Morganella morganii bacteria produces phenol as the sex pheromone of the New Zealand grass grub from tyrosine in the colleterial gland.

Costelytra zealandica (Coleoptera: Scarabeidae) is a univoltine endemic species that has colonised and become a major pest of introduced clover and ryegrass pastures that form about half of the land area of New Zealand. Female beetles were previously shown to use phenol as their sex pheromone produced by symbiotic bacteria in the accessory or colleterial gland. In this study, production of phenol was confirmed from the female beetles, while bacteria were isolated from the gland and tested for attractiveness towards grass grub males in traps in the field. The phenol-producing bacterial taxon was identified by partial sequencing of the 16SrRNA gene, as Morganella morganii. We then tested the hypothesis that the phenol sex pheromone is biosynthesized from the amino acid tyrosine by the bacteria. This was shown to be correct, by addition of isotopically labelled tyrosine ((13)C) to the bacterial broth, followed by detection of the labelled phenol by SPME-GCMS. Elucidation of this pathway provides specific evidence how the phenol is produced as an insect sex pheromone by a mutualistic bacteria.

Performance of a quarter-wavelength particle concentrator.

A series of devices have been investigated which use acoustic radiation forces to concentrate micron sized particles. These multi-layered resonators use a quarter-wavelength resonance in order to position an acoustic pressure node close to the top surface of a fluid layer such that particles migrate towards this surface. As flow-through devices, it is then possible to collect a concentrate of particulates by drawing off the particle stream and separating it from the clarified fluid and so can operate continuously as opposed to batch processes such as centrifugation. The methods of construction are described which include a micro-fabricated, wet-etched device and a modular device fabricated using a micro-mill. These use silicon and macor, a machinable glass ceramic, as a carrier layer between the transducer and fluid channel, respectively. Simulations using an acoustic impedance transfer model are used to determine the influence of various design parameters on the acoustic energy density within the fluid layer and the nodal position. Concentration tests have shown up to 4.4-, 6.0- and 3.2-fold increases in concentration for 9, 3 and 1 microm diameter polystyrene particles, respectively. The effect of voltage and fluid flow rates on concentration performance is investigated and helps demonstrate the various factors which determine the increase in concentration possible.

Investigation of two-dimensional acoustic resonant modes in a particle separator.

Within an acoustic standing wave particles experience acoustic radiation forces, a phenomenon which is exploited in particle or cell manipulation devices. When developing such devices, one-dimensional acoustic characteristics corresponding to the transducer(s) are typically of most importance and determine the primary radiation forces acting on the particles. However, radiation forces have also been observed to act in the lateral direction, perpendicular to the primary radiation force, forming striated patterns. These lateral forces are due to lateral variations in the acoustic field influenced by the geometry and materials used in the resonator. The ability to control them would present an advantage where their effect is either detrimental or beneficial to the particle manipulation process. The two-dimensional characteristics of an ultrasonic separator device have been modelled within a finite element analysis (FEA) package. The fluid chamber of the device, within which the standing wave is produced, has a width to height ratio of approximately 30:1 and it is across the height that a half-wavelength standing wave is produced to control particle movement. Two-dimensional modal analyses have calculated resonant frequencies which agree well with both the one-dimensional modelling of the device and experimentally measured frequencies. However, these two-dimensional analyses also reveal that these modes exhibit distinctive periodic variations in the acoustic pressure field across the width of the fluid chamber. Such variations lead to lateral radiation forces forming particle bands (striations) and are indicative of enclosure modes. The striation spacings predicted by the FEA simulations for several modes compare well with those measured experimentally for the ultrasonic particle separator device. It is also shown that device geometry and materials control enclosure modes and therefore the strength and characteristics of lateral radiation forces, suggesting the potential use of FEA in designing for the control of enclosure modes in similar particle manipulator devices.

A dual frequency, ultrasonic, microengineered particle manipulator.

Ultrasonic standing waves can be used to generate forces on particles within a fluid. Recent work has concentrated on developing devices that manipulate the particles so that they are concentrated near the centre of the cavity. It is also possible to design a device that concentrates the particles at the wall of a cavity. This paper describes a device that has the capability of operating in several modes to allow concentration of particles at either the cavity wall or the centre of the cavity, depending on the driving frequency.

