Inhibition of methanogenesis by nitrate, with or without defaunation, in continuous culture.

Within the rumen, nitrate can serve as an alternative sink for aqueous hydrogen [H2(aq)] accumulating during fermentation, producing nitrite, which ideally is further reduced to ammonium but can accumulate under conditions not yet explained. Defaunation has also been associated with decreased methanogenesis in meta-analyses because protozoa contribute significantly to H2 production. In the present study, we applied a 2 × 2 factorial treatment arrangement in a 4 × 4 Latin square design to dual-flow continuous culture fermentors (n = 4). Treatments were control without nitrate (-NO3-) versus with nitrate (+NO3-; 1.5% of diet dry matter), factorialized with normal protozoa (faunated, FAUN) versus defaunation (DEF) by decreasing the temperature moderately and changing filters over the first 4 d of incubation. We detected no main effects of DEF or interaction of faunation status with +NO3-. The main effect of +NO3- increased H2(aq) by 11.0 µM (+117%) compared with -NO3-. The main effect of +NO3- also decreased daily CH4 production by 8.17 mmol CH4/d (31%) compared with -NO3-. Because there were no treatment effects on neutral detergent fiber digestibility, the main effect of +NO3- also decreased CH4 production by 1.43 mmol of CH4/g of neutral detergent fiber degraded compared with -NO3-. There were no effects of treatment on other nutrient digestibilities, N flow, or microbial N flow per gram of nutrient digested. The spike in H2(aq) after feeding NO3- provides evidence that methanogenesis is inhibited by substrate access rather than concentration, regardless of defaunation, or by direct inhibition of NO2-. Methanogens were not decreased by defaunation, suggesting a compensatory increase in non-protozoa-associated methanogens or an insignificant contribution of protozoa-associated methanogens. Despite adaptive reduction of NO3- to NH4+ and methane inhibition in continuous culture, practical considerations such as potential to depress dry matter intake and on-farm ration variability should be addressed before considering NO3- as an avenue for greater sustainability of greenhouse gas emissions in US dairy production.

Rumen microbial responses to supplemental nitrate. I. Yeast growth and protozoal chemotaxis in vitro as affected by nitrate and nitrite concentrations.

Nitrates have been fed to ruminants, including dairy cows, as an electron sink to mitigate CH4 emissions. In the NO3- reduction process, NO2- can accumulate, which could directly inhibit methanogens and some bacteria. However, little information is available on eukaryotic microbes in the rumen. Protozoa were hypothesized to enhance nitrate reductase but also have more circling swimming behavior, and the yeast Saccharomyces cerevisiae was hypothesized to lessen NO2- accumulation. In the first experiment, a culture of S. cerevisiae strain 1026 was evaluated under 3 growth phases: aerobic, anoxic, or transition to anoxic culture. Each phase was evaluated with a control or 1 of 3 isonitrogenous doses, including NO3-, NO2-, or NH4+ replacing peptone in the medium. Gas head phase, NO3-, or NH4+ did not influence culture growth, but increasing NO2- concentration increasingly inhibited yeast growth. In experiment 2, rumen fluid was harvested and incubated for 3 h in 2 concentrations of NO3-, NO2-, or sodium nitroprusside before assessing chemotaxis of protozoa toward glucose or peptides. Increasing NO2- concentration decreased chemotaxis by isotrichids toward glucose or peptides and decreased chemotaxis by entodiniomorphids but only toward peptides. Live yeast culture was inhibited dose-responsively by NO2- and does not seem to be a viable mechanism to prevent NO2- accumulation in the rumen, whereas a role for protozoal nitrate reductase and NO2- influencing signal transduction requires further research.

Rumen microbial responses to supplemental nitrate. II. Potential interactions with live yeast culture on the prokaryotic community and methanogenesis in continuous culture.

