The effects of deferoxamine mesylate on iron elimination after blood transfusion in neonatal foals.

BACKGROUND: Hepatic failure is one of the more common complications in foals requiring blood transfusion to treat neonatal isoerythrolysis. Iron intoxication is likely the cause of hepatic injury. OBJECTIVES: To determine the effects of deferoxamine on iron elimination in normal foals. ANIMALS: Thirteen neonatal foals. METHODS: Randomized-controlled trial. At 1-3 days of age, foals received either 3 L of washed packed dam's red blood cells (RBC) or 3 L of saline IV once. Foals were treated with deferoxamine (1 g) or saline (5 mL) SC twice daily for 14 days. Foals were randomly assigned to 1 of 3 groups: RBC/deferoxamine (deferoxamine), RBC/saline (placebo), or saline/saline (control). Blood and urine samples and liver biopsy specimens were collected for measurement of hematological, biochemical, and iron metabolism variables. RESULTS: There was a significant (P<.05) increase in hematocrit, RBC count, and hemoglobin in the groups transfused with packed RBC as compared with controls at all times. Biochemical variables and liver biopsy scores were not significantly different between groups at any time. Urine iron concentrations and fractional excretion of iron were significantly higher in deferoxamine treated foals. By 14 days after transfusion, liver iron concentrations in foals treated with deferoxamine (79.9±30.9 ppm) were significantly lower than that of foals receiving placebo (145±53.0 ppm) and similar to that of controls (44.8±4.09 ppm). CONCLUSIONS AND CLINICAL IMPORTANCE: Deferoxamine enhances urinary iron elimination and decreases hepatic iron accumulation after blood transfusion in foals.

Effects of Bt cotton and crylac toxin on survival and development of pink bollworm (Lepidoptera: Gelechiidae).

We evaluated the effects of Bacillus thuringiensis (Bt) toxin CrylAc on survival and development of a susceptible strain and laboratory-selected resistant strains of pink bollworm, Pectinophora gossypiella (Saunders). For susceptible and resistant strains tested on artificial diet, increases in CrylAc concentration reduced developmental rate and pupal weight. In greenhouse tests, survival of resistant larvae on transgenic cotton that produces CrylAc (Bt cotton) was 46% relative to their survival on non-Bt cotton. In contrast, Bt cotton killed all susceptible larvae tested. F1 hybrid progeny of resistant and susceptible adults did not survive on Bt cotton, which indicates recessive inheritance of resistance. Compared with resistant or susceptible larvae reared on non-Bt cotton, resistant larvae reared on Bt cotton had lower survival and slower development, and achieved lower pupal weight and fecundity. Recessive resistance to Bt cotton is consistent with one of the basic assumptions of the refuge strategy for delaying resistance to Bt cotton. Whereas slower development of resistant insects on Bt cotton could increase the probability of mating between resistant adults and accelerate resistance, negative effects of Bt cotton on the survival and development of resistant larvae could delay evolution of resistance.

Variation in susceptibility to Bacillus thuringiensis toxins among unselected strains of Plutella xylostella.

So far, the only insect that has evolved resistance in the field to Bacillus thuringiensis toxins is the diamondback moth (Plutella xylostella). Documentation and analysis of resistant strains rely on comparisons with laboratory strains that have not been exposed to B. thuringiensis toxins. Previously published reports show considerable variation among laboratories in responses of unselected laboratory strains to B. thuringiensis toxins. Because different laboratories have used different unselected strains, such variation could be caused by differences in bioassay methods among laboratories, genetic differences among unselected strains, or both. Here we tested three unselected strains against five B. thuringiensis toxins (Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ca, and Cry1Da) using two bioassay methods. Tests of the LAB-V strain from The Netherlands in different laboratories using different bioassay methods yielded only minor differences in results. In contrast, side-by-side comparisons revealed major genetic differences in susceptibility between strains. Compared with the LAB-V strain, the ROTH strain from England was 17- to 170-fold more susceptible to Cry1Aa and Cry1Ac, respectively, whereas the LAB-PS strain from Hawaii was 8-fold more susceptible to Cry1Ab and 13-fold more susceptible to Cry1Da and did not differ significantly from the LAB-V strain in response to Cry1Aa, Cry1Ac, or Cry1Ca. The relative potencies of toxins were similar among LAB-V, ROTH, and LAB-PS, with Cry1Ab and Cry1Ac being most toxic and Cry1Da being least toxic. Therefore, before choosing a standard reference strain upon which to base comparisons, it is highly advisable to perform an analysis of variation in susceptibility among field and laboratory populations.

Cross-resistance and stability of resistance to Bacillus thuringiensis toxin Cry1C in diamondback moth.

We tested toxins of Bacillus thuringiensis against larvae from susceptible, Cry1C-resistant, and Cry1A-resistant strains of diamondback moth (Plutella xylostella). The Cry1C-resistant strain, which was derived from a field population that had evolved resistance to B. thuringiensis subsp. kurstaki and B. thuringiensis subsp. aizawai, was selected repeatedly with Cry1C in the laboratory. The Cry1C-resistant strain had strong cross-resistance to Cry1Ab, Cry1Ac, and Cry1F, low to moderate cross-resistance to Cry1Aa and Cry9Ca, and no cross-resistance to Cry1Bb, Cry1Ja, and Cry2A. Resistance to Cry1C declined when selection was relaxed. Together with previously reported data, the new data on the cross-resistance of a Cry1C-resistant strain reported here suggest that resistance to Cry1A and Cry1C toxins confers little or no cross-resistance to Cry1Bb, Cry2Aa, or Cry9Ca. Therefore, these toxins might be useful in rotations or combinations with Cry1A and Cry1C toxins. Cry9Ca was much more potent than Cry1Bb or Cry2Aa and thus might be especially useful against diamondback moth.

