Building teams before buildings.
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Biomedical subjects
Publications and source records attributed to T A Larson.
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Enzyme immunoassay (EIA) and fluorescence polarization immunoassay (FPIA) methods are commercially available for quantitation of serum amikacin concentration. The purpose of this study was to determine if the two assay methods were comparable and would provide the same estimates for pharmacokinetic parameters and dosage recommendations. A total of 73 amikacin serum samples were used to evaluate the two assay techniques. Forty-four of these samples, obtained from 10 patients, were used to evaluate the comparability of pharmacokinetic parameters and dosage regimens. The correlation coefficient between the two assay methods was 0.98 (y = 1.03x + 0.64). There were substantial differences in assay performance noted in samples less than 10 mg/L, 10-20 mg/L, and greater than 20 mg/L, typical concentration ranges for serum sampling used in pharmacokinetic analysis. A difference of approximately 10% was observed in the determination of amikacin half-life, total body clearance, and dosage calculation. A 7% difference was noted in the volume of distribution. A significant difference (p less than 0.05) in volume of distribution and dosage recommendations was noted. Although the two methods for determining amikacin serum concentrations appear to be interchangeable on the basis of the in vitro comparison, significant differences were observed between the two assays in pharmacokinetic parameters and dosage recommendations.
Data relating to amikacin resistance among gram-negative bacilli were obtained by means of a review of published literature and resistance surveillance studies. Data from the first several years of amikacin use are difficult to interpret because the 10-micrograms disk used for Kirby-Bauer susceptibility testing resulted in apparent greater resistance than the present 30-micrograms disk. A large United States susceptibility surveillance program that monitors antibiotic use has shown a trend since 1977 of greater susceptibility of Serratia species and greater resistance among Pseudomonas aeruginosa for all the aminoglycosides. Pseudomonas resistance to amikacin has shown the smallest increase of any aminoglycoside. Several hospitals (Strong Memorial Hospital, University of Maryland Cancer Center, and Minneapolis Veterans Administration Medical Center) have reported either no significant change or a decrease in resistance to amikacin when it was the most frequently used aminoglycoside. In a large, 14-center, prospective study, high-level use of amikacin resulted in a significant decrease in resistance to gentamicin and tobramycin (p less than 0.01) and a marginal increase (p less than 0.05) in amikacin resistance. Significantly increased amikacin resistance has been reported from two institutions, neither of which used amikacin as the predominant aminoglycoside. Overall, the high-level use of amikacin in large multi-center surveillance programs for as long as five years has not resulted in a significant increase in amikacin resistance rates at any of the individual institutions surveyed.
The incidence of tobramycin-resistant, gentamicin-susceptible Serratia species at the Minneapolis Veterans Administration Medical Center decreased from an average 42.1 to 2.5% (P less than 0.001) during a 4.5-year period despite the predominant use of amikacin. These organisms were shown to express a 6'-N-acetyltransferase-modifying enzyme (EC 2.3.1.82). Resistance was not shown to be plasmid mediated.
Resistance to amikacin, gentamicin, and tobramycin was surveyed prospectively during controlled aminoglycoside usage in 14 hospitals. Following an initial baseline period (minimum, three months) during which gentamicin use predominated, gentamicin and tobramycin were placed on restrictive control, establishing amikacin as the aminoglycoside of general use (86 percent of total aminoglycoside usage). During an average of 35 months' restriction of gentamicin and tobramycin, significant reductions in gram-negative resistance to gentamicin (8.4 to 7.0 percent, p less than 0.001) and tobramycin (6.0 to 5.3 percent, p less than 0.01) were observed. The most significant decreases in resistance to gentamicin and tobramycin (p less than 0.001) were found for Pseudomonas aeruginosa, Klebsiella species, Serratia species, and Proteus species. Amikacin resistance among gram-negative bacilli was observed to increase marginally from 1.4 to 1.7 percent (p less than 0.05) during the surveillance period, primarily due to a significant increase in resistance among P. aeruginosa (3.0 to 3.9 percent, p = 0.05). These data were compared with data from a similar surveillance program at the 700-bed Minneapolis Veterans Administration Medical Center. Over a period of 54 months, both gentamicin and tobramycin resistance decreased significantly when amikacin was used (p less than 0.001), then increased with reintroduction of gentamicin (p less than 0.05), and decreased significantly with reintroduction of amikacin (p less than 0.001). Despite predominant amikacin use for a total of 38 months, amikacin resistance did not increase and actually decreased significantly (p less than 0.05) in the last 12 months.
