21 results on '"Kime C"'
Search Results
2. Design automation research at The University of Wisconsin—Madison
- Author
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Beetem, J., primary, Dietmeyer, D., additional, Hu, Y., additional, Jain, R., additional, Kime, C., additional, Ramanathan, P., additional, and Saluja, K., additional
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- 1991
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3. Abstracts of Current Computer Literature.
- Author
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Kime, C.
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- 1967
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4. WISPAC: A PARALLEL ARRAY COMPUTER FOR SIMULATION APPLICATIONS
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Rideout, V. C., Eastman, J., Adel Elmaghraby, Finkel, R. A., Frank, A. A., Kaminsky, T. J., Kime, C. R., Mcpherson, J. A., Redmond, M. J., and Smith, S. Diane
5. A New Syndrome Associated with Treatment by Nicotinic Acid
- Author
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Kime, C. E., primary and Palsy, Bellʼs, additional
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- 1958
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6. Computer Group News
- Author
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Kime, C., primary
- Published
- 1966
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7. Bell's Palsy: A New Syndrome Associated with Treatment by Nicotinic Acid: A Guide to Adequate Medical Therapy
- Author
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KIME, C. E., primary
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- 1958
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8. Strategies of pluripotent stem cell-based therapy for retinal degeneration: update and challenges.
- Author
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Maeda T, Mandai M, Sugita S, Kime C, and Takahashi M
- Subjects
- Humans, Retinal Pigment Epithelium, Stem Cell Transplantation methods, Induced Pluripotent Stem Cells, Pluripotent Stem Cells, Retinal Degeneration therapy
- Abstract
Stem cell-based therapy for retinal degeneration is transitioning from the research stage to the clinical stage and is being developed as a treatment across the globe. In clinical studies on induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) transplantation, the safety of the technique has started to clarify, and clinical study on further advances such as the long-desired transplantation of iPSC-derived retina to treat retinitis pigmentosa (RP) has begun. Ophthalmologists are now working closely with basic researchers to incorporate new technology areas with a synergy that is anticipated to realize the practical application of stem cell-based therapy for retinal degeneration., Competing Interests: Declaration of interests None are declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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9. Inducing human retinal pigment epithelium-like cells from somatic tissue.
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Woogeng IN, Kaczkowski B, Abugessaisa I, Hu H, Tachibana A, Sahara Y, Hon CC, Hasegawa A, Sakai N, Nishida M, Sanyal H, Sho J, Kajita K, Kasukawa T, Takasato M, Carninci P, Maeda A, Mandai M, Arner E, Takahashi M, and Kime C
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- Animals, Disulfides pharmacology, Fibroblasts cytology, Gene Expression Regulation, Humans, Indole Alkaloids pharmacology, Machine Learning, Niacinamide pharmacology, Rats, Retina cytology, Retina metabolism, Retina pathology, Retinal Pigment Epithelium cytology, Retinal Pigment Epithelium transplantation, Transcription Factors genetics, Transcription Factors metabolism, Cellular Reprogramming drug effects, Fibroblasts metabolism, Retinal Pigment Epithelium metabolism
- Abstract
Regenerative medicine relies on basic research outcomes that are only practical when cost effective. The human eyeball requires the retinal pigment epithelium (RPE) to interface the neural retina and the choroid at large. Millions of people suffer from age-related macular degeneration (AMD), a blinding multifactor genetic disease among RPE degradation pathologies. Recently, autologous pluripotent stem-cell-derived RPE cells were prohibitively expensive due to time; therefore, we developed a faster reprogramming system. We stably induced RPE-like cells (iRPE) from human fibroblasts (Fibs) by conditional overexpression of both broad plasticity and lineage-specific transcription factors (TFs). iRPE cells displayed critical RPE benchmarks and significant in vivo integration in transplanted retinas. Herein, we detail the iRPE system with comprehensive single-cell RNA sequencing (scRNA-seq) profiling to interpret and characterize its best cells. We anticipate that our system may enable robust retinal cell induction for basic research and affordable autologous human RPE tissue for regenerative cell therapy., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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10. Reprogramming epiblast stem cells into pre-implantation blastocyst cell-like cells.
