Laura A. Coleman

Brighton and Hove City Council

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Edward A. Belongia

Marshfield Clinic

Maria E. Sundaram

Marshfield Clinic

David K. Shay

National Center for Immunization and Respiratory Diseases

Jennifer K. Meece

Marshfield Clinic

Ronenn Roubenoff

Novartis (Switzerland)

Sarah Spencer

Henry M. Jackson Foundation

H. Keipp Talbot

Vanderbilt University Medical Center

Marie R. Griffin

Vanderbilt University

Lawrence H. Kushi

Kaiser Permanente

Gwen Alexander

Henry Ford Health System

Cooperative Institutions

Center for Rheumatology

Harvard University

Centers for Disease Control and Prevention

Brigham and Women's Hospital

National Center for Immunization and Respiratory Diseases

National Institutes of Health

University of Michigan–Ann Arbor

University of Western Australia

Massachusetts General Hospital

Johns Hopkins University

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Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice

AJP Heart and Circulatory Physiology (2008)

Yanli Song Laura A. Coleman Jianru Shi Hideyuki Beppu Kazuki Sato

Heterozygous bone morphogenetic protein receptor-II-knockout (BMPR2(+/-)) mice have a similar genetic trait like that in some idiopathic pulmonary arterial hypertension patients. To examine the effect of pulmonary endothelial injury in BMPR2(+/-) mice, we challenged the mice with two injections of monocrotaline combined with intratracheal instillation of replication-deficient adenovirus expressing 5-lipoxygenase (MCT+Ad5LO). After the challenge (1 wk), BMPR2(+/-) mice exhibited a doubling of right ventricular systolic pressure that was greater than that of wild-type mice and remained elevated for 3 wk before heart failure developed. Muscularization and thickening of small pulmonary arterioles was evident in the BMPR2(+/-) lungs at 2 wk after the challenge and became severe at 3 wk. Marked perivascular infiltration of T cells, B cells, and macrophages was associated with the remodeled vessels. Real-time PCR analysis showed that the expression of six endothelial cell markers in lung tissue was decreased to 20-40% of original levels at 1 wk after the challenge in both BMPR2(+/-) and wild-type mice and largely recovered in wild-type (50-80%) but not BMPR2(+/-) lungs (30-50%) at 3 wk after the challenge. Macrophage inflammatory protein-1alpha and fractalkine receptor expression doubled in BMPR2(+/-) compared with wild-type lungs. Expression of type I and type II BMP receptors, but not transforming growth factor-beta receptors, in the challenged BMPR2(+/-) and wild-type lungs showed a similar pattern of expression as that of endothelial markers. Apoptotic responses at 1 wk after MCT and Ad5LO challenge were also significantly greater in the BMPR2(+/-) lungs than the wild-type lungs. These data show that BMPR2(+/-) mice are more sensitive to MCT+Ad5LO-induced pulmonary hypertension than wild-type mice. Greater endothelial injury and an enhanced inflammatory response could be the underlying causes of the sensitivity and may work in concert with BMPR2 heterozygosity to promote the development of persistent pulmonary hypertension.

BMPR2

Wild type

10.1152/ajpheart.91519.2007

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Citations (96)

Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity

JAMA Network Open (2021)

Steven B. Heymsfield Laura A. Coleman Ram R. Miller Daniel Rooks Didier Laurent

Importance

Antibody blockade of activin type II receptor (ActRII) signaling stimulates skeletal muscle growth. Previous clinical studies suggest that ActRII inhibition with the monoclonal antibody bimagrumab also promotes excess adipose tissue loss and improves insulin resistance.

Objective

To evaluate the efficacy and safety of bimagrumab on body composition and glycemic control in adults with type 2 diabetes and overweight and obesity.

Design, Setting, and Participants

This double-masked, placebo-controlled, 48-week, phase 2 randomized clinical trial was conducted among adults with type 2 diabetes, body mass index between 28 and 40, and glycated hemoglobin (HbA_1c) levels between 6.5% and 10.0% at 9 US and UK sites. The trial was conducted from February 2017 to May 2019. Only participants who completed a full treatment regimen were included in analysis.

Interventions

Patients were randomized to intravenous infusion of bimagrumab (10 mg/kg up to 1200 mg in 5% dextrose solution) or placebo (5% dextrose solution) treatment every 4 weeks for 48 weeks; both groups received diet and exercise counseling.

