine therapy in differentiated thyroid carcinoma, more extensive studies are needed in order to obtain more accurate data on possible occurrence of retinopathy.

  1. Verification of the calculation program for brachytherapy planning system of high dose rate (PLATO)

    International Nuclear Information System (INIS)

    Almansa, J.; Alaman, C.; Perez-Alija, J.; Herrero, C.; Real, R. del; Ososrio, J. L.

    2011-01-01

    In our treatments are performed brachytherapy high dose rate since 2007. The procedures performed include gynecological intracavitary treatment and interstitial. The treatments are performed with a source of Ir-192 activity between 5 and 10 Ci such that small variations in treatment times can cause damage to the patient. In addition the Royal Decree 1566/1998 on Quality Criteria in radiotherapy establishes the need to verify the monitor units or treatment time in radiotherapy and brachytherapy. All this justifies the existence of a redundant system for brachytherapy dose calculation that can reveal any abnormality is present.

  2. Advantages of high-dose rate (HDR) brachytherapy in treatment of prostate cancer

    Science.gov (United States)

    Molokov, A. A.; Vanina, E. A.; Tseluyko, S. S.

    2017-09-01

    One of the modern methods of preserving organs radiation treatment is brachytherapy. This article analyzes the results of prostate brachytherapy. These studies of the advantages of high dose brachytherapy lead to the conclusion that this method of radiation treatment for prostate cancer has a favorable advantage in comparison with remote sensing methods, and is competitive, preserving organs in comparison to surgical methods of treatment. The use of the method of polyfocal transperineal biopsy during the brachytherapy session provides information on the volumetric spread of prostate cancer and adjust the dosimetry plan taking into account the obtained data.

  3. Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer

    International Nuclear Information System (INIS)

    Martinez, Alvaro A.; Gustafson, Gary; Gonzalez, Jose; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

    2002-01-01

    Purpose: To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Methods and Materials: Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level ≥10.0 ng/mL, Gleason score ≥7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose 93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. Results: The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p<0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p=0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Conclusion: Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause

  4. Effect of high dose irradiation on the red cell span in rabbits

    International Nuclear Information System (INIS)

    Kang, T.W.; Koh, J.W.; Woo, K.S.; Lee, O.H.; Youn, C.S.

    1982-01-01

    As a part of studies on acute effects of high dose irradiation in vivo, the present report was carried out to evaluate the changes of the red cell life span in the white rabbits by a single whole body exposure to gamma rays from 60 Co teletherapy unit. The exposure was done in dose levels of 100, 600 and 900 rads to each experimental group of 10 rabbits. The life span apparent half survival time of red cells, and that the red cell volume in the circulting blood were measured by ICSH Reference method using 51 Cr. (Author)

  5. A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease.

    OpenAIRE

    Little, A; Levy, R; Chuaqui-Kidd, P; Hand, D

    1985-01-01

    The first long-term double-blind placebo controlled trial of high dose lecithin in senile dementia of the Alzheimer type is reported. Fifty one subjects were given 20-25 g/day of purified soya lecithin (containing 90% phosphatidyl plus lysophosphatidyl choline) for six months and followed up for at least a further six months. Plasma choline levels were monitored throughout the treatment period. There were no differences between the placebo group and the lecithin group but there was an improve...

  6. MRI dosimetry using an echo-quotient technique for high dose rate brachytherapy

    International Nuclear Information System (INIS)

    Ansbacher, W.

    1996-01-01

    MRI gel dosimetry is a relatively new technique that has many advantages over conventional methods, and is particularly suited to High Dose Rate (HDR) Brachytherapy. The dosimeter has high spatial resolution and a water-equivalent response over a wide range of photon energies. Because it is an integrating dosimeter, it allows for efficient mapping of the dynamically-produced distributions from an HDR source. As an example of this technique, the dose response, which is calibrated in terms of the change in spin-spin relaxation time, has been used to investigate the anisotropy of an HDR source. (author). 1 fig

  7. Effect of high-dose intravenous vitamin C on inflammation in cancer patients

    Directory of Open Access Journals (Sweden)

    Mikirova Nina

    2012-09-01

    Full Text Available Abstract Background An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP are associated with poor prognosis and decreased survival in many types of cancer. Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels. Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients. Methods 45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g after standard treatments by conventional methods. CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests. Results According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment. There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3 and changes in the levels of C-reactive protein. Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments. Conclusions The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases

  8. High dose-rate brachytherapy source position quality assurance using radiochromic film

    International Nuclear Information System (INIS)

    Evans, M.D.C.; Devic, S.; Podgorsak, E.B.

    2007-01-01

    Traditionally, radiographic film has been used to verify high-dose-rate brachytherapy source position accuracy by co-registering autoradiographic and diagnostic images of the associated applicator. Filmless PACS-based clinics that do not have access to radiographic film and wet developers may have trouble performing this quality assurance test in a simple and practical manner. We describe an alternative method for quality assurance using radiochromic-type film. In addition to being easy and practical to use, radiochromic film has some advantages in comparison with traditional radiographic film when used for HDR brachytherapy quality assurance

  9. Peripheral arterial disease in a female using high-dose combined oral contraceptive pills.

    Science.gov (United States)

    Pallavee, P; Samal, Sunita; Samal, Rupal

    2013-01-01

    The association between oral contraceptive (OC) pills and vascular diseases is well-known, although, the present generation of pills is considered to be relatively safer in this regard. Hormonal treatment for severe abnormal uterine bleeding is usually considered after ruling out malignancy, when such bleeding is resistant to all other forms of treatment. We report a case of severe peripheral arterial disease in a female, who had been on high-dose OC pills for an extended period of time for severe uterine bleeding.

  10. On the use of multi-dimensional scaling and electromagnetic tracking in high dose rate brachytherapy

    Science.gov (United States)

    Götz, Th I.; Ermer, M.; Salas-González, D.; Kellermeier, M.; Strnad, V.; Bert, Ch; Hensel, B.; Tomé, A. M.; Lang, E. W.

    2017-10-01

    High dose rate brachytherapy affords a frequent reassurance of the precise dwell positions of the radiation source. The current investigation proposes a multi-dimensional scaling transformation of both data sets to estimate dwell positions without any external reference. Furthermore, the related distributions of dwell positions are characterized by uni—or bi—modal heavy—tailed distributions. The latter are well represented by α—stable distributions. The newly proposed data analysis provides dwell position deviations with high accuracy, and, furthermore, offers a convenient visualization of the actual shapes of the catheters which guide the radiation source during the treatment.

  11. A high dose dosimeter based polyvinyl chloride dyed with malachite green

    International Nuclear Information System (INIS)

    Kattan, M.; Daher, Y.; Alkassiri, H.

    2007-01-01

    Polyvinyl chloride film (PVC) dyed with malachite green has been studied for high dose radiation dosimetry using visible spectrophotometry. A linear relationship between the relative absorbance and the absorbed dose at the wavelength 628 nm in the range of 0-125 kGy was found. The effect of dose rate, irradiation temperature, film thickness and dye intensity were found not to influence the response. The effects of shelf-life and the post-irradiation storage in darkness and indirect daylight conditions on dosimetry performance were discussed. (author)

  12. In phantom calibration of a high dose rate remote afterloading device

    International Nuclear Information System (INIS)

    Alfonso, R.; Tolede, P.; Pich, V.

    1995-01-01

    The high dose-rate (HDR) brachytherapy in Cuba is based on soviet made devices type AGAT-V. In order to calibration one of these for clinical use a method based of the different measurement of absorbed dose at the reference point B in a paraffin phantom was developed. The results of the calibration are shown. From these results an analysis was made of the effective doses to prescription point a considering the Lineal-Quadratic model. The clinical results by using the AGAT-V device are displayed in a comparative way

  13. High-dose treatment with autologous stem cell transplantation versus sequential chemotherapy: the GELA experience.

    Science.gov (United States)

    Bosly, A; Haioun, C; Gisselbrecht, C; Reyes, F; Coiffier, B

    2001-07-01

    Autologous stem-cell transplantation (ASCT) has permitted to deliver high-dose therapy (HDT). In aggressive lymphomas, the GELA group conducted prospective and retrospective studies comparing HDT + ASCT to conventional sequential chemotherapy. In relapsing patients and in partial remission, retrospective studies showed a survival advantage for HDT + ASCT over sequential chemotherapy. In complete response, advantage for HDT + ASCT was demonstrated in a prospective trial only for patients with high intermediate or high risk in the IPI score. The attainment of a maximal reduction of the tumoral mass before going HDT is very important either in first line or in relapsing patients.

  14. Total skin high-dose-rate electron therapy dosimetry using TG-51

    International Nuclear Information System (INIS)

    Gossman, Michael S.; Sharma, Subhash C.

    2004-01-01

    An approach to dosimetry for total skin electron therapy (TSET) is discussed using the currently accepted TG-51 high-energy calibration protocol. The methodology incorporates water phantom data for absolute calibration and plastic phantom data for efficient reference dosimetry. The scheme is simplified to include the high-dose-rate mode conversion and provides support for its use, as it becomes more available on newer linear accelerators. Using a 6-field, modified Stanford technique, one may follow the process for accurate determination of absorbed dose

  15. Applichation of the sulphate ceric dosimetric in the high doses range

    International Nuclear Information System (INIS)

    Prieto Miranda, F.

    1991-01-01

    The ceric-cerous dosimetric system is one of the system more employed in the high dose dosimetry. The spectrophotometric procedure to measure the ceric-concentration is an usual analityc method to determine the absorbed dose. On the other hand, due at increase employ of the irradiation process control. In this paper is realized the ceric-cerous dosimetric calibration in the dose range of 0,6 - 5 kGy and the application in the irradiation process control to differents absorbed dose values

  16. Intravenous high-dose immunotherapy: practical recommendations for use in the treatment of neurological disimmune diseases

    Directory of Open Access Journals (Sweden)

    N. A. Suponeva

    2015-01-01

    Full Text Available Current publication summarizes main indications and benefits of intravenous high-dose immunotherapy (IHI in the treatment of various autoimmune diseases of the peripheral nervous system. Available products of intravenous immunoglobulin (IVIG on the Russian market are reviewed. Tactics for choosing optimal medication for IHI based on its effectiveness and safety are analyzed. Dosage calculation and way of administration of IVIG are described, beeing of a high practical value in neurologist’s daily work.

  17. Application of RADPOS in Vivo Dosimetry for QA of High Dose Rate Brachytherapy

    DEFF Research Database (Denmark)

    Cherpak, A.; Kertzscher Schwencke, Gustavo Adolfo Vladimir; Cygler, J.

    2012-01-01

    cancer, where high dose gradients and movement of the prostate gland can present unique in vivo dosimetry challenges. Financial and technical support has been received from Best Medical Canada and Ascension Technology Corporation. © 2012 American Association of Physicists in Medicine......Purpose: The RADPOS in vivo dosimetry system combines an electromagnetic positioning sensor with MOSFET dosimetry, allowing for simultaneous online measurements of dose and spatial position. In this work, we assess the potential use of RADPOS for measurements of motion and dose during prostate HDR...

  18. Radiation shielding and dose rate distribution for the building of the high dose rate accelerator

    International Nuclear Information System (INIS)

    Matsuda, Koji; Takagaki, Torao; Nakase, Yoshiaki; Nakai, Yohta.

    1984-03-01

    A high dose rate electron accelerator was established at Osaka Laboratory for Radiation Chemistry, Takasaki Establishment, JAERI in the fiscal year of 1975. This report shows the fundamental concept for the radiation shielding of the accelerator building and the results of their calculations which were evaluated through the model experiments. After the construction of the building, the leak radiation was measured in order to evaluate the calculating method of radiation shielding. Dose rate distribution of X-rays was also measured in the whole area of the irradiation room as a data base. (author)

  19. Calibration in a manikin of a high dose rate equipment by remote charge

    International Nuclear Information System (INIS)

    Alfonso La Guardia, Rodolfo; Toledo Jimenez, Pablo; Pich Leon, Victor

    1996-01-01

    The aim of this study was to know the immediate results obtained with laparoscopic cholecystectomy in The use of High Dose Rate brachytherapy in Cuba has been limited to AGAT-V Soviet installations. In order to calibrate one of these installations for its clinical use, it was developed a procedure based on the direct measurement of the dose absorbed in referral point B of a paraffin manikin. Results obtained as a result of calibration are shown. According to these results, it was carried out an evaluation of the effective doses administered on prescription point A by using the linear quadratic model

  20. Collection of radiation resistant characteristics reports for instruments and materials in high dose rate environment

    International Nuclear Information System (INIS)

    Kusano, Joichi

    2008-03-01

    This document presents the collected official reports of radiation irradiation study for the candidate materials to be used in high dose rate environment as J-PARC facility. The effect of radiation damage by loss-beam or secondary particle beam of the accelerators influences the performance and the reliability of various instruments. The knowledge on the radiation resistivity of the materials is important to estimate the life of the equipments, the maintenance interval and dose evaluation for the personnel at the maintenance period. The radiation damage consists with mechanical property, electrical property and gas-evolution property. (author)

  1. Metabolic effects of feeding high doses of propanol and propylacetate to lactating Holstein cows

    DEFF Research Database (Denmark)

    Raun, Birgitte Marie Løvendahl; Kristensen, Niels Bastian

    2012-01-01

    Three lactating Holstein cows implanted with ruminal cannulas and permanent indwelling catheters in major splanchnic blood vessels were used to investigate alcohol metabolism and metabolic effects of feeding high doses of propanol and propylacetate. Cows were fed three diets control (basal ration......; C), propanol (C plus 50 g propanol/kg DM; P), and propylacetate (C plus 50 g propanol/kg DM and 15 g propylacetate/kg DM; PPA) in a 3 × 3 Latin square design with 14 d period. Daily rations were fed in three equally sized portions at 8 hour intervals and 8 hourly sets of ruminal fluid, arterial...

  2. High dose stainless steel swelling data on interior and peripheral oxide fuel pins

    International Nuclear Information System (INIS)

    Boltax, A.; Foster, J.P.; Nayak, U.P.

    1983-01-01

    High dose (2 x 10 23 n/cm 2 , E > 0.1 Mev) swelling data obtained on 20% cold-worked AISI 316 stainless steel (N-lot) cladding from mixed-oxide fuel pins show large differences in swelling incubation dose due to pre-incubation dose temperature changes. Circumferential swelling variations of 1.5 to 4 times were found in peripheral fuel pin cladding which experienced 30 to 60 deg C temperature changes due to movement in a temperature gradient. Consideration is given to the implications of these results to low swelling materials development and core design. (author)

  3. Epithelial regeneration of transposed intestine after high doses of X-irradiation

    International Nuclear Information System (INIS)

    Both, N.J. de; Vermey, M.

    1976-01-01

    The regeneration capacities of normal and transposed small bowel epithelium were compared in rats after applying high doses of X-irradiation. It has been shown that the potency of the mucosa to regenerate was much higher than assumed and that the mucosa could regenerate after single doses varying from 2000 to 5000 R. Even in the villus epithelium and in flat epithelium covering infiltrates of the lamina propria cells survived, which were still able to resume proliferative activity several days after irradiation. (author)

  4. High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia

    International Nuclear Information System (INIS)

    Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo

    2005-01-01

    A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author)

  5. High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo [National Hospital Organization Osaka Minami Medical Center, Kawachinagano (Japan)

    2005-03-01

    A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author)

  6. Effect of uv-irradiation on genetic recombination of Simian virus 40 mutants

    International Nuclear Information System (INIS)

    Gentil, A.; Margot, A.; Sarasin, A.

    1983-01-01

    Genetic recombination in monkey kidney cells has been studied using Simian virus 40 (SV40) as a molecular probe. Control or uv-irradiated cells have been co-infected with two thermosensitive mutants of SV40, tsA58 and tsA30. Recombination between the two viral genomes gives rise to a wild type virus phenotype, able to grow at the restrictive temperature of 41 0 C, which was taken as a measure of the recombination activity of the host cells. Results show that recombination takes place at a low frequency when viruses are not uv-irradiated. Irradiation of one or both viruses increases drastically recombination frequency. Pretreatment of the host cells with uv-light or mitomycin C 24 hours before being infected does not increase recombination frequency measured in our experimental conditions. 23 references, 5 tables

  7. Influence of cell dissociation procedures on the tumorigenicity of Simian Virus 40 transformed fibroblasts

    International Nuclear Information System (INIS)

    Tenforde, T.S.; Risius, J.; Beckmann, A.; Tobias, C.A.; Gurney, E.

