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Lower-Extremity Edema Associated with Gene Transfer of Naked DNA Encoding Vascular Endothelial Growth Factor

Iris Baumgartner, MD; Guenter Rauh, MD; Ann Pieczek, RN; Debra Wuensch, RN; Meredith Magner, BA; Marianne Kearney, BS; Robert Schainfeld, DO; and Jeffrey M. Isner, MD
[+] Article and Author Information

From St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts.


Grant Support: In part by an Academic Award in Vascular Medicine (HL 02824) and grants HL53354 and HL57516 from the National Institutes of Health, Bethesda, Maryland, and by the E.L. Weigand Foundation, Reno, Nevada. Dr. Baumgartner is the recipient of a Swiss National Science Foundation grant. Dr. Rauh is the recipient of a German Humboldt Foundation grant.

Requests for Single Reprints: Jeffrey M. Isner, MD, St. Elizabeth's Medical Center of Boston, 736 Cambridge Street, Boston, MA 02135; e-mail, jisner@opal.tufts.edu.

Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints@mail.acponline.org.

Current Author Addresses: Dr. Baumgartner: University Freiburgstrasse, 3010 Berne, Switzerland.

Dr. Rauh, Ms. Pieczek, Ms. Wuensch, Ms. Magner, Ms. Kearney, Dr. Schainfeld, and Dr. Isner: St. Elizabeth's Medical Center of Boston, 736 Cambridge Street, Boston, MA 02135.

Author Contributions: Conception and design: J.M. Isner.

Analysis and interpretation of the data: I. Baumgartner, G. Rauh, R. Schainfeld, J.M. Isner.

Drafting of the article: I. Baumgartner, G. Rauh.

Critical revision of the article for important intellectual content: A. Pieczek, D. Wuensch, M. Magner, M. Kearney, R. Schainfeld, J.M. Isner.

Final approval of the article: A. Pieczek, D. Wuensch, M. Magner, M. Kearney, R. Schainfeld, J.M. Isner.

Administrative, technical, or logistic support: A. Pieczek, D. Wuensch, M. Magner, M. Kearney, J.M. Isner.

Collection and assembly of data: A. Pieczek, D. Wuensch, M. Magner, M. Kearney.


Ann Intern Med. 2000;132(11):880-884. doi:10.7326/0003-4819-132-11-200006060-00005
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Background: Vascular endothelial growth factor (VEGF) promotes angiogenesis and vascular permeability. The extent to which VEGF may cause tissue edema in humans has not been established.

Objective: To evaluate patients undergoing VEGF gene transfer for evidence of lower-extremity edema.

Design: Prospective consecutive case series.

Setting: Hospital outpatient clinic.

Patients: 62 patients with critical limb ischemia and 28 patients with claudication.

Intervention: Gene transfer of VEGF DNA.

Measurements: Semiquantitative analysis of lower-extremity edema.

Results: Lower-extremity edema was observed in 31 of 90 (34%) patients. Edema was less common in patients with claudication than in those with pain at rest (P = 0.016) or ischemic ulcers (P < 0.001), and it was less common in patients with pain at rest than in those with ischemic ulcers (P = 0.017). Treatment was typically limited to a brief course of oral diuretics.

Conclusions: Vascular endothelial growth factor may enhance vascular permeability in humans. At the doses of plasmid DNA used in this study, lower-extremity edema responded to oral diuretic therapy and did not seem to be associated with serious sequelae.

Figures

Grahic Jump Location
Figure.
Representative examples of lower-extremity edema (asterisks) according to clinical grade in four patients who underwent intramuscular gene transfer of naked plasmid DNA encoding vascular endothelial growth factor.

The extent and distribution of edema were unrelated to the sites of injection. For explanation of grades, see text.

Grahic Jump Location

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Summary for Patients

Leg Swelling after Gene Therapy for Peripheral Vascular Disease

The summary below is from the full report titled “Lower-Extremity Edema Associated with Gene Transfer of Naked DNA Encoding Vascular Endothelial Growth Factor.” It is in the 6 June 2000 issue of Annals of Internal Medicine (volume 132, pages 880-884). The authors are I. Baumgartner, G. Rauh, A. Pieczek, D. Wuensch, M. Magner, M. Kearney, R. Schainfeld, and J.M. Isner.

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