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Pioglitazone improves endothelial function in non-diabetic patients with coronary artery disease

Staniloae, C; Mandadi, V; Kurian, D; Coppola, J; Bernaski, E; El-Khally, Z; Morlote, M; Pinassi, E; Ambrose, J
OBJECTIVE: To test the hypothesis that pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, will improve endothelial function in non-diabetic subjects with coronary artery disease, we conducted a prospective study to evaluate the effect of this medication on the brachial artery vasomotor function and circulating markers of endothelial activation. METHODS: Baseline characteristics were collected. After initial endothelial function assessment, patients were treated with pioglitazone hydrochloride 30 mg daily. The medication was continued for 12 weeks and endothelial function was reassessed as well as the inflammatory markers. The study medication then was stopped, and all the tests were repeated 12 weeks later. RESULTS: Seventeen subjects completed all three-study phases. Mean age was 58 (range: 36-77 years). Compared with the baseline, the endothelium-dependent vasodilation improved significantly with the treatment (p < 0.001) from 4.4 +/- 3.9 to 8.4 +/- 4.1%, a relative increase of 91%. After withdrawal of treatment, the endothelium-dependent vasodilation returned towards baseline values. There was no change in endothelium-independent vasodilatation (12.27 +/- 6.35 to 13.9 +/- 9.23%, to 12.42 +/- 5.35%, p = 0.177). The urine asymmetric dimethlyarginine levels decreased significantly with the treatment, but also returned to the initial values after the wash-out period (1.27 +/- 0.5 micromol/ml to 0.97 +/- 0.3 micromol/ml to 1.34 +/- 0.5 micromol/ml, p = 0.017). No difference in the lipid profile, C-reactive protein, erythrocyte sedimentation rate, or fibrinogen levels was seen. CONCLUSION: Pioglitazone rapidly improves endothelial function in non-diabetic patients with coronary artery disease. This improvement is associated with a change in mean urinary asymmetric dimethylarginine levels, although a cause and effect cannot be determined from this investigation.
PMID: 17077630
ISSN: 1421-9751
CID: 2060872

Value of low-dose dobutamine addition to routine dual isotope gated SPECT myocardial imaging in patients with healed myocardial infarction or abnormal wall thickening by echocardiogram

Heiba, Sherif I; Abdel-Dayem, Hussein M; Gould, Randy; Bernaski, Edward; Morlote, Manuel; El-Zeftawy, Hossam; Ambrose, John A
There is overlap in myocardial viability detection by thallium-201 uptake and contractile reserve (CR) using low-dose dobutamine (LDD). The dual isotope protocol was modified in this study by acquiring thallium-201 images using LDD to enhance viability detection in addition to coronary flow reserve assessment. One hundred twenty-four patients with coronary disease underwent gated single-photon emission computed tomographic thallium-201 imaging at rest with LDD (10 microg/kg/min) during acquisition followed by stress technetium-99m sestamibi myocardial perfusion (MP) imaging with dobutamine, adenosine, or treadmill exercise. F-18-fluorodeoxyglucose (FDG) positron emission tomography was obtained in 41 patients. Myocardial perfusion (MP) imaging was divided into normal, fixed, and ischemic segments, and subclassified by wall motion and/or thickening changes between 1-hour poststress and LDD into normal, fixed, or improved dysfunctional segments (CR present). Mean left ventricular ejection fraction was 39% at 1 hour after stress and 47% with LDD (p <0.001). In dysfunctional myocardium, CR was significantly higher (p <0.001) in ischemic (233 of 368) and fixed segments (150 of 335) than in normal MP segments (43 of 220). Combined MP and CR analysis showed higher accuracy and negative predictive value in identifying FDG-viable myocardium than either method alone, whereas a high positive predictive value was maintained, similar to both markers. Quantitative analysis showed significant increased wall motion and thickening with LDD compared with 1 hour after stress, which was highest in ischemic segments and lowest in fixed segments. Thus, LDD dual isotope is a practical protocol that improves viability detection by simultaneous MP and CR analysis in addition to coronary flow reserve assessment in 1 study. Moreover, it requires no extra imaging time or radioactivity than the routine protocol.
PMID: 14759378
ISSN: 0002-9149
CID: 160173

Failure of gastric emptying and charcoal administration in fatal sustained-release theophylline overdose: pharmacobezoar formation [Case Report]

Bernstein G; Jehle D; Bernaski E; Braen GR
We report the case of a fatal theophylline overdose from a sustained-release preparation in a 54-year-old woman. Initial serum theophylline concentration was 31.3 mg/L. Manifestations of mild toxicity cleared in the emergency department after treatment with gastric lavage, charcoal, and a cathartic. A life-threatening overdose was not suspected, and the patient arrested eight hours after discharge from the ED. At autopsy, her serum theophylline concentration was 190.1 mg/L. A white, waxy mass weighing 318.8 g and containing 29 g theophylline, representing the residue of many sustained-release tablets, was found in her stomach. This case reinforces the importance of obtaining repeat serum theophylline levels in patients with sustained-release theophylline overdose. Gastric pharmacobezoar formation should be considered in cases of sustained-release theophylline overdose with rising theophylline levels and patient deterioration, despite adequate gut decontamination
PMID: 1416337
ISSN: 0196-0644
CID: 37965