Modelling of particle paths passing through an ultrasonic standing wave.

Within an ultrasonic standing wave particles experience acoustic radiation forces causing agglomeration at the nodal planes of the wave. The technique can be used to agglomerate, suspend, or manipulate particles within a flow. To control agglomeration rate it is important to balance forces on the particles and, in the case where a fluid/particle mix flows across the applied acoustic field, it is also necessary to optimise fluid flow rate. To investigate the acoustic and fluid forces in such a system a particle model has been developed, extending an earlier model used to characterise the 1-dimensional field in a layered resonator. In order to simulate fluid drag forces, CFD software has been used to determine the velocity profile of the fluid/particle mix passing through the acoustic device. The profile is then incorporated into a MATLAB model. Based on particle force components, a numerical approach has been used to determine particle paths. Using particle coordinates, both particle concentration across the fluid channel and concentration through multiple outlets are calculated. Such an approach has been used to analyse the operation of a microfluidic flow-through separator, which uses a half wavelength standing wave across the main channel of the device. This causes particles to converge near the axial plane of the channel, delivering high and low particle concentrated flow through two outlets, respectively. By extending the model to analyse particle separation over a frequency range, it is possible to identify the resonant frequencies of the device and associated separation performance. This approach will also be used to improve the geometric design of the microengineered fluid channels, where the particle model can determine the limiting fluid flow rate for separation to occur, the value of which is then applied to a CFD model of the device geometry.

Use of point-of-service health status assessments by community pharmacists to identify and resolve drug-related problems in patients with musculoskeletal disorders.

STUDY OBJECTIVE: To determine whether community pharmacists can use point-of-service health status assessments to identify and resolve drug-related problems (DRPs) in ambulatory patients with selected musculoskeletal (MSK) disorders. DESIGN: Twelve-month, prospective, multicenter demonstration project. SETTING: Twelve independent community pharmacies in eastern Iowa. PATIENTS: Ambulatory patients with self-reported diagnosis of osteoarthritis, rheumatoid arthritis, or low back pain. MEASUREMENTS: During quarterly pharmacy visits for 1 year, patients used touch-screen computers to report their health status. Patients answered questions on the Short Form-36 (SF-36) general health survey, as well as questions assessing limitations associated with their MSK condition. Pharmacists used this data in interviewing patients to assess for DRPs. MAIN RESULTS: The study enrolled 461 patients, of whom 388 returned for the 12-month visit. During this 1-year period, community pharmacists identified 926 cumulative DRPs. Patients with no DRPs had significantly higher physical component summary scores on the SF-36 (p<0.05) than patients with more than one DRP at baseline (36.2 vs 31.6), 6 months (39.2 vs 33.3), and 12 months (40.1 vs 35.4). At 12 months, actions performed by pharmacists led to resolution or improvement of 70.7% of DRPs. CONCLUSION: Drug-related problems are numerous in community-dwelling patients with MSK disorders and correspond to decreased physical health status. Community pharmacists can use patient-reported measures of health status to identify DRPs and initiate processes to resolve them.

Catalytic asymmetric cyclopropanation of heteroaryldiazoacetates.

Rh(2)(S-DOSP)(4)-catalyzed decomposition of heteroaryldiazoacetates in the presence of styrene results in highly diastereoselective and enantioselective cyclopropanations. Heteroaryldiazoacetates containing both electron-rich and electron-deficient heterocycles, such as thiophene, furan, pyridine, indole, oxazole, isoxazole, and benzoxazole, are effective in this chemistry. These studies broaden the range of diazo compounds containing both electron-withdrawing and electron-donating groups, which undergo highly diastereoselective cyclopropanations.

An exploratory study of type II [3 + 4] cycloadditions between vinylcarbenoids and dienes.

