Karen M. Park

Public Citizen

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Peter Lorentzen

University of San Francisco

Deborah A. Nickerson

University of Washington

Karynne Patterson

University of Washington

Eugen Boltshauser

University Children's Hospital Zurich

Seema M. Jamal

Hospital for Sick Children

Jessica X. Chong

University of Washington

Holly K. Tabor

Stanford University

Anita Rauch

University of Zurich

Michael J. Bamshad

University of Washington

Joon‐Ho Yu

Seattle Children's Hospital

Cooperative Institutions

University of Washington

University of Michigan–Ann Arbor

University of Georgia

Columbia University

Texas A&M University

North Carolina State University

European Molecular Biology Laboratory

University of North Carolina at Chapel Hill

Cornell University

University of Iowa

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High‐dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia

Neurology (1997)

Kristine A. Nelson Karen M. Park Elaine Robinovitz Constantine Tsigos Mitchell B. Max

N-methyl-D-aspartate (NMDA) receptor antagonists relieve neuropathic pain in animal models, but side effects of dissociative anesthetic channel blockers, such as ketamine, have discouraged clinical application. Based on the hypothesis that low-affinity NMDA channel blockers might have a better therapeutic ratio, we carried out two randomized, double-blind, crossover trials comparing six weeks of oral dextromethorphan to placebo in two groups, made up of 14 patients with painful distal symmetrical diabetic neuropathy and 18 with postherpetic neuralgia. Thirteen patients with each diagnosis completed the comparison. Dosage was titrated in each patient to the highest level reached without disrupting normal activities; mean doses were 381 mglday in diabetics and 439 mglday in postherpetic neuralgia patients. In diabetic neuropathy, dextromethorphan decreased pain by a mean of 24% (95% CI: 6% to 42%, p = 0.011, relative to placebo. In postherpetic neuralgia, dextromethorphan did not reduce pain (95% CI: 10% decrease in pain to 14% increase in pain, p = 0.72). Five of 31 patients who took dextromethorphan dropped out due to sedation or ataxia during dose escalation, but the remaining patients all reached a reasonably well-tolerated maintenance dose. We conclude that dextromethorphan or other low-affinity NMDA channel blockers may have promise in the treatment of painful diabetic neuropathy.

Postherpetic Neuralgia

Diabetic Neuropathy

Crossover study

Memantine

10.1212/wnl.48.5.1212

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Citations (362)

Pharmacist-Driven Step-Down of Long-Term Proton-Pump Inhibitor Therapy

The Senior Care Pharmacist (2019)

Rachel Afi Quinn Karen M. Park Rita Bodine

OBJECTIVE: To evaluate the appropriateness of proton-pump inhibitor (PPI) prescribing and reduce the number of outpatients on long-term PPI therapy, defined as greater than or equal to one year.
DESIGN: Phase I was retrospective and evaluated the appropriateness of PPI prescribing. Phase II was prospective and involved implementation of a pharmacist-driven PPI step-down protocol.
SETTING: This study was conducted in an outpatient setting at Veterans Affairs Hudson Valley Health Care System.
PATIENTS, PARTICIPANTS: Patients were limited to a single primary care provider and were required to fill an outpatient PPI prescription between August 15, 2015, and August 15, 2016.
INTERVENTIONS: After patients were identified in Phase I as having an inappropriate indication for long-term PPI therapy, they were contacted by a pharmacist to complete the step-down protocol. The patients then received a call two weeks after completing each step.
MAIN OUTCOME MEASURE(S): To determine the number of patients without an indication for long-term PPI therapy that could successfully complete the PPI step-down protocol.
RESULTS: Phase I identified that long-term PPI therapy was not indicated in 68.4% of patients. Phase II implementation demonstrated that 71.4% of patients were able to successfully step-down from PPI therapy in an average of 13 weeks with the use of alternative acid-suppression therapy.
CONCLUSION: This study concluded that a majority of PPI prescriptions were not indicated for a duration of greater than or equal to 1 year. With the implementation of a pharmacist-driven PPI step-down protocol, a majority of patients were able to tolerate the PPI step-down with the use of alternative acidsuppression therapy.

10.4140/tcp.n.2019.520

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Citations (2)

Adult Stem Cells and Niche Cells segregate gradually from common precursors that build the adult Drosophila ovary during pupal development

bioRxiv (Cold Spring Harbor Laboratory) (2020)

Amy Reilein Helen V. Kogan Rachel Misner Karen M. Park Daniel Kalderon

Summary Adult stem cell function relies on the prior development of appropriate numbers and spatial organization of stem cells and supportive niche cells. Drosophila Follicle Stem Cells (FSCs) present a favorable paradigm for understanding those developmental processes. About sixteen FSCs in an adult germarium produce transit-amplifying Follicle Cells (FCs) from their posterior face and quiescent Escort Cells (ECs) to their anterior. Both ECs and FCs also act as niche cells. Here we show that adult ECs, FSCs and FCs derive from common precursors intermingled with germline cells during pupal development, with progeny of a single precursor commonly including ECs and FSCs, FSCs and FCs, or all three adult cell types. Precursors posterior to germline cells become the first FCs and engulf a largely naked germline cyst projected out of the germarium to form the first egg chamber and set up a key posterior signaling center for regulating adult FSC behavior.