Nitrates have been fed to ruminants, including dairy cows, as an electron sink to mitigate CH4 emissions. In the NO3- reduction process, NO2- can accumulate, which could directly inhibit methanogens and possibly other microbes in the rumen. Saccharomyces cerevisiae yeast was hypothesized to decrease NO2- through direct reduction or indirectly by stimulating the bacterium Selenomonas ruminantium, which is among the ruminal bacteria most well characterized to reduce both NO3- and NO2-. Ruminal fluid was incubated in continuous cultures fed diets without or with NaNO3 (1.5% of diet dry matter; i.e., 1.09% NO3-) and without or with live yeast culture (LYC) fed at a recommended 0.010 g/d (scaled from cattle to fermentor intakes) in a 2 × 2 factorial arrangement of treatments. Treatments with LYC had increased NDF digestibility and acetate:propionate by increasing acetate molar proportion but tended to decrease total VFA production. The main effect of NO3- increased acetate:propionate by increasing acetate molar proportion; NO3- also decreased molar proportions of isobutyrate and butyrate. Both NO3- and LYC shifted bacterial community composition (based on relative sequence abundance of 16S rRNA genes). An interaction occurred such that NO3- decreased valerate molar proportion only when no LYC was added. Nitrate decreased daily CH4 emissions by 29%. However, treatment × time interactions were present for both CH4 and H2 emission from the headspace; CH4 was decreased by the main effect of NO3- until 6 h postfeeding, but NO3- and LYC decreased H2 emission up to 4 h postfeeding. As expected, NO3- decreased methane emissions in continuous cultures; however, contrary to expectations, LYC did not attenuate NO2- accumulation.

Using video microscopy to improve quantitative estimates of protozoal motility and cell volume.

The objective of this study was to apply digital imaging to improve quantification of rumen protozoal biomass and distinguish treatment differences in cell motility and volume among ruminal protozoa. Observations of protozoa in rumen fluid treated with essential oils (CinnaGar, CIN; Provimi North America, Brookville, OH) or an ionophore (monensin, MON) indicated possible cell shrinkage. We hypothesized that MON would decrease protozoal motility and interact with CIN on cell volume. In addition, we hypothesized that analysis of still frames from video of swimming protozoa would improve volume prediction accuracy. Flocculated rumen fluid was incubated in batch culture dosed with N-free feed only (control), MON, CIN, or a combination of MON+CIN. Samples were taken at 0, 3, or 6 h post-treatment and wet-mounted on a microscope fitted with a high-definition camera. At 3 h post-inoculation, there was a treatment interaction for average speed such that CIN attenuated the effect of MON, with treatment means of 243, 138, 211, and 183 µm/s for control, MON, CIN, and MON+CIN, respectively. At 6 h post-inoculation, MON decreased average speed by 79.2 µm/s compared with the main effect mean without MON. We measured both minimum and maximum diameters (depth and width, respectively) perpendicular to the longitudinal axis of swimming protozoa, yielding a 3-dimensional estimate of protozoal volume. The ellipsoid formula (4/3)πabc, where a = 1/2 length, b = 1/2 width, and c = 1/2 depth, was compared with previously published volume estimations using genera-specific coefficients (genera-specific coefficient × length × width2). Residuals (genera-specific coefficients - ellipsoid) were plotted against predicted (ellipsoid) and centered to the mean (Xi-x¯) to evaluate both mean and slope biases. For Entodinium spp., Y = 0.248 (±0.037) (Xi - 7.98 × 104) + 1.97 × 104 (±1.48 × 103); n = 100; r2 [coefficient of determination (squared correlation coefficient)] = 0.31, with significant slope and mean biases. For family Isotrichidae, Y = -0.124 (±0.068) (Xi - 2.54 × 106) - 1.21 × 104 (±4.86 × 104); n = 32; r2 = 0.10, where slope tended to be different from zero but with no mean bias. For Epidinium spp., Y = 0.375 (±0.056) (Xi - 2.45 × 105) + 6.65 × 104 (±0.28 × 104); n = 64; r2 = 0.43, with both mean and slope biases. The present regression analyses demonstrate that the genera-specific coefficient-based method more likely overestimates volume for Entodinium and Epidinium than for the teardrop-shaped Isotrichidae. Based on simulations derived from previous literature reporting treatments that depress protozoal populations or among-animal changes in protozoal population structures, our proposed ellipsoid method offers potential to advance the prediction of treatment effects on protozoal volume and to shift focus from the number of cells present to the diversity, function, and biomass of protozoa under various treatment conditions.