The intramolecular type II [3 + 4] cycloaddition between vinylcarbenoids and furans is a practical method for the construction of 5-oxo-10-oxatricyclo[6.2.1.0(4,9)]undeca-3, 8(11)-dienes, containing two anti-Bredt double bonds. These tricyclic systems are well functionalized for eventual elaboration to the natural product CP-263,114. The rhodium-stabilized vinylcarbenoids are generated by dirhodium tetracarboxylate catalyzed decomposition of vinyldiazoacetates. The [3 + 4] cycloaddition is generally considered to occur by a tandem cyclopropanation/Cope rearrangement, although evidence is presented that with these substrates the [3 + 4] cycloaddition may occur in a concerted manner.

Pharmacoeconomics in the new millennium. A pharmaceutical industry perspective.

The primary purpose of pharmacoeconomic research is to assist in making healthcare decisions. Rapid growth in the supply of pharmacoeconomic data over the past few years suggests that pharmacoeconomics can be of help in delivering good, cost-effective healthcare. Greater challenges in decision-making coupled with improvements in the techniques of pharmacoeconomic research point to a greater role for pharmacoeconomics into the new millennium. This in turn will have consequences for companies in the pharmaceutical industry. More successful access to markets and better commercialisation of products will be the rewards for those companies committing to pharmacoeconomics and to the broader goal of delivering value for money in healthcare.

Outcomes measurement. The key to the appropriate use of pharmaceuticals.

Outcomes measurement will be key to the appropriate use of pharmaceuticals as health care costs continue to rise. The generation of data showing the clinical, economic, and humanistic outcomes of pharmaceutical care will be essential to avoid decision making based solely on cost and to ensure that cost-effective, high-quality health care remains the health care system's top priority.

Measuring the functional status and well-being of patients with migraine headache.

OBJECTIVE: Compare adult migraineurs' health related quality of life to adults in the general U.S. population reporting no chronic conditions, and to samples of patients with other chronic conditions. METHODS: Subjects (n = 845) were surveyed 2-6 months after participation in a placebo-controlled clinical trial and asked to complete a questionnaire including the SF-36 Health Survey, a migraine severity measurement scale and demographics. Results were adjusted for severity of illness and comorbidities. Scores were compared with responses to the same survey by the U.S. sample and by patients with other chronic conditions. RESULTS: Response rate was 67%. After adjustment for comorbid conditions, SF-36 scale scores were significantly (P 0.001) lower in migraineurs, relative to age and sex-adjusted norms for the U.S. sample with no chronic conditions. Some health dimensions were more affected by migraine than other chronic conditions, while other dimensions were less affected by migraine. Measures of bodily pain, role disability due to physical health and social functioning discriminated best between migraineurs, the U.S. sample, and patients with other chronic conditions. Patients reporting moderate, severe and very severe migraines scored significantly (P < or = 0.001) lower on five of the eight SF-36 scales than the U.S. sample. CONCLUSIONS: Migraine has a unique, significant quality of life burden.

Serum inhibitory and bactericidal activity against methicillin-resistant Staphylococcus aureus in volunteers receiving novobiocin and rifampin alone and in combination.

The combination of novobiocin and rifampin is effective in eliminating colonization due to methicillin-resistant Staphylococcus aureus (MRSA) and in treating experimental MRSA soft tissue infections. To evaluate novobiocin, rifampin, and the combination of the two agents for potential oral therapy in patients with MRSA infections, we measured the serum inhibitory and bactericidal activity from four volunteers against 20 MRSA strains obtained from seven different institutions. When Stratton-Reller methods employing 50% human serum were used to perform the assay, rifampin produced peak mean serum inhibitory titers of 1:40, whereas novobiocin alone produced essentially no inhibitory activity. The combination of novobiocin plus rifampin had similar inhibitory activity as rifampin alone. The bactericidal titers produced by the three regimens were significantly less than inhibitory titers. In additional studies, involving serum from five volunteers tested against seven representative strains, peak mean serum inhibitory activity of novobiocin was 1:232 when Mueller-Hinton broth was used as the diluent compared with < 1:2 when 50% human serum was used. We conclude that despite the high degree of activity of novobiocin in broth, its activity against MRSA in serum is minimal, probably related to the high degree of protein binding of that antibiotic.

