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Biomedical subjects

A W Longmire

Publications and source records attributed to A W Longmire.

12 recordsLinked to original sources

Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage.

BACKGROUND: It has been hypothesized that the pathogenesis of diseases induced by cigarette smoking involves oxidative damage by free radicals. However, definitive evidence that smoking causes the oxidative modification of target molecules in vivo is lacking. We conducted a study to determine whether the production of F2-isoprostanes, which are novel products of lipid peroxidation, is enhanced in persons who smoke. METHODS: We measured the levels of free F2-isoprostanes in plasma, the levels of F2-isoprostanes esterified to plasma lipids, and the urinary excretion of metabolites of F2-isoprostanes in 10 smokers and 10 nonsmokers matched for age and sex. The short-term effects of smoking (three cigarettes smoked over 30 minutes) and the effects of two weeks of abstinence from smoking on levels of F2-isoprostanes in the circulation were also determined in the smokers. RESULTS: Plasma levels of free and esterified F2-isoprostanes were significantly higher in the smokers (242 +/- 147 and 574 +/- 217 pmol per liter, respectively) than in the nonsmokers (103 +/- 19 and 345 +/- 65 pmol per liter; P = 0.02 for free F2-isoprostanes and P = 0.03 for esterified F2-isoprostanes). Smoking had no short-term effects on the circulating levels of F2-isoprostanes. However, the levels of free and esterified F2-isoprostanes fell significantly after two weeks of abstinence from smoking (250 +/- 156 and 624 +/- 214 pmol per liter, respectively, before the cessation of smoking, as compared with 156 +/- 67 and 469 +/- 108 pmol per liter after two weeks' cessation; P = 0.03 for free F2-isoprostanes and P = 0.02 for esterified F2-isoprostanes). CONCLUSIONS: The increased levels of F2-isoprostanes in the circulation of persons who smoke support the hypothesis that smoking can cause the oxidative modification of important biologic molecules in vivo.

Adult↗

Effect of oxygen tension on the generation of F2-isoprostanes and malondialdehyde in peroxidizing rat liver microsomes.

Although numerous methods have been developed for the detection of lipid peroxidation, it is generally recognized that most of these lack specificity and/or sensitivity, particularly when applied to in vivo situations. We have reported recently that a series of prostaglandin F2-like compounds, termed F2-isoprostanes, are formed in vivo from the free radical catalyzed peroxidation of arachidonic acid and appear to be a useful marker of oxidant stress. Because of formation of other products of lipid peroxidation, such as alkanes and malondialdehyde (MDA), are affected by oxygen tension, which may influence their usefulness as markers of oxidant stress, we carried out a systematic study of the generation of F2-isoprostanes at various oxygen concentrations and compared these changes with the generation of MDA. The disappearance of the F2-isoprostane precursor, arachidonic acid, was used as a reference measure. Rat liver microsomes were peroxidized using an iron-ascorbate system. The incubations were carried out in sealed flasks at 37 degrees under N2 and various concentrations of O2 up to 100%. F2-isoprostanes were quantified by mass spectrometry and MDA by the thiobarbituric acid reaction. Microsomal fatty acids were measured by gas chromatography. Both MDA and F2-isoprostane formation increased in a time-dependent manner up to 15 min. Their formation correlated with a loss of polyunsaturated fatty acid and with an increase in O2 tension up to 21% O2. At oxygen tensions above 21%, MDA generation continued to increase, while F2-isoprostane generation and arachidonic acid loss did not. Levels of MDA and F2-isoprostanes increased a maximum of 65 and 9.4 times baseline values, respectively. These studies, therefore, define factors that influence the formation of F2-isoprostanes in an in vitro model of lipid peroxidation. Further, they demonstrate that higher O2 tensions do not block formation of F2-isoprostanes and validate their usefulness for assessing lipid peroxidation under high, as well as low, oxygen tension.

Animals↗

Actions of the E2-isoprostane, 8-ISO-PGE2, on the platelet thromboxane/endoperoxide receptor in humans and rats: additional evidence for the existence of a unique isoprostane receptor.

