Comparison of inhalation toxicity studies of gentamicin in rats and dogs.

Nebulized gentamicin solution was administered to rats (nose-only) and dogs (face mask) for 14 days with a 14-day recovery period. Control groups of each were exposed to saline aerosols. Mean estimated inhaled lung doses of gentamicin were 39, 123 and 245 mg/kg for rats (deposited doses 6, 17 and 34 mg/kg) over 30, 90 and 180 min, respectively. Since dogs do not tolerate exposures as long as rats, inhaled lung doses were limited to 7, 14 and 41 mg/kg (deposited doses of 1, 3 and 8 mg/kg) over 15, 30 and 60 min. Comparable doses were achieved at the low dose for rats and high dose for dogs. Serum AUCs (14 ± 2 µg/mL h (mean ± SD) at 6 mg/kg in rats and 11 ± 7 µg/mL h at 8 mg/kg in dogs) showed comparable exposure between the two, implying similar absorbed doses and confirming similar deposited lung doses. Rat exposures resulted in dose-related lung pathology (including low dose) manifested as upper respiratory tract irritant reactions with alveolar histiocytosis, inflammation, airway epithelial metaplasia and lymphomegaly in lung tissue. This was associated with high lung tissue gentamicin levels 24 h post-dose on Day 14 (375 ± 33 µg/g at deposited dose of 6 mg/kg). Dose-related kidney tubular necrosis (a well-known toxicity of parenteral gentamicin) was observed, but no test-article related effects on lung histopathology in dogs (even at highest deposited dose of 8 mg/kg) and low levels of lung tissue gentamicin (42 ± 11 µg/g) 24 h post-dose on Day 14.

Acute myeloid leukemia with hepatic infiltration presenting as obstructive jaundice.

We present the case of a 55-year-old woman who presented with laboratory studies concerning for acute myeloid leukemia (AML) as well as obstructive cholestasis. In similar previously reported cases, concerns of chemotherapy toxicity exacerbated by liver dysfunction or concerns of untreated, concurrent cholecystitis in a neutropenic patient often delay initiation of chemotherapy for full medical workup. At admission, our patient was started on the cytoreductive agent hydroxyurea. By day 10 of her medical workup, her liver function had improved with total bilirubin levels normalizing. At that time, full-dose 7 + 3 induction with cytarabine and daunorubicin was then initiated.

Ascorbylated 4-hydroxy-2-nonenal as a potential biomarker of oxidative stress response.

Oxidative stress, resulting from the generation of reactive oxygen species, contributes to the development of a multitude of age-related diseases. Current methods of assessing oxidative stress levels range from the detection of lipid peroxidation products, such as F(2)-isoprostanes and malondialdehyde, to monitoring the redox status of glutathione. While useful, traditional biomarkers of oxidative stress are not without their drawbacks, including low in vitro concentrations and possible artifact formation. In the present study, we utilize liquid chromatography coupled with tandem mass spectrometry for investigation into the use of a novel compound, ascorbylated 4-hydroxy-2-nonenal, as a potential biomarker of oxidative stress.