    1975-11-01

    Mouse fibroblasts transformed by Simian Virus 40 (SV40) were examined for tumor forming ability in syngeneic BALB/c mice following dissociation from tissue culture dishes by two procedures. A significantly greater in vivo proliferative capacity was observed for cells dissociated by the tryspin-EDTA procedure, with the injected cell dose for tumor production in 50 percent of recipient mice (the TPD 50 ) being 16-fold lower than the TPD 50 for cells dissociated by the EDTA procedure. Host immunosuppression with 300 rad whole-body γ irradiation led to a significant 7-fold decrease in the TPD 50 for cells dissociated by the EDTA procedure, while no significant decrease in TPD 50 was observed for cells dissociated by the tryspin-EDTA procedure

  8. Formation of pyrimidine dimers in Simian virus 40 chromosomes and DNA in vitro: effects of salt

    International Nuclear Information System (INIS)

    Edenberg, H.J.

    1984-01-01

    Simian virus 40 chromosomes were used to determine whether packaging of DNA into chromatin affected the yield of cylcobutane pyrimidine dimers introduced by ultraviolet light (254 nm). SV40 chromatin and purified SV40 DNA (radioactively labeled with different isotopes) were mixed and irradiated in vitro. The proteins were extracted and pyrimidine dimers detected as sites sensitive to the UV-endonuclease encoded by bacteriophage T4. When irradiation was carried out in the presence of at least 0.05 M NaCl the same number of dimers were formed in chromatin as in free DNA. Irradiation in the absence of NaCl, however, reduced the relative yield of dimers in chromatin to 89% of that in free DNA. Different methods of chromatin preparation did not influence these results. (author)

  9. Feline Immunodeficiency Virus Cross-Species Transmission: Implications for Emergence of New Lentiviral Infections.

    Science.gov (United States)

    Lee, Justin; Malmberg, Jennifer L; Wood, Britta A; Hladky, Sahaja; Troyer, Ryan; Roelke, Melody; Cunningham, Mark; McBride, Roy; Vickers, Winston; Boyce, Walter; Boydston, Erin; Serieys, Laurel; Riley, Seth; Crooks, Kevin; VandeWoude, Sue

    2017-03-01

    Owing to a complex history of host-parasite coevolution, lentiviruses exhibit a high degree of species specificity. Given the well-documented viral archeology of human immunodeficiency virus (HIV) emergence following human exposures to simian immunodeficiency virus (SIV), an understanding of processes that promote successful cross-species lentiviral transmissions is highly relevant. We previously reported natural cross-species transmission of a subtype of feline immunodeficiency virus, puma lentivirus A (PLVA), between bobcats ( Lynx rufus ) and mountain lions ( Puma concolor ) for a small number of animals in California and Florida. In this study, we investigate host-specific selection pressures, within-host viral fitness, and inter- versus intraspecies transmission patterns among a larger collection of PLV isolates from free-ranging bobcats and mountain lions. Analyses of proviral and viral RNA levels demonstrate that PLVA fitness is severely restricted in mountain lions compared to that in bobcats. We document evidence of diversifying selection in three of six PLVA genomes from mountain lions, but we did not detect selection among 20 PLVA isolates from bobcats. These findings support the hypothesis that PLVA is a bobcat-adapted virus which is less fit in mountain lions and under intense selection pressure in the novel host. Ancestral reconstruction of transmission events reveals that intraspecific PLVA transmission has occurred among panthers ( Puma concolor coryi ) in Florida following the initial cross-species infection from bobcats. In contrast, interspecific transmission from bobcats to mountain lions predominates in California. These findings document outcomes of cross-species lentiviral transmission events among felids that compare to the emergence of HIV from nonhuman primates. IMPORTANCE Cross-species transmission episodes can be singular, dead-end events or can result in viral replication and spread in the new species. The factors that determine which

  10. Cell and molecular biology of simian virus 40: implications for human infections and disease

    Science.gov (United States)

    Butel, J. S.; Lednicky, J. A.

    1999-01-01

    Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discovered in 1960 as a contaminant of polio vaccines that were distributed to millions of people from 1955 through early 1963. SV40 is a potent DNA tumor virus that induces tumors in rodents and transforms many types of cells in culture, including those of human origin. This virus has been a favored laboratory model for mechanistic studies of molecular processes in eukaryotic cells and of cellular transformation. The viral replication protein, named large T antigen (T-ag), is also the viral oncoprotein. There is a single serotype of SV40, but multiple strains of virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the T-ag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pathogenic in immunocompromised animals, and multiple tissues can be infected. SV40 can replicate in certain types of simian and human cells. SV40-neutralizing antibodies have been detected in individuals not exposed to contaminated polio vaccines. SV40 DNA has been identified in some normal human tissues, and there are accumulating reports of detection of SV40 DNA and/or T-ag in a variety of human tumors. This review presents aspects of replication and cell transformation by SV40 and considers their implications for human infections and disease pathogenesis by the virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV40 in certain human cancers, but additional studies are necessary to prove etiology.

  11. Techniques for high dose dosimetry in industry, agriculture and medicine. Proceedings of a symposium

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    In radiation processing, it is important that the irradiated products are reliable and safe. For processes that impact directly on public health, dosimetry provides a formal means of regulation. For other applications, measurements are indispensable for process control to improve quality and the measurements have to be standardized. Thus, dosimetry is an essential part of quality standards for radiation processes. In the developing world, establishment of such quality standards is only in the embryonic stage, and the IAEA should and does play a role in the development and implementation of these standards. The IAEA initiated a programme of high dose dosimetry in 1977 to accomplish dose standardization on an industrial scale, to promote dosimetry as a quality control measure in radiation processing, and to help develop new dosimetry techniques. Since dosimetry has such a key role in these processes, the IAEA organized this international symposium to provide a forum for presentation and discussion of up-to-date developments in this field. Since the International Symposium on High Dose Dosimetry for Radiation Processing held in 1990 the field of dosimetry has deepened and broadened. There is a definite shift towards quality assurance, which calls for dependable dosimetry systems with well established traceability to national or international standards. Also, many new applications of radiation have been developed and for these new and innovative dosimetry methods are needed. This symposium has provided a forum for the discussion of many of these developments and consideration of the outstanding issues in these vital areas Refs, figs, tabs

  12. Techniques for high dose dosimetry in industry, agriculture and medicine. Proceedings of a symposium

    International Nuclear Information System (INIS)

    1999-03-01

    In radiation processing, it is important that the irradiated products are reliable and safe. For processes that impact directly on public health, dosimetry provides a formal means of regulation. For other applications, measurements are indispensable for process control to improve quality and the measurements have to be standardized. Thus, dosimetry is an essential part of quality standards for radiation processes. In the developing world, establishment of such quality standards is only in the embryonic stage, and the IAEA should and does play a role in the development and implementation of these standards. The IAEA initiated a programme of high dose dosimetry in 1977 to accomplish dose standardization on an industrial scale, to promote dosimetry as a quality control measure in radiation processing, and to help develop new dosimetry techniques. Since dosimetry has such a key role in these processes, the IAEA organized this international symposium to provide a forum for presentation and discussion of up-to-date developments in this field. Since the International Symposium on High Dose Dosimetry for Radiation Processing held in 1990 the field of dosimetry has deepened and broadened. There is a definite shift towards quality assurance, which calls for dependable dosimetry systems with well established traceability to national or international standards. Also, many new applications of radiation have been developed and for these new and innovative dosimetry methods are needed. This symposium has provided a forum for the discussion of many of these developments and consideration of the outstanding issues in these vital areas

  13. High-dose proton beam therapy for sinonasal mucosal malignant melanoma

    International Nuclear Information System (INIS)

    Fuji, Hiroshi; Yoshikawa, Shusuke; Kasami, Masako; Murayama, Shigeyuki; Onitsuka, Tetsuro; Kashiwagi, Hiroya; Kiyohara, Yoshio

    2014-01-01

    The significance of definitive radiotherapy for sinonasal mucosal melanoma (SMM) is sill controvertial. This study was to evaluate the role of high-dose proton beam therapy (PBT) in patients with SMM. The cases of 20 patients with SMM localized to the primary site who were treated by PBT between 2006 and 2012 were retrospectively analyzed. The patterns of overall survival and morbidity were assessed. The median follow-up time was 35 months (range, 6–77 months). The 5-year overall and disease-free survival rates were 51% and 38%, respectively. Four patients showed local failure, 2 showed regrowth of the primary tumor, and 2 showed new sinonasal tumors beyond the primary site. The 5-year local control rate after PBT was 62%. Nodal and distant failure was seen in 7 patients. Three grade 4 late toxicities were observed in tumor-involved optic nerve. Our findings suggested that high-dose PBT is an effective local treatment that is less invasive than surgery but with comparable outcomes

  14. The use of caffeine to assess high dose exposures to ionising radiation by dicentric analysis

    International Nuclear Information System (INIS)

    Pujol, M.; Puig, R.; Caballin, M. R.; Barrios, L.; Barquinero, J. F.

    2012-01-01

    Dicentric analysis is considered as a 'gold standard' method for biological dosimetry. However, due to the radiation-induced mitotic delay or inability to reach mitosis of heavily damaged cells, the analysis of dicentrics is restricted to doses up to 4-5 Gy. For higher doses, the analysis by premature chromosome condensation technique has been proposed. Here, it is presented a preliminary study is presented in which an alternative method to analyse dicentrics after high dose exposures to ionising radiation (IR) is evaluated. The method is based on the effect of caffeine in preventing the G2/M checkpoint allowing damaged cells to reach mitosis. The results obtained indicate that the co-treatment with Colcemide and caffeine increases significantly increases the mitotic index, and hence allows a more feasible analysis of dicentrics. Moreover in the dose range analysed, from 0 to 15 Gy, the dicentric cell distribution followed the Poisson distribution, and a simulated partial-body exposure has been clearly detected. Overall, the results presented here suggest that caffeine has a great potential to be used for dose-assessment after high dose exposure to IR. (authors)

  15. High-dose steroid therapy for idiopathic optic perineuritis: a case series

    Directory of Open Access Journals (Sweden)

    Mimura Tatsuya

    2010-12-01

    Full Text Available Abstract Introduction It has been reported that the prognosis of optic perineuritis may be poor when initiation of treatment is delayed. Here we report the successful treatment of three patients with idiopathic optic perineuritis, including two in whom initiation of therapy was delayed. Case presentation Three Japanese patients (two women aged 73 and 66 years, and one man aged 27 years presented with loss of vision (for five months, several months, and two months respectively and pain on eye movement in the third case only, and were diagnosed as having idiopathic optic perineuritis. Fat-suppressed T2-weighted magnetic resonance images showed high signal intensity areas around the affected optic nerves, suggesting the presence of optic perineuritis. Two patients received steroid pulse therapy and the third was given high-dose steroid therapy. The visual acuity improved in all three cases. Conclusion High-dose steroid therapy may be effective for idiopathic perineuritis in patients without optic nerve atrophy, even if initial treatment (including moderate-dose steroids has failed.

  16. Effects of high dose rate gamma radiation on survival and reproduction of Biomphalaria glabrata

    International Nuclear Information System (INIS)

    Cantinha, Rebeca S.; Nakano, Eliana; Silva, Luanna R.S.

    2009-01-01

    Ionizing radiations are known as mutagenic agents, causing lethality and infertility. This characteristic has motivated its application on animal biological control. In this context, the freshwater snail Biomphalaria glabrata can be considered an excellent experimental model to study effects of ionizing radiations on lethality and reproduction. This work was designed to evaluate effects of 60 Co gamma radiation at high dose rate (10.04 kGy/h) on B. glabrata. For this purpose, adult snails were selected and exposed to doses ranging from 20 to 100 Gy, with 10 Gy intervals; one group was kept as control. There was not effect of dose rate in the lethality of gamma radiation; the value of 64,3 Gy of LD 50 obtained in our study was similar to that obtained by other authors with low dose rates. Nevertheless, our data suggest that there was a dose rate effect in the reproduction. On all dose levels, radiation improved the production of embryos for all exposed individuals. However, viability indexes were below 6% and, even 65 days after irradiation, fertility was not recovered. These results are not in agreement with other studies using low dose rates. Lethality was obtained in all groups irradiated, and the highest doses presented percentiles of dead animals above 50%. The results demonstrated that doses of 20 and 30 Gy were ideal for population control of B. glabrata. Further studies are needed; nevertheless, this research evidenced great potential of high dose rate gamma radiation on B. glabrata reproductive control. (author)

  17. Early and late effects of local high dose radiotherapy of the brain on memory and attention

    International Nuclear Information System (INIS)

    Duchstein, S.; Gademann, G.; Peters, B.

    2003-01-01

    Early and Late Effects of Local High Dose Radiotherapy of the Brain on Memory and Attention Background: Stereotactic radiotherapy of benign tumors of the base of skull shows excellent tumor control and long survival. Aim is to study the impact of high dose radiation therapy on functions of memory and attention over time. Patients and Methods: 21 patients (age 42 ± 11 years) with tumors of the base of skull (meningiomas, pituitary gland adenomas) were treated by fractionated stereotactic radiotherapy (mean total dose 56,6 Gy/1,8 Gy). Comprehensive neuropsychological tests and MRI brain scans were performed before, 3, 9 and 21 months after therapy. 14 healthy volunteers were tested in parallel at baseline. In the follow-ups patients were their own controls. Results: In pretreatment tests there were significantly worse test results in comparison to the control group in ten of 32 tests. In postradiation tests only few changes were found in the early-delayed period and not much difference was seen in comparison to the baseline tests. In MRI scans tumor recurrences or radiation induced changes were not found. Conclusion: Radiation with high local doses in target volume extremely close to sensitive brain structures like temporal lobes did not induce significant decline of cognitive functions. (orig.) [de

  18. Mechanical Performance of Ferritic Martensitic Steels for High Dose Applications in Advanced Nuclear Reactors

    Science.gov (United States)

    Anderoglu, Osman; Byun, Thak Sang; Toloczko, Mychailo; Maloy, Stuart A.

    2013-01-01

    Ferritic/martensitic (F/M) steels are considered for core applications and pressure vessels in Generation IV reactors as well as first walls and blankets for fusion reactors. There are significant scientific data on testing and industrial experience in making this class of alloys worldwide. This experience makes F/M steels an attractive candidate. In this article, tensile behavior, fracture toughness and impact property, and creep behavior of the F/M steels under neutron irradiations to high doses with a focus on high Cr content (8 to 12) are reviewed. Tensile properties are very sensitive to irradiation temperature. Increase in yield and tensile strength (hardening) is accompanied with a loss of ductility and starts at very low doses under irradiation. The degradation of mechanical properties is most pronounced at martensitic steels exhibit a high fracture toughness after irradiation at all temperatures even below 673 K (400 °C), except when tested at room temperature after irradiations below 673 K (400 °C), which shows a significant reduction in fracture toughness. Creep studies showed that for the range of expected stresses in a reactor environment, the stress exponent is expected to be approximately one and the steady state creep rate in the absence of swelling is usually better than austenitic stainless steels both in terms of the creep rate and the temperature sensitivity of creep. In short, F/M steels show excellent promise for high dose applications in nuclear reactors.

  19. On-Line High Dose-rate Gamma Irradiation Test of the Profibus/DP module

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jai Wan; Choi, Young Soo; Kim, Chang Hoi; Koo, In Soo; Hong, Seok Boong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2009-05-15

    The field bus data communication is considered for application in nuclear environments. The nuclear facilities, including nuclear power plants, high radioactivity waste disposals, reprocessing plants and thermonuclear fusion installations can benefit from the unique advantages of the field bus communication network for the smart field instruments and controls. A major problem which arises when dealing with one in these nuclear environments, in special circumstances such as the RCS (reactor coolant system) area, is the presence of high gamma-ray irradiation fields. Radioactive constraints for the DBA(design basis accident) qualification of the RTD transmitter installed in the inside of the RCS pump are typically on the order of 4kGy/h with total doses up to 10kGy. In order to use an industrial field bus communication network as an ad-hoc sensor data link in the vicinity of the RCS area of the nuclear power plant, the robust survivability of these system in such intense gamma-radiation fields therefore needs to be verified. We have conducted high dose-rate (up to 4kGy) gamma irradiation experiments on a profibus/DP communication module. In this paper we describe the evolution of its basic characteristics with high dose-rate gamma irradiation and shortly explain the observed phenomena.

  20. Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration.

    Science.gov (United States)

    McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2011-08-01

    Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a "challenge" high-dose METH regimen when administered at PND90. Mechanisms underlying this "resistance" were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity. Copyright © 2011 Wiley-Liss, Inc.