The monthly variation in geometric mean MICs (GMICs) of amikacin, tobramycin, and gentamicin for Escherichia coli and Pseudomonas aeruginosa laboratory controls and clinical isolates was followed for 30 months. For 19 months, MICs were determined by using Micro-Media system (MMS; Micro-Media Systems, Inc., Potomac, Md.) microdilution panels, and for the other 11 months, MicroScan (MS; American Scientific Products, McGaw Park, Ill.) MIC test panels were used. The aminoglycoside GMICs for control E. coli and P. aeruginosa were significantly lower with the MS system than with the MMS system. A significant correlation was observed between the GMICs for controls and clinical isolates more frequently with the MMS system than with the MS system. Differences are believed to be related to the criteria used in the selection of quality control strains.
Netilmicin and tobramycin penetration in a rabbit Visking chamber model was studied after administration of multiple intramuscular doses of 2 mg of either drug per kg every 4 h in a double-crossover design. The mean serum half-life, mean peak concentration in serum, and mean area under the plasma concentration curve were similar. The mean peak concentration in the chamber and mean area under the plasma concentration curve were likewise not significantly different.
Thirteen normal subjects were given 2, 3, or 4 g of ceftizoxime intravenously in a prospective single-blinded study. Serum and urine concentrations were measured for 48 h. The beta-phase serum half-life ranged from 1.4 to 1.7 h. Approximately 100% of the agent was recovered unchanged in the urine over 48 h. Six of 13 subjects reported subjective complaints consisting of mild dizziness and moderate headache, all of which were transient. One subject also had a minimally elevated serum glutamic oxalacetic transaminase level 1 day after drug administration. Based on serum pharmacokinetics and serum protein binding determined in this investigation, unbound ceftizoxime appeared to distribute with the total body water.
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At present, relatively little national data are available concerning the involvement of social workers in medical education. This article presents the results of a study conducted recently to obtain a comprehensive, up-to-date profile of graduate-level social workers teaching in medical schools and to survey the opinions of medical school deans regarding their present and future status. Continuing research in this area is essential if we are to acquire a greater understanding of the contribution social workers make to contemporary medical education. Only then will we be better equipped to assess social work's potentials for the future and take those steps necessary to bring them to fruition.
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OBJECTIVES: (1) Define "incident-to" rules for Medicare reimbursement; (2) Describe how pharmacists can meet incident-to rules; (3) Provide examples of models of practice in rural areas that could be useful for meeting incident-to rules; and (4) Develop a strategy for creating a pharmacy practice model that could meet Medicare reimbursement rules in rural areas. DESIGN AND PARTICIPANTS: A survey of participants from the Pharmacy Rural Education, Practice and Policy Institute and the College of Pharmacy, University of Minnesota. SETTING: Community, hospital, and clinic practice sites in rural Minnesota. RESULTS: Four distinct models of practice have evolved that meet the incident-to rules of Medicare for reimbursement. Travel, proximity to physicians, and employment are the major determinants of the models described. CONCLUSION: Pharmacists in rural areas have demonstrated the ability to satisfy the incident-to rules for Medicare reimbursement. Collaborative agreements with physicians must include specific employment, practice, and supervisory relationships in order to satisfy these rules.
STUDY OBJECTIVE: To describe the pharmacokinetics of fluconazole in immune-compromised children with leukemia or other hematologic disease. DESIGN: Prospective. SETTING: Children's Health Care-Minneapolis hematology/oncology inpatient ward and outpatient clinic. PATIENTS: Ten immune-compromised children (mean +/- SD age 7.4 +/- 4.0 yrs, weight 31.6 +/- 25.9 kg) with leukemia or other hematologic disease. INTERVENTIONS: Serum was sampled before and after a single 6-mg/kg intravenous dose and after seven oral 3-mg/kg doses of fluconazole. MEASUREMENTS AND MAIN RESULTS: Mean (SD) pharmacokinetics were distribution half-life 1.67 (1.25) hours, elimination half-life 15.62 (3.21) hours, total body clearance 0.63 (0.19) ml/min/kg, volume of distribution for the central compartment 0.56 (0.10) L/kg, volume of distribution at steady state 0.77 (0.12) L/kg, absorption half-life 0.41 (0.26) hour, and oral bioavailability 0.92 (0.09). Volume of distribution for the central compartment was highly correlated with body surface area (r2 = 0.891) and weight (r2 = 0.949). Volume of distribution at steady state correlated with body surface area (r2 = 0.986), and total body clearance correlated with body surface area (r2 = 0.867). CONCLUSIONS: Fluconazole elimination was well described using a two-compartment model. Oral absorption was rapid and nearly complete. Children have a larger volume of distribution for the central compartment and faster elimination rate than adults. Body surface area and weight are important factors in determining pharmacokinetics in these patients.