Main Outcomes and Measures

The primary end point was least square mean change from baseline to week 48 in total body fat mass (FM); secondary and exploratory end points were lean mass (LM), waist circumference (WC), HbA_1clevel, and body weight (BW) changes from baseline to week 48.

Results

A total of 75 patients were randomized to bimagrumab (n = 37; 23 [62.2%] women) or placebo (n = 38; 12 [31.6%] women); 58 (77.3%) completed the 48-week study. Patients at baseline had a mean (SD) age of 60.4 (7.7) years; mean (SD) BMI of 32.9 (3.4); mean (SD) BW of 93.6 (14.9) kg; mean (SD) FM of 35.4 (7.5) kg; and mean (SD) HbA_1clevel of 7.8% (1.0%). Changes at week 48 for bimagrumab vs placebo were as follows: FM, −20.5% (−7.5 kg [80% CI, −8.3 to −6.6 kg]) vs −0.5% (−0.18 kg [80% CI, −0.99 to 0.63 kg]) (P < .001); LM, 3.6% (1.70 kg [80% CI, 1.1 to 2.3 kg]) vs −0.8% (−0.4 kg [80% CI, −1.0 to 0.1 kg]) (P < .001); WC, −9.0 cm (80% CI, −10.3 to −7.7 cm) vs 0.5 cm (80% CI, −0.8 to 1.7 cm) (P < .001); HbA_1clevel, −0.76 percentage points (80% CI, −1.05 to −0.48 percentage points) vs 0.04 percentage points (80% CI, −0.23 to 0.31 percentage points) (P = .005); and BW, −6.5% (−5.9 kg [80% CI, −7.1 to −4.7 kg]) vs −0.8% (−0.8 kg [80% CI, −1.9 to 0.3 kg]) (P < .001). Bimagrumab’s safety and tolerability profile was consistent with prior studies.

Conclusions and Relevance

In this phase 2 randomized clinical trial, ActRII blockade with bimagrumab led to significant loss of FM, gain in LM, and metabolic improvements during 48 weeks in patients with overweight or obesity who had type 2 diabetes. ActRII pathway inhibition may provide a novel approach for the pharmacologic management of excess adiposity and accompanying metabolic disturbances.

Trial Registration

ClinicalTrials.gov number:NCT03005288

Clinical endpoint

Glycated hemoglobin

10.1001/jamanetworkopen.2020.33457

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The Marshfield Youth Health Study: design, objectives and cohort characteristics.

Laura A. Coleman Bickol N. Mukesh Po‐Huang Chyou Charles S McCauley James Thompson

PROBLEM The Marshfield Youth (MY) Health Study was designed to identify parental and infant factors associated with childhood and adolescent overweight. METHODS The study examined 867 children (age 5-17 years) from the Marshfield Public Schools. Heights and weights were measured by standard methods. Age- and gender-specific body mass index (BMI) percentiles and z-scores were determined. Definitions of overweight from the Centers for Disease Control and Prevention were applied. Family characteristics were self-reported by questionnaire and included parents' BMI, employment, education, smoking, physical activity; and child's daycare attendance, and television/computer use. Maternal and child medical records were reviewed. RESULTS The MY Health cohort included 361 families. The mean +/- SD age of the children was 12.1 +/- 3.0 yrs; 511 (59%) were born in Marshfield, Wis. Of the children studied, 70% had a healthy body weight (BMI >5th and or = 85th and or = 95th percentile). There were no differences in gender or weight status between the study cohort and all Marshfield school children (n=2782). CONCLUSIONS Children in the MY Health Study are representative of all school-age children in Marshfield. This cohort will be studied to identify factors associated with overweight among children.