  1. Quality of life in a cohort of high-dose benzodiazepine dependent patients.

    Science.gov (United States)

    Lugoboni, Fabio; Mirijello, Antonio; Faccini, Marco; Casari, Rebecca; Cossari, Anthony; Musi, Gessica; Bissoli, Giorgia; Quaglio, Gianluca; Addolorato, Giovanni

    2014-09-01

    Benzodiazepines (BZD) are among the most widely prescribed drugs in developed countries. Since BZD can produce tolerance and dependence even in a short time, their use is recommended for a very limited time. However, these recommendations have been largely disregarded. The chronic use of BZD causes a number of serious side effects, i.e., cognitive impairment, falls, traffic accidents, dependence and tolerance. The aim of the present study was to evaluate quality of life (QoL) in a cohort of 62 consecutive high-dose BZD-dependent patients seeking a BZD detoxification. Patients seeking BZD detoxification were evaluated using the General Health Questionnaire (GHQ-12) and the short form-36 questionnaire (SF-36). Patients showed a significant reduction of QoL as measured by either SF-36 or GHQ-12. In particular, the greater impairment was observed in the items exploring physical and emotional status. Physical functioning was the item more influenced by the length of BZD abuse. Female patients showed a greater reduction of QoL compared to male, at least in some of the explored items. Social functioning scores were greatly reduced. The present study shows for the first time that high-doses BZD dependent patients have a reduced QoL and a reduced social functioning, along with high levels of psychological distress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Dosimetric properties of bio minerals applied to high-dose dosimetry using the TSEE technique

    International Nuclear Information System (INIS)

    Vila, G. B.; Caldas, L. V. E.

    2014-08-01

    The study of the dosimetric properties such as reproducibility, the residual signal, lower detection dose, dose-response curve and fading of the thermally stimulated emission exo electronic (TSEE) signal of Brazilian bio minerals has shown that these materials present a potential use as radiation dosimeters. The reproducibility within ± 10% for oyster shell, mother-of-pearl and coral reef samples showed that the signal dispersion is small when compared with the mean value of the measurements. The study showed that the residual signal can be eliminated with a thermal treatment at 300 grades C/1 h. The lower detection dose of 9.8 Gy determined for the oyster shell samples when exposed to beta radiation and 1.6 Gy for oyster shell and mother-of-pearl samples when exposed to gamma radiation can be considered good, taking into account the high doses of this study. The materials presented linearity at the dose response curves in some ranges, but the lack of linearity in other cases presents no problem since a good mathematical description is possible. The fading study showed that the loss of TSEE signal can be minimized if the samples are protected from interferences such as light, heat and humidity. Taking into account the useful linearity range as the main dosimetric characteristic, the tiger shell and oyster shell samples are the most suitable for high-dose dosimetry using the TSEE technique. (Author)

  3. Effects of high dose rate gamma radiation on survival and reproduction of Biomphalaria glabrata

    Energy Technology Data Exchange (ETDEWEB)

    Cantinha, Rebeca S.; Nakano, Eliana [Instituto Butantan, Sao Paulo, SP (Brazil). Lab. de Parasitologia], e-mail: rebecanuclear@gmail.com, e-mail: eliananakano@butantan.gov.br; Borrely, Sueli I. [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil). Centro de Tecnologia das Radiacoes], e-mail: sborrely@ipen.br; Amaral, Ademir; Melo, Ana M.M.A. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear. Grupo de Estudos em Radioprotecao e Radioecologia (GERAR)], e-mail: amaral@ufpe.br; Silva, Luanna R.S. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Biofisica e Radiobiologia. Lab. de Radiobiologia], e-mail: amdemelo@hotmail.com, e-mail: luannaribeiro_lua@hotmail.com

    2009-07-01

    Ionizing radiations are known as mutagenic agents, causing lethality and infertility. This characteristic has motivated its application on animal biological control. In this context, the freshwater snail Biomphalaria glabrata can be considered an excellent experimental model to study effects of ionizing radiations on lethality and reproduction. This work was designed to evaluate effects of {sup 60}Co gamma radiation at high dose rate (10.04 kGy/h) on B. glabrata. For this purpose, adult snails were selected and exposed to doses ranging from 20 to 100 Gy, with 10 Gy intervals; one group was kept as control. There was not effect of dose rate in the lethality of gamma radiation; the value of 64,3 Gy of LD{sub 50} obtained in our study was similar to that obtained by other authors with low dose rates. Nevertheless, our data suggest that there was a dose rate effect in the reproduction. On all dose levels, radiation improved the production of embryos for all exposed individuals. However, viability indexes were below 6% and, even 65 days after irradiation, fertility was not recovered. These results are not in agreement with other studies using low dose rates. Lethality was obtained in all groups irradiated, and the highest doses presented percentiles of dead animals above 50%. The results demonstrated that doses of 20 and 30 Gy were ideal for population control of B. glabrata. Further studies are needed; nevertheless, this research evidenced great potential of high dose rate gamma radiation on B. glabrata reproductive control. (author)

  4. Prognosis of emergency room stabilization of decompensated congestive heart failure with high dose lasix

    Directory of Open Access Journals (Sweden)

    Mahboob Pouraghaei

    2015-06-01

    Full Text Available Objective: Congestive heart failure (CHF has become one of the most important health care problems in western countries. This article focuses on the outpatient diagnosis and management of heart failure. We want to compare the outcome of patients who were treated with high dose diuretics in the emergency department (ED without admission with patients who were admitted to hospital for standard treatment. Methods: This was a randomized prospective clinical trial study. The patients who came to the ED from March 20, 2008 up to August 20, 2008 were divided into two groups randomly. The length of ED stay in the experimental group was documented. Also, readmission and mortality in 6 months and satisfaction in both groups were taken into consideration. All data were analyzed using SPSS 15.0. Results: In experimental group, the rate of recurrent admission, expiration, discharge, clinic visit, and clinic admission was 8%, 4%, 29%, 18%, and 0% respectively. On the other hand, in control group it was 16%, 40%, 18%, 22%, and 2% respectively. Additionally, there was a significant difference between these groups (P = 0.00. Conclusion: This study is the first regional prospective trial to comprehensively examine the therapeutic management in patients with CHF. This study, comparing the high dose diuretic efficacy in the decreasing of hospital stay and readmission; and decreasing mortality rate with routine therapy, showed that there was a significant difference between these two strategies in the mortality rate, readmission, and length of hospital stay (P = 0.00.

  5. Radiation safety program in high dose rate brachytherapy facility at INHS Asvini

    Directory of Open Access Journals (Sweden)

    Kirti Tyagi

    2014-01-01

    Full Text Available Brachytherapy concerns primarily the use of radioactive sealed sources which are inserted into catheters or applicators and placed directly into tissue either inside or very close to the target volume. The use of radiation in treatment of patients involves both benefits and risks. It has been reported that early radiation workers had developed radiation induced cancers. These incidents lead to continuous work for the improvement of radiation safety of patients and personnel The use of remote afterloading equipment has been developed to improve radiation safety in the delivery of treatment in brachytherapy. The widespread adoption of high dose rate brachytherapy needs appropriate quality assurance measures to minimize the risks to both patients and medical staff. The radiation safety program covers five major aspects: quality control, quality assurance, radiation monitoring, preventive maintenance, administrative measures and quality audit. This paper will discuss the radiation safety program developedfor a high dose rate brachytherapy facility at our centre which may serve as a guideline for other centres intending to install a similar facility.

  6. Low- and high-dose laser irradiation effects on cell migration and destruction

    Science.gov (United States)

    Layton, Elivia; Gallagher, Kyra A.; Zukerman, Sara; Stevens, Brianna; Zhou, Feifan; Liu, Hong; Chen, Wei R.

    2018-02-01

    Metastases are the cause of more than 90 percent of cancer-related deaths. Current treatment methods, including chemotherapy, radiation, and surgery, fail to target the metastases effectively. One potential treatment for metastatic cancer is laser immunotherapy (LIT). LIT combines the use of a photothermal laser with an immunoadjuvant, Glycated Chitosan (GC). GC combined with single-walled carbon nanotubes (SWNTs) has proven to be a viable alternative to traditional cancer treatment methods, when under irradiation of laser with appropriate wavelength. In this study, the effects of low dose and high dose laser irradiation on metastatic pancreatic cancer cell migration were observed. It was found that low dose irradiation increased the migration rate, but the high dose irradiation significantly decreased the migration rate of the cancer cells. When using LIT, the goal is to kill tumor cells and to prompt the correct immune response. If the tumor were irradiated with a low dose, it would promote metastasis. If the dose of irradiation were too high, it would destroy the entire tumor and the immune response would not recognize the tumor. Therefore, the laser dose plays an important role in LIT, particularly when using SWNT as light absorbing agent. Our results from this study will delineate the optimal laser irradiation dose for destroying tumor cells and at the same time preserve and release tumor antigens as a precursor of antitumor immune response.

  7. Dose-reduction techniques for high-dose worker groups in nuclear power plants

    International Nuclear Information System (INIS)

    Khan, T.A.; Baum, J.W.; Dionne, B.J.

    1991-03-01

    This report summarizes the main findings of a study of the extent of radiation dose received by special work groups in the nuclear power industry. Work groups which chronically get large doses were investigated, using information provided by the industry. The tasks that give high doses to these work groups were examined and techniques described that were found to be particularly successful in reducing dose. Quantitative information on the extent of radiation doses to various work groups shows that significant numbers of workers in several critical groups receive doses greater than 1 and even 2 rem per year, particularly contract personnel and workers at BWR-type plants. The number of radiation workers whose lifetime dose is greater than their age is much less. Although the techniques presented would go some way in reducing dose, it is likely that a sizeable reduction to the high-dose work groups may require development of new dose-reduction techniques as well as major changes in procedures. 10 refs., 26 tabs

  8. High-dose-rate brachytherapy using molds for oral cavity cancer. The technique and its limitations

    International Nuclear Information System (INIS)

    Nishimura, Yasumasa; Yokoe, Yoshihiko; Nagata, Yasushi; Okajima, Kaoru; Nishida, Mitsuo; Hiraoka, Masahiro

    1998-01-01

    With the availability of a high-dose-rate (HDR) remote afterloading device, a Phase I/II protocol was initiated at our institution to assess the toxicity and efficacy of HDR intracavitary brachytherapy, using molds, in the treatment of squamous cell carcinomas of the oral cavity. Eight patients with squamous cell carcinoma of the oral cavity were treated by the technique. The primary sites of the tumors were the buccal mucosa, oral floor, and gingiva. Two of the buccal mucosal cancers were located in the retromolar trigon. For each patient, a customized mold was fabricated, in which two to four afterloading catheters were placed for an 192 Ir HDR source. Four to seven fractions of 3-4 Gy, 5 mm below the mold surface, were given following external radiation therapy of 40-60 Gy/ 2 Gy. The total dose of HDR brachytherapy ranged from 16 to 28Gy. Although a good initial complete response rate of 7/8 (88%) was achieved, there was local recurrence in four of these seven patients. Both of the retromolar trigon tumors showed marginal recurrence. No serious (e.g., ulcer or bone exposure) late radiation damage has been observed thus far in the follow up period of 15-57 months. High-dose-rate brachytherapy using the mold technique seems a safe and useful method for selected early and superficial oral cavity cancer. However, it is not indicated for thick tumors and/or tumors located in the retromolar trigon. (author)

  9. Update on pediatric resuscitation drugs: high dose, low dose, or no dose at all.

    Science.gov (United States)

    Sorrentino, Annalise

    2005-04-01

    Pediatric resuscitation has been a topic of discussion for years. It is difficult to keep abreast of changing recommendations, especially for busy pediatricians who do not regularly use these skills. This review will focus on the most recent guidelines for resuscitation drugs. Three specific questions will be discussed: standard dose versus high-dose epinephrine, amiodarone use, and the future of vasopressin in pediatric resuscitation. The issue of using high-dose epinephrine for cardiopulmonary resuscitation refractory to standard dose epinephrine has been a topic of debate for many years. Recently, a prospective, double-blinded study was performed to help settle the debate. These results will be reviewed and compared with previous studies. Amiodarone is a medication that was added to the pediatric resuscitation algorithms with the most recent recommendations from the American Heart Association in 2000. Its use and safety will also be discussed. Another topic that is resurfacing in resuscitation is the use of vasopressin. Its mechanism and comparisons to other agents will be highlighted, although its use in the pediatric patient has not been thoroughly studied. Pediatric resuscitation is a constantly evolving subject that is on the mind of anyone taking care of sick children. Clinicians are continually searching for the most effective methods to resuscitate children in terms of short- and long-term outcomes. It is important to be familiar with not only the agents being used but also the optimal way to use them.

  10. Primary treatment of acromegaly with high-dose lanreotide: a case series

    Directory of Open Access Journals (Sweden)

    Cordes Uwe

    2010-03-01

    Full Text Available Abstract Introduction The first-line treatment for acromegaly is transsphenoidal surgery. In approximately 50% of patients, however, a cure is not possible with surgery and alternatives are needed. Somatostatin analog therapy is the recommended first-line treatment in patients with such cases. Here we provide the first report of a high-dose lanreotide primary therapy in patients with acromegaly. Case presentation Six patients who were not suitable for surgery were given 60 mg of lanreotide (Autogel® every four weeks. All patients were German nationals and Caucasian. When the response of our patients was unsatisfactory, the dose was increased sequentially to 90 mg every four weeks, 120 mg every four weeks, 120 mg every three weeks and 180 mg every three weeks. Treatment duration was 12 to 24 months. In all cases, the lanreotide dose was 120 mg every 4 weeks or higher. In five of our patients, growth hormone (GH levels were successfully reduced (in three patients GH Tumor shrinkage or degeneration was observed in the five responding patients. No drug-related adverse events were noted. Conclusions These results suggest that lanreotide at high doses of 120 mg every four weeks or more is an effective first-line therapy for patients with acromegaly that surgery alone cannot treat.

  11. Preoperative High-Dose Steroid Has Long-Term Beneficial Effects for Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Syuichi Tetsuka

    2013-01-01

    Full Text Available Previous studies addressing preoperative steroid treatment have revealed that control of myasthenia gravis (MG with steroids prior to surgery appeared to stabilize postoperative status. The purpose of our study was to clarify the clinical benefits of the preoperative programmed high-dose steroid treatment on the long-term outcomes of MG patients. We retrospectively reviewed the records of 171 MG patients who were followed up after undergoing thymectomy in our hospital between 1988 and 2006. One hundred and thirteen patients in the programmed treatment group had received preoperative steroid treatment, while 58 patients received no steroid treatment during the preoperative period. Clinical remission, which was defined as the achievement of the modified pharmacologic remission (PR for at least 1 year, and clinical benefits were compared between the two groups. With regard to the remission after thymectomy, Kaplan-Meier life-table curves for patients in the preoperative steroid treatment group versus those for patients in the no steroid preoperative treatment group revealed a significantly higher probability of the PR in the preoperative steroid treatment group (log-rank test, P<0.01. This study might be the first, as per our knowledge, to indicate that preoperative programmed high-dose steroid treatment has long-term beneficial effects for MG patients.

  12. Acute Changes in Mentation in a Patient with Hepatic Cirrhosis Treated with High Doses of Dexamethasone.

    Science.gov (United States)

    Dabul, Luis; Droney, Andrew; Oms, Juan; Sanchez-Gonzalez, Marcos A

    2017-09-10

    Despite the anti-inflammatory benefits of steroids in the management of multiple medical conditions, they are associated with undesired metabolic and psychiatric side effects. We present a case of a 57-year-old Hispanic man with hepatic cirrhosis due to hepatitis C and no past medical history of psychiatric illnesses who became delirious after treatment with high doses of intravenous Dexamethasone. The patient presented to Larkin Community Hospital, USA with complaints of lower back pain requiring treatment with steroids for severe lumbar central canal stenosis. After three days of treatment, the patient became disoriented to time and place, grossly psychotic with auditory hallucinations and disorganized behavior, manic, aggressive, combative, restless, hard to redirect, and unable to follow commands. He met the criteria for a diagnosis of substance-induced psychotic disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM) V. Furthermore, the patient had worsening hepatic profile, a high ammonia level of 125 umol/L, and clinical findings consistent with West Haven classification grade 2 encephalopathy. Head computed tomography (CT) scan was normal. He was treated with discontinuation of steroids, lactulose, and Haloperidol returning to baseline mental status after 48 hours. The patient's hospitalization was complicated with a prolonged hospital stay after lumbar surgery. This case illustrates that treatment with high doses of Dexamethasone in a patient with hepatic cirrhosis can cause acute changes in mental status by (i) inducing delirium, and (ii) precipitating hepatic encephalopathy.

