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276 results on '"Hagler, D."'

1. Polygenic risk for psychiatric disorders correlates with executive function in typical development.

Author

Schork, A J, Brown, T T, Hagler, D J, Thompson, W K, Chen, C-H, Dale, A M, Jernigan, T L, and Akshoomoff, N

Abstract

Executive functions are a diverse and critical suite of cognitive abilities that are often disrupted in individuals with psychiatric disorders. Despite their moderate to high heritability, little is known about the molecular genetic factors that contribute to variability in executive functions and how these factors may be related to those that predispose to psychiatric disorders. We examined the relationship between polygenic risk scores built from large genome-wide association studies of psychiatric disorders and executive functioning in typically developing children. In our discovery sample (N = 417), consistent with previous reports on general cognitive abilities, polygenic risk for autism spectrum disorder was associated with better performance on the Dimensional Change Card Sort test from the NIH Cognition Toolbox, with the largest effect in the youngest children. Polygenic risk for major depressive disorder was associated with poorer performance on the Flanker test in the same sample. This second association replicated for performance on the Penn Conditional Exclusion Test in an independent cohort (N = 3681). Our results suggest that the molecular genetic factors contributing to variability in executive function during typical development are at least partially overlapping with those associated with psychiatric disorders, although larger studies and further replication are needed.

Published
2018

3. Genome-wide association study of shared components of reading disability and language impairment

Author

Eicher, J. D., Powers, N. R., Miller, L. L., Akshoomoff, N., Amaral, D. G., Bloss, C. S., Libiger, O., Schork, N. J., Darst, B. F., Casey, B. J., Chang, L, Ernst, T., Frazier, J., Kaufmann, W. E., Keating, B., Kenet, T., Kennedy, D., Mostofsky, S., Murray, S. S., Sowell, E. R., Bartsch, H., Kuperman, J. M., Brown, T. T., Hagler, D. J., Jr., Dale, A. M., Jernigan, T. L., St. Pourcain, B., Davey Smith, G., Ring, S. M., and Gruen, J. R.

Published
2013
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14. Baseline brain function in the preadolescents of the ABCD Study

Author

Chaarani, B., Hahn, S., Allgaier, N., Adise, S., Owens, M. M., Juliano, A. C., Yuan, D. K., Loso, H., Ivanciu, A., Albaugh, M. D., Dumas, J., Mackey, S., Laurent, J., Ivanova, M., Hagler, D. J., Cornejo, M. D., Hatton, S., Agrawal, A., Aguinaldo, L., Ahonen, L., Aklin, W., Anokhin, A. P., Arroyo, J., Avenevoli, S., Babcock, D., Bagot, K., Baker, F. C., Banich, M. T., Barch, D. M., Bartsch, H., Baskin-Sommers, A., Bjork, J. M., Blachman-Demner, D., Bloch, M., Bogdan, R., Bookheimer, S. Y., Breslin, F., Brown, S., Calabro, F. J., Calhoun, V., Casey, B. J., Chang, L., Clark, D. B., Cloak, C., Constable, R. T., Constable, K., Corley, R., Cottler, L. B., Coxe, S., Dagher, R. K., Dale, A. M., Dapretto, M., Delcarmen-Wiggins, R., Dick, A. S., Do, E. K., Dosenbach, N. U. F., Dowling, G. J., Edwards, S., Ernst, T. M., Fair, D. A., Fan, C. C., Feczko, E., Feldstein-Ewing, S. W., Florsheim, P., Foxe, J. J., Freedman, E. G., Friedman, N. P., Friedman-Hill, S., Fuemmeler, B. F., Galvan, A., Gee, D. G., Giedd, J., Glantz, M., Glaser, P., Godino, J., Gonzalez, M., Gonzalez, R., Grant, S., Gray, K. M., Haist, F., Harms, M. P., Hawes, S., Heath, A. C., Heeringa, S., Heitzeg, M. M., Hermosillo, R., Herting, M. M., Hettema, J. M., Hewitt, J. K., Heyser, C., Hoffman, E., Howlett, K., Huber, R. S., Huestis, M. A., Hyde, L. W., Iacono, W. G., Infante, M. A., Irfanoglu, O., Isaiah, A., Iyengar, S., Jacobus, J., James, R., Jean-Francois, B., Jernigan, T., Karcher, N. R., Kaufman, A., Kelley, B., Kit, B., Ksinan, A., Kuperman, J., Laird, A. R., Larson, C., LeBlanc, K., Lessov-Schlagger, C., Lever, N., Lewis, D. A., Lisdahl, K., Little, A. R., Lopez, M., Luciana, M., Luna, B., Madden, P. A., Maes, H. H., Makowski, C., Marshall, A. T., Mason, M. J., Matochik, J., McCandliss, B. D., McGlade, E., Montoya, I., Morgan, G., Morris, A., Mulford, C., Murray, P., Nagel, B. J., Neale, M. C., Neigh, G., Nencka, A., Noronha, A., Nixon, S. J., Palmer, C. E., Pariyadath, V., Paulus, M. P., Pelham, W. E., Pfefferbaum, D., Pierpaoli, C., Prescot, A., Prouty, D., Puttler, L. I., Rajapaske, N., Rapuano, K. M., Reeves, G., Renshaw, P. F., Riedel, M. C., Rojas, P., de la Rosa, M., Rosenberg, M. D., Ross, M. J., Sanchez, M., Schirda, C., Schloesser, D., Schulenberg, J., Sher, K. J., Sheth, C., Shilling, P. D., Simmons, W. K., Sowell, E. R., Speer, N., Spittel, M., Squeglia, L. M., Sripada, C., Steinberg, J., Striley, C., Sutherland, M. T., Tanabe, J., Tapert, S. F., Thompson, W., Tomko, R. L., Uban, K. A., Vrieze, S., Wade, N. E., Watts, R., Weiss, S., Wiens, B. A., Williams, O. D., Wilbur, A., Wing, D., Wolff-Hughes, D., Yang, R., Yurgelun-Todd, D. A., Zucker, R. A., Potter, A., and Garavan, H. P.