- Author
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Tomoda K, Hu H, Sahara Y, Sanyal H, Takasato M, and Kime C
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- Animals, Cell Lineage drug effects, Cell Lineage genetics, Embryonic Stem Cells drug effects, Embryonic Stem Cells metabolism, Gene Expression Regulation, Developmental drug effects, Genes, Reporter, Leukemia Inhibitory Factor pharmacology, Mice, Inbred C57BL, Models, Biological, RNA metabolism, Time Factors, Mice, Blastocyst cytology, Cellular Reprogramming drug effects, Cellular Reprogramming genetics, Embryo Implantation drug effects, Embryo Implantation genetics, Embryonic Stem Cells cytology, Germ Layers cytology
- Abstract
Recently, a new wave of synthetic embryo systems (SESs) has been established from cultured cells for efficient and ethical embryonic development research. We recently reported our epiblast stem cell (EPISC) reprogramming SES that generates numerous blastocyst (BC)-like hemispheres (BCLH) with pluripotent and extraembryonic cell features detected by microscopy. Here, we further explored the system over key time points with single-cell RNA-sequencing analysis. We found broad induction of the 2C-like reporter MERVL and RNA velocities diverging to three major cell populations with gene expression profiles resembling those of pluripotent epiblast, primitive endoderm, and trophectoderm. Enrichment of those three induced BC-like cell fates involved key gene-regulatory networks, zygotic genome activation-related genes, and specific RNA splicing, and many cells closely resembled in silico models. This analysis confirms the induction of extraembryonic cell populations during EPISC reprogramming. We anticipate that our unique BCLH SES and rich dataset may uncover new facets of cell potency, improve developmental biology, and advance biomedicine., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2021
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11. Synthetic embryology: Early mammalian embryo modeling systems from cell cultures.
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Tomoda K and Kime C
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- Animals, Cell Differentiation, Humans, Cell Culture Techniques, Embryo, Mammalian cytology, Models, Biological
- Abstract
Recently, the fields of embryology, developmental biology, stem cell biology, and cell reprogramming, have intersected with synthetic embryo systems (SESs) from cultured cells. Among such SESs, several approaches have engaged early-embryo-like cells, cells with atypical potency, or assembled traditional in vitro stem cell populations with synergy, to advance life discovery systems that may yield emergent knowledge and biotechnical advance. Such models center on the competent generation of blastocyst-like and post-implantation embryo-like forms. Our group, and several others have recently pioneered unique SES strategies covering a broad spectrum of key early embryo-like developmental stages and features to seed an emerging SES field. Herein, we provide a comprehensive perspective of synthetic embryology and the powerful promise that excites us., (© 2021 Japanese Society of Developmental Biologists.)
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- 2021
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12. Induced 2C Expression and Implantation-Competent Blastocyst-like Cysts from Primed Pluripotent Stem Cells.
- Author
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Kime C, Kiyonari H, Ohtsuka S, Kohbayashi E, Asahi M, Yamanaka S, Takahashi M, and Tomoda K
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- Adaptor Proteins, Signal Transducing metabolism, Animals, Blastocyst cytology, Cell Cycle Proteins metabolism, Cell Differentiation, Cell Lineage, DNA-Binding Proteins metabolism, Embryonic Development, Female, Genes, Reporter, Mice, Mice, Inbred ICR, Pluripotent Stem Cells metabolism, RNA-Binding Proteins metabolism, Transcription Factors metabolism, Uterus pathology, YAP-Signaling Proteins, Blastocyst metabolism, Pluripotent Stem Cells cytology
- Abstract
Soon after fertilization, the few totipotent cells of mammalian embryos diverge to form a structure called the blastocyst (BC). Although numerous cell types, including germ cells and extended-pluripotency stem cells, have been developed from pluripotent stem cells (PSCs) in vitro, generating functional BCs only from PSCs remains elusive. Here, we describe induced self-organizing 3D BC-like cysts (iBLCs) generated from mouse PSC culture. Resembling natural BCs, iBLCs have a blastocoel-like cavity and were formed with outer cells expressing trophectoderm lineage markers and with inner cells expressing pluripotency markers. iBLCs transplanted to pseudopregnant mice uteruses implanted, induced decidualization, and exhibited growth and development before resorption, demonstrating that iBLCs are implantation competent. iBLC precursor intermediates required the transcription factor Prdm14 and concomitantly activated the totipotency-related cleavage-stage MERVL reporter and 2C genes. Thus, our system may contribute to the understanding of molecular mechanisms underpinning totipotency, embryogenesis, and implantation., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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13. Critical Functionality Effects from Storage Temperature on Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cell Suspensions.
