Effect of intravenous calcium administration on gentamicin-induced nephrotoxicosis in ponies.

OBJECTIVE: To determine whether supplemental i.v. calcium administration would attenuate or prevent gentamicin-induced acute renal failure, defined as an increase in serum creatinine concentration > or = 50% above baseline. ANIMALS: 10 healthy pony mares. PROCEDURE: Pony mares were randomly assigned to receive calcium at a dosage of 20 mg/kg of body weight or saline solution i.v., twice daily for 14 days. All pony mares received gentamicin at a dosage of 20 mg/kg i.v. every 8 hours for 14 days. Gentamicin pharmacokinetic, serum biochemical, and urinalysis data were measured every other day for the 14-day study period. Renal histologic examination was performed, and results were scored at the end of the 14-day period. RESULTS: 4 of 5 mares not receiving calcium supplementation developed acute renal failure. Only 1 of the 5 mares receiving calcium supplementation developed acute renal failure. Over the course of the study, pony mares receiving calcium supplementation had significantly fewer changes in urinalysis variables, and significantly less microscopic renal damage. CONCLUSION: Daily i.v. administration of calcium attenuated gentamicin-induced acute renal failure. CLINICAL RELEVANCE: Calcium supplementation may help diminish the risk of acute renal failure associated with aminoglycoside antibiotics.

Evaluation of single-drug and combination antifungal therapy in an experimental model of candidiasis in rabbits with prolonged neutropenia.

We developed an experimental model of candidiasis in rabbits with prolonged neutropenia. Rabbits were made neutropenic with cytosine arabinoside (Ara-C) administered through an indwelling silastic catheter that had been surgically implanted in the external jugular vein. Neutropenia was sustained with intravenous Ara-C, and bacterial complications were prevented with parenteral ceftazidime plus ampicillin. Candidiasis was established by intravenously administering Candida albicans or Candida tropicalis (1-2 x 10(5) colony-forming units) and resulted in hepatic and splenic lesions that mimicked those associated with hepatosplenic candidiasis in humans. The kidney proved to be the site most refractory to eradication of Candida spp. and offered a target organ for assessing antifungal therapy. We evaluated amphotericin B, 5-flucytosine, ketoconazole, and rifampin, alone and in combination. Although each agent reduced the colony counts of Candida in the liver, spleen, and lung, the combination of amphotericin B and 5-flucytosine was the only regimen effective in eradicating renal candidiasis.

Distribution of iodized oil within the liver after hepatic arterial injection.

Radiography and microscopy were used to investigate the hepatic distribution of iodized oil injected into the hepatic artery in a rabbit VX2 tumor model. Iodized oil accumulates within hepatic metastases and in a ringlike fashion around them. Radiographic and histologic appearances were correlated, and it was concluded that ringlike deposition occurs in peritumoral sinusoids. There was no evidence that iodized oil is cleared by hepatic lymphatics. Early clearance of iodized oil into bile may possibly be caused by localized hepatic ischemia from oil microemboli or by direct phagocytosis by Kupffer cells. The remaining oil is washed through hepatic vasculature, circulates systemically, and is cleared by reticuloendothelial cells in lung, spleen, liver, and bone marrow. This mode of clearance, which has not been considered previously, may be important in the prediction of toxic effects caused by lipid and lipophilic antitumor agents administered via the hepatic artery.

CT of the liver and spleen with EOE-13: review of 225 examinations.

EOE-13 is an experimental liver-spleen-specific computed tomographic (CT) contrast agent developed at the National Institutes of Health. Experience with this agent in 225 clinical examinations is described. On average, use of EOE-13 increases the attenuation of normal liver by 32.5 H and that of normal spleen by 52.3 H. Tumors in these organs increase only 2.6 H, making them more easily detectable. Most of the iodine in EOE-13 appears to clear from the liver and spleen by 24 hr after injection. No deaths or permanent morbidity have been observed. The complication rate is 3.6%. EOE-13 is valuable for the detection of hepatic and splenic tumors.

Experimental evaluation of five liver-spleen specific CT contrast agents.

We tested five experimental liver-spleen specific computed tomography (CT) contrast agents, all of which are aqueous emulsions of iodinated vegetable oils. These compounds were compared with ethiodized oil emulsion 13 (EOE-13) and with a 5% dextrose in water control. We evaluated three animal/dose level models with both histology and CT to determine the best screening method for compounds of this type. We compared a rat/high dose model, a rat/medium dose model, and a rabbit/low dose model; the best discrimination was seen with the rabbit/low dose model. Histology of liver, spleen, and lung did not correlate with the attenuation values obtained from CT. We conclude that use of CT and a rabbit/low dose model is superior for screening compounds of this type. Of the compounds tested, only one, an emulsion of ethyl monoiodostearate (compound 208E), approached the effectiveness of EOE-13.

Computed tomography of the liver and spleen with intravenous lipoid contrast material: review of 60 examinations.

In 60 computed tomographic examinations of the liver and spleen in 55 patients, a new intravenous lipoid contrast material, Ethiodized Oil Emulsion 13, was used. This organ-specific contrast material, retained by the reticuloendothelial cells of the liver and spleen, caused marked increase in the attenuation of the liver and spleen, but did not appreciably change the attenuation of the tumor involving these organs, thereby significantly increasing the density differential between normal and abnormal tissue. Toxicity was considered to be well within tolerable limits with the most frequently noted untoward side effects of chills, fever, headaches, and foul metallic taste. Ethiodized Oil Emulsion 13 holds the promise to become a valuable clinical tool by which hepatic and splenic imaging may be significantly improved and lesions less than 1 cm in diameter demonstrated in the liver and spleen.