Abstract

The Adolescent Brain Cognitive Development (ABCD) Study®is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N= 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N= 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N= 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Published
2021
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18. SU-F-T-118: Characterization of Change in Fractional Anisotropy After Radiation Therapy: Does Nearby Disruption Predict for White Matter Damage?

Author

Pettersson, N, primary, Karunamuni, R, additional, Connor, M, additional, Moiseenko, V, additional, Dale, A, additional, Bartsch, H, additional, Brewer, J, additional, Krishnan, A, additional, Kuperman, J, additional, Hagler, D, additional, McDonald, C, additional, Farid, N, additional, White, N, additional, Hattangadi-Gluth, J, additional, and Cervino, L, additional

Published
2016
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19. PV-0476: Fractional anisotropy dose-response relationship of the corpus callosum

Author

Pettersson, N., primary, Bartsch, H., additional, Brewer, J., additional, Cervino, L., additional, Connor, M., additional, Dale, A., additional, Hagler, D., additional, Karunamuni, R., additional, Krishnan, A., additional, Kuperman, J., additional, McDonald, C., additional, Farid, N., additional, White, N., additional, Hattangadi-Gluth, J., additional, and Moiseenko, V., additional

Published
2016
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20. Long-term influence of normal variation in neonatal characteristics on human brain development

Author

Walhovd, K. B., Fjell, A. M., Brown, T. T., Kuperman, J. M., Chung, Y., Hagler, D. J., Roddey, J. C., Erhart, M., McCabe, C., Akshoomoff, N., Amaral, D. G., Bloss, C. S., Libiger, O., Schork, N. J., Darst, B. F., Casey, B. J., Chang, L., Ernst, T. M., Frazier, J., Gruen, J. R., Kaufmann, W. E., Murray, S. S., van Zijl, P., Mostofsky, S., Dale, A. M., Jernigan, T. L., Newman, E., Ernst, T., Van Zijl, P., Kuperman, J., Murray, S., Bloss, C., Appelbaum, M., Gamst, A., Thompson, W., Bartsch, H., Keating, B., Amaral, D., Sowell, E., Kaufmann, W., Ruberry, E. J., Powers, A., Rosen, B., Kenet, T., Kennedy, D., and Gruen, J.