  13. Dosimetric properties of bio minerals applied to high-dose dosimetry using the TSEE technique

    Energy Technology Data Exchange (ETDEWEB)

    Vila, G. B.; Caldas, L. V. E., E-mail: gbvila@ipen.br [Instituto de Pesquisas Energeticas e Nucleares / CNEN, Av. Lineu Prestes 2242, Cidade Universitaria, 05508-000 Sao Paulo (Brazil)

    2014-08-15

    The study of the dosimetric properties such as reproducibility, the residual signal, lower detection dose, dose-response curve and fading of the thermally stimulated emission exo electronic (TSEE) signal of Brazilian bio minerals has shown that these materials present a potential use as radiation dosimeters. The reproducibility within ± 10% for oyster shell, mother-of-pearl and coral reef samples showed that the signal dispersion is small when compared with the mean value of the measurements. The study showed that the residual signal can be eliminated with a thermal treatment at 300 grades C/1 h. The lower detection dose of 9.8 Gy determined for the oyster shell samples when exposed to beta radiation and 1.6 Gy for oyster shell and mother-of-pearl samples when exposed to gamma radiation can be considered good, taking into account the high doses of this study. The materials presented linearity at the dose response curves in some ranges, but the lack of linearity in other cases presents no problem since a good mathematical description is possible. The fading study showed that the loss of TSEE signal can be minimized if the samples are protected from interferences such as light, heat and humidity. Taking into account the useful linearity range as the main dosimetric characteristic, the tiger shell and oyster shell samples are the most suitable for high-dose dosimetry using the TSEE technique. (Author)

  14. Can high-dose fotemustine reverse MGMT resistance in glioblastoma multiforme?

    Science.gov (United States)

    Gallo, Chiara; Buonerba, Carlo; Di Lorenzo, Giuseppe; Romeo, Valeria; De Placido, Sabino; Marinelli, Alfredo

    2010-11-01

    Glioblastoma multiforme (GBM), the highest grade malignant glioma, is associated with a grim prognosis-median overall survival is in the range 12-15 months, despite optimum treatment. Surgery to the maximum possible extent, external beam radiotherapy, and systemic temozolomide chemotherapy are current standard treatments for newly diagnosed GBM, with intracerebral delivery of carmustine wafers (Gliadel). Unfortunately, the effectiveness of chemotherapy can be hampered by the DNA repair enzyme O6-methylguanine methyltransferase (MGMT), which confers resistance both to temozolomide and nitrosoureas, for example fotemustine and carmustine. MGMT activity can be measured by PCR and immunohistochemistry, with the former being the current validated technique. High-dose chemotherapy can deplete MGMT levels in GBM cells and has proved feasible in various trials on temozolomide, in both newly diagnosed and recurrent GBM. We here report the unique case of a GBM patient, with high MGMT expression by immunohistochemistry, who underwent an experimental, high-dose fotemustine schedule after surgery and radiotherapy. Although treatment caused two episodes of grade 3-4 thrombocytopenia, a complete response and survival of more than three years were achieved, with a 30% increase in dose intensity compared with the standard fotemustine schedule.

  15. Medical and Psychiatric Effects of Long-Term Dependence on High Dose of tramadol.

    Science.gov (United States)

    El-Hadidy, Mohmed Adel; Helaly, Ahmed Mohamed Nabil

    2015-04-01

    Tramadol dependence has been studied recently after large-scale exposure. Although tramadol dependence has increased rapidly in Egypt since 2004, no studies have evaluated the effect of high dose long-term tramadol dependence. To address the chronic sequel of tramadol dependence over at least 5 years duration with a large dose (more than 675 mg/day, three tablets or more, each tablet of 225 mg). The study was aimed to check the physical and psychiatric status during tramadol dependence and 3 months after complete treatment. The present study was applied on 79 patients with single tramadol-dependence dose of 675 mg or more for 5 years or more. We examined the physical and psychological impact of tramadol abuse before and after 3 months of stoppage of the drug. The blood chemistry was nearly within normal parameters, although slight nonsignificant rise in liver enzymes was reported in some cases. Patients during tramadol dependence period were angry, hostile, and aggressive. On the other hand, after treatment the main problem observed was the significant increase in comorbid anxiety, depressive, and obsessive-compulsive symptoms, but no increase was found in psychotic symptoms. Tramadol-dependence dose was more important than duration of use in psychiatric illness. Tramadol dependence on high dose could be physically safe to some limit, but psychiatrically it has many side effects.

  16. Definitive intraoperative very high-dose radiotherapy for localized osteosarcoma in the extremities

    International Nuclear Information System (INIS)

    Oya, Natsuo; Kokubo, Masaki; Mizowaki, Takashi; Shibamoto, Yuta; Nagata, Yasushi; Sasai, Keisuke; Nishimura, Yasumasa; Tsuboyama, Tadao; Toguchida, Junya; Nakamura, Takashi; Hiraoka, Masahiro

    2001-01-01

    Purpose: To evaluate the outcome and adverse effects in patients with osteosarcoma treated with very high-dose definitive intraoperative radiotherapy (IORT), with the intention of saving the affected limb. Methods and Materials: Thirty-nine patients with osteosarcoma in their extremities were treated with definitive IORT. The irradiation field included the tumor plus an adequate wide margin and excluded the major vessels and nerves. Forty-five to 80 Gy of electrons or X-rays were delivered. The median follow-up of the surviving patients was 124 months. Results: The cause-specific and relapse-free 5-year survival rate was 50% and 43%, respectively. Distant metastasis developed in 23 patients; 19 died and 4 were alive for >10 years. Nine local recurrences were found 4-29 months after IORT in the affected limb. No radiation-induced skin reaction or nerve palsy was observed in the patients treated with X-rays. Experiments using phantoms also confirmed that the scatter dose was below the toxic level in the IORT setting with X-rays. Conclusions: Very high-dose definitive IORT combined with preventive nailing and chemotherapy appeared to be a promising quality-of-life-oriented alternative to treating patients with osteosarcomas in the extremities, although the problem of recurrences from the surrounding unirradiated soft tissue remains to be solved

  17. High-Dose Radioiodine Outpatient Treatment: An Initial Experience in Thailand

    International Nuclear Information System (INIS)

    Nantajit, Danupon; Saengsuda, Sureerat; NaNakorn, Pattama; Saengsuda, Yuthana

    2015-01-01

    The aim of this study was to determine whether high-dose radioactive iodine (Na 131 I) outpatient treatment of patients with thyroid carcinoma is a pragmatically safe approach, particularly for the safety of caregivers. A total of 79 patients completed the radiation-safety questionnaires prior to receiving high-dose radioactive iodine treatment. The questionnaire studied the subjects’ willingness to be treated as outpatients, along with the radiation safety status of their caregivers and family members. In patients, who were selected to be treated as outpatients, both internal and external radiation exposures of their primary caregivers were measured, using thyroid uptake system and electronic dosimeter, respectively. Overall, 62 out of 79 patients were willing to be treated as outpatients; however, only 44 cases were eligible for the treatment. The primary reason was that the patients did not use exclusive, separated bathrooms. The caregivers of 10 subjects, treated as outpatients, received an average radiation dose of 138.1 microsievert (mSv), which was almost entirely from external exposure; the internal radiation exposures were mostly at negligible values. Therefore, radiation exposure to caregivers was significantly below the public exposure limit (1 mSv) and the recommended limit for caregivers (5 mSv). A safe 131 I outpatient treatment in patients with thyroid carcinoma could be achieved by selective screening and providing instructions for patients and their caregivers

  18. Fatal Gastrointestinal Hemorrhage in a Young Boy with Newly Diagnosed Metastatic Medulloblastoma on High Dose Dexamethasone

    Directory of Open Access Journals (Sweden)

    Victor Wong

    2014-01-01

    Full Text Available A 10-year-old boy with newly diagnosed metastatic medulloblastoma was placed on high dose dexamethasone and ranitidine prior to surgery. The child underwent subtotal resection and was discharged 5 days postoperatively with an uneventful hospital course on a tapering dose of dexamethasone and ranitidine. Over the next 2 days the patient complained of mild abdominal distension with flatulence, without pain, vomiting, or dysmotility. On follow-up in clinic 5 days after discharge, he had normal vital signs when he suddenly became pale and had loss of consciousness. Emergent computerized tomography of the head showed no acute hemorrhage and complete blood count revealed hemoglobin of 4.2 gm/dL. In spite of maximum resuscitation with copious blood products the patient died. Autopsy revealed evidence of duodenal perforation with intraluminal hemorrhage. This case demonstrates a rare fatal complication of high dose dexamethasone therapy even with concurrent gastrointestinal prophylactic therapy. We provide a review of the limited literature on steroid use in pediatric neurooncology with regard to gastrointestinal bleeding.

  19. Human immunodeficiency virus and menopause.

    Science.gov (United States)

    Kanapathipillai, Rupa; Hickey, Martha; Giles, Michelle

    2013-09-01

    This article aims to review currently available evidence for women infected with human immunodeficiency virus (HIV) and menopause and to propose clinical management algorithms. Key studies addressing HIV and menopause have been reviewed, specifically age of menopause onset in HIV-infected women, frequency of menopausal symptoms, comorbidities associated with HIV and aging (including cardiovascular disease and bone disease), treatment of menopausal symptoms, and prevention of comorbidities in HIV-infected women. Studies suggest an earlier onset of menopause in HIV-infected women, with increased frequency of symptoms. Cardiovascular disease risk may be increased in this population, with combination antiretroviral therapy (cART) and chronic inflammation associated with HIV, contributing to increased risk. Chronic inflammation and cART have been independently implicated in bone disease. No published data have assessed the safety and efficacy of hormone therapy in relation to symptoms of menopause, cardiovascular risk, and bone disease among HIV-infected women. Few studies on menopause have been conducted in HIV-infected women compared with HIV-uninfected women. Many questions regarding age of menopause onset, frequency of menopausal symptoms and associated complications such as bone disease and cardiovascular disease, and efficacy of treatment among HIV-infected women remain. The incidence and severity of some of these factors may be increased in the setting of HIV and cART.

  20. Safety of high-dose daptomycin in patients with severe renal impairment

    Directory of Open Access Journals (Sweden)

    Tai CH

    2018-03-01

    Full Text Available Chih-Hsun Tai,1 Chi-Hao Shao,2 Chen-You Chen,2 Shu-Wen Lin,1–3 Chien-Chih Wu1,2 1Department of Pharmacy, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; 2School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan Background: Treatment options are limited for infections due to multidrug-resistant Gram-positive pathogens. Daptomycin is a lipopeptide antibiotic with concentration-dependent killing characteristic and dose-dependent post-antibiotic effect. To achieve optimized pharmacodynamic effect, some experts advocated using a high dose of daptomycin (≥9 mg/kg for severe infections. However, the safety of high-dose therapy in patients with renal impairment remains unknown. This study was aimed to evaluate the safety of daptomycin in patients with severe renal impairment. Methods: This was a retrospective study performed by reviewing electronic medical records. Patients with severe renal impairment who were treated with daptomycin in a tertiary teaching hospital between January 1, 2013, and June 30, 2016, were included for evaluation. The incidence rates of creatine kinase (CK elevation between high-dose (≥9 mg/kg and standard-dose (<9 mg/kg groups were compared. Results: Overall, 164 patients met the inclusion criteria, and 114 (69.5% of them were on renal replacement therapy. Vancomycin-resistant enterococci were the most common pathogens (61.3% of the patients with documented pathogens. The treatment success rate was 51.6% in the 91 patients with bacteremia. The average dose of daptomycin was 8.0±2.3 mg/kg, and 37 (22.6% patients received ≥9 mg/kg. CK levels were followed in 108 (65.9% patients. Significantly higher incidence of CK elevation was found in the high-dose group compared with that in the standard-dose group (10.8% vs 1.6%, P<0.05. Moreover

  1. Relationship between current level of immunodeficiency and non-acquired immunodeficiency syndrome-defining malignancies

    DEFF Research Database (Denmark)

    Reekie, Joanne; Kosa, Csaba; Engsig, Frederik

    2010-01-01

    In the combined antiretroviral therapy (cART) era, non-acquired immunodeficiency syndrome (AIDS)-defining malignancies account for more morbidity and mortality in human immunodeficiency virus-infected patients than AIDS-defining malignancies. However, conflicting data have been reported...

  2. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline.

    Science.gov (United States)

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören; Nordvall, S Lennart; Pedroletti, Christophe; Bengtsson, Thomas; Johannes-Hellberg, Ingegerd; Rosenborg, Johan

    2004-10-01

    To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis) 4.5 microg (F4.5) or terbutaline (Bricanyl) 500 microg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. Formoterol and terbutaline had significant beta2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48-3.65) mmol l(-1) on the day of no treatment to 2.98 (CI: 2.90-3.08) after 10 x F4.5 and 2.70 (CI: 2.61-2.78) mmol l(-1) after 10 x T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422-435) ms on the day of no treatment, to 455 (CI: 448-462) ms after 10 x F4.5 and 470 (CI: 463-476) ms after 10 x T500. Estimates of relative dose potency indicated that F4.5 microg had the same systemic activity as the clinically less effective dose of 250 microg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 microg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h. Multiple inhalations over 2.5 h of

  3. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6–11 years-old than cumulative high doses of inhaled terbutaline

    Science.gov (United States)

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören; Nordvall, S Lennart; Pedroletti, Christophe; Bengtsson, Thomas; Johannes-Hellberg, Ingegerd; Rosenborg, Johan

    2004-01-01

    Objectives To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Methods Twenty boys and girls (6–11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis®) 4.5 µg (F4.5) or terbutaline (Bricanyl®) 500 µg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler®) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. Results Formoterol and terbutaline had significant β2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48–3.65) mmol l−1 on the day of no treatment to 2.98 (CI: 2.90–3.08) after 10 × F4.5 and 2.70 (CI: 2.61–2.78) mmol l−1 after 10 × T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422–435) ms on the day of no treatment, to 455 (CI: 448–462) ms after 10 × F4.5 and 470 (CI: 463–476) ms after 10 × T500. Estimates of relative dose potency indicated that F4.5 µg had the same systemic activity as the clinically less effective dose of 250 µg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 µg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h

  4. Relationship between irreversible alopecia and exposure to cyclophosphamide, thiotepa and carboplatin (CTC) in high-dose chemotherapy

    NARCIS (Netherlands)

    de Jonge, M. E.; Mathôt, R. A. A.; Dalesio, O.; Huitema, A. D. R.; Rodenhuis, S.; Beijnen, J. H.