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Adolescent Health

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Comparison of response rates, intake estimates, and preferences between the National Cancer Institute’s Automated Self‐Administered 24‐Hour Recall and interviewer‐administered Automated Multiple Pass Method recalls (36.7)

The FASEB Journal (2014)

Amy F. Subar Sujata Dixit‐Joshi Nancy Potischman Sharon I. Kirkpatrick Gwen Alexander

Objective: To compare response rates, intake estimates, and preferences between ASA24 and interviewer‐administered AMPM recalls. Methods: About 1200 participants were recruited from three integrated health systems using quota sampling to ensure representation of a range of ages and race/ethnicity groups. Participants were asked to complete two 24HRs, 4‐7 weeks apart, and randomized into four study groups: 1) two ASA24s; 2) two AMPMs; 3) ASA24 first and AMPM second; and 4) AMPM first and ASA24 second. Results: Almost all enrolled participants (95%) completed at least one recall and 80% completed two; response rates did not differ by recall mode. Estimated intakes of energy, nutrients and food groups were comparable for ASA24 and AMPM; for example, energy, 2132 vs. 2126 kcal; fat, 84.9 vs. 82.8 g; saturated fat, 27.9 vs. 26.9 g; fiber, 18.4 vs. 18.4 g; and fruits and vegetables, 3.0 vs. 3.1 cup equivalents. Of participants completing one ASA24 and one AMPM, a greater percentage overall and by sex and site preferred ASA24. Discussion: These findings show that ASA24 performs well relative to AMPM recalls. ASA24 offers significant savings over interviewer‐administered recalls, is publicly available from NCI at no charge, and has been used in over 800 studies to collect over 113,000 recalls, indicating its feasibility for use in large‐scale research. ASA24 is currently being updated to run on mobile applications.

Interview

Portion size

10.1096/fasebj.28.1_supplement.36.7

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Vitamin E, vitamin A, and zinc status are not related to serologic response to influenza vaccine in older adults: an observational prospective cohort study

Nutrition Research (2013)

Maria E. Sundaram Simin Nikbin Meydani Mary Vandermause David K. Shay Laura A. Coleman

Seroconversion

Trivalent influenza vaccine

10.1016/j.nutres.2013.12.004

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Partnerships in Translation: Advancing Research and Clinical Care. The 14th Annual HMO Research Network Conference, April 13-16, 2008, Minneapolis, Minnesota

Clinical Medicine & Research (2008)

Robert T. Greenlee Laura A. Coleman Andrew Nelson Joe V. Selby

The Health Maintenance Organization Research Network held its annual meeting in Minneapolis in April of 2008, with more than 300 investigators, research staff, clinical leaders, and academic partners gathering in conjunction with the conference theme 'Partnerships in Translation: Advancing Research and Clinical Care.' This article provides some background on the network, its research activities, and the annual conference. Also featured is an article by Coleman and colleagues summarizing the conference's first plenary session, where operational leaders of health care organizations discussed the optimization of health care through research. This issue of Clinical Medicine & Research also includes a selection of scientific abstracts presented at the meeting on a wide range of clinical and population health topics.

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Research center

Foundation (evidence)

10.3121/cmr.2008.842

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Abstract 5451: Deficiency of Glutathione Peroxidase-3 Promotes Platelet Activation in vivo

Circulation (2008)

Richard C. Jin Christopher E. Mahoney Laura A. Coleman Filomena G. Ottaviano Yingyi Zhang

Plasma glutathione peroxidase (GPx-3) is a selenocysteine-containing protein with antioxidant properties. GPx-3 plays an important role in plasma against oxidant stress by scavenging reactive oxygen species. A deficiency of this enzyme has been associated with platelet dependent thrombosis. We recently developed an animal model to assess platelet function in GPx-3 deficient mice. We hypothesized that GPx-3 deficiency induces platelet activation in vivo . GPx-3 (−/−) mice showed an attenuated bleeding time compared with wild-type mice (94.5 ± 28.8 s versus 153.4 ± 32.3, P<0.05). We also noted an increase in the plasma levels of soluble P-selectin, a marker of platelet activation and prothrombotic activity, in GPx-3 (−/−) mice compared with wild-type mice (137.8 ± 12.3 ng/ml plasma versus 101.5 ± 8.8, P<0.05). Cyclic GMP, a key intracellular second messenger molecule and marker for activation of soluble guanylyl cyclase by nitric oxide, was decreased in the plasma of GPx-3 (−/−) mice compared with wild-type mice (5.38 ± 1.75 pmol/ml plasma versus 23.67 ± 3.59, P<0.001), consistent with less bioactive NO in GPx-3 (−/−) mice. ADP was infused into the right ventricle of mice to induce platelet aggregation in the pulmonary vasculature; this assay resulted in higher pulmonary artery pressure in GPx-3 (−/−) compared with wild-type mice suggesting a more robust platelet activation response in the GPx-3 (−/−) mice. To confirm this interpretation, histological sections from the pulmonary vasculature of GPx-3 (−/−) compared with wild-type mice showed increased thrombi per 7.5 mm 2 section normalized to wild-type mice based on staining intensity for P-selectin (1.7 ± 0.4 versus 1.0 ± 0.1, P<0.001), as well as a higher percentage of occluded vessels (0.82 ± 0.16 % versus 0.54 ± 0.21, P<0.05). These findings demonstrate that GPx-3 deficiency causes platelet activation resulting in a prothrombotic state. These data illustrate the importance of this plasma antioxidant enzyme in regulating platelet activity and platelet-dependent thrombosis.