Subjects
Male, Adolescent, Birth weight, Developmental psychology, Fetal Development, Young Adult, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Image Processing, Computer-Assisted, medicine, Birth Weight, Humans, Attention deficit hyperactivity disorder, Young adult, Child, 030304 developmental biology, 0303 health sciences, Fetus, Multidisciplinary, Age Factors, Infant, Newborn, Brain, Organ Size, Human brain, Biological Sciences, medicine.disease, Magnetic Resonance Imaging, Personality disorders, United States, medicine.anatomical_structure, Socioeconomic Factors, Schizophrenia, Regression Analysis, Female, Psychology, Neurocognitive, 030217 neurology & neurosurgery, Demography
Abstract

It is now recognized that a number of cognitive, behavioral, and mental health outcomes across the lifespan can be traced to fetal development. Although the direct mediation is unknown, the substantial variance in fetal growth, most commonly indexed by birth weight, may affect lifespan brain development. We investigated effects of normal variance in birth weight on MRI-derived measures of brain development in 628 healthy children, adolescents, and young adults in the large-scale multicenter Pediatric Imaging, Neurocognition, and Genetics study. This heterogeneous sample was recruited through geographically dispersed sites in the United States. The influence of birth weight on cortical thickness, surface area, and striatal and total brain volumes was investigated, controlling for variance in age, sex, household income, and genetic ancestry factors. Birth weight was found to exert robust positive effects on regional cortical surface area in multiple regions as well as total brain and caudate volumes. These effects were continuous across birth weight ranges and ages and were not confined to subsets of the sample. The findings show that ( i ) aspects of later child and adolescent brain development are influenced at birth and ( ii ) relatively small differences in birth weight across groups and conditions typically compared in neuropsychiatric research (e.g., Attention Deficit Hyperactivity Disorder, schizophrenia, and personality disorders) may influence group differences observed in brain parameters of interest at a later stage in life. These findings should serve to increase our attention to early influences.

Published
2012
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27. Point-light biological motion perception activates human premotor cortex

Author

Saygin, A. P., Wilson, S. M., Hagler, D. J., Bates, E., and Sereno, M. I.

Subjects
biological motion, premotor cortex, functional MRI, action observation, motion, frontal, SURFACE-BASED ANALYSIS, CORTICAL SURFACE, GRASP REPRESENTATIONS, VISUAL-PERCEPTION, COORDINATE SYSTEM, MIRROR NEURONS, BRAIN ACTIVITY, FMRI, AREAS, PSYCHOPHYSICS
Abstract

Motion cues can be surprisingly powerful in defining objects and events. Specifically, a handful of point-lights attached to the joints of a human actor will evoke a vivid percept of action when the body is in motion. The perception of point-light biological motion activates posterior cortical areas of the brain. On the other hand, observation of others' actions is known to also evoke activity in motor and premotor areas in frontal cortex. In the present study, we investigated whether point-light biological motion animations would lead to activity in frontal cortex as well. We performed a human functional magnetic resonance imaging study on a high-field-strength magnet and used a number of methods to increase signal, as well as cortical surface-based analysis methods. Areas that responded selectively to point-light biological motion were found in lateral and inferior temporal cortex and in inferior frontal cortex. The robust responses we observed in frontal areas indicate that these stimuli can also recruit action observation networks, although they are very simplified and characterize actions by motion cues alone. The finding that even point-light animations evoke activity in frontal regions suggests that the motor system of the observer may be recruited to "fill in" these simplified displays.