- Author
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Kitahata S, Tanaka Y, Hori K, Kime C, Sugita S, Ueda H, and Takahashi M
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- Humans, Induced Pluripotent Stem Cells metabolism, Microtubules metabolism, Retinal Pigment Epithelium metabolism, Suspensions, rho GTP-Binding Proteins metabolism, Cell Death, Cell Differentiation, Cell Hypoxia, Induced Pluripotent Stem Cells pathology, Retinal Pigment Epithelium pathology, Temperature
- Abstract
Human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (hiPSC-RPE) cells suspension have the potential for regenerative treatment. However, practical regenerative applications with hiPSC-RPE cells require the development of simple and cost-effective non-freezing preservation methods. We investigated the effect of non-freezing temperatures on suspended hiPSC-RPE cells in various conditions and analysed mechanisms of cell death, anoikis, Rho GTPases, hypoxia, microtubule destruction, and cell metabolism. Cells stored at 37 °C had the lowest viability due to hypoxia from high cell metabolism and cell deposits, and cells preserved at 4 °C were damaged via microtubule fragility. Cell suspensions at 16 °C were optimal with drastically reduced apoptosis and negligible necrosis. Moreover, surviving cells proliferated and secreted key proteins normally, compared to cells without preservation. hiPSC-RPE cell suspensions were optimally preserved at 16 °C. Temperatures above or below the optimal temperature decreased cell viability significantly yet differentially by mechanisms of cell death, cellular metabolism, microtubule destruction, and oxygen tension, all relevant to cell conditions. Surviving cells are expected to function as grafts where high cell death is often reported. This study provides new insight into various non-freezing temperature effects on hiPSC-RPE cells that are highly relevant to clinical applications and may improve cooperation between laboratories and hospitals.
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- 2019
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14. Efficacy of additional topical betamethasone in persistent cystoid macular oedema after carbonic anhydrase inhibitor treatments in retinitis pigmentosa.
- Author
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Kitahata S, Hirami Y, Takagi S, Kime C, Fujihara M, Kurimoto Y, and Takahashi M
- Abstract
Objective: We investigated the efficacy of additional topical betamethasone in persistent cystoid macular oedema (CMO) after carbonic anhydrase inhibitors (CAIs) therapy., Methods and Analysis: This retrospective cohort study included 16 eyes of 10 patients with retinitis pigmentosa (RP). All patients were previously administered CAI for at least 3 months to treat CMO secondary to RP and lacking an effective reduction (≥11%) of central foveal thickness (CFT). We administered topical 0.1% betamethasone daily in each affected eye following a preceding course of the CAI medication as a first treatment. CMO was diagnosed using spectral-domain optical coherence tomography. CFT was regarded as the average of vertical and horizontal foveal thickness. Best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were obtained from patient medical records. We compared the CFT and BCVA between baseline and the average of 1-3, 5-7, 10-14 and 16-20 months period., Results: In treatments with brinzolamide in 14 eyes, dorzolamide in 2 eyes and bromfenac in 2 eyes, CFT effectively decreased in 12 of 16 eyes (81%). CFT decreased significantly in 1-3 months (326±102 µm; n=16; P=0.029) and 5-7 months (297±102 µm; n=12; P=0.022) compared with baseline but not within 10-14 months (271±96 µm; n=9; P=0.485) or 16-20 months (281±134 µm; n=9; P=0.289). There were no significant intergroup differences in BCVA throughout the study. Betamethasone treatment was stopped in three patients because of IOP elevation., Conclusion: Our data suggested that additional betamethasone might improve treatments for persistent CMO. Topical steroids could be an alternative option for managing persistent CMO in RP., Competing Interests: Competing interests: None declared.
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- 2018
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15. Autotaxin-mediated lipid signaling intersects with LIF and BMP signaling to promote the naive pluripotency transcription factor program.
