Publications by authors named "Julie Crawford"

19 Publications

  • Page 1 of 1

International observational atopic dermatitis cohort to follow natural history and treatment course: TARGET-DERM AD study design and rationale.

BMJ Open 2020 11 27;10(11):e039928. Epub 2020 Nov 27.

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Introduction: As new topical and systemic treatments become available for atopic dermatitis (AD), there is a need to understand how treatments are being used in routine clinical practice, their comparative effectiveness and their long-term safety in diverse clinical settings.

Methods And Analysis: The TARGET-DERM AD cohort is a longitudinal, observational study of patients with AD of all ages, designed to provide practical information on long-term effectiveness and safety unobtainable in traditional registration trials. Patients with physician-diagnosed AD receiving prescription treatment (topical or systemic) will be enrolled at academic and community clinical centres. Up to 3 years of retrospective medical records, 5 years of prospective medical records, and optional biological samples and patient-reported outcomes will be collected. The primary aims include characterisation of AD treatment regimens, evaluation of response to therapy, and description of adverse events.

Ethics And Dissemination: TARGET-DERM has been approved by a central IRB (Copernicus Group IRB, 5000 Centregreen Way Suite 200, Cary, North Carolina 27513) as well as local and institutional IRBs. No additional Ethics Committee reviews. Results will be reviewed by a publications committee and submitted to peer-reviewed journals.

Trial Registration Number: NCT03661866, pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-039928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703415PMC
November 2020

Reply to authors.

Clin Infect Dis 2020 Oct 22. Epub 2020 Oct 22.

Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine Center for Liver Disease, New York, New York, USA.

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http://dx.doi.org/10.1093/cid/ciaa1621DOI Listing
October 2020

Patient Characteristics and Outcomes of 11,721 Patients with COVID19 Hospitalized Across the United States.

Clin Infect Dis 2020 Aug 28. Epub 2020 Aug 28.

Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine Center for Liver Disease, New York, NY, USA.

Background: As COVID-19 disseminates throughout the US, a better understanding of patient characteristics associated with hospitalization, morbidity and mortality in diverse geographic regions is essential.

Methods: Hospital chargemaster data on adult patients with COVID-19 admitted to 245 hospitals across 38 states between February 15 and April 20, 2020 were assessed. Clinical course from admission through hospitalization to discharge or death was analyzed.

Results: A total of 11,721 patients were included (majority were >60 years of age [59.9%] and male [53.4%]). Comorbidities included hypertension (46.7%), diabetes (27.8%), cardiovascular disease (18.6%), obesity (16.1%), and chronic kidney disease (12.2%). Mechanical ventilation was required by 1,967 patients (16.8%). Mortality among hospitalized patients was 21.4% and increased to 70.5% among those on mechanical ventilation. Male sex, older age, obesity, geographic region, and the presence of chronic kidney disease or preexisting cardiovascular disease were associated with an increased odds of mechanical ventilation. All aforementioned risk factors, with the exception of obesity, were associated with an increased odds of death (all p& 0.001). Many patients received investigational medications for treatment of COVID-19, including 48 patients on remdesivir and 4,232 on hydroxychloroquine.

Conclusion: This large observational cohort describes the clinical course and identifies factors associated with outcomes of hospitalized patients with COVID-19 across the US. These data can inform strategies to prioritize prevention and treatment for this disease.
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http://dx.doi.org/10.1093/cid/ciaa1268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499515PMC
August 2020

Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma Alliance/MD Anderson Cancer Center experience.

Br J Haematol 2021 Mar 16;192(6):1049-1053. Epub 2020 Jul 16.

Department of Haematology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.

Primary and secondary central nervous system lymphomas (PCNSL/SCNSL) are aggressive rare malignancies with dismal outcomes. Encouraging data have emerged from Phase I/II clinical trials treating relapsed/refractory PCNSL/SCNSL with ibrutinib. We analysed 33 patients who received ibrutinib, alone or with other therapies, for PCNSL (n = 9) or SCNSL (n = 24). The objective response rate was 58% (complete response 55%). The median progression-free survival and overall survival for patients with PCNSL were both 3·1 months; for SCNSL, 10·2 and 11·5 months respectively. Only one invasive fungal infection was observed, despite concurrent or recent use of dexamethasone 8-16 mg daily in 14 patients (42%). Ibrutinib has encouraging activity in these aggressive malignancies.
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http://dx.doi.org/10.1111/bjh.16946DOI Listing
March 2021

GATA4 represses RANKL in osteoblasts via multiple long-range enhancers to regulate osteoclast differentiation.