Pharmacoeconomic research and clinical trials: concepts and issues.

The purpose of this article is to provide an overview of the emerging discipline of pharmacoeconomics. Specific methodologies and terms are defined. Pharmacoeconomic research is described, related to, and contrasted with clinical drug trials. Additionally, we present a brief overview of the general steps taken designing a pharmacoeconomic study. Finally, several issues centering around pharmacoeconomic analysis are presented for discussion and debate. The need for high-quality pharmacoeconomic research is stressed along with the need for appropriate education of individuals trained in the health sciences.

Pharmacokinetic evaluation of two dosage regimens of clindamycin phosphate.

Interpretation of the majority of data on the disposition of clindamycin is confounded by the presence of active metabolites, which may interfere with commonly employed bioassays. We undertook a multiple-dose study of the disposition of clindamycin phosphate and clindamycin, given either as 600 mg intravenously every 6 h or 1,200 mg intravenously every 12 h for five and three doses, respectively, in six healthy volunteers. Concentrations in serum and urine were analyzed by a specific gas chromatography assay. Maximum and minimum clindamycin concentrations in serum and the area under the serum concentration-time curve following the first dose were similar to those observed at the steady state. The mean and standard deviation of the maximum, 1-h postdose, and minimum concentrations in serum at steady state for the 600-mg dose given every 6 h were 16.8 +/- 6.0, 7.6 +/- 0.7, and 2.3 +/- 0.9 microgram/ml, whereas for the 1,200-mg dose given every 12 h they were 17.2 +/- 3.5, 9.8 +/- 1.5, and 0.6 +/- 0.3 microgram/ml, respectively. For the 12-h regimen, clindamycin concentrations in serum remained above 2 micrograms/ml for 7 h. The decay of clindamycin phosphate levels in serum was rapid, with virtually 100% of the phosphate eliminated within the first 1.5 h following the dose. Approximately 0.35 and 4.5% of the administered dose were recovered in the urine as clindamycin phosphate and clindamycin, respectively. Further pharmacokinetic evaluation of the 12-hourly dosage regimen should be done before clinical evaluation in infected patients is undertaken.

Examining nursing personnel costs: controlled versus noncontrolled oral analgesic agents.

To date, few evaluations have focused on nursing personnel costs generated by practices of other clinicians. The authors used traditional industrial engineering and cost accounting techniques to determine nursing personnel costs generated by the use of controlled versus noncontrolled oral analgesic agents. The findings indicate that additional nursing labor costs are generated for drug administration and inventory activities for controlled agents when compared with noncontrolled agents. On an annual basis, the additional costs for drug administration generate approximately +34,000 in hospital expenses for the three nursing units included in this evaluation. This type of interdisciplinary investigation may be valuable as nursing departments face increasing pressures to decrease costs by reducing overtime and eliminating positions.

Comparative pharmacokinetics and serum inhibitory activity of clindamycin in different dosing regimens.

The comparative pharmacokinetics and serum inhibitory effects of clindamycin were evaluated in six healthy male subjects given multiple-dose infusions of the following regimens in a crossover fashion: 600 mg every 6 h, 900 mg every 8 h, and 1,200 mg every 12 h. Serial blood samples were obtained after the last dose in each regimen and analyzed for clindamycin by a sensitive and specific high-performance liquid chromatography assay technique. Clindamycin pharmacokinetics were estimated by using noncompartmental methods, and serum inhibitory titers were serially determined against Bacteroides fragilis ATCC 25285 and evaluated by using area under the serum inhibitory curve (AUIC). Maximum and minimum concentrations in plasma averaged 12.2 +/- 1.6 and 1.2 +/- 0.6, 16.3 +/- 4.0 and 0.9 +/- 0.5, and 16.8 +/- 2.5 and 0.4 +/- 0.2 micrograms/ml for the 600-, 900-, and 1,200-mg regimens, respectively. Clindamycin plasma clearance and elimination half-life averaged 23.3 +/- 4.0 liters/h and 1.9 +/- 0.4 h for the 600-mg regimen, 25.6 +/- 8.2 liters/h and 2.1 +/- 0.4 h for the 900-mg regimen, and 26.4 +/- 4.7 liters/h and 2.1 +/- 0.4 h for the 1,200-mg regimen. These results were not significantly different. Apparent volume of distribution increased significantly for the 1,200-mg regimen compared with the 600-mg regimen. Mean maximum reciprocal serum inhibitory titers were 96 +/- 35, 101 +/- 43, and 160 +/- 78 for the 600-, 900-, and 1,200-mg regimens, respectively. Minimum reciprocal serum inhibitory titers averaged 12 +/- 4, 6 +/- 3, and 5 +/- 2 for the low-, medium-, and high-dose regimens, respectively. Mean AUIC increased roughly in proportion to dose. Similar daily values for the area under the concentration-time curve and for AUIC for each of the regimens suggest similar daily drug exposure and serum inhibitory activity. A regimen of 1,200 mg every 12 h may represent an alternative dosing strategy for clindamycin.