Developmental Biology

10.1101/2020.06.25.171447

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Assessor Status Influences Pain Recall

Journal of Pain (2007)

David A. Williams Karen M. Park Kirsten Ambrose Daniel J. Clauw

Recall bias

Pain catastrophizing

10.1016/j.jpain.2006.10.005

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Citations (26)

Gene discovery for Mendelian conditions via social networking: de novo variants in KDM1A cause developmental delay and distinctive facial features

Genetics in Medicine (2015)

Jessica X. Chong Joon‐Ho Yu Peter Lorentzen Karen M. Park Seema M. Jamal

Mendelian inheritance

Exome

Identification

10.1038/gim.2015.161

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Citations (109)

Evaluation of neuropathic pain

Birkhäuser Basel eBooks (2002)

Karen M. Park Richard H. Gracely

Normally, the experience of pain results from activation of neural transducers sensitive to actual or impending tissue damage from mechanical, chemical, thermal, and other physical insults. These transducers, termed nociceptors by Sherrington [1], form the end of an extensive wiring harness that transmits information to the brain, leading to the perception of pain. This "nociceptive" pain is associated with physical harm and, in most cases, can be treated by analgesics. In contrast, "neuropathic pain" does not reflect transduction by nociceptors but damage to the wiring system. Neural injury can create the impression of pain in an undamaged region innervated by the nerve. Input from damaged nerves can also initiate processes of central sensitization that result in pain and tenderness in neighboring undamaged regions. Neuropathic pain is generally more difficult to treat than nociceptive pain. Clinicians typically treat all pains initially as nociceptive and only when these treatments fail do they ask the question, "Could the etiology be neuropathic?"

Nociceptor

Referred pain

10.1007/978-3-0348-8129-6_10

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Evaluation of computer-aided design software methods for assessment of the three-dimensional geometry of the canine radius

American Journal of Veterinary Research (2021)

Karen M. Park Denis J. Marcellin‐Little Tanya C. Garcia

To describe methods to measure the 3-D orientation of the proximal, diaphyseal, and distal segments of the canine radius by use of computer-aided design software (CADS) and to compare the repeatability and reliability of measurements derived by those methods.31 canine radii with biapical deformities and 24 clinically normal (control) canine radii.Select CT scans of radii were imported into a CADS program. Cartesian coordinate systems for the humerus and proximal, diaphyseal, and distal radial segments were developed. The orientation of each radial segment in the frontal, sagittal, and transverse planes was measured in triplicate by 3 methods. The repeatability and reliability of those measurements were calculated and compared among the 3 measurement methods.The mean ± SD within-subject repeatability of radial angular measurements for all 3 methods was 1.40 ± 0.67° in the frontal plane, 3.17 ± 2.21° in the sagittal plane, and 3.01 ± 1.11° in the transverse plane for control radii and 2.56 ± 1.95° in the frontal plane, 3.59 ± 2.39° in the sagittal plane, and 3.47 ± 1.19° in the transverse plane for abnormal radii. Mean ± SD bias between radial measurement methods was 1.88 ± 2.07° in the frontal plane, 6.44 ± 6.80° in the sagittal plane, and 2.27 ± 2.81° in the transverse plane.Results indicated that use of CADS to assess the 3-D orientation of the proximal, diaphyseal, and distal segments of normal and abnormal canine radii yielded highly repeatable and reliable measurements.

Repeatability

10.2460/ajvr.82.6.435

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Citations (1)

What Is Your Neurologic Diagnosis?

Journal of the American Veterinary Medical Association (2018)

Karen M. Park Juliet F. Armstrong Jennifer Lynn Ruby Renee M. Barber Janet A. Grimes

10.2460/javma.253.10.1253

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Pathological LSD1 mutations repress enhancer-mediated gene regulatory networks in early differentiation

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Daria Bunina Pierre‐Luc Germain Alejandro Tobon Nadine Fernandez-Novel Marx Christian Arnold

Abstract Lysine-specific demethylase 1 (LSD1/KDM1A) demethylates both histone and non-histone substrates, recruits repressive chromatin complexes, and is increased in cancers. De novo LSD1 mutations impairing protein function lead to a rare developmental disorder, but the molecular details of the pathology remains unclear. Using patient-derived fibroblasts, reprogrammed pluripotent stem cells, and differentiated cells, we found over 4000 differentially expressed genes and 68 transcription factors (TFs) whose motif accessibilities changed upon LSD1 mutation. An enhancer-mediated gene regulatory network approach identified transcriptional repressors with impaired activity in fibroblast and stem cells, leading to erroneous activation of their target genes. We also revealed overall decreases in TF target gene expression during early lineage differentiation of LSD1 mutant stem cells, likely caused by increased activity of repressive histone deacetylases (HDACs), co-factors of LSD1. Indeed, an HDACs inhibitor restored changes in gene expression including downregulation phenotype. Our findings characterize the molecular pathogenesis of LSD1 mutations and suggest potential therapeutic strategies for the developmental disorder and cancers caused by LSD1 dysregulations.

Demethylase

10.1101/2021.08.11.455900

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Citations (2)

Gene discovery for Mendelian conditions via social networking: de novo variants in KDM1A cause developmental delay and distinctive facial features Running title: Mendelian gene discovery by social networking

Jessica X. Chong Joon‐Ho Yu Peter Lorentzen Karen M. Park Seema M. Jamal

1. Department of Pediatrics, University of Washington, Seattle, WA 98195, USA 2. Department of Political Science, University of California, Berkeley, Berkeley, CA 94720, USA 3. citizen scientist, San Francisco, CA, USA 94131 4. Treuman Katz Center for Pediatric Bioethics, Seattle Children's Research Institute, Seattle, WA 98101, USA 5. Institute for Medical Genetics, University of Zurich, Zurich, Switzerland 6. Department of Pediatrics, University of Colorado, Aurora, CO 80045, USA 7. Children's Hospital of the University of Zurich, Zurich, Switzerland 8. Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA 9. Division of Genetic Medicine, Seattle Children’s Hospital, Seattle, WA 98105, USA

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