Published
2004

28. Identification of common variants associated with human hippocampal and intracranial volumes

Author

Stein, J., Medland, S., Vasquez, A., Hibar, D., Senstad, R., Winkler, A., Toro, R., Appel, K., Bartecek, R., Bergmann, O., Bernard, M., Brown, A., Cannon, D., Chakravarty, M., Christoforou, A., Domin, M., Grimm, O., Hollinshead, M., Holmes, A., Homuth, G., Hottenga, J., Langan, C., Lopez, L., Hansell, N., Hwang, K., Kim, S., Laje, G., Lee, P., Liu, X., Loth, E., Lourdusamy, A., Mattingsdal, M., Mohnke, S., Maniega, S., Nho, K., Nugent, A., O'Brien, C., Papmeyer, M., Putz, B., Ramasamy, A., Rasmussen, J., Rijpkema, M., Risacher, S., Roddey, J., Rose, E., Ryten, M., Shen, L., Sprooten, E., Strengman, E., Teumer, A., Trabzuni, D., Turner, J., van Eijk, K., van Erp, T., van Tol, M., Wittfeld, K., Wolf, C., Woudstra, S., Aleman, A., Alhusaini, S., Almasy, L., Binder, E., Brohawn, D., Cantor, R., Carless, M., Corvin, A., Czisch, M., Curran, J., Davies, G., de Almeida, M., Delanty, N., Depondt, C., Duggirala, R., Dyer, T., Erk, S., Fagerness, J., Fox, P., Freimer, N., Gill, M., Goering, H., Hagler, D., Hoehn, D., Holsboer, F., Hoogman, M., Hosten, N., Jahanshad, N., Johnson, M., Kasperaviciute, D., Kent, J., Kochunov, P., Lancaster, J., Lawrie, S., Liewald, D., Mandl, R., Matarin, M., Mattheisen, M., Meisenzahl, E., Melle, I., Moses, Eric, Muehleisen, T., Nauck, M., Noethen, M., Olvera, R., Pandolfo, M., Pike, G., Puls, R., Reinvang, I., Renteria, M., Rietschel, M., Roffman, J., Royle, N., Rujescu, D., Savitz, J., Schnack, H., Schnell, K., Seiferth, N., Smith, C., Steen, V., Hernandez, M., Van den Heuvel, M., van der Wee, N., Van Haren, N., Veltman, J., Voelzke, H., Walker, R., Westlye, L., Whelan, C., Agartz, I., Boomsma, D., Cavalleri, G., Dale, A., Djurovic, S., Drevets, W., Hagoort, P., Hall, J., Heinz, A., Jack, C., Foroud, T., Le Hellard, S., Macciardi, F., Montgomery, G., Poline, J., Porteous, D., Sisodiya, S., Starr, J., Sussmann, J., Toga, A., Veltman, D., Walter, H., Weiner, M., Bis, J., Ikram, M., Smith, A., Gudnason, V., Tzourio, C., Vernooij, M., Launer, L., DeCarli, C., Seshadri, S., Andreassen, O., Apostolova, L., Bastin, M., Blangero, J., Brunner, H., Buckner, R., Cichon, S., Coppola, G., de Zubicaray, G., Deary, I., Donohoe, G., de Geus, E., Espeseth, T., Fernandez, G., Glahn, D., Grabe, H., Hardy, J., Pol, H., Jenkinson, M., Kahn, R., McDonald, C., McIntosh, A., McMahon, F., McMahon, K., Meyer-Lindenberg, A., Morris, D., Mueller-Myhsok, B., Nichols, T., Ophoff, R., Paus, T., Pausova, Z., Penninx, B., Potkin, S., Saemann, P., Saykin, A., Schumann, G., Smoller, J., Wardlaw, J., Weale, M., Martin, N., Franke, B., Wright, M., Thompson, P., Stein, J., Medland, S., Vasquez, A., Hibar, D., Senstad, R., Winkler, A., Toro, R., Appel, K., Bartecek, R., Bergmann, O., Bernard, M., Brown, A., Cannon, D., Chakravarty, M., Christoforou, A., Domin, M., Grimm, O., Hollinshead, M., Holmes, A., Homuth, G., Hottenga, J., Langan, C., Lopez, L., Hansell, N., Hwang, K., Kim, S., Laje, G., Lee, P., Liu, X., Loth, E., Lourdusamy, A., Mattingsdal, M., Mohnke, S., Maniega, S., Nho, K., Nugent, A., O'Brien, C., Papmeyer, M., Putz, B., Ramasamy, A., Rasmussen, J., Rijpkema, M., Risacher, S., Roddey, J., Rose, E., Ryten, M., Shen, L., Sprooten, E., Strengman, E., Teumer, A., Trabzuni, D., Turner, J., van Eijk, K., van Erp, T., van Tol, M., Wittfeld, K., Wolf, C., Woudstra, S., Aleman, A., Alhusaini, S., Almasy, L., Binder, E., Brohawn, D., Cantor, R., Carless, M., Corvin, A., Czisch, M., Curran, J., Davies, G., de Almeida, M., Delanty, N., Depondt, C., Duggirala, R., Dyer, T., Erk, S., Fagerness, J., Fox, P., Freimer, N., Gill, M., Goering, H., Hagler, D., Hoehn, D., Holsboer, F., Hoogman, M., Hosten, N., Jahanshad, N., Johnson, M., Kasperaviciute, D., Kent, J., Kochunov, P., Lancaster, J., Lawrie, S., Liewald, D., Mandl, R., Matarin, M., Mattheisen, M., Meisenzahl, E., Melle, I., Moses, Eric, Muehleisen, T., Nauck, M., Noethen, M., Olvera, R., Pandolfo, M., Pike, G., Puls, R., Reinvang, I., Renteria, M., Rietschel, M., Roffman, J., Royle, N., Rujescu, D., Savitz, J., Schnack, H., Schnell, K., Seiferth, N., Smith, C., Steen, V., Hernandez, M., Van den Heuvel, M., van der Wee, N., Van Haren, N., Veltman, J., Voelzke, H., Walker, R., Westlye, L., Whelan, C., Agartz, I., Boomsma, D., Cavalleri, G., Dale, A., Djurovic, S., Drevets, W., Hagoort, P., Hall, J., Heinz, A., Jack, C., Foroud, T., Le Hellard, S., Macciardi, F., Montgomery, G., Poline, J., Porteous, D., Sisodiya, S., Starr, J., Sussmann, J., Toga, A., Veltman, D., Walter, H., Weiner, M., Bis, J., Ikram, M., Smith, A., Gudnason, V., Tzourio, C., Vernooij, M., Launer, L., DeCarli, C., Seshadri, S., Andreassen, O., Apostolova, L., Bastin, M., Blangero, J., Brunner, H., Buckner, R., Cichon, S., Coppola, G., de Zubicaray, G., Deary, I., Donohoe, G., de Geus, E., Espeseth, T., Fernandez, G., Glahn, D., Grabe, H., Hardy, J., Pol, H., Jenkinson, M., Kahn, R., McDonald, C., McIntosh, A., McMahon, F., McMahon, K., Meyer-Lindenberg, A., Morris, D., Mueller-Myhsok, B., Nichols, T., Ophoff, R., Paus, T., Pausova, Z., Penninx, B., Potkin, S., Saemann, P., Saykin, A., Schumann, G., Smoller, J., Wardlaw, J., Weale, M., Martin, N., Franke, B., Wright, M., and Thompson, P.