Genetics of pink bollworm resistance to Bacillus thuringiensis toxin Cry1Ac.

Laboratory selection increased resistance of pink bollworm (Pectinophora gossypiella) to the Bacillus thuringiensis toxin Cry1Ac. Three selections with Cry1Ac in artificial diet increased resistance from a low level to >100-fold relative to a susceptible strain. We used artificial diet bioassays to test F1 hybrid progeny from reciprocal crosses between resistant and susceptible strains. The similarity between F1 progeny from the two reciprocal crosses indicates autosomal inheritance of resistance. The dominance of resistance to Cry1Ac depended on the concentration. Resistance was codominant at a low concentration of Cry1Ac, partially recessive at an intermediate concentration, and completely recessive at a high concentration. Comparison of the artificial diet results with previously reported results from greenhouse bioassays shows that the high concentration of Cry1Ac in bolls of transgenic cotton is essential for achieving functionally recessive inheritance of resistance.

Cyt1A from Bacillus thuringiensis lacks toxicity to susceptible and resistant larvae of diamondback moth (Plutella xylostella) and pink bollworm (Pectinophora gossypiella).

We tested Cyt1Aa, a cytolytic endotoxin of Bacillus thuringiensis, against susceptible and Cry1A-resistant larvae of two lepidopteran pests, diamondback moth (Plutella xylostella) and pink bollworm (Pectinophora gossypiella). Unlike previous results obtained with mosquito and beetle larvae, Cyt1Aa alone or in combination with Cry toxins was not highly toxic to the lepidopteran larvae that we examined.

Impact of a clinical pharmacokinetic service on patients treated with aminoglycosides: a cost-benefit analysis.

In a prospective, randomized study, 75 adults receiving aminoglycosides were followed by a clinical pharmacokinetic service and 70 followed as controls. The two groups were similar in age, gender, height, and APACHE II score. A cost-to-charge ratio was used to derive direct costs of hospitalization and calculate cost-benefit. Excluded from this comparison were patients with incomplete acceptance of pharmacokinetic service recommendations and patients followed by other clinical pharmacists. Pharmacokinetic service patients had shorter hospitalizations (322.67 +/- 270.28 h; controls 442.89 +/- 536.81, p = 0.087) and febrile periods (50.05 +/- 79.38 h; controls 92.23 +/- 122.50, p less than 0.05). More pharmacokinetic service patients had adequate peak levels. Pharmacokinetic service direct costs were lower ($7,102.56 +/- 9,898.19; controls $13,758.64 +/- 22,874.31, p less than 0.05). Calculated direct cost of the service was $85.00/patient. Annual savings for 500 patients is $2,220,540.00.

Does accepting pharmacokinetic recommendations impact hospitalization? A cost-benefit analysis.

In a prospective, randomized study, 110 adults receiving aminoglycosides were randomized to follow-up by a clinical pharmacokinetic service (CPS). Of the 110 patients, 35 accepted pharmacokinetic recommendations less than 100% of the time. The two groups were similar in age, sex, height, APACHE II score, and initial creatinine clearance. A cost-to-charge ratio was used to derive direct costs of hospitalization and calculate cost-benefit. Patients whose physicians accepted pharmacokinetic recommendations 100% of the time had shorter hospitalizations (322.67 +/- 270.28 h; CPS less than 100%, 699.54 +/- 806.35; p = 0.001) and febrile periods (50.05 +/- 79.38 h; CPS less than 100%, 120.00 +/- 153.23; p = 0.002). Acceptance of CPS recommendations led to adequate peak levels. Acceptance of CPS recommendations led to lower direct costs ($7,102.56 +/- 9,898.19; CPS less than 100%, $19,629.94 +/- 28,051.89; p less than 0.001). Calculated direct cost of the service was $85/patient.

Impact of a clinical pharmacokinetic service on patients treated with aminoglycosides for gram-negative infections.

The present study was a retrospective, case-control design aimed at evaluating whether the clinical pharmacokinetic service (CPS) is cost-effective, as assessed by lengths of hospital stay and aminoglycoside therapy, incidence of a decrease in renal function, and time for resolution of infection as determined by vital signs. Forty-six patients were entered into this study, and were matched by defined criteria. The results of the study demonstrated a six-day difference in hospital stay for the CPS group (p less than 0.05). Length of aminoglycoside therapy was 33 hours shorter for the CPS group. Additionally, the time necessary for resolution of the infection was significantly shorter for this group, as assessed by vital signs returning to normal or baseline. Three patients in each group expired. Two patients in the CPS group and five in the control group developed aminoglycoside-associated increases in serum creatinine. No significant difference was found between the two groups in age, weight, or APACHE II score. Additionally, the two groups were similar with respect to concomitant diseases and concomitant antibiotics used. The approximate cost of the CPS was calculated as $56 per patient. Use of the CPS decreasing hospital stay by six days (mean $1875/patient) would translate to an annual savings of $654,375 in hospital charges, assuming 365 patients received aminoglycoside therapy per year.

A pharmacy fellowship in a family practice training program.

An evaluation of the two-year experience since the institution of the postdoctoral pharmacy fellowship in family practice has revealed the program to be a valuable one not only for the fellows completing the program but to the departments cosponsoring this experimental training program. The two individuals who have completed the program have gone to clinical practice positions. In both academic and hospital settings, the fellow gains an understanding of the philosophical basis of family medicine while at the same time gaining specialized experience in an area of interest as well as research design and implementation. The department of family practice has benefited by the provision of additional clinical pharmacy services and education. It has also enabled the department to expand its involvement in research activities.