    2002-01-01

    Reversible alopecia is a commonly observed, important and distressing complication of chemotherapy. Permanent alopecia, however, is rare after standard-dose therapy, but has occasionally been observed after high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin (CTC). We evaluated

  5. Bladder–Rectum Spacer Balloon in High-Dose-Rate Brachytherapy in Cervix Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Rai, Bhavana [Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh (India); Patel, Firuza D., E-mail: firuzapatel@gmail.com [Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh (India); Chakraborty, Santam; Sharma, Suresh C.; Kapoor, Rakesh [Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh (India); Aprem, Abi Santhosh [Corporate R and D Division, HLL Lifecare Limited, Karamana, Trivandrum (India)

    2013-04-01

    Purpose: To compare bladder and rectum doses with the use of a bladder–rectum spacer balloon (BRSB) versus standard gauze packing in the same patient receiving 2 high-dose-rate intracavitary brachytherapy fractions. Methods and Materials: This was a randomized study to compare the reduction in bladder and rectum doses with the use of a BRSB compared with standard gauze packing in patients with carcinoma of the cervix being treated with high-dose-rate intracavitary brachytherapy. The patients were randomized between 2 arms. In arm A, vaginal packing was done with standard gauze packing in the first application, and BRSB was used in the second application. Arm B was the reverse of arm A. The International Commission for Radiation Units and Measurement (ICRU) point doses and doses to 0.1-cm{sup 3}, 1-cm{sup 3}, 2-cm{sup 3}, 5-cm{sup 3}, and 10-cm{sup 3} volumes of bladder and rectum were compared. The patients were also subjectively assessed for the ease of application and the time taken for application. Statistical analysis was done using the paired t test. Results: A total of 43 patients were enrolled; however, 3 patients had to be excluded because the BRSB could not be inserted owing to unfavorable local anatomy. Thus 40 patients (80 plans) were evaluated. The application was difficult in 3 patients with BRSB, and in 2 patients with BRSB the application time was prolonged. There was no significant difference in bladder doses to 0.1 cm{sup 3}, 1 cm{sup 3}, 2 cm{sup 3}, 5 cm{sup 3}, and 10 cm{sup 3} and ICRU bladder point. Statistically significant dose reductions to 0.1-cm{sup 3}, 1-cm{sup 3}, and 2-cm{sup 3} volumes for rectum were observed with the BRSB. No significant differences in 5-cm{sup 3} and 10-cm{sup 3} volumes and ICRU rectum point were observed. Conclusion: A statistically significant dose reduction was observed for small high-dose volumes in rectum with the BRSB. The doses to bladder were comparable for BRSB and gauze packing. Transparent balloons of

  6. Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery

    International Nuclear Information System (INIS)

    Moussazadeh, Nelson; Lis, Eric; Katsoulakis, Evangelia; Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily; Bilsky, Mark H.; Yamada, Yoshiya; Laufer, Ilya

    2015-01-01

    Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen

  7. Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

    Science.gov (United States)

    Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

    2011-01-01

    Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

  8. Effect of Concurrent High-Dose Cisplatin Chemotherapy and Conformal Radiotherapy on Cervical Esophageal Cancer Survival

    International Nuclear Information System (INIS)

    Huang Shaohui; Lockwood, Gina; Brierley, James; Cummings, Bernard; Kim, John; Wong, Rebecca; Bayley, Andrew; Ringash, Jolie

    2008-01-01

    Purpose: To determine whether a change in treatment policy to conformal, elective nodal radiotherapy and concurrent high-dose cisplatin improved survival for cervical esophageal cancer patients. Methods and Materials: All cervical esophageal cancer patients treated between 1997 and 2005 were restaged (1983 American Joint Committee on Cancer criteria). Patients treated before 2001 (previous cohort [PC]) were compared with those treated from 2001 onward (recent cohort [RC]). The PC institutional chemoradiotherapy protocol was 54 Gy in 20 fractions within 4 weeks, with 5-fluorouracil (1,000 mg/m 2 ) on Days 1-4 and either mitomycin C (10 mg/m 2 ) or cisplatin (75 mg/m 2 ) on Day 1. The RC institutional chemoradiotherapy protocol was conformal radiotherapy, 70 Gy in 35 fractions within 7 weeks, to the primary tumor and elective nodes, with high-dose cisplatin (100 mg/m 2 ) on Days 1, 22, and 43. Results: The median follow-up was 3.1 years (PC, 8.1 and RC, 2.3). Of 71 patients (25 women and 46 men), 21 of 29 in the PC and 29 of 42 in the RC were treated curatively (curative subgroup, n = 50). Between the two groups, no differences in overall survival or locoregional relapse-free survival were seen. The overall survival rate at 2 and 5 years was 35% (range, 24-47%) and 21% (range, 12-32%) in the whole group and 46% (range 32-60%) and 28% (range, 15-42%) in the curative group, respectively. In the curative group, no statistically significant prognostic factors were found. Trends toward better locoregional relapse-free survival were seen in women (2-year rate, 73% vs. for men, 36%; p = 0.08) and in patients aged >64 years (2-year rate, 68% vs. age ≤64 years, 34%; p = 0.10). Conclusion: No survival improvement could be demonstrated after changing the treatment policy to high-dose cisplatin-based, conventionally fractionated conformal chemoradiotherapy. Female gender and older age might predict for better outcomes

  9. Prospective study in the management of high-dose radioactive iodine therapy induced gastritis

    International Nuclear Information System (INIS)

    Carbonell, C.; Ogbac, R.V.

    2007-01-01

    Full text: Gastritis is simply defined as inflammation of the gastric mucosa. In post-RAI patients, this is one of the most common complications that are encountered. Some patients may even require repetitive administration of high doses of radioactive iodine (I-131). Small doses of radiation (up to 1500 R) cause reversible mucosal damage, whereas higher radiation doses cause irreversible damage with atrophy and ischemic-related ulceration. Reversible changes consist of degenerative changes in epithelial cells and nonspecific chronic inflammatory infiltrate in the lamina propria. Higher amounts of radiation cause permanent mucosal damage, with atrophy of fundic glands, mucosal erosions, and capillary hemorrhage. Associated submucosal endarteritis results in mucosal ischemia and secondary ulcer development. Recurrent gastritis, if left untreated, may be a predisposing factor for gastric malignancy. Methods:A total of thirty post-RAI subjects were evaluated for signs and symptoms of gastritis and were divided into 3 groups which were given drugs for gastritis (H2-receptor antagonist, proton pump inhibitor, and sucralfate). Survey forms were distributed to evaluate the presence of nausea, vomiting, epigastric pain (graded according to severity of pain), and gastrointestinal bleeding. Results were tallied accordingly. Results and Discussion: In a total of 3 subjects who were given sucralfate, all of them did not experience any nausea and vomiting. One subject experienced mild epigastric discomfort and another subject was able to experience a non-specific symptom of abdominal bloatedness. (Note: Subjects are still for completion) In theory, radiation irritates the mucosa causing inflammation and mucosal damage which is further irritated by gastric acid secretion. The administration of H2-receptor blockers and proton pump inhibitors only inhibit gastric acid secretion while existing inflammation of mucosa due to high doses of radiation is left untreated. However

  10. Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Moussazadeh, Nelson [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States); Lis, Eric [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Katsoulakis, Evangelia [Department of Radiation Oncology, New York Methodist Hospital, Brooklyn, New York (United States); Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Bilsky, Mark H. [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States); Yamada, Yoshiya [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Laufer, Ilya, E-mail: lauferi@mskcc.org [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States)

    2015-10-01

    Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen

  11. High-Dose Opioid Prescribing and Opioid-Related Hospitalization: A Population-Based Study.

    Directory of Open Access Journals (Sweden)

    Kimberly Fernandes

    Full Text Available To examine the impact of national clinical practice guidelines and provincial drug policy interventions on prevalence of high-dose opioid prescribing and rates of hospitalization for opioid toxicity.Interventional time-series analysis.Ontario, Canada, from 2003 to 2014.Ontario Drug Benefit (ODB beneficiaries aged 15 to 64 years from 2003 to 2014.Publication of Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain (May 2010 and implementation of Ontario's Narcotics Safety and Awareness Act (NSAA; November 2011.Three outcomes were explored: the rate of opioid use among ODB beneficiaries, the prevalence of opioid prescriptions exceeding 200 mg and 400 mg morphine equivalents per day, and rates of opioid-related emergency department visits and hospital admissions.Over the 12 year study period, the rate of opioid use declined 15.2%, from 2764 to 2342 users per 10,000 ODB eligible persons. The rate of opioid use was significantly impacted by the Canadian clinical practice guidelines (p-value = .03 which led to a decline in use, but no impact was observed by the enactment of the NSAA (p-value = .43. Among opioid users, the prevalence of high-dose prescribing doubled (from 4.2% to 8.7% over the study period. By 2014, 40.9% of recipients of long-acting opioids exceeded daily doses of 200 mg morphine or equivalent, including 55.8% of long-acting oxycodone users and 76.3% of transdermal fentanyl users. Moreover, in the last period, 18.7% of long-acting opioid users exceeded daily doses of 400 mg morphine or equivalent. Rates of opioid-related emergency department visits and hospital admissions increased 55.0% over the study period from 9.0 to 14.0 per 10,000 ODB beneficiaries from 2003 to 2013. This rate was not significantly impacted by the Canadian clinical practice guidelines (p-value = .68 or enactment of the NSAA (p-value = .59.Although the Canadian clinical practice guidelines for use of opioids in chronic non

  12. High dose rate brachytherapy for carcinoma of the cervix: risk factors for late rectal complications

    International Nuclear Information System (INIS)

    Uno, Takashi; Itami, Jun; Aruga, Moriyo; Kotaka, Kikuo; Fujimoto, Hajime; Minoura, Shigeki

    1996-01-01

    Purpose/Objective: To determine the incidence of late rectal complications in patients treated with high dose rate brachytherapy for FIGO stage IIB, IIIB carcinoma of the uterine cervix, and to evaluate the treatment factors associated with an increased probability of treatment complications. Materials and Methods: Records of 100 patients with FIGO IIB or IIIB cervical carcinoma treated with definitive irradiation using high dose rate intracavitary brachytherapy (HDR-ICR) between 1977 and 1994 were retrospectively reviewed. For each HDR-ICR session, 6 Gy isodose volume was reconstructed three dimensionally and the following three parameters were determined to represent this isodose volume, length (L); maximum longitudinal distance of 6 Gy isodose area in an oblique frontal plane containing the intrauterine applicator, width (W); maximum width of 6 Gy isodose area in the same plane, height (H); maximum dimension of 6 Gy isodose area perpendicular to the intrauterine applicator determined in the oblique sagittal plane. Point P/Q (2 cm ventral/dorsal from the proximal retention point of the intrauterine source) and point R/S (2 cm ventral/dorsal from the midpoint of the ovoid sources) were also defined retrospectively and HDR-ICR dose at these points were calculated. Statistical analyses were performed to determine the treatment factors predictive of late rectal complications. Results: The 5-year cumulative cause-specific disease-free survival rate was 50% for all, 74% for Stage IIB, and 38% for Stage IIIB, with a significant difference between two FIGO Stages (p=0.0004). Of patients treated for both stages, 30% and 36% had experienced moderate to severe (Grade 2-4) complications at 3 and 5 years, respectively. Average H value (p=0.013) and cumulative point S dose by HDR-ICR (p=0.020) were significantly correlated with the incidence of late rectal complications (Student's t-test), whereas these factors did not significantly affect the probability of pelvic control. No

  13. A genetically engineered live-attenuated simian-human immunodeficiency virus that co-expresses the RANTES gene improves the magnitude of cellular immunity in rhesus macaques

    International Nuclear Information System (INIS)

    Shimizu, Yuya; Inaba, Katsuhisa; Kaneyasu, Kentaro; Ibuki, Kentaro; Himeno, Ai; Okoba, Masashi; Goto, Yoshitaka; Hayami, Masanori; Miura, Tomoyuki; Haga, Takeshi

    2007-01-01

    Regulated-on-activation-normal-T-cell-expressed-and-secreted (RANTES), a CC-chemokine, enhances antigen-specific T helper (Th) type-1 responses against HIV-1. To evaluate the adjuvant effects of RANTES against HIV vaccine candidate in SHIV-macaque models, we genetically engineered a live-attenuated SHIV to express the RANTES gene (SHIV-RANTES) and characterized the virus's properties in vivo. After the vaccination, the plasma viral loads were same in the SHIV-RANTES-inoculated monkeys and the parental nef-deleted SHIV (SHIV-NI)-inoculated monkeys. SHIV-RANTES provided some immunity in monkeys by remarkably increasing the antigen-specific CD4 + Th cell-proliferative response and by inducing an antigen-specific IFN-γ ELISpot response. The magnitude of the immunity in SHIV-RANTES-immunized animals, however, failed to afford greater protection against a heterologous pathogenic SHIV (SHIV-C2/1) challenge compared to control SHIV-NI-immunized animals. SHIV-RANTES immunized monkeys, elicited robust cellular CD4 + Th responses and IFN-γ ELISpot responses after SHIV-C2/1 challenge. These findings suggest that the chemokine RANTES can augment vaccine-elicited, HIV-specific CD4 + T cell responses

  14. Induction of immune response in macaque monkeys infected with simian-human immunodeficiency virus having the TNF-α gene at an early stage of infection

    International Nuclear Information System (INIS)

    Shimizu, Yuya; Miyazaki, Yasuyuki; Ibuki, Kentaro; Suzuki, Hajime; Kaneyasu, Kentaro; Goto, Yoshitaka; Hayami, Masanori; Miura, Tomoyuki; Haga, Takeshi

    2005-01-01

    TNF-α has been implicated in the pathogenesis of, and the immune response against, HIV-1 infection. To clarify the roles of TNF-α against HIV-1-related virus infection in an SHIV-macaque model, we genetically engineered an SHIV to express the TNF-α gene (SHIV-TNF) and characterized the virus's properties in vivo. After the acute viremic stage, the plasma viral loads declined earlier in the SHIV-TNF-inoculated monkeys than in the parental SHIV (SHIV-NI)-inoculated monkeys. SHIV-TNF induced cell death in the lymph nodes without depletion of circulating CD4 + T cells. SHIV-TNF provided some immunity in monkeys by increasing the production of the chemokine RANTES and by inducing an antigen-specific proliferation of lymphocytes. The monkeys immunized with SHIV-TNF were partly protected against a pathogenic SHIV (SHIV-C2/1) challenge. These findings suggest that TNF-α contributes to the induction of an effective immune response against HIV-1 rather than to the progression of disease at the early stage of infection

  15. Transfer of primer binding site-mutated simian immunodeficiency virus vectors by genetically engineered artificial and hybrid tRNA-like primers

    DEFF Research Database (Denmark)

    Hansen, A C; Grunwald, T; Lund, Anders Henrik

    2001-01-01

    could be obtained by cotransfection of a gene for an engineered tRNA(Pro)-tRNA hybrid with a match to PBS-Pro. The importance of tRNA backbone identity was further analyzed by complementing the PBS-X2 vector with a gene for a matching x2 primer with a tRNA backbone, which led to three- to fourfold...

  16. Induction of Th1-Biased T Follicular Helper (Tfh) Cells in Lymphoid Tissues during Chronic Simian Immunodeficiency Virus Infection Defines Functionally Distinct Germinal Center Tfh Cells.

    Science.gov (United States)

    Velu, Vijayakumar; Mylvaganam, Geetha Hanna; Gangadhara, Sailaja; Hong, Jung Joo; Iyer, Smita S; Gumber, Sanjeev; Ibegbu, Chris C; Villinger, Francois; Amara, Rama Rao

    2016-09-01

    Chronic HIV infection is associated with accumulation of germinal center (GC) T follicular helper (Tfh) cells in the lymphoid tissue. The GC Tfh cells can be heterogeneous based on the expression of chemokine receptors associated with T helper lineages, such as CXCR3 (Th1), CCR4 (Th2), and CCR6 (Th17). However, the heterogeneous nature of GC Tfh cells in the lymphoid tissue and its association with viral persistence and Ab production during chronic SIV/HIV infection are not known. To address this, we characterized the expression of CXCR3, CCR4, and CCR6 on GC Tfh cells in lymph nodes following SIVmac251 infection in rhesus macaques. In SIV-naive rhesus macaques, only a small fraction of GC Tfh cells expressed CXCR3, CCR4, and CCR6. However, during chronic SIV infection, the majority of GC Tfh cells expressed CXCR3, whereas the proportion of CCR4(+) cells did not change, and CCR6(+) cells decreased. CXCR3(+), but not CXCR3(-), GC Tfh cells produced IFN-γ (Th1 cytokine) and IL-21 (Tfh cytokine), whereas both subsets expressed CD40L following stimulation. Immunohistochemistry analysis demonstrated an accumulation of CD4(+)IFN-γ(+) T cells within the hyperplastic follicles during chronic SIV infection. CXCR3(+) GC Tfh cells also expressed higher levels of ICOS, CCR5, and α4β7 and contained more copies of SIV DNA compared with CXCR3(-) GC Tfh cells. However, CXCR3(+) and CXCR3(-) GC Tfh cells delivered help to B cells in vitro for production of IgG. These data demonstrate that chronic SIV infection promotes expansion of Th1-biased GC Tfh cells, which are phenotypically and functionally distinct from conventional GC Tfh cells and contribute to hypergammaglobulinemia and viral reservoirs. Copyright © 2016 by The American Association of Immunologists, Inc.

  17. Attenuation of Pathogenic Immune Responses during Infection with Human and Simian Immunodeficiency Virus (HIV/SIV) by the Tetracycline Derivative Minocycline

    Science.gov (United States)

    Drewes, Julia L.; Szeto, Gregory L.; Engle, Elizabeth L.; Liao, Zhaohao; Shearer, Gene M.; Zink, M. Christine; Graham, David R.

    2014-01-01

    HIV immune pathogenesis is postulated to involve two major mechanisms: 1) chronic innate immune responses that drive T cell activation and apoptosis and 2) induction of immune regulators that suppress T cell function and proliferation. Both arms are elevated chronically in lymphoid tissues of non-natural hosts, which ultimately develop AIDS. However, these mechanisms are not elevated chronically in natural hosts of SIV infection that avert immune pathogenesis despite similarly high viral loads. In this study we investigated whether minocycline could modulate these pathogenic antiviral responses in non-natural hosts of HIV and SIV. We found that minocycline attenuated in vitro induction of type I interferon (IFN) and the IFN-stimulated genes indoleamine 2,3-dioxygenase (IDO1) and TNF-related apoptosis inducing ligand (TRAIL) in human plasmacytoid dendritic cells and PBMCs exposed to aldrithiol-2 inactivated HIV or infectious influenza virus. Activation-induced TRAIL and expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in isolated CD4+ T cells were also reduced by minocycline. Translation of these in vitro findings to in vivo effects, however, were mixed as minocycline significantly reduced markers of activation and activation-induced cell death (CD25, Fas, caspase-3) but did not affect expression of IFNβ or the IFN-stimulated genes IDO1, FasL, or Mx in the spleens of chronically SIV-infected pigtailed macaques. TRAIL expression, reflecting the mixed effects of minocycline on activation and type I IFN stimuli, was reduced by half, but this change was not significant. These results show that minocycline administered after infection may protect against aspects of activation-induced cell death during HIV/SIV immune disease, but that in vitro effects of minocycline on type I IFN responses are not recapitulated in a rapid progressor model in vivo. PMID:24732038

  18. Cocirculation of Two env Molecular Variants, of Possible Recombinant Origin, in Gorilla and Chimpanzee Simian Foamy Virus Strains from Central Africa.

