Fuel spill identification using solid-phase extraction and solid-phase microextraction. 1. Aviation turbine fuels.

The water-soluble fraction of aviation jet fuels is examined using solid-phase extraction and solid-phase microextraction. Gas chromatographic profiles of solid-phase extracts and solid-phase microextracts of the water-soluble fraction of kerosene- and nonkerosene-based jet fuels reveal that each jet fuel possesses a unique profile. Pattern recognition analysis reveals fingerprint patterns within the data characteristic of fuel type. By using a novel genetic algorithm (GA) that emulates human pattern recognition through machine learning, it is possible to identify features characteristic of the chromatographic profile of each fuel class. The pattern recognition GA identifies a set of features that optimize the separation of the fuel classes in a plot of the two largest principal components of the data. Because principal components maximize variance, the bulk of the information encoded by the selected features is primarily about the differences between the fuel classes.

Regioselective enzymatic aminoacylation of lobucavir to give an intermediate for lobucavir prodrug.

Synthesis of lobucavir prodrug, L-valine, [(1S,2R,3R)-3-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)-2-(hydroxymethyl) cyclobutyl]methyl ester monohydrochloride (BMS 233866), requires regioselective coupling of one of the two hydroxyl groups of lobucavir (BMS 180194) with valine. Either hydroxyl group of lobucavir could be selectively aminoacylated with valine by using enzymatic reactions. N-[(Phenylmethoxy)carbonyl]-L-valine, [(1R,2R,4S)-2-(2-amino-6-oxo-1H-purin-9-yl)-4-(hydroxymethyl)cyclobutyl]methyl ester (3, 82.5% yield), was obtained by selective hydrolysis of N,N'-bis[(phenylmethoxy)carbonyl]bis[L-valine], O,O'-[(1S,2R,3R)-3-(2-amino-6-oxo-1H-purin-9-yl)cyclobuta-1,2-diyl]methyl ester (1) with lipase M, and L-valine, [(1R,2R,4S)-2-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)-4-(hydroxymethyl)cyclobutyl]methyl ester monohydrochloride (4, 87% yield) was obtained by hydrolysis of bis[L-valine], O,O'-[(1S,2R,3R)-3-(2-amino-6-oxo-1H-purin-9-yl)cyclobuta-1,2-diyl]methyl ester, dihydrochloride (2), with lipase from Candida cylindracea. The final intermediate for lobucavir prodrug, N-[(phenylmethoxy)carbonyl]-L-valine, [(1S,2R,4R)-3-(2-amino-6-oxo-1H-purin-9-yl)-2-(hydroxymethyl)cyclobutyl]methyl ester (5), could be obtained by transesterification of lobucavir using ChiroCLEC BL (61% yield), or more selectively by using immobilized lipase from Pseudomonas cepacia (84% yield).

Breast-feeding after inferior pedicle reduction mammaplasty.

The breast-feeding practices of a series of postpartum women, who had undergone prior reduction mammaplasty by means of an inferior pedicle approach, are reported in this retrospective study. Also identified are the factors that influenced the decision to breast-feed postoperatively. From a patient pool of 544 individuals who elected to have reduction mammaplasty between 1984 and 1994 (age range, 15 to 35 years), 334 could be contacted and interviewed by means of telephone by using a standardized questionnaire. Successful breast-feeding was defined as the ability to feed for a duration equal to or greater than 2 weeks. Seventy-eight patients had children after their breast reduction surgery. Fifteen of the 78 patients (19.2 percent) breast-fed exclusively, 8 (10.3 percent) breast-fed with formula supplementation, 14 (17.9 percent) had an unsuccessful breast-feeding attempt, and 41 (52.6 percent) did not attempt breast-feeding. Of the 41 patients not attempting to breast-feed, 9 patients did so as a direct consequence of discouragement by a health care professional. Further reasons for feeding with supplementation, having an unsuccessful attempt, and not attempting to breast-feed are presented. Of the 78 women who had children postoperatively, a total of 27 were discouraged from breast-feeding by medical professionals with only 8 of the 27 (29.6 percent) subsequently attempting, despite this recommendation. In comparison, 26 patients were encouraged to breast-feed; nineteen (73.1 percent) of them did subsequently attempt breast-feeding. This rate is statistically significant by using a chi2 test with 1 df(p = 0.0016). Postpartum breast engorgement and lactation was experienced by 31 of the 41 patients not attempting to breast-feed. Of these 31 patients, 19 believed that they would have been able to breast-feed due to the extent of breast engorgement and lactation experienced. Given the use of an inferior flap mammaplasty technique and patient encouragement, the possibility for breast-feeding after reduction mammaplasty exists. This prevalence falls near the breast-feeding rate found in the population not having undergone breast surgery, according to an article in the Canadian Journal of Public Health.

Enzymatic synthesis of L-6-hydroxynorleucine.

L-6-Hydroxynorleucine, a key chiral intermediate used for synthesis of a vasopeptidase inhibitor, was prepared in 89% yield and > 99% optical purity by reductive amination of 2-keto-6-hydroxyhexanoic acid using glutamate dehydrogenase from beef liver. In an alternate process, racemic 6-hydroxynorleucine produced by hydrolysis of 5-(4-hydroxybutyl)hydantoin was treated with D-amino acid oxidase to prepare a mixture containing 2-keto-6-hydroxyhexanoic acid and L-6-hydroxynorleucine followed by the reductive amination procedure to convert the mixture entirely to L-6-hydroxynorleucine, with yields of 91 to 97% and optical purities of > 99%.

Upper limb Escherichia coli cellulitis in the immunocompromised.