- Author
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Kime C, Sakaki-Yumoto M, Goodrich L, Hayashi Y, Sami S, Derynck R, Asahi M, Panning B, Yamanaka S, and Tomoda K
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- Animals, Ascorbic Acid pharmacology, Cell Line, Cellular Reprogramming drug effects, Cellular Reprogramming genetics, Drug Synergism, Gene Expression Regulation drug effects, Kruppel-Like Factor 4, Mice, Inbred C57BL, Pluripotent Stem Cells metabolism, Transcription Factors genetics, Vitamins pharmacology, Bone Morphogenetic Protein 4 pharmacology, Leukemia Inhibitory Factor pharmacology, Lysophospholipids pharmacology, Phosphoric Diester Hydrolases metabolism, Pluripotent Stem Cells drug effects, Transcription Factors metabolism
- Abstract
Developmental signaling molecules are used for cell fate determination, and understanding how their combinatorial effects produce the variety of cell types in multicellular organisms is a key problem in biology. Here, we demonstrate that the combination of leukemia inhibitory factor (LIF), bone morphogenetic protein 4 (BMP4), lysophosphatidic acid (LPA), and ascorbic acid (AA) efficiently converts mouse primed pluripotent stem cells (PSCs) into naive PSCs. Signaling by the lipid LPA through its receptor LPAR1 and downstream effector Rho-associated protein kinase (ROCK) cooperated with LIF signaling to promote this conversion. BMP4, which also stimulates conversion to naive pluripotency, bypassed the need for exogenous LPA by increasing the activity of the extracellular LPA-producing enzyme autotaxin (ATX). We found that LIF and LPA-LPAR1 signaling affect the abundance of signal transducer and activator of transcription 3 (STAT3), which induces a previously unappreciated Kruppel-like factor (KLF)2-KLF4-PR domain 14 (PRDM14) transcription factor circuit key to establish naive pluripotency. AA also affects this transcription factor circuit by controlling PRDM14 expression. Thus, our study reveals that ATX-mediated autocrine lipid signaling promotes naive pluripotency by intersecting with LIF and BMP4 signaling., Competing Interests: S.Y. is a scientific advisor of iPS Academia Japan without salary. K.T. and C.K. are filing a patent related to this study.
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- 2016
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16. Efficient CRISPR/Cas9-Based Genome Engineering in Human Pluripotent Stem Cells.
- Author
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Kime C, Mandegar MA, Srivastava D, Yamanaka S, Conklin BR, and Rand TA
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- Cell Culture Techniques methods, Cells, Cultured, Humans, INDEL Mutation, Reproducibility of Results, CRISPR-Cas Systems, Genetic Engineering methods, Genome, Human genetics, Pluripotent Stem Cells metabolism
- Abstract
Human pluripotent stem cells (hPS cells) are rapidly emerging as a powerful tool for biomedical discovery. The advent of human induced pluripotent stem cells (hiPS cells) with human embryonic stem (hES)-cell-like properties has led to hPS cells with disease-specific genetic backgrounds for in vitro disease modeling and drug discovery as well as mechanistic and developmental studies. To fully realize this potential, it will be necessary to modify the genome of hPS cells with precision and flexibility. Pioneering experiments utilizing site-specific double-strand break (DSB)-mediated genome engineering tools, including zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), have paved the way to genome engineering in previously recalcitrant systems such as hPS cells. However, these methods are technically cumbersome and require significant expertise, which has limited adoption. A major recent advance involving the clustered regularly interspaced short palindromic repeats (CRISPR) endonuclease has dramatically simplified the effort required for genome engineering and will likely be adopted widely as the most rapid and flexible system for genome editing in hPS cells. In this unit, we describe commonly practiced methods for CRISPR endonuclease genomic editing of hPS cells into cell lines containing genomes altered by insertion/deletion (indel) mutagenesis or insertion of recombinant genomic DNA., (Copyright © 2016 John Wiley & Sons, Inc.)
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- 2016
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17. Practical Integration-Free Episomal Methods for Generating Human Induced Pluripotent Stem Cells.
- Author
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Kime C, Rand TA, Ivey KN, Srivastava D, Yamanaka S, and Tomoda K
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- Cell Culture Techniques, Cell Separation, Fibroblasts cytology, Fibroblasts metabolism, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells metabolism, Humans, Transfection, Cellular Reprogramming, Cellular Reprogramming Techniques, Induced Pluripotent Stem Cells cytology, Induced Pluripotent Stem Cells metabolism, Plasmids genetics
- Abstract
The advent of induced pluripotent stem (iPS) cell technology has revolutionized biomedicine and basic research by yielding cells with embryonic stem (ES) cell-like properties. The use of iPS-derived cells for cell-based therapies and modeling of human disease holds great potential. While the initial description of iPS cells involved overexpression of four transcription factors via viral vectors that integrated within genomic DNA, advances in recent years by our group and others have led to safer and higher quality iPS cells with greater efficiency. Here, we describe commonly practiced methods for non-integrating induced pluripotent stem cell generation using nucleofection of episomal reprogramming plasmids. These methods are adapted from recent studies that demonstrate increased hiPS cell reprogramming efficacy with the application of three powerful episomal hiPS cell reprogramming factor vectors and the inclusion of an accessory vector expressing EBNA1., (Copyright © 2015 John Wiley & Sons, Inc.)