Investigation of ammonium lactate supplementation on fermentation end products and bacterial assimilation of nitrogen in dual-flow continuous culture.

Supplements investigated throughout the present study are produced by fermenting lactose that is present in whey to lactate, yielding products differing in ammonium relative to lactate concentrations and in physical form (liquid or dry). Trials 1 and 2 investigated Lacto-Whey (LW; Fermented Nutrition Corp., Luxemburg, WI) and GlucoBoost (GB; Fermented Nutrition Corp.), respectively, using dual-flow continuous culture systems (n = 4), each with a 4 × 4 Latin square design. A greater proportion of nonprotein nitrogen was present in GB than in LW. In trial 1, the treatment with LW was isonitrogenously dosed against soybean meal (SBM) as a control (no LW) and factorialized with either a wheat- or corn-based concentrate (55% inclusion rate, dry matter basis). We hypothesized that LW would increase propionate production and that the combination of +LW with wheat would increase bacterial assimilation of NH3-N into cellular N. No differences were observed for total volatile fatty acid (VFA) production per day. However, treatment × time interactions revealed that +LW increased lactate concentration at 0, 0.5, and 1 h and tended to increase molar percentage of propionate at 1 and 1.5 h postfeeding, documenting the immediate availability of lactate converted to propionate in the +LW treatments. The main effect of corn increased the proportion of bacterial N derived from NH3-N. Trial 2 was designed to investigate GB; isonitrogenous treatments included an SBM control, crystal GB, liquid GB (LGB), and LGB with yeast culture, which were dosed twice daily. We hypothesized that GB would increase propionate production and bacterial assimilation of NH3-N; the combination of LGB and yeast culture was expected to have a positive additive effect, yielding the greatest VFA production and bacterial NH3-N assimilation. No differences were observed for total VFA production; however, LGB decreased molar percentage of acetate and increased propionate and butyrate molar percentages. There were no differences in non-NH3-N flow or microbial N flow. Under the conditions of our studies, lactate in LW and GB was fermented extensively to propionate, and microbial protein synthesis in these treatments was comparable with that in SBM controls.

Small-molecule inhibition of inflammatory ß-cell death.

With the worldwide increase in diabetes prevalence there is a pressing unmet need for novel antidiabetic therapies. Insufficient insulin production due to impaired ß-cell function and apoptotic reduction of ß-cell mass is a common denominator in the pathogenesis of diabetes. Current treatments are directed at improving insulin sensitivity, and stimulating insulin secretion or replacing the hormone, but do not target progressive apoptotic ß-cell loss. Here we review the current development of small-molecule inhibitors designed to rescue ß-cells from apoptosis. Several distinct classes of small molecules have been identified that protect ß-cells from inflammatory, oxidative and/or metabolically induced apoptosis. Although none of these have yet reached the clinic, ß-cell protective small molecules alone or in combination with current therapies provide exciting opportunities for the development of novel treatments for diabetes.

Emerging diabetes therapies: Bringing back the ß-cells.

BACKGROUND: Stem cell therapies are finally coming of age as a viable alternative to pancreatic islet transplantation for the treatment of insulin-dependent diabetes. Several clinical trials using human embryonic stem cell (hESC)-derived ß-like cells are currently underway, with encouraging preliminary results. Remaining challenges notwithstanding, these strategies are widely expected to reduce our reliance on human isolated islets for transplantation procedures, making cell therapies available to millions of diabetic patients. At the same time, advances in our understanding of pancreatic cell plasticity and the molecular mechanisms behind ß-cell replication and regeneration have spawned a multitude of translational efforts aimed at inducing ß-cell replenishment in situ through pharmacological means, thus circumventing the need for transplantation. SCOPE OF REVIEW: We discuss here the current state of the art in hESC transplantation, as well as the parallel quest to discover agents capable of either preserving the residual mass of ß-cells or inducing their proliferation, transdifferentiation or differentiation from progenitor cells. MAJOR CONCLUSIONS: Stem cell-based replacement therapies in the mold of islet transplantation are already around the corner, but a permanent cure for type 1 diabetes will likely require the endogenous regeneration of ß-cells aided by interventions to restore the immune balance. The promise of current research avenues and a strong pipeline of clinical trials designed to tackle these challenges bode well for the realization of this goal.