    Science.gov (United States)

    Richard, Léa; Rua, Réjane; Betsem, Edouard; Mouinga-Ondémé, Augustin; Kazanji, Mirdad; Leroy, Eric; Njouom, Richard; Buseyne, Florence; Afonso, Philippe V; Gessain, Antoine

    2015-12-01

    Simian foamy virus (SFV) is a ubiquitous retrovirus in nonhuman primates (NHPs) that can be transmitted to humans, mostly through severe bites. In the past few years, our laboratory has identified more than 50 hunters from central Africa infected with zoonotic SFVs. Analysis of the complete sequences of five SFVs obtained from these individuals revealed that env was the most variable gene. Furthermore, recombinant SFV strains, some of which involve sequences in the env gene, were recently identified. Here, we investigated the variability of the env genes of zoonotic SFV strains and searched for possible recombinants. We sequenced the complete env gene or its surface glycoprotein region (SU) from DNA amplified from the blood of (i) a series of 40 individuals from Cameroon or Gabon infected with a gorilla or chimpanzee foamy virus (FV) strain and (ii) 1 gorilla and 3 infected chimpanzees living in the same areas as these hunters. Phylogenetic analyses revealed the existence of two env variants among both the gorilla and chimpanzee FV strains that were present in zoonotic and NHP strains. These variants differ greatly (>30% variability) in a 753-bp-long region located in the receptor-binding domain of SU, whereas the rest of the gene is very conserved. Although the organizations of the Env protein sequences are similar, the potential glycosylation patterns differ between variants. Analysis of recombination suggests that the variants emerged through recombination between different strains, although all parental strains could not be identified. SFV infection in humans is a great example of a zoonotic retroviral infection that has not spread among human populations, in contrast to human immunodeficiency viruses (HIVs) and human T-lymphotropic viruses (HTLVs). Recombination was a major mechanism leading to the emergence of HIV. Here, we show that two SFV molecular envelope gene variants circulate among ape populations in Central Africa and that both can be transmitted to

  19. Characterization of High Dose Mn, Fe, and Ni implantation into p-GaN

    CERN Document Server

    Pearton, S J; Thaler, G; Abernathy, C R; Theodoropoulou, N; Hebard, A F; Chu, S N G; Wilson, R G; Zavada, J M; Polyakov, A Y; Osinsky, A V; Norris, P E; Chow, P P; Wowchack, A M; Hove, J M V; Park, Y D

    2002-01-01

    The magnetization of p-GaN or p-AlGaN/GaN superlattices was measured after implantation with high doses (3-5x10 sup 1 sup 6 cm sup - sup 2) of Mn, Fe, or Ni and subsequent annealing at 700-1000 deg. C. The samples showed ferromagnetic contributions below temperatures ranging from 190-250 K for Mn to 45-185 K for Ni and 80-250 K for Fe. The use of superlattices to enhance the hole concentration did not produce any change in ferromagnetic ordering temperature. No secondary phase formation was observed by x-ray diffraction, transmission electron microscopy, or selected area diffraction pattern analysis for the doses we employed.

  20. Low, but not high, dose caffeine is a readily available probe for adenosine actions.

    Science.gov (United States)

    Fredholm, Bertil B; Yang, Jiangning; Wang, Yingqing

    2017-06-01

    Caffeine is very widely used and knowledge of its mode of action can be used to gain an understanding of basal physiological regulation. This review makes the point that caffeine is - in low doses - an antagonist of adenosine acting at A 1 , A 2A and A 2B receptors. We use published and unpublished data to make the point that high dose effects of caffeine are not only qualitatively different but have a different underlying mechanism. Therefore one must be careful in only using epidemiological or experimental data where rather low doses of caffeine are used to draw conclusions about the physiology and pathophysiology of adenosine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. [Effect of IV hydration with sodium bicarbonate on high-dose methotrexate disposition kinetics].

    Science.gov (United States)

    Tsuda, N; Goto, M; Konishi, H; Yamashina, H

    1984-04-01

    Following two-compartment kinetic analysis, the effect of loading of transfusion with sodium bicarbonate on methotrexate disposition was investigated in 13 cases with malignant tumor, being treated with high-dose methotrexate. The mean values of total body clearance, when administered at doses 50 mg and 100 mg per kg body weight, were 0.369 and 0.402 (l/h) per kg, respectively. No significant relationship was observed between alpha value and total amount of transfusion, of urine or dosage of sodium bicarbonate. The other kinetic parameters on elimination, beta value, K10 and total body clearance, did not also correlate with those values described above. These results suggest that the elimination profile of methotrexate show linear kinetics, and that massive administration of transfusion with sodium bicarbonate be not necessary if pH value of urine exceeds 7.0.

  2. Dosimetric advancement of high-dose-rate after-loading 192Ir source

    International Nuclear Information System (INIS)

    Zhang Shuxu; Li Wenhua; Xu Hairong

    2004-01-01

    High-dose-rate (HDR) 192 Ir source is a nuclide commonly used in the brachytherapy system. The basic dosimetry data of the near source area is usually measured by pin ion chambers or TLD techniques, but these methods have a lower spatial resolution than Electron spin resonance (ESR) dosimetry which has a spatial resolution of 156 μm, and the Monte Carlo photon transport simulations are taken as the golden standard of those measures. The precision in two-dimensional dose distribution measured by GafChromic film is reported to be 1.0%. In vivo dosimetry using TLD during HDR intracavitary after-loading brachytherapy is a good predictor of late rectal complications. The accuracy of magnetic resonance imaging (MRI) Fricke-gel dosimetry for three-dimensional dose distribution is about 2.5% with a spatial resolution of 1.56 mm. The optical computed tomography polymer gel dosimetry has a unique advance than MRI gel dosimetry

  3. Improved Behavior and Neuropsychological Function in Children With ROHHAD After High-Dose Cyclophosphamide.

    Science.gov (United States)

    Jacobson, Lisa A; Rane, Shruti; McReynolds, Lisa J; Steppan, Diana A; Chen, Allen R; Paz-Priel, Ido

    2016-07-01

    Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare, generally progressive, and potentially fatal syndrome of unclear etiology. The syndrome is characterized by normal development followed by a sudden, rapid hyperphagic weight gain beginning during the preschool period, hypothalamic dysfunction, and central hypoventilation, and is often accompanied by personality changes and developmental regression, leading to substantial morbidity and mortality. We describe 2 children who had symptomatic and neuropsychological improvement after high-dose cyclophosphamide treatment. Our experience supports an autoimmune pathogenesis and provides the first neuropsychological profile of patients with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation. Copyright © 2016 by the American Academy of Pediatrics.

  4. Long-term high-dose oral morphine in phantom limb pain with no addiction risk

    Directory of Open Access Journals (Sweden)

    Vinod Kumar

    2015-01-01

    Full Text Available Chronic phantom limb pain (PLP is a type of neuropathic pain, which is located in the missing/amputated limb. Phantom pain is difficult to treat as the exact basis of pain mechanism is still unknown. Various methods of treatment for PLP have been described, including pharmacological (NSAIDs, opioids, antiepileptic, antidepressants and non-pharmacological (TENS, sympathectomy, deep brain stimulation and motor cortex stimulation. Opioids are used for the treatment of neuropathic pain and dose of opioid is determined based on its effect and thus there is no defined ceiling dose for opioids. We report a case where a patient receiving high-dose oral morphine for chronic cancer pain did not demonstrate signs of addiction.

  5. Radiation-damage studies, irradiations and high-dose dosimetry for LHC detectors

    CERN Document Server

    Coninckx, F; León-Florián, E; Leutz, H; Schönbacher, Helmut; Sonderegger, P; Tavlet, Marc; Sopko, B; Henschel, H; Schmidt, H U; Boden, A; Bräunig, D; Wulf, F; Cramariuc, R; Ilie, D; Fattibene, P; Onori, S; Miljanic, S; Paic, G; Razen, B; Razem, D; Rendic, D; CERN. Geneva. Detector Research and Development Committee

    1991-01-01

    The proposal is divided into a main project and special projects. The main project consists of a service similar to the one given in the past to accelerator construction projects at CERN (ISR,SPS,LEP) on high-dose dosimetry, material irradiations, irradiations tests, standardization of test procedures and data compilations. Large experience in this field and numerous radiation damage test data of insulating and structural materials are available. The special projects cover three topics which are of specific interest for LHC detector physicists and engineers at CERN and in other high energy physics institutes, namely: Radiation effects in scintillators; Selection of radiation hard optical fibres for data transmission; and Selection and testing of radiation hard electronic components.

  6. Acute effects of high-dose intragastric nicotine on mucosal defense mechanisms

    DEFF Research Database (Denmark)

    Lindell, G; Bukhave, Klaus; Lilja, I

    1997-01-01

    Peptic ulcer disease is overrepresented among smokers; they also heal slowly and relapse frequently. Data are accumulating that smoking is detrimental to gastroduodenal mucosal cytoprotection. This study was designed to assess acute effects of high-dose intragastric nicotine, as it has been shown...... that nicotine is accumulated in gastric juice when smoking, Seven healthy smokers were given nicotine base (6 mg) as tablets, which yielded very high intragastric concentrations and plasma levels comparable to those seen when smoking. In addition to nicotine analysis, concentration levels of prostaglandin E(2......) (PGE(2)), phospholipase A(2) (PLA(2)), and phospholipid classes were measured before and after nicotine administration, Nicotine inhibited PGE(2) levels by 27-81%, whereas PLA(2) and total phospholipids were unaffected. Lysolecithin, a degradation product of the main constituent of gastric surfactant...

  7. High-dose-rate intraoperative radiation therapy: the nuts and bolts of starting a program

    Science.gov (United States)

    Moningi, Shalini; Armour, Elwood P.; Terezakis, Stephanie A.; Efron, Jonathan E.; Gearhart, Susan L.; Bivalacqua, Trinity J.; Kumar, Rachit; Le, Yi; Kien Ng, Sook; Wolfgang, Christopher L.; Zellars, Richard C.; Ellsworth, Susannah G.; Ahuja, Nita

    2014-01-01

    High-dose-rate intraoperative radiation therapy (HDR-IORT) has historically provided effective local control (LC) for patients with unresectable and recurrent tumors. However, IORT is limited to only a few specialized institutions and it can be difficult to initiate an HDR-IORT program. Herein, we provide a brief overview on how to initiate and implement an HDR-IORT program for a selected group of patients with gastrointestinal and pelvic solid tumors using a multidisciplinary approach. Proper administration of HDR-IORT requires institutional support and a joint effort among physics staff, oncologists, surgeons, anesthesiologists, and nurses. In order to determine the true efficacy of IORT for various malignancies, collaboration among institutions with established IORT programs is needed. PMID:24790628

  8. Influence of environmental factors on some high dose dosimeter responses in Yazd Radiation Processing Center

    International Nuclear Information System (INIS)

    Ziaie, F.; Tahami, S.M.; Zareshahi, H.; Lanjanian, H.; Durrani, S.A.

    2008-01-01

    In this paper attempt has been made to study the influence of temperature and UV light (exist in laboratory due to the fluorescent light or diffused sunlight) on some high dose dosimetry responses that are being used in Yazd Radiation Processing Center (YRPC). The CTA, FWT and B3 film dosimeters were used for this investigation. The correction of the read response of the dosimeters to the real absorbed dose values is very important especially while we need to measure the precise dose values in the medical devices and in foodstuff materials. Yazd city is near to the desert, and so temperature and UV light due to the sun are very different in compare to other cities. Therefore, we tried to investigate the temperature and UV light effects on the dosimeter response in different doses and obtain its variation as a function of temperature (up to ∼60 0 C) and exposure time (up to ∼1 year), respectively

  9. Brachytherapy. High dose rate brachytherapy - Radiation protection: medical sheet ED 4287

    International Nuclear Information System (INIS)

    Celier, D.; Aubert, B.; Vidal, J.P.; Biau, A.; Lahaye, T.; Gauron, C.; Barret, C.; Boisserie, G.; Branchet, E.; Gambini, D.; Gondran, C.; Le Guen, B.; Guerin, C.; Nguyen, S.; Pierrat, N.; Sarrazin, T.; Donnarieix, D.

    2010-02-01

    After having indicated the required authorization to implement brachytherapy techniques, this document presents the various aspects and measures related to radiation protection when performing high-dose-rate brachytherapy treatments. It presents the concerned personnel, describes the operational process, indicates the associated hazards and the risk related to ionizing radiation, and describes how the risk is to be assessed and how exposure levels are to be determined (elements of risk assessment, delimitation of controlled and monitored areas, personnel classification, and choice of the dose monitoring method). It describes the various components of a risk management strategy (risk reduction, technical measures regarding the installation and the personnel, training and information, prevention and medical monitoring). It briefly presents how risk management is to be assessed, and mentions other related risks (biological risk, handling and posture, handling of heavy loads, mental workload, chemical risk)

  10. Human reliability in high dose rate afterloading radiotherapy based on FMECA

    International Nuclear Information System (INIS)

    Deng Jun; Fan Yaohua; Yue Baorong; Wei Kedao; Ren Fuli

    2012-01-01

    Objective: To put forward reasonable and feasible recommendations against the procedure with relative high risk during the high dose rate (HDR) afterloading radiotherapy, so as to enhance its clinical application safety, through studying the human reliability in the process of carrying out the HDR afterloading radiotherapy. Methods: Basic data were collected by on-site investigation and process analysis as well as expert evaluation. Failure mode, effect and criticality analysis (FMECA) employed to study the human reliability in the execution of HDR afterloading radiotherapy. Results: The FMECA model of human reliability for HDR afterloading radiotherapy was established, through which 25 procedures with relative high risk index were found,accounting for 14.1% of total 177 procedures. Conclusions: FMECA method in human reliability study for HDR afterloading radiotherapy is feasible. The countermeasures are put forward to reduce the human error, so as to provide important basis for enhancing clinical application safety of HDR afterloading radiotherapy. (authors)

  11. Polycarbonate-based benzo-δ-sultam films for high-dose dosimetry in radiation processing

    International Nuclear Information System (INIS)

    Feizi, Shazad; Nuclear Science and Technology Research Institute, Tehran; Ziaie, Farhood; Ghandi, Mehdi

    2015-01-01

    In this work characteristics of the polycarbonate films with 20 μm in thickness containing different weight percentage of Benzo-δ-sultam were studied for use as a high dose dosimetry system in radiation processing facilities. The sensitivity of the dosimeters and the linearity of dose-response curves were investigated under 60 Co γ-rays in a dose range of 0-100 kGy, and obtained results were compared with the commercial CTA and FWT film dosimeters. The results show that the absorbance at 348 nm depends linearly on the dose in the investigated dose range. The effects of pre-irradiation (shelf-life) and post-irradiation storage in dark and in indirect sunlight are also discussed. The results show that the dosimeters characteristics are stable within 1% at 25 C, 3 months after the irradiation.

  12. Polycarbonate-based benzo-δ-sultam films for high-dose dosimetry in radiation processing

    Energy Technology Data Exchange (ETDEWEB)

    Feizi, Shazad [University of Tehran, Tehran (India). School of Chemistry; Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Application Research School; Ziaie, Farhood [Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Application Research School; Ghandi, Mehdi [University of Tehran, Tehran (India). School of Chemistry

    2015-05-01

    In this work characteristics of the polycarbonate films with 20 μm in thickness containing different weight percentage of Benzo-δ-sultam were studied for use as a high dose dosimetry system in radiation processing facilities. The sensitivity of the dosimeters and the linearity of dose-response curves were investigated under {sup 60}Co γ-rays in a dose range of 0-100 kGy, and obtained results were compared with the commercial CTA and FWT film dosimeters. The results show that the absorbance at 348 nm depends linearly on the dose in the investigated dose range. The effects of pre-irradiation (shelf-life) and post-irradiation storage in dark and in indirect sunlight are also discussed. The results show that the dosimeters characteristics are stable within 1% at 25 C, 3 months after the irradiation.