D2/E2-isoprostanes, are a recently discovered series of novel prostaglandin-like compounds that are produced in vivo as products of free radical-catalyzed peroxidation of arachidonic acid independent of the cyclooxygenase enzyme. One of the E-ring compounds expected to be produced in abundance by this mechanism, 8-iso-prostaglandin E2 (8-iso-PGE2), is a potent renal vasoconstrictor in the rat, and this effect can be abrogated by the thromboxane/endoperoxide (TxA2/PGH2) receptor antagonist SQ29548, suggesting that 8-iso-PGE2 exerts these effects by interaction with this receptor in the vasculature. Nonetheless, it has recently been suggested that 8-iso-PGE2 induces vasoconstriction by interaction with a unique receptor similar to, but distinct from, the TxA2/PGH2 receptor. Because this issue has not been resolved, we carried out studies to further examine the interaction of this compound with the TxA2/PGH2 receptor on human and rat platelets. Only at concentrations of 10(-5) M or greater did 8-iso-PGE2 induce human platelet aggregation. The aggregation was unaffected by indomethacin but was inhibited by the TxA2/PGH2 receptor antagonist SQ29548. Conversely, 8-iso-PGE2 inhibited the thromboxane receptor agonists U46619 (10(-6) M) and IBOP (3.3 x 10(-7) M) with an IC50 of 5 x 10(-7) M and 5 x 10(-6) M, respectively. 8-iso-PGE2 also inhibited platelet aggregation induced by arachidonic acid but not by ADP. Similarly in rat platelets, 8-iso-PGE2 alone.

Animals↗

Topics in clinical pharmacology: flumazenil, a benzodiazepine antagonist.

Flumazenil is a central antagonist of the sedative effects of benzodiazepines. It has been used to reverse benzodiazepine effects in conscious sedation, general anesthesia, and overdose with restoration of alertness and psychomotor function within minutes of administration. Seizures have followed the use of flumazenil. Overdose patients who have co-ingested cyclic antidepressants are especially at risk for this complication. Flumazenil is administered intravenously in small, incremental doses.

Anesthesia, General↗

The medical care of Iraqi enemy prisoners of war.

During Operation Desert Storm, Approximately 62,000 enemy prisoners of war (EPWs) were captured by allied forces. Most of these EPWs were taken during the ground war and the weeks following. Over 20,000 of these were interned at East Camp, which was located approximately 125 miles south of the Kuwaiti border. The 300th Field Hospital was tasked to provide inpatient and outpatient care to the EPWs. This paper summarizes the experience, analyzing the diseases encountered, the types of medicines needed, and the unique problems of treating non-English speaking EPWs. From January 27 to February 23, 1991, approximately 308 patients were treated. From the beginning of the ground war on February 24, through March 30, approximately 8,979 patients were treated. The most common condition seen was dental disease (24.0%). Other commonly treated conditions were upper respiratory infection (12.4%), headache (11.7%), and urinary tract infections (9.6%). The unique problems of language barriers and security requirements increased the difficulty and the time required to conduct sick call for Iraqi EPWs.

Humans↗

Morbidity of Hurricane Elena.

On Sept 2, 1985, Hurricane Elena struck the Gulf Coast of Mississippi. We conducted a retrospective review of Emergency Department logs for a one-week period before and a two-week period after the storm to determine what additional support would be needed to manage such a disaster. There was a significant increase in the number of patients treated for psychiatric problems and trauma. These findings are similar to the results obtained in a study at the same hospital after Hurricane Frederic in 1979.

Adolescent↗

Morbidity of Hurricane Frederic.

On September 12, 1979, Hurricane Frederic struck the Gulf Coasts of Mississippi and Alabama. A retrospective review of emergency department logs for a three-week period surrounding the storm was conducted to determine the amount and type of back up needed for an emergency department to cope with the results of such a disaster. There was a significant increase in the number of patients presenting to the emergency department for at least two weeks after the storm, with the greatest demand being for professionals skilled in outpatient trauma management. The nature of hurricanes is discussed, as are specific items to be considered in disaster planning for areas subjected to these storms.

Disaster Planning↗

Mechanical bull injuries: the empty saddle syndrome.

We reviewed the cases of 30 patients presenting to the emergency department over a four-month period with a total of 31 injuries suffered while riding a mechanical bull. The majority of injuries were sprains and contusions. The most severe injuries included seven fractures, one dislocation, and one fracture-dislocation. Three patients required hospitalization, including one with a compression fracture of C7. The majority (74%) of injuries involved the upper extremities.

Adult↗