Development of nanophosphors for light emitting diodes.

We report the development of new nanophosphor structures based on the Mn-doped ZnSeS material system to enhance the color properties, luminosity and efficiency of white LEDs. These structures have been demonstrated for phosphor-based white LED applications utilizing both blue and UV LED systems. Bandgap tuning for near UV (405 nm) and blue (460 nm) excitations are reported. Using various optimization procedures, we have produced ZnSe:Mn nanoparticles with an external quantum yield greater than 80%.

Intranasal oxytocin treatment does not attenuate the hypothalamo-pituitary-adrenal axis in beef heifers subjected to isolation stress or restraint and isolation stress.

Changes in the physiological, psychological, and behavioral manifestations of stress have been observed in association with increases in circulating oxytocin (OXT). Providing OXT intranasally has been shown to attenuate stressor-induced hypothalamo-pituitary-adrenal (HPA) axis activation in humans and rodents; however, anxiolytic effects may be context and species specific. The present study aimed to investigate the effect of intranasal OXT supplementation on stressor-induced activation of the HPA axis in beef cattle. We hypothesized that OXT would attenuate activation of the HPA axis, ultimately decreasing plasma cortisol and adrenocorticotropic hormone (ACTH). Twenty-eight Bos taurus heifers were blocked by bodyweight and randomly allocated to one of four treatment groups, in a 2 × 2 factorial arrangement: (1) saline, isolated, standing, and unrestrained (S-isolation stress [IS], 0.015 mL/kg BW 0.9% isotonic saline, n = 7); (2) saline, isolated, and restrained (S-restraint and isolation stress [RIS]; 0.015 mL/kg BW 0.9% isotonic saline; n = 7); (3) OXT, IS (OXT-IS, 0.3 IU/kg BW oxytocin; n = 7); and (4) OXT and RIS (OXT-RIS, 0.3 IU/kg BW oxytocin; n = 7). Oxytocin and saline were administered intranasally. Intranasal treatments were given followed by a waiting time of 30 min when each of the stress treatments was applied for 2 h. Blood samples were collected via jugular catheters directly after stressor application and every 10 min thereafter, for 2 h. Cortisol concentrations increased over time in animals exposed to RIS (P < 0.01) and decreased over time in animals exposed to IS (P < 0.01). Concentrations of ACTH decreased over time for the IS-treated heifers but remained elevated for the RIS-treated heifers (P < 0.01). Under the conditions of the present study, OXT treatment did not affect measured indicators of HPA axis activation. A treatment × time interaction (P < 0.01) was detected for OXT, such that OXT heifers exhibited greater initial OXT concentrations followed by a decline; saline-treated heifers had consistently stable oxytocin concentrations. The RIS-treated heifers increased their glucose (P < 0.01) and lactate (P < 0.01) concentrations throughout the application of the stressors compared with the IS-treated heifers. Overall, restraint stress increased cortisol and oxytocin in B taurus heifers compared with heifers subjected only to isolation. Finding a more intermediate stress model may better allow for detection of the effects of oxytocin on the stress response.

Short communication: pharmacokinetics of oxytocin administered intranasally to beef cattle.

Providing the neuropeptides oxytocin and vasopressin intranasally increased concentrations in plasma and cerebral spinal fluid in humans and primates, respectively. This is of interest because of the documented anxiolytic effects of oxytocin observed in humans and rodents. To date, a transnasal approach of hormone administration has not been investigated in beef cattle. Defining the pharmacokinetics of intranasal oxytocin in cattle is necessary for determining optimum sampling and dosing timelines for future investigations. Five, weaned Bos taurus steers were used in a 3 × 3 Latin square design. Treatments included 1) 0.33 IU oxytocin/kg BW (A, n = 5), 2) 0.66 IU oxytocin/kg BW (B, n = 5), and 3) 1.32 IU oxytocin/kg BW (C, n = 5). Steers were acclimated to handling and restraint procedures for 4 wk leading up to the start of the experiment. Frequent blood collection occurred every 2 min for the first 30 min and every 5 min for the second 30 min, relative to administration of intranasal treatment. No treatment by time interaction was detected; however, there was an effect of time (P < 0.001) and treatment (P = 0.002) on oxytocin concentrations over time. Pharmacokinetic parameters, determined by PKSolver excel add-in, demonstrated an average maximum concentration (CMAX) of 63.3 pg/mL at 3.5 min after intranasal dose administration. An average half-life (T1/2) of 12.1 min after intranasal administration was determined. Pharmacokinetic parameters to a single bolus were not dose-dependent.