Bone 2018 11 19;116:78-86. Epub 2018 Jul 19.

Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN, United States. Electronic address:

GATA4 is a transcription factor that is responsible for tissue-specific gene regulation in many tissues, and more recent studies showed that it is necessary for osteoblast differentiation. Previously, we showed that in vivo deletion of Gata4 using Cre-recombinase under the control of the Col1a1 2.3 kb promoter, showed significantly reduced trabecular bone properties. To understand the role of GATA4 in more differentiated cells, GATA4 mice were crossed with mice expressing Cre-recombinase under the control of the osteocalcin promoter. MicroCT analysis of trabecular bone properties of the femur and tibia from 14-week-old female osteocalcin-Cre/GATA4 (OCN-cKO) mice showed a significant reduction in percentage bone volume, a decrease in trabecular number and an increase in trabecular spacing. In vivo, histomorphometric analysis revealed a decrease in the number of osteoblasts and an increase in the number of osteoclasts in the tibiae of OCN-cKO mice. In vivo and in vitro systems correlated a decrease in Gata4 mRNA with increased RANKL gene expression. To determine if RANKL is a direct target of GATA4, chromatin immunoprecipitation (ChIP)-sequencing was performed, and it demonstrated that GATA4 is recruited to seven enhancers near RANKL. Furthermore, when Gata4 is knocked down, the chromatin at the RANKL region is further opened, as detected by a reduction in histone 3 lysine 27 trimethylation (H3K27me3) and an increase in histone 3 lysine 4 dimethylation (H3K4me2) in the RANKL locus. In vitro, TRAP staining of cells from bone marrow cultures from Gata4 knockout cells show that the increased levels of RANKL are sufficient for osteoclast formation. Together, the data suggest that GATA4 directly represses RANKL expression via seven cis-regulatory regions and plays an important role in maintaining proper bone development and osteoclast formation.
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http://dx.doi.org/10.1016/j.bone.2018.07.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158087PMC
November 2018

A real-world observational cohort of patients with primary biliary cholangitis: TARGET-primary biliary cholangitis study design and rationale.

Hepatol Commun 2018 May 23;2(5):484-491. Epub 2018 Mar 23.

University of North Carolina Chapel Hill NC.

Primary biliary cholangitis (PBC) is a rare chronic cholestatic liver disease that may progress to biliary cirrhosis if left untreated. The first-line therapy for PBC is ursodeoxycholic acid (UDCA). Unfortunately, 1 of 3 patients does not respond to UDCA. These patients are at risk for developing clinical events, including cirrhosis, complications of portal hypertension, hepatocellular carcinoma, liver transplant, or death. Recently, the U.S. Food and Drug Administration approved obeticholic acid to be used in certain patients with PBC. Off-label therapies are also used, and several other therapies are currently under evaluation. Real-world effectiveness of newly approved and off-label therapies remains unknown. TARGET-PBC is a 5-year, longitudinal, observational study of patients with PBC that will evaluate the effectiveness of clinical practice interventions and provide practical information unobtainable in registration trials. Enrollment will take place at both academic and community sites. In addition to consenting to medical records review, participants will be asked to provide an annual blood sample and complete patient reported outcome surveys at predetermined intervals. Any available liver biopsies will be digitally preserved. Key study outcomes will be the evaluation of the safety and effectiveness of PBC interventions and the assessment of disease progression under real-world conditions. ( 2018;2:484-491).
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http://dx.doi.org/10.1002/hep4.1173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944592PMC
May 2018

In vivo mononuclear cell tracking using superparamagnetic particles of iron oxide: feasibility and safety in humans.

Circ Cardiovasc Imaging 2012 Jul 10;5(4):509-17. Epub 2012 Jul 10.

Centre of Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom .

Background: Cell therapy is an emerging and exciting novel treatment option for cardiovascular disease that relies on the delivery of functional cells to their target site. Monitoring and tracking cells to ensure tissue delivery and engraftment is a critical step in establishing clinical and therapeutic efficacy. The study aims were (1) to develop a Good Manufacturing Practice-compliant method of labeling competent peripheral blood mononuclear cells with superparamagnetic particles of iron oxide (SPIO), and (2) to evaluate its potential for magnetic resonance cell tracking in humans.