  13. High dose effect of gamma and neutrons on the N-JFET electronic components

    International Nuclear Information System (INIS)

    Assaf, Jamal-Eddin

    2006-11-01

    Two types of N-JFET components have been irradiated by high doses of thermal neutrons and gamma rays up to 2000x10 12 n/cm 2 and 1000 kGy, respectively. The static tests show a decrease of the g m and I d s parameters. The behaviour of electronic noise on the output was the principal dynamic test after irradiation. The result of this test gives an increase of the noise with radiation dose increasing. The noise was described as the Equivalent Noise of Charge (ENC) at the output of the measurements set-up. The quantities and the qualities of the noise depend on the N-JEET type and the type of radiation (neutrons or gamma). Other tests were carried out like the relaxation or recovery phenomena after radiation, and the superposed effects of gamma and neutrons.(author)

  14. Low dose rate and high dose rate intracavitary treatment for cervical cancer

    International Nuclear Information System (INIS)

    Hareyama, Masato; Oouchi, Atsushi; Shidou, Mitsuo

    1997-01-01

    From 1984 through 1993, 144 previous untreated patients with carcinoma of uterine cervix were treated with either low dose rate 137 Cs therapy (LDR) or high dose rate 60 Co therapy (HDR). The local failure rates for more than 2-years for the primary lesions were 11.8% (8 of 63 patients) for LDR and 18.0% (11 of 61 patients). Rectal complication rates were significantly lower for HDR versus LDR (14.3% VS. 32.8%. p<0.01). Also, bladder complication rates were significantly lower for HDR versus LDR (0% VS. 10.4%, p<0.005). Treatment results in term of local control were equivalent for HDR and LDR treatment. However, the incidence of complications was higher for the LDR group than for the HDR group. (author)

  15. CD34-positive cells as stem cell support after high dose therapy

    International Nuclear Information System (INIS)

    Kvalheim, G.; Pharo, A.; Holte, H.

    1996-01-01

    Six patients, five with breast cancer and one with non-Hodgkin's lymphoma, were mobilized by chemotherapy and G-CSF. CD34-positive cells were isolated by means of immunomagnetic beads and Isolex 300 Cell Separator. Mean purity of isolated CD34-positive cells was 97% and mean yield was 54%. Three patients were treated with high dose therapy followed by reinfusion of CD34-positive cells as stem cell support. Recovery of neutrophils occurred at day 8, 11 and 13 and of platelets at day 9, 14 and 32. It is concluded that immunomagnetic isolated CD34-positive cells give high purity and yield. Although use of CD34-positive cells reduces the content of contaminating tumours cells in the graft, breast cancer cells were still detectable in two out of five CD34-positive cell products. 20 refs., 2 figs., 1 tab

  16. Safety and toxicology assessment of chicken breast for high-dose irradiation

    International Nuclear Information System (INIS)

    Zhu Jiating; Feng Min; Yan Jianmin; Yang Ping; Wang Dening; Gao Meixu; Ha Yiming; Liu Chunquan

    2011-01-01

    Feeding wholesomeness tests of irradiated chicken breast were studied by using acute oral toxicology, Ames, micronucleus of born marrow cell, sperm shape abnormality in mice and 30 d feeding test. The LD 50 of all the rats and mice were more than 10 g/kg · BW, which means that the pet foods belonged to actually non-toxic grade; ames test, and the tests of micronucleus of born marrow cell, sampan shape abnormality in mice were all negative results; 30 d feeding test in rats demonstrated that it had no distinctive effects on routine blood, body weight and biochemical index. It is concluded that pet foods irradiated up to 25 kGy high dose were no safety and toxicology problems. (authors)

  17. High dose-rate brachytherapy source localization: positional resolution using a diamond detector

    International Nuclear Information System (INIS)

    Nakano, T; Suchowerska, N; Bilek, M M; McKenzie, D R; Ng, N; Kron, T

    2003-01-01

    A potential real-time source position verification process for high dose-rate (HDR) brachytherapy treatment is described. This process is intended to provide immediate confirmation that a treatment is proceeding according to plan, so that corrective action can be taken if necessary. We show that three dosimeters are in principle sufficient and demonstrate the feasibility of the process using a diamond detector and an Ir-192 source. An error analysis including all identified sources of error shows that this detector is capable of locating the distance to the source to within 2 mm for distances up to 12 cm. This positional accuracy is less than the diameter of typical HDR catheters indicating that a diamond detector can be used to accurately determine the distance to the source. The uncertainty in the distance is found to increase with distance

  18. Radiation exposure for 'caregivers' during high-dose outpatient radioiodine therapy

    International Nuclear Information System (INIS)

    Marriott, C. J.; Webber, C. E.; Gulenchyn, K. Y.

    2007-01-01

    On 27 occasions, radiation doses were measured for a family member designated as the 'caregiver' for a patient receiving high-dose radioiodine outpatient therapy for differentiated thyroid carcinoma. For 25 of the administrations, patients received 3.7 GBq of 131 I. Radiation doses for the designated caregivers were monitored on an hourly basis for 1 week using electronic personal dosemeters. The average penetrating dose was 98±64 μSv. The maximum penetrating dose was 283 μSv. Measured dose rate profiles showed that, on average, one-third of the caregiver dose was received during the journey home from hospital. The mean dose rate profile showed rapid clearance of 131 I with three distinct phases. The corresponding clearance half-times were 131 I contaminating the home. (authors)

  19. Allogeneic bone marrow transplantation in adults after fractionated body irradiation and high dose cyclophosphamide

    International Nuclear Information System (INIS)

    Brinch, L.; Evensen, S.A.; Albrechtsen, D.; Egeland, T.; Solheim, B.G.; Rollag, H.; Naalsund, A.; Jacobsen, A.B.

    1991-01-01

    The authors present short and long-term results of allogeneic bone marrow transplantation after hyper-fractionated total body irradiation and high dose cyclophosphamide in ten patients treated for leukaemia during th period 1985-89. Three patients died from complications connected to the transplantation, while seven are living free from leukaemia 18 to 59 months after transplantation. Two patients need treatment for chronic graft versus host disease. Allogeneic bone marrow transplantation is expensive and risky. Close cooperation between clinicians and laboratory specialists is essential. The treatment increases long term survival and probably cures certain patients with leukaemia. Some of the patients will need treatment for chronic graft versus host disease and other late sequelae. 19 refs., 2 tabs

  20. Controlled localised melting in silicon by high dose germanium implantation and flash lamp annealing

    International Nuclear Information System (INIS)

    Voelskow, Matthias; Skorupa, Wolfgang; Pezoldt, Joerg; Kups, Thomas

    2009-01-01

    High intensity light pulse irradiation of monocrystalline silicon wafers is usually accompanied by inhomogeneous surface melting. The aim of the present work is to induce homogeneous buried melting in silicon by germanium implantation and subsequent flash lamp annealing. For this purpose high dose, high energy germanium implantation has been employed to lower the melting temperature of silicon in a predetermined depth region. Subsequent flash lamp irradiation at high energy densities leads to local melting of the germanium rich buried layer, whereby the thickness of the molten layer depends on the irradiation energy density. During the cooling down epitaxial crystallization takes place resulting in a largely defect-free layer. The combination of buried melting and dopant segregation has the potential to produce unusually buried doping profiles or to create strained silicon structures.

  1. Study of the response reduction of LiF:Mg, Ti dosimeter for high dose dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Torkzadeh, Falamarz [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Applications Research School; AEOI, Tehran (Iran, Islamic Republic of); Faripour, Heidar [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Laser and Optics Research School; AEOI, Tehran (Iran, Islamic Republic of); Mardashti, Forough; Manouchehri, Farhad [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Applications Research School

    2017-07-15

    A single crystal and 5 polycrystalline samples of LiF:Mg, Ti and their pellets were prepared and investigated so as to apply thermoluminescence high gamma dose dosimetry. Three zones of single crystal with dopant concentrations of 200 ppm of Mg and 20 ppm of Ti were also used to prepare the single crystal samples. For polycrystalline samples, dopant concentrations of 0.062 mol% Mg and Ti concentrations in the range of 0.016 and 0.046 mol% were used. All the samples were exposed to gamma doses of 1 kGy to 700 kGy and their response changes were determined by a gamma dose test of about 60 mGy. According to the results obtained, the use of response reduction by curve-fitting up to about 300 kGy can be performed reliably for high dose gamma dosimetry.

  2. Case of severe intestinal complications caused by high dose-rate intracavitary irradiation for cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Koga, Kenji; Nishikawa, Kiyoshi; Matsuki, Kazuhiko; Watanabe, Katsushi

    1987-02-01

    A 46-year-old woman with severe intestinal complication caused by high dose-rate intracavitary irradiation is reported. She received radiation treatment of stage IIb cervical cancer between July 24 and September 26, 1984: a dose of 2400 rad to a point A concurrently with 2000 rad to the parametrium following 4000 rad to the whole pelvis. Eight months later she developed diarrhea and bloody stool. Barium enema study revealed a stenosis at 20 to 25 cm from the anal ring and romanoscopy oozing coagula at the same site. On November 29, 1985 transverse colostomy was performed because of continuing bloody stool and abdominal pain. On January 30, 1986 resection of the ileum and ileostomy were done because of the ileum perforation located 26 cm apart from the ileum end. Some discussion on the causes of this complication are made, suggesting that short length of a tandem and deep location of ovoids influence its cause.

  3. Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

    Directory of Open Access Journals (Sweden)

    Rui-Rui Peng

    2017-03-01

    Full Text Available Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai.Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13% and 0.35% (95% CI: 0.06-1.39%, respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients, fatigue (2 patients, cough (1 patient, sore throat (1 patient, diarrhea (1 patient and erythematous rash (1 patient. The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05. Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia.Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for

  4. Dosimetric Effects of Air Pockets Around High-Dose Rate Brachytherapy Vaginal Cylinders

    International Nuclear Information System (INIS)

    Richardson, Susan; Palaniswaamy, Geethpriya; Grigsby, Perry W.

    2010-01-01

    Purpose: Most physicians use a single-channel vaginal cylinder for postoperative endometrial cancer brachytherapy. Recent published data have identified air pockets between the vaginal cylinders and the vaginal mucosa. The purpose of this research was to evaluate the incidence, size, and dosimetric effects of these air pockets. Methods and Materials: 25 patients receiving postoperative vaginal cuff brachytherapy with a high-dose rate vaginal cylinders were enrolled in this prospective data collection study. Patients were treated with 6 fractions of 200 to 400 cGy per fraction prescribed at 5 mm depth. Computed tomography simulation for brachytherapy treatment planning was performed for each fraction. The quantity, volume, and dosimetric impact of the air pockets surrounding the cylinder were quantified. Results: In 25 patients, a total of 90 air pockets were present in 150 procedures (60%). Five patients had no air pockets present during any of their treatments. The average number of air pockets per patient was 3.6, with the average total air pocket volume being 0.34 cm 3 (range, 0.01-1.32 cm 3 ). The average dose reduction to the vaginal mucosa at the air pocket was 27% (range, 9-58%). Ten patients had no air pockets on their first fraction but air pockets occurred in subsequent fractions. Conclusion: Air pockets between high-dose rate vaginal cylinder applicators and the vaginal mucosa are present in the majority of fractions of therapy, and their presence varies from patient to patient and fraction to fraction. The existence of air pockets results in reduced radiation dose to the vaginal mucosa.

  5. High-Dose-Rate Endobronchial Brachytherapy for Recurrent Airway Obstruction From Hyperplastic Granulation Tissue

    International Nuclear Information System (INIS)

    Tendulkar, Rahul D.; Fleming, Peter A.; Reddy, Chandana A.; Gildea, Thomas R.; Machuzak, Michael; Mehta, Atul C.

    2008-01-01

    Purpose: Benign endobronchial granulation tissue causes airway obstruction in up to 20% of patients after lung transplantation or stent placement. High-dose-rate endobronchial brachytherapy (HDR-EB) has been successful in some cases refractory to standard bronchoscopic interventions. Methods and Materials: Between September 2004 and May 2005, 8 patients with refractory benign airway obstruction were treated with HDR-EB, using one to two fractions of Ir-192 prescribed to 7.1 Gy at a radius of 1 cm. Charts were retrospectively reviewed to evaluate subjective clinical response, forced expiratory volume in 1 second (FEV 1 ), and frequency of therapeutic bronchoscopies over 6-month periods before and after HDR-EB. Results: The median follow-up was 14.6 months, and median survival was 10.5 months. The mean number of bronchoscopic interventions improved from 3.1 procedures in the 6-month pretreatment period to 1.8 after HDR-EB. Mean FEV 1 improved from 36% predicted to 46% predicted. Six patients had a good-to-excellent subjective early response, but only one maintained this response beyond 6 months, and this was the only patient treated with HDR-EB within 24 h from the most recent bronchoscopic intervention. Five patients have expired from causes related to their chronic pulmonary disease, including one from hemoptysis resulting from a bronchoarterial fistula. Conclusion: High-dose-rate-EB may be an effective treatment for select patients with refractory hyperplastic granulation tissue causing recurrent airway stenosis. Performing HDR-EB within 24-48 h after excision of obstructive granulation tissue could further improve outcomes. Careful patient selection is important to maximize therapeutic benefit and minimize toxicity. The optimal patient population, dose, and timing of HDR-EB should be investigated prospectively

  6. A comparison of high dose Ga-67 SPECT and FDG PET imaging in malignant melanoma

    International Nuclear Information System (INIS)

    Kaliff, V.; Hicks, R.J.; Binns, D.S.; Henderson, M.A.; Ainslie, J.; Jenner, D.A.

    1998-01-01

    Full text: Ga-67 imaging for tumour localisation lost favour in the 1970's. With improvement in technology and use of higher doses, it has now found an important role in lymphoma. A similar phenomenon may be possible in the staging of melanoma. This study therefore compares high dose (370 MBq) Ga-67 imaging using a day 5 and 7 whole-body and comprehensive SPECT protocol, with (100 MBq) F-18 fluorodeoxyglucose (FDG) imaging using positron emission tomography (PET): a technique recently shown to be highly accurate in this condition. 85 patients; 46 males, mean age 52+17 yrs: range 22-83 yrs, underwent both studies within 9±16 days (max-91 days). Scans were judged as positive (+ve), negative (-ve) or equivocal (EQ) for local, regional and distant disease. Clinical follow-up resolved discordant scan findings. PET and Ga-67 results were concordant in 61 (70%) patients (19 with +ve, 37 -ve and 5 EQ scans). None of the 9 ps with one EQ and one eye scan had disease on follow-up. Follow-up was available in 4/5 patients with discordantly +ve (3 patients) or more extensive Ga-67 abnormality: 3 patients had disease confirmed, 1 patient false +ve (asymmetric lung hilum). Follow-up was available in 9/10 patients with discordantly +ve (3 patients) or more extensive PET abnormality: 4 patients had confirmed disease, l pt false +ve (bladder diverticulum). A further 4 patients had second primaries (2 rectal carcinomas, 1 plasmacytoma, 1 basal cell carcinoma). High dose Ga-67 scanning incorporating SPECT appears to be a reasonable alternative to FDG PET for screening patients with melanoma. In this series PET's main advantages were in the detection of other occult tumours, greater patient convenience and lower radiation dosimetry

  7. Interstitial high-dose rate brachytherapy as boost for anal canal cancer

    International Nuclear Information System (INIS)

    Falk, Alexander Tuan; Claren, Audrey; Benezery, Karen; François, Eric; Gautier, Mathieu; Gerard, Jean-Pierre; Hannoun-Levi, Jean-Michel

    2014-01-01

    To assess clinical outcomes of patients treated with a high-dose rate brachytherapy boost for anal canal cancer (ACC). From August 2005 to February 2013, 28 patients presenting an ACC treated by split-course external beam radiotherapy (EBRT) and HDR brachytherapy with or without chemotherapy in a French regional cancer center in Nice were retrospectively analyzed. Median age was 60.6 years [34 – 83], 25 patients presented a squamous cell carcinoma and 3 an adenocarcinoma; 21 received chemotherapy. Median dose of EBRT was 45 Gy [43.2 – 52]. Median dose of HDR brachytherapy was 12 Gy [10 - 15] with a median duration of 2 days. Median overall treatment time was 63 days and median delay between EBRT and brachytherapy was 20 days. Two-year local relapse free, metastatic free, disease free and overall survivals were 83%, 81.9%, 71.8% and 87.7% respectively. Acute toxicities were frequent but not severe with mostly grade 1 toxicities: 37% of genito-urinary, 40.7% of gastro-intestinal and 3.7% of cutaneous toxicities. Late toxicities were mainly G1 (43.1%) and G2 (22%). Two-year colostomy-free survival was 75.1%, one patient had a definitive sphincter amputation. High-dose rate brachytherapy for anal canal carcinoma as boost represents a feasible technique compared to low or pulsed-dose rate brachytherapy. This technique remains an excellent approach to precisely boost the tumor in reducing the overall treatment time