The neutropenic state characteristic of acute lymphoblastic leukaemia (ALL) predisposes to infections involving Gram-negative bacilli. An Escherichia coli cellulitis originating in the first web space of the hand is described in a patient undergoing reinduction chemotherapy for ALL. Proximal extension of the infection progressed at a very rapid rate and required a forequarter amputation as a life saving measure. Due to the blunted inflammatory response in neutropenic patients, the need for close monitoring and quick intervention is stressed.

Partial hippocampal kindling affects retention but not acquisition and place but not cue tasks on the radial arm maze.

The performance of rats that were partially kindled in the hippocampus was assessed on an 8-arm radial arm maze with 4 baited arms. In rats first trained and then kindled, deficits were found on a place task in which rats reached the goal arms of the maze using salient extramaze spatial cues, but not on an intramaze cue task in which rats reached the goal arms using salient intramaze cues. Acquisition of a new place task on the maze was not different between kindled and control rats. In conclusion, partial hippocampal kindling disrupted the retention but not the acquisition of a spatial or place task; retention of a nonspatial cue task was not disrupted.

The pharmacokinetics and liver metabolism of N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA) in rats.

The metabolism and disposition of N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA) was studied by utilizing rat liver slices as well as by intravenous pharmacokinetic studies in rats. In the liver slice experiments, N-OH MDA (16 micrograms/ml) was incubated with rat liver slices and the disappearance of N-OH MDA and the appearance of MDA were observed over 2 hours. Drug and metabolites were assayed by a reverse phase high performance liquid chromatographic procedure including a C8 column and UV detection. N-OH MDA disappeared from the plasma at an apparent first-order rate with a t1/2 of 36.3 +/- 8.4 min. By the end of 2 hours, approximately 85% of the N-OH MDA was biotransformed to MDA. Following placement of jugular cannulas in rats, a dose of 15 mg/kg of N-OH MDA was administered intravenously. With rapid blood sampling, a t1/2 of 0.86 +/- 0.12 min was observed for N-OH MDA. A total body clearance of 9.09 +/- 2.06 L/hr/kg and a volume of distribution of 0.184 +/- 0.022 L/kg were noted. Plasma concentrations of MDA were observed after the N-OH MDA dose to rats. The MDA t1/2 after N-OH MDA dosing was 1.68 +/- 0.29 hours with peak plasma concentrations at 8 min. No other major metabolites could be detected in liver slice, plasma, or urine samples. Both sets of studies demonstrate the rapid conversion of N-OH MDA to MDA in rats.

Effect of a perfluorochemical emulsion on the rat hepatic mixed function oxidase system.

The perfluorochemical components of synthetic oxygen transporting emulsions may persist in hepatic tissue. After a single 30% blood exchange with the perfluorochemical emulsion, Fluosol-DA 20%, the effects on the microsomal metabolism of 7-methoxycoumarin and 7-ethoxycoumarin were studied over a 9-week period. Fluosol-DA treated animals were compared with controls (sham) and hetastarch-treated controls. Changes in dealkylase activities were compared with induction by phenobarbitone and 3-methylcholanthrene. The liver to body weight ratio increased by 49% in Fluosol-DA-treated rats over the controls at 1 week and the microsomal protein was increased in the Fluosol-DA-treated rats after 4 and 9 weeks. Fluosol-DA treatment induced 7-methoxycoumarin demethylase with peak differences occurring at 1 week and a Vmax 75% greater than controls. Fluosol-DA was a more potent inducer of demethylase than phenobarbitone. In addition, 7-ethoxycoumarin de-ethylase was induced by Fluosol-DA with a peak induction at 4 weeks. The Vmax at 4 weeks in Fluosol-DA-treated rats was 122% greater than control. In this case, Fluosol-DA produced less induction in de-ethylase than 3-methylcholanthrene. These studies show that Fluosol-DA induces more than one form of cytochrome P450 and the effects resemble those of phenobarbitone more than those of 3-methylcholanthrene. Hetastarch, a plasma expander, did not affect liver weights, microsomal protein content, or the cytochrome P450 system.

Pharmacists' opinions about and compliance with recommendations for intravenous admixture practices.

Hospital pharmacy departments nationwide were surveyed to determine compliance with and opinions on the importance of recommended practices for preparation of i.v. admixtures. Questionnaires that included 84 recommendations by the National Coordinating Committee on Large-Volume Parenterals, the American Society of Hospital Pharmacists, and the Joint Commission on Accreditation of Hospitals were mailed to 625 randomly selected acute-care hospitals. Questions covered the compounding area and recommended equipment; selection, education, and training of personnel; compounding procedures; quality assurance; labeling and record keeping; and reference materials and professional services. The response rate was 43% (198 usable replies). Responses indicated that 42 (50%) of the recommended practices were followed in fewer than 75% of the hospitals, 25 (30%) in fewer than 50% of the hospitals, and 17 (20%) in fewer than 25% of the hospitals. Twenty of the recommendations were considered marginal in importance. Adherence to published guidelines for i.v. admixture services varies among hospitals in the United States; compilation of a single set of guidelines should be considered.

Resident-preceptor retreat for re-evaluating a pharmacy residency program.

The organization of a resident-preceptor retreat as one component of a process to re-evaluate a pharmacy residency program is described. Changes in the ASHP standards for residency training and recommendations from a recent reaccreditation survey as well as recent changes in the health-care environment prompted a re-evaluation of the existing 24-month residency and degree program at The Ohio State University Hospitals. Three task forces were created to evaluate issues in seven areas of residency training. Members of the task forces, which consisted of current residents and staff members with preceptorial responsibilities, discussed the issues assigned to them during a retreat at a state park. Recommendations made at the retreat were assigned to individual task force members for implementation. Within nine months of the retreat, 15 of 17 recommendations had been implemented. A retreat involving both residents and preceptors can be an effective forum for discussing and critically evaluating a pharmacy residency program.