Definition of the supraclavicular and infraclavicular nodes: implications for three-dimensional CT-based conformal radiation therapy.

PURPOSE: To delineate with computed tomography (CT) the anatomic regions containing the supraclavicular (SCV) and infraclavicular (IFV) nodal groups, to define the course of the brachial plexus, to estimate the actual radiation dose received by these regions in a series of patients treated in the traditional manner, and to compare these doses to those received with an optimized dosimetric technique. MATERIALS AND METHODS: Twenty patients underwent contrast material-enhanced CT for the purpose of radiation therapy planning. CT scans were used to study the location of the SCV and IFV nodal regions by using outlining of readily identifiable anatomic structures that define the nodal groups. The brachial plexus was also outlined by using similar methods. Radiation therapy doses to the SCV and IFV were then estimated by using traditional dose calculations and optimized planning. A repeated measures analysis of covariance was used to compare the SCV and IFV depths and to compare the doses achieved with the traditional and optimized methods. RESULTS: Coverage by the 90% isodose surface was significantly decreased with traditional planning versus conformal planning as the depth to the SCV nodes increased (P < .001). Significantly decreased coverage by using the 90% isodose surface was demonstrated for traditional planning versus conformal planning with increasing IFV depth (P = .015). A linear correlation was found between brachial plexus depth and SCV depth up to 7 cm. CONCLUSION: Conformal optimized planning provided improved dosimetric coverage compared with standard techniques.

Aqueous and vitreous penetration of ciprofloxacin following different modes of systemic administration.

The overall importance of the peak or the mean serum concentrations as predictors of ocular drug penetration is unknown. To address this fundamental question with an agent which shows promise as adjunctive therapy in the treatment of endophthalmitis, we studied the penetration of ciprofloxacin into the aqueous and vitreous humors following three different modes of systemic administration. New Zealand white rabbits received either a single bolus dose (40 mg kg-1), three intermittent doses of 13.33 mg kg-1 evenly spaced over an 8 hr period, or a continuous infusion of 40 mg kg-1 over an 8 hr period. Pharmacokinetic analysis was performed using RSTRIP II, a non-linear, least square regression model analysis program. The serum area under the concentration-time curve (AUC) values for each mode of drug administration were similar: 32.9 micrograms hr ml-1 for single dose, 31.9 micrograms hr ml-1 for intermittent dose, and 33.8 micrograms hr ml-1 for continuous infusion modes. The percentage penetration into the aqueous and vitreous were also similar; 30.5% and 6.5% for a single dose, 31.6% and 7.4% for intermittent doses and 30.0% and 7.5% for continuous infusion. The penetration into the aqueous and vitreous humors was not influenced by mode of administration. As with other quinolones we have studied, elimination rates were similar for the central and peripheral compartments in the post-distributive phase. Vitreous humor ciprofloxacin concentrations achieved were below that which inhibits most Staphylococcus epidermidis, the most common isolate in patients with post-operative endophthalmitis.

Sequential parenteral and oral ciprofloxacin regimen versus parenteral therapy for bacteremia: a pharmacoeconomic analysis.

OBJECTIVE: To compare, in patients with gram-negative bacteremia, a course of parenteral antibiotic therapy alone with initial parenteral therapy followed by oral ciprofloxacin in terms of the length of hospitalization, clinical effectiveness, toxicity, and cost. DESIGN: A prospective, controlled, randomized, open trial in select hospitalized patients. SETTING: Large metropolitan teaching hospital. PATIENTS: Fifty hospitalized patients with proven gram-negative bacteremia were randomized to receive either oral ciprofloxacin (group 1) following a 72-hour initial intravenous antibiotic regimen or to continue parenteral therapy alone (group 2). To compare the length of hospitalization, an additional group of 50 hospitalized patients with bacteremia (not enrolled in the study, group 3) were analyzed. INTERVENTION: Parenteral antibiotics for 72 hours followed by continuation of a parenteral regimen or oral ciprofloxacin 750 mg bid. MAIN OUTCOME MEASURES: Clinical response, toxicity, and length of hospitalization. RESULTS: Clinical resolution was comparable in the 24 group 1 patients receiving intravenous antibiotics followed by oral ciprofloxacin (83%), the 26 group 2 patients receiving parenteral therapy alone (77%), and the 50 comparison patients (76%). There was little toxicity noted in any group, and the initial parenteral antibiotic regimens were similar. The mean numbers of hospital days on antibiotics were 9.1, 11.2, and 10.6 days in groups 1,2, and 3, respectively (p < 0.05 for group 1 vs. group 2 or 3), and the lengths of hospitalization were 9.8, 15.7, and 12.1 days, respectively (p < 0.05 for group 1 vs. group 2 or 3). Shortening the length of hospitalization and days of antibiotic therapy was associated with a cost savings of up to $78 000 for group 1 patients. CONCLUSIONS: Parenteral therapy for 72 hours followed by oral ciprofloxacin significantly shortened both the number of hospital days taking antibiotics and the length of stay compared with parenteral therapy alone. Both regimens were equally effective and safe in the therapy of gram-negative bacteremia, and initial parenteral therapy followed by oral ciprofloxacin was cost-effective.

Fleroxacin pharmacokinetics in aqueous and vitreous humors determined by using complete concentration-time data from individual rabbits.

Although composite data from separate subjects can be used to generate single-subject estimates, intersubject variation precludes rigorous ocular pharmacokinetic analysis. Therefore, a rabbit model in which sequential aqueous and vitreous humor samples were obtained following the administration of the quinolone fleroxacin was developed. Mean data from individual animals were used for pharmacokinetic analysis. Following direct intravitreal or systemic drug administration, sequential paracenteses did not alter pharmacokinetic constants or ocular penetration and were not associated with an increase in ocular protein; contamination of vitreous humor with blood was minimal (less than 0.1%). Following direct injection or intravenous administration, vitreous humor concentration-time data were best described by one- and two-compartment models, respectively. The maximum concentration and the penetration into the aqueous and vitreous humors were 1.54 and 0.5 micrograms/ml and 27 and 10%, respectively. Elimination rates from aqueous and vitreous humors and serum were similar following parenteral drug administration. Drug elimination following direct injection was rapid, and the elimination rate from the vitreous humor was not prolonged by the coadministration of probenecid. Our animal model provides a new approach to the rigorous examination of the ocular pharmacokinetics of quinolone antimicrobial agents in the eye.