Methods And Results: Peripheral blood mononuclear cells 1-5 × 10(9) were labeled with SPIO. SPIO-labeled cells had similar in vitro viability, migratory capacity, and pattern of cytokine release to unlabeled cells. After intramuscular administration, up to 10(8) SPIO-labeled cells were readily identifiable in vivo for at least 7 days using magnetic resonance imaging scanning. Using a phased-dosing study, we demonstrated that systemic delivery of up to 10(9) SPIO-labeled cells in humans is safe, and cells accumulating in the reticuloendothelial system were detectable on clinical magnetic resonance imaging. In a healthy volunteer model, a focus of cutaneous inflammation was induced in the thigh by intradermal injection of tuberculin. Intravenously delivered SPIO-labeled cells tracked to the inflamed skin and were detectable on magnetic resonance imaging. Prussian blue staining of skin biopsies confirmed iron-laden cells in the inflamed skin.

Conclusions: Human peripheral blood mononuclear cells can be labeled with SPIO without affecting their viability or function. SPIO labeling for magnetic resonance cell tracking is a safe and feasible technique that has major potential for a range of cardiovascular applications including monitoring of cell therapies and tracking of inflammatory cells. Clinical Trial Registration- URL: http://www.clinicaltrials.gov; Unique identifier: NCT00972946, NCT01169935.
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http://dx.doi.org/10.1161/CIRCIMAGING.112.972596DOI Listing
July 2012

Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease.

J Clin Oncol 2010 Aug 12;28(23):3701-8. Epub 2010 Jul 12.

Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA.

Purpose: Interleukin-6 (IL-6) has emerged as a key factor in the pathogenesis of the atypical lymphoproliferative disorder Castleman's disease (CD). Siltuximab is a new anti-IL-6, chimeric monoclonal antibody with potential therapeutic benefit in patients with CD.

Methods: We report interim results from an open-label, dose-finding, seven-cohort, phase I study in which patients with symptomatic, multicentric or unresectable, unicentric CD received siltuximab at 1-, 2-, or 3-week intervals. The main efficacy end point of clinical benefit response (CBR) was defined as a composite of clinical and laboratory measures relevant to the management of CD. In addition, radiologic response was independently assessed by using modified Cheson criteria.

Results: Eighteen (78%) of 23 patients (95% CI, 56% to 93%) achieved CBR, and 12 patients (52%) demonstrated objective tumor response. All 11 patients (95% CI, 72% to 100%) treated with the highest dose of 12 mg/kg achieved CBR, and eight patients (73%) achieved objective tumor response. Overall objective-response duration ranged from 44 to > or = 889 days, and one patient had complete response for > or = 318 days. Hemoglobin increased markedly in 19 patients (median increase, 2.1 g/dL; range, 0.2 to 4.7 g/dL) in the absence of transfusion or erythropoiesis-stimulating agents. No dose-limiting toxicity was reported, and only three patients had grade 3 or higher adverse events after a median exposure of 331 days (range, 1 to 1,148 days).

Conclusion: These interim results strongly suggest that siltuximab is an effective treatment with favorable safety for the management of CD. An additional study is planned to fully evaluate safety and efficacy at the recommended dose of 12 mg/kg every 3 weeks.
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http://dx.doi.org/10.1200/JCO.2009.27.2377DOI Listing
August 2010

Smoking cessation in pregnancy: why, how, and what next...

Clin Obstet Gynecol 2008 Jun;51(2):419-35

Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon, USA.

Smoking cessation in pregnancy has been shown to reduce low birth weight, preterm birth, and infant morbidities. The effectiveness and safety profile of current cessation approaches in pregnancy are presented. The highest cessation rates are associated with counseling and behavioral interventions. Further studies are needed to evaluate the safety and efficacy of pharmacotherapy in pregnancy including nicotine replacement therapy, bupropion and the recently approved drug Varenicline. The risks and benefits of nicotine replacement therapy in heavy smokers and bupropion are discussed. Data on fetal risk are not yet available for Varenicline.
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http://dx.doi.org/10.1097/GRF.0b013e31816fe9e9DOI Listing
June 2008

Prolonged haematological toxicity from the hyper-CVAD regimen: manifestations, frequency, and natural history in a cohort of 125 consecutive patients.

Ann Hematol 2008 Sep 10;87(9):727-34. Epub 2008 Apr 10.

Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St, Victoria 8006, Australia.

The hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (hyper-CVAD) regimen has impressive efficacy in several haematological malignancies but is associated with considerable short-term haematological toxicity. Secondary myelodysplasia (MDS) or acute myeloid leukaemia (AML) also occurs. In this retrospective study, we also describe other prolonged haematological sequelae of this regimen. One hundred and twenty-five patients were treated with a median of six hyper-CVAD cycles and followed for a median of 28 months. Follow-up for cytopenias was censored at the next cytotoxic therapy. At 3 months post-therapy, 77 patients were evaluable. Cytopenias persisted in 59% of patients. Requirement for dose attenuation was the only factor significantly associated with persisting cytopenias (p<0.05). The median time to normalisation of counts for those with post-treatment cytopenias in the respective lineages was 9 months (range, 6-12) for anaemia, 6 months (range, 6-30) for neutropenia and 9 months (range, 6-30) for thrombocytopenia. MDS/AML was diagnosed in four patients at 4, 21, 24 and 37 months after therapy with a cumulative incidence rate of 4.43% at 4 years. These results indicate a considerable rate of prolonged haematological toxicity after hyper-CVAD and a modest rate of MDS at this limited follow-up. These findings likely reflect cumulative damage to haematopoietic stem cells.
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http://dx.doi.org/10.1007/s00277-008-0488-6DOI Listing
September 2008

The effects of vasopressin injection on uterine artery blood flow during dilation and evacuation.

Am J Obstet Gynecol 2007 May;196(5):e38-9

Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR 97239, USA.

Objective: This study was undertaken to determine whether vasopressin decreases uterine artery blood flow and blood loss in early second-trimester surgical abortions (dilation and evacuation).

Study Design: Randomized, double blind, placebo-controlled trial of a saline paracervical block with or without vasopressin before dilation and evacuation. Uterine artery pulsatility index and blood loss were measured.

Results: Demographics were similar in both groups (mean gestational age 16.8 weeks, SD 1.7). Of 35 randomly assigned patients, Doppler waveforms were adequate in 28 patients (vasopressin, n = 13; placebo, n = 15). The mean difference in uterine artery pulsatility index before and after injection between groups was not significantly different (P = .14). Procedural blood loss was no different.

Conclusion: Paracervical vasopressin compared to placebo injection did not result in significant changes in uterine artery pulsatility index in early second-trimester dilation and evacuation procedures.
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http://dx.doi.org/10.1016/j.ajog.2006.10.389DOI Listing
May 2007

Amniocentesis results and novel proteomic analysis in a case of occult candidal chorioamnionitis.

J Matern Fetal Neonatal Med 2006 Oct;19(10):667-70

Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA.

We report a case of subclinical Candida albicans chorioamnionitis with mid-trimester cervical dilation diagnosed by amniotic fluid culture and Gram stain. Proteomic analysis of amniotic fluid demonstrated protein biomarkers previously associated only with bacterial intra-amniotic infections. We hypothesize that since amniotic fluid culture of yeast may take days, novel tests such as proteomic profiling may lead to the development of rapid diagnostic tests for fungal intra-amniotic infections.
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http://dx.doi.org/10.1080/14767050600738289DOI Listing
October 2006

Safety and efficacy of pegfilgrastim compared to granulocyte colony stimulating factor (G-CSF) supporting a dose-intensive, rapidly cycling anti-metabolite containing chemotherapy regimen (Hyper-CVAD) for lymphoid malignancy.

Leuk Lymphoma 2006 Sep;47(9):1813-7

Department of Haematology, School of Medicine, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, Australia 4102.

Pegfilgrastim (Neulasta) has proven efficacy as supportive therapy in a variety of 21-day chemotherapy regimens, but has not been studied in dose intensive, rapidly cycling regimens utilising cell-cycle active drugs (e.g. anti-metabolites) such as hyper-CVAD. This study examined whether pegfilgrastim was safe and lead to similar kinetics of neutrophil recovery as daily granulocyte colony stimulating factor (G-CSF). Using retrospective analysis, patients receiving pegfilgrastim (6 mg) were matched with controls (G-CSF 5 microg kg-1 per day) for a cycle of chemotherapy, prior chemotherapy, dose of cytarabine received, age (<60 or >60 years), diagnosis and bone marrow involvement. The primary endpoint was duration of grade IV neutropenia (absolute neutrophil count, ANC < 500 microl-1). Secondary endpoints included time to neutrophil recovery, incidence of febrile neutropenia, positive blood cultures and delay in subsequent chemotherapy. This study identified 124 pegfilgrastim supported cycles in 43 patients and successfully matched them to 124 G-CSF supported cycles from 38 patients treated between January 1999 and July 2005. There were no significant differences between pegfilgrastim and G-CSF groups in baseline or treatment-related variables. The median duration of grade IV neutropenia was 4 days in both groups (P = 0.55). Time to neutrophil recovery, incidence of febrile neutropenia, positive blood cultures and delay in subsequent chemotherapy were similar in both groups. Once per cycle dosing of pegfilgrastim appears safe and as effective as daily G-CSF for supporting the hyper-CVAD chemotherapy regimen.
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http://dx.doi.org/10.1080/10428190600632832DOI Listing
September 2006

Translocation (X;20) involving the inactive X chromosome in a patient with myeloproliferative disorder.