GPX1

10.1161/circ.118.suppl_18.s_552

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Partnering Care Delivery and Research to Optimize Health

Clinical Medicine & Research (2008)

Laura A. Coleman Thomas E. Kottke Bryan D. Rank Douglas J. Reding Mark J. Selna

Laura A. Coleman, PhD, Thomas E. Kottke, MD, MSPH, Brian Rank, MD, Douglas J. Reding, MD, MPH, Mark Selna, MD, George J. Isham, MD, MS, Andrew F. Nelson, MPH and Robert T. Greenlee, PhD, MPH Laura A. Coleman, PhD, Epidemiology Research Center, Marshfield Clinic Research Foundation, Marshfield, Wisconsin 54449 Thomas E. Kottke, MD, MSPH, HealthPartners Research Foundation, Minneapolis, Minnesota 55440 Brian Rank, MD, HealthPartners Medical Group & Clinics, Minneapolis, Minnesota 55440 Douglas J. Reding, MD, MPH, Department of Hematology/Oncology, Marshfield Clinic, Marshfield, Wisconsin 54449 Mark Selna, MD, Geisinger Health System, Danville, Pennsylvania 17821 George J. Isham, MD, MS, HealthPartners, Minneapolis, Minnesota 55440 Andrew F. Nelson, MPH, HealthPartners Research Foundation, Minneapolis, Minnesota 55440 Robert T. Greenlee, PhD, MPH, Epidemiology Research Center, Marshfield Clinic Research Foundation, Marshfield, Wisconsin 54449 Reprint Requests: Laura Coleman, PhD, Epidemiology Research Center, Marshfield Clinic Research Foundation, 1000 North Oak Avenue, ML2, Marshfield, WI 54449, Tel: 715-389-3350, Fax: 715-389-3880, coleman.laura{at}mcrf.mfldclin.edu

Health care delivery

Health Care Delivery

Value (mathematics)

10.3121/cmr.2008.843

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Influence of Vitamins E and B₆ on Immune Response

Annals of the New York Academy of Sciences (1992)

Simin Nikbin Meydani Michael Hayek Laura A. Coleman

Annals

10.1111/j.1749-6632.1992.tb17094.x

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GPs have key role in early diagnosis of endometriosis.

PubMed (2015)

Laura A. Coleman Caroline Overton

Endometriosis is defined as the presence of endometrial-like tissue outside the uterus. Deposits are commonly distributed on the ovaries, uterosacral ligaments, pouch of Douglas, rectum and sigmoid colon, bladder and ureter. Endometriosis is common, affecting 10% of the female adult population and up to 50% of women with infertility. Risk factors include early menarche, late menopause, delayed childbearing, vaginal outflow obstruction and a first-degree relative affected. Women commonly present to their GP with pelvic pain, painful intercourse or subfertility. Classically the pain starts several days before the period which is extremely painful. After the period, symptoms tend to improve until mid-cycle when the pattern repeats again. Patients also complain of fatigue. Abdominal palpation, bimanual and speculum examination are important to identify signs of endometriosis, but also to exclude alternative diagnoses such as fibroid uterus, infection or pregnancy. However, a normal examination does not exclude a diagnosis of endometriosis. Serum CA125 can be raised in endometriosis but is not specific or sensitive for the condition and is therefore not recommended as a screening test. A normal pelvic ultrasound scan does not exclude a diagnosis of endometriosis. The gold standard investigation for endometriosis is laparoscopy and biopsy with histological confirmation. Referral should be considered if pain is not controlled with simple analgesia or the diagnosis is suspected in a woman who is actively trying to conceive. Early referral should be considered in women with abnormal examination findings, or an abnormal ultrasound result.

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Pelvic examination

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