A one-bead, one-stock solution approach to chemical genetics: part 2.

BACKGROUND: Chemical genetics provides a systematic means to study biology using small molecules to effect spatial and temporal control over protein function. As complementary approaches, phenotypic and proteomic screens of structurally diverse and complex small molecules may yield not only interesting individual probes of biological function, but also global information about small molecule collections and the interactions of their members with biological systems. RESULTS: We report a general high-throughput method for converting high-capacity beads into arrayed stock solutions amenable to both phenotypic and proteomic assays. Polystyrene beads from diversity-oriented syntheses were arrayed individually into wells. Bound compounds were cleaved, eluted, and resuspended to generate 'mother plates' of stock solutions. The second phase of development of our technology platform includes optimized cleavage and elution conditions, a novel bead arraying method, and robotic distribution of stock solutions of small molecules into 'daughter plates' for direct use in chemical genetic assays. This library formatting strategy enables what we refer to as annotation screening, in which every member of a library is annotated with biological assay data. This phase was validated by arraying and screening 708 members of an encoded 4320-member library of structurally diverse and complex dihydropyrancarboxamides. CONCLUSIONS: Our 'one-bead, multiple-stock solution' library formatting strategy is a central element of a technology platform aimed at advancing chemical genetics. Annotation screening provides a means for biology to inform chemistry, complementary to the way that chemistry can inform biology in conventional ('investigator-initiated') small molecule screens.

Comparison of intranasal midazolam and sufentanil premedication in pediatric outpatients.

BACKGROUND: Intranasally administered midazolam was compared with sufentanil as a premedicant for 60 patients, aged 1/2 to 6 years, undergoing outpatient surgery of 2 hours or less. METHODS: Thirty minutes before anesthetic induction (halothane in 50% nitrous oxide/oxygen), patients were randomly assigned to receive either intranasal midazolam (0.2 mg/kg) or sufentanil (2 microg/kg). A "blinded" observer evaluated preoperative emotional state, response to premedication, induction, and emergence from anesthesia and side effects. RESULTS: Children who had not previously cried were more likely to cry when midazolam was administered compared with sufentanil (71% versus 20%, p = 0.0031). Of 31 midazolam patients, 20 experienced nasal irritation. Approximately 15 to 20 minutes after drug administration, most patients in both groups could be comfortably separated from their parents. The sufentanil group appeared to be more sedated and more cooperative during induction of anesthesia. Vital signs and oxygen saturation did not change significantly with either medication before or after surgery, although two sufentanil patients had a moderate reduction in ventilatory compliance after anesthetic induction. Sufentanil was associated with more nausea and vomiting than midazolam (34% versus 6%, p < 0.02). CONCLUSION: Both intranasal midazolam and sufentanil provide rapid, safe, and effective sedation in small children before anesthesia for ambulatory surgery. Sufentanil provided somewhat better conditions for induction and emergence. Midazolam causes more nasal irritation during instillation, and sufentanil causes more postoperative nausea and vomiting. Both drugs enabled patients to be separated from their parents with a minimum of distress. Patients in the midazolam group were discharged approximately 40 minutes earlier (p <0.005).

Pharmacokinetics and pharmacodynamics of sedatives and analgesics in the treatment of agitated critically ill patients.