Cancer Genet Cytogenet 2005 Apr;158(1):81-3

Department of Haematology, Royal Perth Hospital, GPO Box X2213, Perth, Western Australia 6847.

We report a patient with an unclassifiable myeloproliferative disorder and the rare t(X;20)(q13;q13.3) as the sole cytogenetic abnormality. The breakpoint on Xq is consistent with other reports of translocations involving the X chromosome with breakpoints that cluster to Xq13 and association with myeloid disorders. Late replication studies demonstrated the inactive X chromosome was involved in this translocation. The critical event in patients with myeloproliferative disease and deletion of 20q appears to be the loss of tumor suppressor genes. This may also be the mechanism in this patient with a potential cryptic deletion associated with the translocation. Alternatively, spreading of X inactivation into the derivative chromosome 20 provides a second mechanism for the loss of function of tumor suppressor genes on 20q. The finding in this patient of t(X;20) together with three others reported in the literature indicates that this may represent a primary non-random abnormality associated with myeloid malignancy, which may take on clinical significance with the accumulation of more cases.
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http://dx.doi.org/10.1016/j.cancergencyto.2004.08.029DOI Listing
April 2005

Recurrent palmar-plantar erythrodysaesthesia following high-dose cytarabine treatment for acute lymphoblastic leukemia.

Eur J Haematol 2002 Nov-Dec;69(5-6):315-7

Royal Perth Hospital, Perth, Western Australia, Australia.

Palmar-plantar erythrodysaesthesia (PPE) is an uncommon cutaneous complication of cytotoxic chemotherapy which generally presents as a painful erythema involving the palms and soles. It has been suggested that PPE caused by cytarabine does not recur with subsequent cytarabine re-challenge. We report a patient with recurrent, increasingly severe episodes of PPE, ultimately complicated by a severe bullous eruption, following successive cycles of high-dose cytarabine for the treatment of acute lymphoblastic leukaemia. Contrary to previous recommendations, our experience cautions against the further use of high-dose cytarabine in patients who develop PPE, and is a timely reminder of the potential toxicity of this agent, which is now increasingly being used as first-line treatment in the management of haematologic malignancies.
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http://dx.doi.org/10.1034/j.1600-0609.2002.02834.xDOI Listing
March 2003

Differential half-maximal effects of human insulin and its analogs for in situ glucose transport and protein synthesis in rat soleus muscle.

Metabolism 2002 Aug;51(8):1065-70

Department of Biochemistry and Molecular Biophysics, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA.

Analogs of human insulin have been used to discriminate between responses of metabolic and mitogenic (growth-related) pathways. This study compared the stimulatory effects of human insulin (HI) and 2 analogs (X2, B-Asp(9), B-Glu(27) and H2, A-His(8),B-His(4),B-Glu(10), B-His(27)) on glucose uptake and protein synthesis in rat soleus muscle in situ. Glucose uptake, estimated by intramuscular (IM) injection of 2-deoxy[1,2-3H]glucose with or without insulin, was maximally increased at 10(-6) mol/L for HI and X2 and 10(-7) mol/L for H2. HI had a larger effect (318%) than either X2 (156%) or H2 (124%). The half-maximal effect (ED(50)) values for HI, X2, and H2 were 3.3 x10(-8) mol/L, 1.7 x 10(-7) mol/L, and 1.6 x 10(-9) mol/L, respectively. Protein synthesis, estimated by protein incorporation of [(3)H]phenylalanine injected into muscles with or without insulin, was maximally increased at 10(-5) mol/L for HI and 10(-6) for X2 and H2. HI had a larger effect in stimulating protein synthesis (34%) than either X2 (25%) or H2 (19.8%). The ED(50) values for HI, X2, and H2 were 3.0 x 10(-7) mol/L, 3.2 x 10(-7) mol/L, and 1.0 x 10(-9) mol/L, respectively. The biological potency of each analog (ED(50)insulin/ED(50)analog) showed X2 to be less potent than HI for both glucose uptake (0.2) and protein synthesis (0.9), whereas H2 is more potent than HI with ratios of 20 and 300, respectively. These data suggest that this approach for studying insulin responsiveness in a single muscle in situ may be a useful tool for investigating insulin signaling in muscle in vivo.
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http://dx.doi.org/10.1053/meta.2002.34044DOI Listing
August 2002