  8. Implementation of microsource high dose rate (mHDR) brachytherapy in developing countries

    International Nuclear Information System (INIS)

    2001-11-01

    Brachytherapy using remote afterloading of a single high dose rate 192 Ir microsource was developed in the 1970s. After its introduction to clinics, this system has spread rapidly among developed Member States and has become a highly desirable modality in cancer treatment. This technique is now gradually being introduced to the developing Member States. The 192 Ir sources are produced with a high specific activity. This results in a high dose rate (HDR) to the tumour and shorter treatment times. The high specific activity simultaneously results in a much smaller source (so-called micro source, around I mm in diameter) which may be easily inserted into tissue through a thin delivery tube, the so-called interstitial treatment, as well as easily inserted into body cavities, the so-called intracavitary or endoluminal treatment. Another advantage is the ability to change dwell time (the time a source remains in one position) of the stepping source which allows dose distribution to match the target volume more closely. The purpose of this TECDOC is to advise radiation oncologists, medical physicists and hospital administrators in hospitals which are planning to introduce 192 Ir microsource HDR (mHDR) remote afterloading systems. The document supplements IAEA-TECDOC-1040, Design and Implementation of a Radiotherapy Programme: Clinical, Medical Physics, Radiation Protection and Safety Aspects, and will facilitate implementation of this new brachytherapy technology, especially in developing countries. The operation of the system, 'how to use the system', is not within the scope of this document. This TECDOC is based on the recommendations of an Advisory Group meeting held in Vienna in April 1999

  9. Fatherhood in tall men treated with high-dose sex steroids during adolescence.

    Science.gov (United States)

    Hendriks, A E J; Boellaard, W P A; van Casteren, N J; Romijn, J C; de Jong, F H; Boot, A M; Drop, S L S

    2010-12-01

    Sex steroid treatment to reduce final height of tall boys has been available since the 1950s. In women, it has been shown to interfere with fertility. In men, no such data are available. We therefore evaluated fertility and gonadal function in tall men who did or did not receive high-dose androgen treatment in adolescence. We conducted a retrospective cohort study of 116 tall men, of whom 60 had been treated. Reproductive and gonadal function was assessed by standardized interview, semen analysis, endocrine parameters, ultrasound imaging, and fatherhood. Mean age at treatment commencement was 14.2 yr, and mean follow-up was 21.2 yr. Sixty-six men (36 treated and 30 untreated) had attempted to achieve fatherhood. The probability of conceiving their first pregnancy within 1 yr was similar in treated and untreated men (26 vs. 24; Breslow P=0.8). Eleven treated and 13 untreated men presented with a left-sided varicocele (P=0.5). Testicular volume, sperm quality, and serum LH, FSH, and inhibin B levels were comparable between treated and untreated men. However, treated men had significantly reduced serum T levels, adjusted for known confounders [mean (sd) 13.3 (1.8) vs. 15.2 (1.9) nmol/liter; P=0.005). In addition, testicular volume and serum inhibin B and FSH levels in treated men were significantly correlated with age at treatment commencement. At a mean follow-up of 21 yr after high-dose androgen treatment, we conclude that fatherhood and semen quality in tall treated men are not affected. Serum testosterone levels, however, are reduced in androgen-treated men. Future research is required to determine whether declining testosterone levels may become clinically relevant for these men as they age.

  10. Plasma methylphenidate concentrations in youths treated with high-dose osmotic release oral system formulation.

    Science.gov (United States)

    Stevens, Jonathan R; George, Robert A; Fusillo, Steven; Stern, Theodore A; Wilens, Timothy E

    2010-02-01

    Children and adolescents are being treated increasingly for attention-deficit/hyperactivity disorder (ADHD) with a variety of stimulants in higher than Food and Drug Administration (FDA)-approved doses and in combination with other medications. We sought to determine methylphenidate (MPH) concentrations in children and adolescents treated with high-dose, extended-release osmotic release oral system (OROS) MPH plus concomitant medications, and to examine MPH concentrations with respect to the safety and tolerability of treatment. Plasma MPH concentrations were measured by liquid chromatography-mass spectrometry 4-5 hours after administration of medication in a sample of youths diagnosed with ADHD. These youths were treated naturalistically with higher than FDA-approved doses of OROS MPH in addition to their concomitant medications. Markers of safety and tolerability (e.g., measures of blood pressure and heart rate) were also examined. Among the 17 patients (with a mean age of 16.2 +/- 2 years and a mean number of concurrent medications of 2.23 +/- 0.94), the mean plasma MPH concentration was 28 +/- 9.1 ng/mL, despite a mean daily dose of OROS MPH of 169 +/- 5 mg (3.0 +/- 0.8 mg/kg per day). No patient had a plasma MPH level >or=50 ng/mL or clinical signs of stimulant toxicity. No correlation was found between plasma MPH concentrations and OROS MPH dose or changes in vital signs. High-dose OROS MPH, used in combination with other medications, was not associated with either unusually elevated plasma MPH concentrations or with clinically meaningful changes in vital signs. Study limitations include a single time-point sampling of MPH concentrations, a small sample size, and a lack of outcome measures to address treatment effectiveness.

  11. High-dose simultaneously integrated breast boost using intensity-modulated radiotherapy and inverse optimization

    International Nuclear Information System (INIS)

    Hurkmans, Coen W.; Meijer, Gert J.; Vliet-Vroegindeweij, Corine van; Sangen, Maurice J. van der; Cassee, Jorien

    2006-01-01

    Purpose: Recently a Phase III randomized trial has started comparing a boost of 16 Gy as part of whole-breast irradiation to a high boost of 26 Gy in young women. Our main aim was to develop an efficient simultaneously integrated boost (SIB) technique for the high-dose arm of the trial. Methods and Materials: Treatment planning was performed for 5 left-sided and 5 right-sided tumors. A tangential field intensity-modulated radiotherapy technique added to a sequentially planned 3-field boost (SEQ) was compared with a simultaneously planned technique (SIB) using inverse optimization. Normalized total dose (NTD)-corrected dose volume histogram parameters were calculated and compared. Results: The intended NTD was produced by 31 fractions of 1.66 Gy to the whole breast and 2.38 Gy to the boost volume. The average volume of the PTV-breast and PTV-boost receiving more than 95% of the prescribed dose was 97% or more for both techniques. Also, the mean lung dose and mean heart dose did not differ much between the techniques, with on average 3.5 Gy and 2.6 Gy for the SEQ and 3.8 Gy and 2.6 Gy for the SIB, respectively. However, the SIB resulted in a significantly more conformal irradiation of the PTV-boost. The volume of the PTV-breast, excluding the PTV-boost, receiving a dose higher than 95% of the boost dose could be reduced considerably using the SIB as compared with the SEQ from 129 cc (range, 48-262 cc) to 58 cc (range, 30-102 cc). Conclusions: A high-dose simultaneously integrated breast boost technique has been developed. The unwanted excessive dose to the breast was significantly reduced

  12. Complications Associated With High-dose Corticosteroid Administration in Children With Spinal Cord Injury.

    Science.gov (United States)

    Cage, Jason M; Knox, Jeffrey B; Wimberly, Robert L; Shaha, Steve; Jo, ChanHee; Riccio, Anthony I

    2015-01-01

    Complications with high-dose steroid administration for spinal cord injury are documented in adult patients. Our purpose was to determine the incidence of early complications of this therapy in pediatric patients with spinal cord injuries. An IRB-approved retrospective review was performed for patients treated for spinal cord injury at a level 1 pediatric trauma center between 2003 and 2011. Demographic data, injury characteristics, and surgical interventions were documented. Complications were divided into 4 categories: infectious, gastrointestinal (GI), hyperglycemia/endocrine, and wound healing problems. Complication rates were compared using a Student's t test and Fischer's exact test. Thirty-four spinal cord injury patients were identified. Twenty-three patients (mean age 6.6 y) in the treatment group received high-dose steroid treatment and 11 patients (mean age 8.4 y) did not and comprised the control group. No statistical difference was detected between the 2 groups regarding age, mechanism of injury, rate of surgical intervention, level of injury, and injury severity. Hyperglycemia was the most common complication and was present in all patients in both the treatment and control groups. The overall infection rate was 64% in the control group compared with 26% in the treatment (Pspinal trauma in a pediatric population. Hyperglycemia was found in all spinal cord injury patients, regardless of steroid treatment. Paradoxically, infection rates were noted to be higher in the control group. GI and wound problems were not significantly different. Larger, multicenter prospective studies are needed to better understand the risks in pediatric SCI patients.

  13. Dose intercomparison studies for standardization of high-dose dosimetry in Viet Nam

    International Nuclear Information System (INIS)

    Mai Hoang Hoa; Duong Nguyen Dinh; Kojima, T.

    1999-01-01

    The Irradiation Center of the Vietnam Atomic Energy Commission (IC-VAEC) is planning to establish a traceability system for high-dose dosimetry and to provide high-dose standards as a secondary standard dosimetry laboratory (SSDL) level in Vietnam. For countries which do not have a standard dosimetry laboratory, the participation in the International Dose Assurance Service (IDAS) operated by the International Atomic Energy Agency (IAEA) is the most common means to verify own dosimetry performance with a certain uncertainty. This is, however, only one-direction dose intercomparison with evaluation by IAEA including unknown parameter at participant laboratories. The SSDL level laboratory should have traceability as well as compatibility, ability to evaluate uncertainties of its own dosimetry performance by itself In the present paper, we reviewed our dosimetry performance through two-way dose intercomparison studies and self-evaluation of uncertainty in our dosimetry procedure. The performance of silver dichromate dosimeter as reference transfer dosimeter in IC-VAEC was studied through two-way blind dose intercomparison experiments between the IC-VAEC and JAERI. As another channel of dose intercomparison with IAEA, alanine dosimeters issued by IDAS were simultaneously irradiated with the IC-VAEC dichromate dosimeters at IC-VAEC and analyzed by IAEA. Dose intercomparison between IC-VAEC and JAERI results into a good agreement (better than ±2.5%), and IDAS results also show similar agreement within ±3.0%. The uncertainty was self-estimated on the basis of the JAERI alanine dosimetry, and a preliminary value of about 1.86% at a 68% confidence level is established. The results from these intercomparisons and our estimation of the uncertainty are consistent. We hope that our experience is valuable to other countries which do not have dosimetry standard laboratories and/or are planning to establish them. (author)

  14. Gafchromic EBT-XD film: Dosimetry characterization in high-dose, volumetric-modulated arc therapy.

    Science.gov (United States)

    Miura, Hideharu; Ozawa, Shuichi; Hosono, Fumika; Sumida, Naoki; Okazue, Toshiya; Yamada, Kiyoshi; Nagata, Yasushi

    2016-11-08

    Radiochromic films are important tools for assessing complex dose distributions. Gafchromic EBT-XD films have been designed for optimal performance in the 40-4,000 cGy dose range. We investigated the dosimetric characteristics of these films, including their dose-response, postexposure density growth, and dependence on scanner orientation, beam energy, and dose rate with applications to high-dose volumetric-modulated arc therapy (VMAT) verification. A 10 MV beam from a TrueBeam STx linear accelerator was used to irradiate the films with doses in the 0-4,000 cGy range. Postexposure coloration was analyzed at postirradiation times ranging from several minutes to 48 h. The films were also irradiated with 6 MV (dose rate (DR): 600 MU/min), 6 MV flattening filter-free (FFF) (DR: 1,400 MU/ min), and 10 MV FFF (DR: 2,400 MU/min) beams to determine the energy and dose-rate dependence. For clinical examinations, we compared the dose distribu-tion measured with EBT-XD films and calculated by the planning system for four VMAT cases. The red channel of the EBT-XD film exhibited a wider dynamic range than the green and blue channels. Scanner orientation yielded a variation of ~ 3% in the net optical density (OD). The difference between the film front and back scan orientations was negligible, with variation of ~ 1.3% in the net OD. The net OD increased sharply within the first 6 hrs after irradiation and gradually afterwards. No significant difference was observed for the beam energy and dose rate, with a variation of ~ 1.5% in the net OD. The gamma passing rates (at 3%, 3 mm) between the film- measured and treatment planning system (TPS)-calculated dose distributions under a high dose VMAT plan in the absolute dose mode were more than 98.9%. © 2016 The Authors.

  15. High doses of the histone deacetylase inhibitor sodium butyrate trigger a stress-like response.

    Science.gov (United States)

    Gagliano, Humberto; Delgado-Morales, Raul; Sanz-Garcia, Ancor; Armario, Antonio

    2014-04-01

    The hypothalamic-pituitary-adrenal (HPA) axis is activated by a wide range of stimuli, including drugs. Here we report that in male rats, a dose of sodium butyrate (NaBu) that is typically used to inhibit histone deacetylation (1200 mg/kg) increased the peripheral levels of HPA hormones and glucose. In a further experiment, we compared the effects of two different doses of NaBu (200 and 1200 mg/kg) and equimolar saline solutions on peripheral neuroendocrine markers and brain c-Fos expression to demonstrate a specific stress-like effect of NaBu that is not related to hypertonicity and to localise putatively involved brain areas. Only the high dose of NaBu increased the plasma levels of stress markers. The equimolar (hypertonic) saline solution also activated the HPA axis and the c-Fos expression in the paraventricular nucleus of the hypothalamus (PVN), a key area for the control of the HPA axis, but the effects were of a lower magnitude than those of NaBu. Regarding other brain areas, group differences in c-Fos expression were not observed in the medial prefrontal cortex or the medial amygdala, but they were observed in the central amygdala and the lateral ventral septum. However, only the latter area of the NaBu group showed enhanced c-Fos expression that was significantly higher than that after hypertonic saline. The present data indicate that high doses of NaBu appear to act as a pharmacological stressor, and this fact should be taken into account when using this drug to study the role of epigenetic processes in learning and emotional behaviour. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. The effects of high dose and highly fractionated radiation on distraction osteogenesis in the murine mandible

    International Nuclear Information System (INIS)

    Monson, Laura A; Cavaliere, Christi M; Deshpande, Sagar S; Ayzengart, Alexander L; Buchman, Steven R

    2012-01-01

    The ability of irradiated tissue to support bony growth remains poorly defined, although there are anecdotal cases reported showing mixed results for the use of mandibular distraction osteogenesis after radiation for head and neck cancer. Many of these reports lack objective measures that would allow adequate analysis of outcomes or efficacy. The purpose of this experiment was to utilize a rat model of mandibular distraction osteogenesis after high dose and highly fractionated radiation therapy and to evaluate and quantify distracted bone formation under these conditions. Male Sprague–Dawley rats underwent 12 fractions of external beam radiation (48 Gray) of the left mandible. Following a two week recovery period, an external frame distractor was applied and gradual distraction of the mandible was performed. Tissue was harvested after a twenty-eight day consolidation period. Gross, radiologic and histological evaluations were undertaken. Those animals subjected to pre-operative radiation showed severe attenuation of bone formation including bone atrophy, incomplete bridging of the distraction gap, and gross bony defects or non-union. Although physical lengthening was achieved, the irradiated bone consistently demonstrated marked damaging effects on the normal process of distraction osteogenesis. This murine model has provided reliable evidence of the injurious effects of high dose radiation on bone repair and regeneration in distraction osteogenesis utilizing accurate and reproducible metrics. These results can now be used to assist in the development of therapies directed at mitigating the adverse consequences of radiation on the regeneration of bone and to optimize distraction osteogenesis so it can be successfully applied to post-oncologic reconstruction

  17. Drug elution from high-dose antibiotic-loaded acrylic cement: a comparative, in vitro study.

    Science.gov (United States)

    Gasparini, Giorgio; De Gori, Marco; Calonego, Giovanni; Della Bora, Tommaso; Caroleo, Benedetto; Galasso, Olimpio

    2014-11-01

    High-dose antibiotic-loaded acrylic cement (ALAC) is used for managing peri-prosthetic joint infections (PJIs). The marked increase in resistant high-virulence bacteria is drawing the attention of physicians toward alternative antimicrobial formulations loaded into acrylic bone cement. The aim of this in vitro study was to determine the elution kinetics of 14 different high-dose ALACs. All ALAC samples showed a burst release of antibiotics in the first hour, progressively decreasing over time, and elution curves strictly adhered to a nonlinear regression analysis formula. Among aminoglycosides, commonly seen as the most appropriate antibiotics to be loaded into the bone cement, the highest elution rate was that of tobramycin. Among the glycopeptides, a class of antibiotics that should be considered to treat PJIs because of the prevalence of aminoglycoside resistance, vancomycin showed better elution than teicoplanin. Clindamycin, which can be associated with aminoglycosides to prepare ALACs and represents a useful option against the most common pathogens responsible for PJIs, showed the highest absolute and relative elutions among all the tested