0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
ARTICLE |

The Metabolic Effects of Platelet-Activating Factor Antagonism in Endotoxemic Man

William A. Thompson, MD; Susette Coyle, RN; Kimberly Van Zee, MD; Hester Oldenburg, MD; Rhonda Trousdale; Michael Rogy, MD; Diane Felsen, PhD; Lyle Moldawer, PhD; Stephen F. Lowry, MD
Arch Surg. 1994;129(1):72-79. doi:10.1001/archsurg.1994.01420250084011.
Text Size: A A A
Published online

Objective:  To determine if the inflammatory phospholipid platelet-activating factor (PAF) participated in the symptomatologic, metabolic, and counterregulatory hormonal responses of human endotoxemia.

Design:  In a double-blind, placebo-controlled study, five subjects received 10 mg of the PAF antagonist Ro 24-4736 orally, while five control subjects received a placebo. Eighteen hours later, all subjects were administered 4 ng/kg of endotoxin (lipopolysaccharide) intravenously.

Setting:  The Clinical Research Center of The New York Hospital—Cornell Medical Center.

Participants:  Healthy male volunteers.

Main Outcome Measures:  Repeated measurements of vital signs, symptoms, cytokine and hormone levels, resting energy expenditure, platelet aggregation, and bleeding times were performed during a 24-hour period.

Results:  Subjects who were pretreated with the PAF antagonist experienced fewer symptoms, including rigors at 1 hour (P<.05) and myalgias at 1 through 4 hours (P<.05) after administration of lipopolysaccharide. This was in concert with a diminished peak cortisol level (668±107 vs 959± 159 nmol/L in controls; P<.05), epinephrine secretion (1057±165 vs 2029±431 nmol/L in controls; P<.05), and almost complete inhibition of PAF-induced platelet aggregation ex vivo.

Conclusions:  These findings in the face of unaltered circulating cytokines tumor necrosis factor α, interleukin 1β, and interleukin 6, as well as the tumor necrosis factor receptor-I s, suggest that PAF may influence some endotoxin-induced, counterregulatory hormonal responses and symptoms through cytokine-independent mechanisms. This study further supports the role of PAF antagonists as an adjunct to cytokine blockade in the treatment of gram-negative sepsis.(Arch Surg. 1994;129:72-79)

Topics

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

First Page Preview

View Large
First page PDF preview

Figures

Tables

References

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

Customize your page view by dragging & repositioning the boxes below.

Jobs
brightcove.createExperiences();