Abstract

Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10 -16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10 -12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10 -7). © 2012 Nature America, Inc. All rights reserved.

Published
2012

32. One-Year Brain Atrophy Evident in Healthy Aging

Author

Fjell, A. M., primary, Walhovd, K. B., additional, Fennema-Notestine, C., additional, McEvoy, L. K., additional, Hagler, D. J., additional, Holland, D., additional, Brewer, J. B., additional, and Dale, A. M., additional

Published
2009
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39. Voyage to North America, 1844-45: Prince Carl of Solms's Texas Diary of People, Places, and Events

Author

Hagler, D. Harland

Subjects
Voyage to North America, 1844-45: Prince Carl of Solms's Texas Diary of People, Places, and Events (Book), Books -- Book reviews, History, Regional focus/area studies
Abstract

Translation from German and notes by Wolfram M. Von-Maszewski. Introduction by Theodore Gish. (Denton: German-Texan Heritage Society and University of North Texas Press, c. 2000. Pp. x, 244. $32.50, ISBN [...]

Published
2002

42. CETP polymorphisms associate with brain structure, atrophy rate, and Alzheimer's disease risk in an APOE-dependent manner.

Author

Murphy, Elizabeth, Roddey, John, McEvoy, Linda, Holland, Dominic, Hagler, D., Dale, Anders, and Brewer, James

Abstract

Two alleles in cholesteryl ester transfer protein (CETP) gene polymorphisms have been disputably linked to enhanced cognition and decreased risk of Alzheimer's disease (AD): the V and A alleles of I405V and C-629A. This study investigates whether these polymorphisms affect brain structure in 188 elderly controls and 318 AD or mild cognitive impairment (MCI) subjects from the Alzheimer's Disease Neuroimaging Initiative cohort. Nominally signficant associations were dependent on APOE ε4 carrier status. In APOE ε4 carriers, the V and A alleles, both of which decrease CETP and increase HDL, associated with greater baseline cortical thickness and less 12-month atrophy in the medial temporal lobe. Conversely, in APOE ε4 non-carriers, the I allele, which increases CETP and decreases HDL, associated with greater baseline thickness, less atrophy and lower risk of dementia. These results suggest CETP may contribute to the genetic variability of brain structure and dementia susceptibility in an APOE-dependent manner. [ABSTRACT FROM AUTHOR]

Published
2012
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45. Blastogenic responses to Pneumocystis carinii among patients with human immunodeficiency (HIV) infection.

Author

Hagler, D. N., Deepe, G. S., Pogue, Cheryl L., and Walzer, P. D.