The pharmacokinetics and pharmacodynamics of sedatives and analgesics are significantly altered in the critically ill. These changes may account for the large differences in drug dosage requirements compared with other patient populations. Drugs that in other settings may be considered short-acting often have significantly altered onset and duration of action in critically ill patients, necessitating a change in dosage. Of the benzodiazepines, lorazepam is the drug whose parameters are the least likely to be altered in critical illness. The presence of active metabolites with other benzodiazepines complicates their use during periods of prolonged use. Similarly, the presence of active metabolites of morphine and pethidine (meperidine) warrants caution in patients with renal insufficiency. The fewer cardiovascular effects seen with high-potency opioids, such as fentanyl and sufentanil, increase their usefulness in haemodynamically compromised patients. The pharmacodynamics of propofol are not significantly altered in the critically ill. Ketamine should be used with a benzodiazepine to prevent the emergence of psychomimetic reactions. Lower sedative doses of benzodiazepines and anaesthetics may not provide reliable amnesia. Barbiturates and propofol probably do not induce hyperalgesia and lack intrinsic analgesic activity. The antipsychotic agent haloperidol has a calming effect on patients and administration to the point of sedation is generally not necessary. Combinations of sedatives and analgesics are synergistic in producing sedation. The costs of sedation and analgesia are very variable and closely linked to the pharmacokinetics and pharmacodynamics of the drug. Monitoring of sedation and analgesia is difficult in uncooperative patients in the intensive care unit. In the future, specific monitoring tools may assist clinicians in the regulation of infusions of sedative and analgesic agents.

Efficacy and safety of patient-controlled analgesia for morbidly obese patients following gastric bypass surgery.

BACKGROUND: Adequate postoperative pain control is important to reduce potential cardiopulmonary complications. It is often difficult to determine dosages of narcotics for morbidly obese patients following Roux-en-Y gastric bypass (RYGBP) due to respiratory depression. Individualization of analgesic therapy, patient-controlled analgesia (PCA), can provide optimal dosage for pain control and minimize the side-effects. METHOD: 25 morbidly obese patients who received PCA with morphine sulfate following RYGBP. PCA settings we re as follows: morphine, 20 microg/kg of ideal body weight, 10-minute lock out interval and 80 % of a calculated amount for a 4-hour limit. W e measured arterial blood gas, heart rate, mean arterial pressure, arterial oxygen saturation, respiratory rate, opioid amount, patient satisfaction, visual analog pain scale (VAS), and the incidence of nausea, vomiting, pruritus and sedation. RESULTS: Average morphine usage was 44.2+/-28.7 mg during the day of surgery (DOS); 49.1+/-27.4 mg during POD (postoperative day) #1; and 36.6+/-22.8 mg during POD#2 (p < 0.01). 24 patients were satisfied with their pain control on POD#1. VAS was 5.4+/-2.1 on the day of surgery, but remained below 4 thereafter. Arterial oxygen saturation and vital signs were maintained without significant changes. 5 patients experienced mild sedation on the day of surgery and 3 patients experienced mild sedation on POD#1. 1 patient experienced nausea and vomiting and 4 patients had pruritus; however, none required treatment. CONCLUSION: PCA is safe and effective for morbidly obese patients following RYGBP.

Cost analysis of propofol versus thiopental induction anesthesia in outpatient laparoscopic gynecologic surgery.

This study investigated the cost of propofol versus thiopental anesthesia in 243 patients who underwent outpatient laparoscopic gynecologic surgery. Patients records were analyzed for medication use, duration of surgery, anesthesia, recovery room stay, and associated costs. Despite the higher drug cost for propofol, the total mean cost was $273.00 less per patient for patients receiving propofol induction anesthesia. Extension of these data translates into cost savings of approximately $7900.00 if propofol had been used for all patients. Although the duration of surgery for the propofol group was shorter by nearly 12 minutes, the anesthesia duration and recovery room stay were both longer for the thiopental group, reflecting the longer duration of action of thiopental. Although the realized cost savings of drugs, surgery, anesthesia, and recovery time when propofol versus thiopental is used for outpatient laparoscopic gynecologic surgery are relatively small on an individual patient basis, cost savings may become more significant if larger patient populations are studied.

Pharmacoeconomic analysis of sevoflurane versus isoflurane anesthesia in elective ambulatory surgery.

