Evidence map›Paper›PMID 38271331›Full record

Observational studyPloS one2024

Elimination of 15N-thymidine after oral administration in human infants.

Niyatie Ammanamanchi, Jessie Yester, Anita P Bargaje, Dawn Thomas, Kathryn C Little, Shannon Janzef, Kimberly Francis, Jacqueline Weinberg, Jennifer Johnson, Thomas Seery and 12 more

Open access · goldAbstract readObservational Study
In one paragraph

Observational study in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact, top 99% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 4 institutions in 1 country.

Niyatie AmmanamanchiDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Jessie YesterDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.ORCID 0000-0003-2242-1634
Anita P BargajeDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Dawn ThomasDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Kathryn C LittleDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Shannon JanzefDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Kimberly FrancisDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Jacqueline WeinbergDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Jennifer JohnsonDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Thomas SeeryDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Tyler Hutchinson HarrisDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Bryan J FunariDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Kirsten Rose-FelkerDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Matthew ZinnDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Susan A MillerDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Shawn C WestDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Brian FeingoldDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.ORCID 0000-0003-4244-709X
Hairu ZhouDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.
Matthew L SteinhauserUPMC Heart and Vascular Institute, UPMC Presbyterian, Pittsburgh, PA, United States of America.
Timothy CsernicaDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, United States of America.
Robert MichenerDepartment of Biology, Boston University Stable Isotope Laboratory, Boston, MA, United States of America.
Bernhard KühnDivision of Pediatric Cardiology, Pediatric Institute for Heart Regeneration and Therapeutics (I-HRT), UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States of America.ORCID 0000-0002-1855-7072
University of Pittsburgh · USBoston University · USCalifornia Institute of Technology · USChildren's Hospital of Pittsburgh · US

Funding

University of Pittsburgh Clinical and Translational Science InstituteUL1TR001857 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2016 to 2025
$129.3M
Institutional Career Development CoreKL2TR001856 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RAY, KRISTIN N, RUBIO, DORIS M · 2016 to 2025
$13.8M
NRSA Training CoreTL1TR001858 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI RADOMSKI, THOMAS, RUBIO, DORIS M · 2016 to 2025
$11.1M
Research Training Program for Pediatric Subspecialty FellowsT32HD071834 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TERENCE S. DERMODY · 2013 to 2026
$4.7M
Mechanistic clinical trial of β-blocker administration for reactivating cardiomyocyte division in Tetralogy of FallotR01HL155597 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI KUHN, BERNHARD · 2021 to 2025
$3.4M
Quantification of the decline of heart muscle cell proliferation and its reversal in pediatric patientsR01HL151386 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI KUHN, BERNHARD · 2020 to 2023
$1.7M
NCATS NIH HHS KL2 TR001856NCATS NIH HHS TL1 TR001858NCATS NIH HHS UL1 TR001857NHLBI NIH HHS R01 HL151386NHLBI NIH HHS R01 HL155597NICHD NIH HHS T32 HD071834
6 · The paper itself

Abstract

backgroundWe have developed a new clinical research approach for the quantification of cellular proliferation in human infants to address unanswered questions about tissue renewal and regeneration. The approach consists of oral 15N-thymidine administration to label cells in S-phase, followed by Multi-isotope Imaging Mass Spectrometry for detection of the incorporated label in cell nuclei. To establish the approach, we performed an observational study to examine uptake and elimination of 15N-thymidine. We compared at-home label administration with in-hospital administration in infants with tetralogy of Fallot, a form of congenital heart disease, and infants with heart failure.

methodsWe examined urine samples from 18 infants who received 15N-thymidine (50 mg/kg body weight) by mouth for five consecutive days. We used Isotope Ratio Mass Spectrometry to determine enrichment of 15N relative to 14N (%) in urine. RESULTS/

findings15N-thymidine dose administration produced periodic rises of 15N enrichment in urine. Infants with tetralogy of Fallot had a 3.2-fold increase and infants with heart failure had a 4.3-fold increase in mean peak 15N enrichment over baseline. The mean 15N enrichment was not statistically different between the two patient populations (p = 0.103). The time to peak 15N enrichment in tetralogy of Fallot infants was 6.3 ± 1 hr and in infants with heart failure 7.5 ± 2 hr (mean ± SEM). The duration of significant 15N enrichment after a dose was 18.5 ± 1.7 hr in tetralogy of Fallot and in heart failure 18.2 ± 1.8 hr (mean ± SEM). The time to peak enrichment and duration of enrichment were also not statistically different (p = 0.617 and p = 0.887).

conclusionsThe presented results support two conclusions of significance for future applications: (1) Demonstration that 15N-thymidine label administration at home is equivalent to in-hospital administration. (2) Two different types of heart disease show no differences in 15N-thymidine absorption and elimination. This enables the comparative analysis of cellular proliferation between different types of heart disease.

Indexed as

Heart FailureTetralogy of FallotAdministration, OralHumansMouthNitrogen IsotopesNitrogen-15Nitrogen Isotopes

Identifiers

PMID38271331
PMCPMC10810423
OpenAlexW4391217014

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.