Subjects
*HIV-positive persons, *HIV infections, *IMMUNODEFICIENCY, *LYMPHOID tissue, *CLOSTRIDIUM diseases, *ANAEROBIC infections
Abstract

Proliferative responses by human peripheral blood mononuclear cells and rat spleen cells were measured to Pneumocystis carinii in a blastogenic assay using organisms obtained from rat lungs and propagated in (issue culture as the antigen. Responses occurred only in subjects with known prior exposure to P. carinii and the magnitude of the response varied with the number of organisms present in the antigen preparation and days in culture. Healthy human adults showed higher proliferative responses to P. carinii than did patients with Class II (asymptomatic) or Class III (lymphadenopathy) human immunodeficiency virus (HIV) infection. No responses to the preparation were found among Class IV HIV patients with the acquired immunodeficiency syndrome, including those with prior episodes of P. carinii pneumonia or those receiving azidothymidine. Overall, the blastogenic responses obtained with P. carinii were similar to those obtained with tetanus toxoid and phytohemagglutinin, and correlated well with the number of circulating CD4 cells. The data suggest that the blastogenic assay using tissue culture-derived rat P. carinii is specific for the organism and should be helpful in studying the cellular immune responses in pneumocystosis among different human patient populations. [ABSTRACT FROM AUTHOR]

Published
1988

49. Clinical evaluation of efficacy, pharmacokinetics, and safety of teicoplanin for serious gram-positive infections

Author

Bibler, M R, Frame, P T, Hagler, D N, Bode, R B, Staneck, J L, Thamlikitkul, V, Harris, J E, Haregewoin, A, and Bullock, W E

Abstract

Nineteen patients hospitalized for serious gram-positive infections were treated with teicoplanin, a new glycopeptide antibiotic. A variety of infections were treated, including endocarditis, septic thrombophlebitis, osteomyelitis, pyogenic arthritis, and soft tissue infection. Of 13 infections that could be evaluated in 12 patients, there were 8 clinical cures, 2 improvements, 1 recurrence, and 2 failures. Of the eight patients with Staphylococcus aureus bacteremia, seven were clinically cured or improved with teicoplanin therapy. Of the nine patients in whom the bacteriological response to treatment could be fully evaluated, six were cured; there was recurrence of infection in one, and treatment failed in two patients. In vitro testing showed the 13 bacterial isolates (9 S. aureus, 3 S. epidermidis, and 1 group B streptococcus) to be uniformly susceptible to teicoplanin, with MICs ranging from 0.12 to 0.5 microgram/ml. Every isolate was more susceptible in vitro to teicoplanin than to vancomycin. Three of the staphylococcal isolates were resistant to methicillin. Pharmacokinetic studies demonstrated that after an initial drug-accumulation period, a single daily dose adequately maintained the teicoplanin concentrations in serum within therapeutic ranges. Teicoplanin also penetrated well into synovial fluid. The drug was well tolerated by either intravenous or intramuscular administration. The most significant adverse reaction was an urticarial rash which required discontinuation of therapy in one patient; a second patient experienced a modest decrease in high-frequency auditory threshold. Asymptomatic eosinophilia and mild elevation of serum transaminases were noted as well. The results of this study suggest that teicoplanin is a safe and effective new agent for treatment of serious infections caused by gram-positive organisms.

Published
1987
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50. Blastogenic responses to Pneumocystis carinii among patients with human immunodeficiency (HIV) infection

Author

Hagler, D N, Deepe, G S, Pogue, C L, and Walzer, P D

Subjects
Male, Acquired Immunodeficiency Syndrome, Immunity, Cellular, Pneumocystis, Dose-Response Relationship, Immunologic, Antibodies, Protozoan, Mitosis, Antigens, Protozoan, Rats, Inbred Strains, T-Lymphocytes, Helper-Inducer, Lymphocyte Activation, respiratory tract diseases, Rats, Rats, Inbred Lew, Leukocytes, Mononuclear, Animals, Humans, Research Article
Abstract

Proliferative responses by human peripheral blood mononuclear cells and rat spleen cells were measured to Pneumocystis carinii in a blastogenic assay using organisms obtained from rat lungs and propagated in tissue culture as the antigen. Responses occurred only in subjects with known prior exposure to P. carinii and the magnitude of the response varied with the number of organisms present in the antigen preparation and days in culture. Healthy human adults showed higher proliferative responses to P. carinii than did patients with Class II (asymptomatic) or Class III (lymphadenopathy) human immunodeficiency virus (HIV) infection. No responses to the preparation were found among Class IV HIV patients with the acquired immunodeficiency syndrome, including those with prior episodes of P. carinii pneumonia or those receiving azidothymidine. Overall, the blastogenic responses obtained with P. carinii were similar to those obtained with tetanus toxoid and phytohemagglutinin, and correlated well with the number of circulating CD4 cells. The data suggest that the blastogenic assay using tissue culture-derived rat P. carinii is specific for the organism and should be helpful in studying the cellular immune responses in pneumocystosis among different human patient populations.

Published
1988

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