This study investigated the economic aspects of sevoflurane and isoflurane anesthesia in 47 healthy women undergoing elective ambulatory surgery, as part of a randomized, prospective clinical trial. Patient records were analyzed for anesthetic; duration of surgery, anesthesia, and recovery room stay; and associated charges. Sevoflurane is shorter acting than isoflurane, but it was not associated with a shorter duration of anesthesia or surgical unit stay, or earlier hospital discharge. Total charges associated with sevoflurane anesthesia were greater than those for isoflurane ($2641 and $2230, respectively) and primarily related to prolonged anesthesia and surgical unit stay. A minor decrease in recovery room charges ($15) associated with earlier discharge was observed with sevoflurane (p>0.05), but the agent was not associated with lower hospital charges. Larger trials and assessment of other patient populations may show sevoflurane to be more pharmacoeconomically advantageous than isoflurane.

Faculty have few incentives for becoming board certified in pharmacotherapy.

A telephone survey of all colleges of pharmacy in the United States (including Puerto Rico) and Canada was conducted to assess the incentives offered for pharmacy practice faculty to become board-certified pharmacotherapy specialists (BCPS). Board certification is not a requirement for employment at any college of pharmacy; however, it plays a part in promotion, tenure, and merit salary increases at several schools. Fewer than half of the schools provide at least partial reimbursement of examination-related expenses. Sixteen have initiated BCPS study groups. We perceive that faculty must have more incentives to take the examination. It may be difficult to change institutional policies regarding merit increases or promotion and tenure, but colleges of pharmacy can do more to decrease the cost burden and to promote study groups within the department.

Retrospective analysis of postoperative nausea and vomiting to determine antiemetic activity of droperidol added to propofol: a possible drug interaction.

Propofol decreases the frequency of postoperative nausea and vomiting. We investigated whether its antiemetic activity could be improved further by coadministration of droperidol. We retrospectively reviewed the records of 266 women who underwent laparoscopic operations with nitrous oxide anesthesia and thiopental or propofol induction. The records were screened for frequency and time of occurrence of nausea and vomiting, concurrent drug use, duration of surgery, and times of recovery room admission and discharge. The combination of droperidol and thiopental decreased the frequency of nausea and vomiting over droperidol plus propofol, propofol alone, and thiopental alone. The addition of droperidol to propofol anesthesia doubled the frequency of multiple nausea and vomiting episodes, suggesting a possible interaction between the drugs. We cannot recommend that droperidol be added to propofol anesthesia for prophylaxis of postoperative nausea and vomiting.

Hemodynamic effects of intravenous famotidine in patients undergoing cardiac surgery.

STUDY OBJECTIVE: To determine the hemodynamic effects of famotidine in patients undergoing cardiac surgery. DESIGN: A prospective, randomized, double-blinded, placebo-controlled study. SETTING: A large university teaching hospital. PATIENTS: Twenty-one patients undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: The patients received a rapid intravenous bolus injection of famotidine 20 mg or saline placebo after anesthesia induction. A second dose was given 12 hours after surgery in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: Serial hemodynamic measurements (heart rate, arterial blood pressure, cardiac index, pulmonary arterial pressure, central venous pressure, systemic vascular resistance) were obtained after each famotidine or placebo dose and analyzed by ANOVA: The values were not altered (p > 0.05) after intraoperative or postoperative famotidine or placebo administration. CONCLUSIONS: Rapid intravenous bolus administration of famotidine does not alter patient hemodynamics after anesthesia induction or in the intensive care unit after cardiac surgery.

A double-blind, placebo-controlled evaluation of intranasal metoclopramide in the prevention of postoperative nausea and vomiting.

Nausea and vomiting are common complaints in the postoperative period and contribute to patient distress and delay of discharge for outpatient surgical procedures. Laparoscopic procedures are associated with a high incidence of postoperative nausea and vomiting (PONV) episodes. Parenteral use of metoclopramide prevents and treats PONV. The intranasal route provides rapid and complete absorption of metoclopramide without many of the adverse effects observed with parenteral administration of the drug. We performed a prospective, double-blinded, randomized, placebo-controlled study to evaluate the safety and efficacy of metoclopramide 20 mg administered intranasally for emetic prophylaxis in laparoscopic surgery patients. The results from 109 patients enrolled in the study showed that this intranasal dose of metoclopramide may be ineffective in preventing the occurrence of PONV. The poor performance of the intranasal metoclopramide formulation in this study cannot be attributed to patient-specific and perioperative factors. It may be due to an inadequate dose or slow absorption of the drug. The small sample size, however, may also have been a factor.