- Published
- 2015
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18. Patterns of inpatient care for newly diagnosed immune thrombocytopenia in US children's hospitals.
- Author
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Kime C, Klima J, Rose MJ, and O'Brien SH
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- Adolescent, Child, Child, Preschool, Cohort Studies, Cost-Benefit Analysis, Databases, Factual, Female, Follow-Up Studies, Hospital Mortality trends, Hospitals, Pediatric economics, Hospitals, Pediatric statistics & numerical data, Humans, Immunoglobulins, Intravenous economics, Immunoglobulins, Intravenous therapeutic use, Infant, Length of Stay economics, Male, Patient Admission economics, Patient Admission statistics & numerical data, Patient Care methods, Patient Discharge statistics & numerical data, Patient Discharge trends, Patient Readmission economics, Patient Readmission statistics & numerical data, Purpura, Thrombocytopenic, Idiopathic economics, Retrospective Studies, Survival Analysis, Treatment Outcome, United States, Hospital Costs, Inpatients statistics & numerical data, Length of Stay trends, Patient Care trends, Purpura, Thrombocytopenic, Idiopathic diagnosis, Purpura, Thrombocytopenic, Idiopathic therapy
- Abstract
Objective: Although recent evidence-based guidelines for the management of immune thrombocytopenia (ITP) recommend a conservative, observation-based approach for the majority of patients with newly diagnosed pediatric ITP, current practice patterns are unknown. This study used the Pediatric Health Information System database to examine patterns of inpatient care in newly diagnosed ITP in freestanding US children's hospitals and to examine geographic differences in care., Methods: Data were extracted from Pediatric Health Information System for all newly diagnosed ITP admissions aged 1 to 18 years discharged between January 2008 and December 2010. Clinical data obtained included age, gender, length of stay, diagnoses, medications, and discharge status., Results: We identified 2314 unique patients meeting the study diagnosis of newly diagnosed ITP. Noncutaneous bleeding occurred in 12% of patients (intracranial hemorrhage 0.6%), with epistaxis the most commonly reported symptom. Ninety percent of hospitalized patients received ITP-directed therapy, with intravenous immunoglobulin G the most commonly used therapy (78% of patients). We identified significant variation by geographic region in treatment strategies, length of stay, hospital charges, and likelihood of readmission., Conclusions: A substantial number of children with newly diagnosed ITP continue to be hospitalized and receive intravenous medications, although the majority of these patients do not have clinical bleeding events during the admission. By using these results as a backdrop, future studies will be able to identify if the number of ITP admissions, costs of care, and geographic variability in care decrease with the dissemination and implementation of recently published guidelines.
- Published
- 2013
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19. Are there good ways to give 'bad news'?
- Author
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Krahn GL, Hallum A, and Kime C
- Subjects
- Humans, Infant, Newborn, Parents, Physician-Patient Relations, Truth Disclosure
- Abstract
There has been considerable speculation about the inevitability of parental dissatisfaction with being informed about their child's disability. Mothers and fathers of 24 infants with a recently diagnosed disability were interviewed regarding their preferences for how to be told the "bad news." Qualitative analyses revealed nine themes of parental preferences for how to communicate difficult information. Parents affirmed communication themes previously discussed in the literature, such as being told early and together, and identified new ones, such as affective tone and physical contact with their baby. The importance of these themes is presented for this sample. Recommendations for how to present "bad news" can be concisely drawn from these findings. Results suggest that parental dissatisfaction with the process of telling is not inevitable.
- Published
- 1993
20. Bell's palsy: a new syndrome associated with treatment by nicotinic acid; a guide to adequate medical therapy.
- Author
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KIME CE
- Subjects
- Humans, Bell Palsy, Facial Paralysis therapy, Niacin therapeutic use, Nicotinic Acids, Syndrome
- Published
- 1958
- Full Text
- View/download PDF
21. Criteria for tracheotomy in the unconscious patient.
- Author
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KIME CE
- Subjects
- Trachea surgery, Tracheotomy, Unconsciousness
- Published
- 1958
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