Clindamycin pharmacokinetics and tissue penetration after head and neck surgery.

Penetration of clindamycin into surgical wounds was studied in 10 patients undergoing radical head and neck surgery. Patients received one preoperative and three postoperative intravenous doses of clindamycin 600 mg. During surgery, samples of plasma and sternocleidomastoid muscle were obtained. Additional plasma samples were collected just before the fourth dose of clindamycin, just after that dose was infused, and 1, 2, 4, 6, 8, and 12 hours after dosing. Samples of wound exudate were collected at 2, 4, 6, 8, and 12 hours after the fourth dose. The muscle, plasma, and wound exudate samples were assayed for clindamycin base by a gas-liquid chromatographic method. Plasma and wound exudate samples obtained during surgery and one and eight hours after the fourth dose were assayed by a radial immunodiffusion technique for content of alpha 1-acid glycoprotein (AAG), the major binding protein for clindamycin. Pharmacokinetic values for plasma and wound drainage were calculated and compared. Concentrations of clindamycin in muscle (three to six hours after the first dose) ranged from 0.6 to 5.1 micrograms/g; the ratio of tissue to plasma concentrations ranged from 0.24 to 0.82. The highest mean clindamycin concentration in wound drainage was 4.9 micrograms/mL after the fourth dose, approximately 90% of simultaneous plasma concentrations. Concentrations in wound exudate exceeded those measured in plasma four hours after the dose, and elimination from the wound was slower than from plasma. AAG concentrations in plasma increased from a mean of 89 mg/dL intraoperatively to 134 mg/dL postoperatively. AAG was present in wound exudate in concentrations that were approximately 53% of those observed in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Compatibility of clindamycin phosphate with aztreonam in polypropylene syringes and with cefoperazone sodium, cefonicid sodium, and cefuroxime sodium in partial-fill glass bottles.

The stability and compatibility of clindamycin phosphate admixed with four beta-lactams, an experimental monobactam (aztreonam), and three cephalosporins (cefoperazone sodium, cefonicid sodium, and cefuroxime sodium), were studied. Aztreonam alone and the combination of clindamycin phosphate-aztreonam were prepared in duplicate polypropylene syringes. Each cephalosporin antibiotic as well as the three clindamycin phosphate-cephalosporin combinations were admixed in duplicate 100 ml partial-fill glass bottles containing either dextrose 5% in water or NaCl 0.9%. All solutions were examined, antibiotic concentrations were determined, and pH was measured at the time of admixture and 1, 4, 8, 12, 24, and 48 hours later. The solutions were maintained at room temperature under fluorescent lighting for the length of the study. Antibiotic concentrations were determined by drug-specific high performance liquid chromatographic assays. Significant instability or incompatibility was defined as a decrease in concentration of greater than ten percent relative to the initial concentration measured at the time of admixture. All antibiotics were stable for 48 hours. In the combination studies, clindamycin was stable for 48 hours, both in partial-fill glass bottles and syringes. Aztreonam, cefoperazone, cefonicid, and cefuroxime were also stable for 48 hours.