Toxic agents resulting from the oxidative metabolism of steroid hormones and drugs

The oxidative metabolism of some exogenous compounds, and possibly some endogenous compounds as well, can lead to the formation of reactive metabolites. These intermediates react as electrophiles, and they lead in some instances to cell death or cell transformation. Three routes (other routes are also known) of toxicity are discussed. These are the epoxide/dihydrodiol pathway, the catechol/o-quinone pathway, and the alkylation pathway. The possible formation of electrophiles from diethylstilbestrol, from natural estrogens, and from ethynylestradiol is discussed in terms of protein binding. Protein binding is presumptive evidence of electrophile formation, but it does not necessarily indicate that the parent compound is highly cytotoxic, mutagenic, or carcinogenic. Mutagenic and carcinogenic activity is presumed to require reaction of an electrophile with nuclear material. There is evidence for protein binding for these estrogens (diethylstilbestrol, natural estrogens, ethnylestradiol) as a consequence of oxidative metabolism.     

Glutamine preserves liver glutathione after lethal hepatic injury.

Glutathione (GSH) is a major antioxidant that protects tissues from free radical injury. Glutamine augments host defenses and may be important in GSH synthesis. Acetaminophen toxicity causes hepatic GSH depletion and hepatic necrosis. The authors hypothesized that glutamine-supplemented nutrition would enhance liver GSH stores and diminish hepatic injury and death after acetaminophen overdose. Wistar rats received either a standard total parenteral nutrition (TPN) solution (STD) or an isocaloric, isonitrogenous glutamine-supplemented solution (GLN). On the 5th day of feeding, animals were given acetaminophen (400 mg/kg intraperitoneally) and then killed at various time points. Standard TPN solution animals had a rapid depletion of hepatic glutathione, whereas GLN animals were resistant to this drop and rapidly repleted hepatic GSH stores. Glutamine-supplemented animals maintained higher plasma glutamine concentrations, had lesser elevations in hepatic enzymes, and sustained significantly fewer complications compared with STD animals. The authors conclude that glutamine-supplemented nutrition preserves hepatic glutathione, protects the liver, and improves survival during acetaminophen toxicity. Glutamine may augment host defenses by enhancing antioxidant protection.     

Glomus tympanicum chemodectomas: radiographic and clinical characteristics

Glomus tympanicum chemodectomas are benign neoplasms that develop from normal glomus bodies located along the Jacobson (tympanic) nerve in the middle ear. The medical charts and radiographic studies of 55 patients with these tumors were reviewed. Women outnumbered men in a ratio of 3.5:1, and the patients' average age when they initially reported symptoms was 52 years. Tinnitus, ear pulsations, and diminished hearing were the most frequent symptoms. No patient had a second chemodectoma, and none of seven patients who were tested had elevated neuroendocrine compounds. Review of the radiographic examinations showed that direct coronal, thin-section computed tomography (CT) was the most sensitive means of demonstrating glomus tympanicum chemodectomas. Magnification angiography was also a sensitive diagnostic study, typically depicting a trapezoidal, hypervascular, middle-ear mass that appeared initially in the middle-to-late arterial phase and quickly disappeared in the venous phase. Differentiation from an aberrant internal carotid artery is critical to prevent arterial biopsy.     

Two-dimensional and Doppler echocardiographic assessment of neonatal arterial repair for transposition of the great arteries

The arterial switch procedure has become an accepted reparative technique for transposition of the great arteries with or without ventricular septal defect. In this study the accuracy of prospective noninvasive imaging in detecting arterial tract obstruction and the prevalence and severity of arterial valvular regurgitation (as assessed by Doppler ultrasound) were evaluated in survivors of arterial repair. All 53 study patients underwent two-dimensional echocardiographic examination 2 days to 20 months (median 7 months) postoperatively; 43 patients also had pulsed and continuous wave Doppler studies. The accuracy of the noninvasive evaluation of arterial tract obstruction was determined by comparison of Doppler maximal instantaneous gradients with peak to peak gradients at nonsimultaneous catheterization in 26 patients. Twenty-one (81%) of the 26 patients underwent catheterization and successful pulsed and continuous wave Doppler examination of the right heart; 17 (81%) of these 21 had a maximal pressure gradient within 20 mm Hg of the peak to peak gradient obtained at catheterization. Echocardiographic identification of the stenotic site was correct in all eight of the patients in this group requiring reoperation. Twenty-three (88%) of the 26 patients who underwent catheterization had successful Doppler interrogation of the aortic tract; 22 (96%) of these 23 had a maximal instantaneous gradient within 20 mm Hg of the peak to peak catheterization gradient. Fourteen (32%) of 43 patients had mild or moderate pulmonary regurgitation by Doppler study. Three (7%) of the 43 had mild aortic regurgitation.     

Pheochromocytoma and the normal adrenal medulla: improved visualization with I-123 MIBG scintigraphy

The radiopharmaceutical iodine 131 metaiodobenzylguanidine (I-131 MIBG) has been shown to locate pheochromocytomas scintigraphically with a false-negative rate of approximately 13%. To improve image quality and reduce the false-negative rate, I-123 was examined as a radioactive label for MIBG, as it has many advantages over I-131, including superior dosimetry and better detection efficiency. Diagnostic doses of 0.5 mCi (18.5 MBq) I-131 MIBG and 10.0 mCi (370.0 MBq) I-123 MIBG with nearly equivalent radiation dosimetries were compared in 18 patients with known or suspected pheochromocytomas. Images of superior quality were obtained with I-123 MIBG in 18 of 18 patients, and in eight cases lesions not visualized on I-131 MIBG scintigraphy were portrayed. A further advantage of I-123 MIBG is that it permits single photon emission computed tomography (SPECT). This was performed in six cases and provided additional information in three cases. The adrenal medullae were definitely visualized using I-123 scintigraphy in eight of 14 patients still possessing adrenal glands, whereas I-131 MIBG images portrayed the adrenal medulla in only one of 14 cases. Five remaining patients had multiple abdominal tumor deposits that were difficult to differentiate from normal adrenal medullae.