Standard gentamicin dosage regimen in neonates.

A standard gentamicin dosage regimen intended to result in fewer trough concentrations of >2 microg/mL was studied. At a neonatal intensive care unit, gentamicin dosage guidelines of 2.5 mg/kg (as the sulfate) administered i.v. over 30 minutes every 12, 18, or 24 hours to neonates with a gestational age (GA) of > or =30 weeks were resulting in some relatively high trough serum concentrations (>2 microg/mL). Pharmacokinetic values derived for this baseline group were used to predict the gentamicin concentrations that would result from a standard regimen of gentamicin 3.5 mg/kg i.v. over 30 minutes every 24 hours. No patient in the baseline group was predicted to have a trough of >2 microg/mL with the new regimen, which was then approved for routine use. The new regimen was used for every neonate with a GA of > or =30 weeks who was admitted and treated with gentamicin (the protocol group). One set of concentrations was collected for each infant. Compared with the baseline group, the protocol group had significantly lower trough and significantly higher peak gentamicin concentrations. The total frequency of high troughs in the baseline group (23 [33%] of 69 patients) differed significantly from that in the protocol group (3 [4%] of 74 patients). No patient had or developed renal impairment. A gentamicin dosage protocol of 3.5 mg/kg every 24 hours for neonates with a GA of > or =30 weeks resulted in higher gentamicin peaks, lower troughs, and a lower frequency of troughs of >2 microg/mL, compared with previous dosage practice.

Efficacy of recombinant fowl poxvirus vaccine in protecting chickens against a highly pathogenic Mexican-origin H5N2 avian influenza virus.

Internationally and nationally, governments and the poultry industries have used various strategies to control avian influenza (AI), ranging from a minimum of living with mildly pathogenic AI virus (AIV) infections to the other extreme of implementing a total quarantine-slaughter approach for eradication of highly pathogenic (HP) forms of the disease. However, recent economic considerations in various countries have prompted a broader reevaluation of vaccination as one of several tools to be used in AI control programs, including H5 and H7 HP AI. In the current study, 1-day-old chickens were immunized with a recombinant fowl poxvirus vaccine containing a hemagglutinin gene insert (Vector-HA) from an H5 AIV. Vector-HA- and negative control (vector-control)-vaccinated chicks were challenged with a HP H5N2 AIV isolated from chickens in Mexico. All immunized chickens were antibody negative on the agar gel precipitin test, indicating that vaccination would not interfere with routine AI serologic surveillance programs in the United States. However, in the hemagglutinin-inhibition test, a few immunized chickens (8%) had low serologic titers. Protection against illness (90-100%) and death (90-100%) was provided by the vector-HA vaccine from 3 wk of age to the end of the 20-wk study. The number of chickens shedding the challenge AIV from their enteric tracts was significantly reduced (50-75%) and the quantity of challenge AIV shed from respiratory and enteric tracts was significantly reduced (10(1)-10(2.1) mean embryo lethal dose/ml) in most vector-HA vaccine groups when compared with vector-control groups. Furthermore, vector-HA vaccination reduced in contact transmission of HP AI challenge virus to both vector-HA- and vector-control-vaccinated chickens. These findings indicate the recombinant fowl poxvirus vaccine can be a useful tool in an AI control program by preventing illness and death in chickens and reducing intestinal and respiratory shedding of H5 AIV. However, for an AI control program to be successful, enhanced biosecurity and surveillance must be practiced, and the vaccine's use must be controlled by an industry and/or government task force.

Efficacy of a recombinant fowl pox-based Newcastle disease virus vaccine candidate against velogenic and respiratory challenge.

A fowl pox-based recombinant virus TROVAC-NDV (vFP96.5) was developed expressing the fusion and hemagglutinin-neuraminidase glycoproteins from a velogenic strain of Newcastle disease virus (NDV). Studies in specific-pathogen-free birds indicated that inoculation of a single dose of the recombinant led to the induction of significant levels of hemagglutination-inhibiting antibody that were maintained to 8 wk postinoculation. Further, the recombinant induced protective immunity against a combined intramuscular velogenic NDV challenge and respiratory NDV challenge. In commercial broiler chickens that were inoculated in the presence of maternally derived NDV immunity, the level of the NDV-specific humoral response was dampened, but significant levels of protection against both a lethal intramuscular NDV challenge and a fowl poxvirus challenge were obtained.

Evaluation of pharmacists' practice in patient education when dispensing a metered-dose inhaler.

Improper inhalation technique with beta-agonist metered-dose inhalers (MDIs) decreases efficacy of the bronchodilator. The success of demonstrating the correct technique and the pharmacist's role in patient education has been reported. To obtain information regarding the routine patient education practice of pharmacists when dispensing a beta-agonist MDI (albuterol), the following study was performed. Fifty-two prescriptions for an albuterol MDI were presented to 52 randomly chosen community pharmacists in three Tennessee cities. Twenty-six independent and 26 chain pharmacies wer evaluated. Pharmacists' practice with regard to patient education, instruction, and demonstration of the correct usage of the MDI was observed and recorded. Overall, 13 percent of the pharmacists initially offered to educate the patient-investigator (PI) regarding the correct usage of the MDI without being asked for information. Fifty-three percent of pharmacists offered information only upon being asked specifically how to use the MDI. Of the pharmacists who offered to educate the PI, 71 percent discussed less than half of the eight steps correctly. Only 1 of the 52 pharmacists actually demonstrated MDI inhalation technique, and this in response to a request. No pharmacist asked the PI to perform the technique while he/she observed. No pharmacist offered information on delivery enhancement devices. Our results demonstrate that few pharmacists educate patients on the correct usage of an MDI, and that many pharmacists are not aware of the correct technique.

Review of diclofenac and evaluation of its place in therapy as a nonsteroidal antiinflammatory agent.

Diclofenac sodium is a nonsteroidal antiinflammatory drug (NSAID) that has been used in 120 countries since its introduction in Japan in 1974. It is currently the eighth largest-selling drug and the most frequently used NSAID in the world. Diclofenac, a phenylacetic acid derivative, is a potent inhibitor of cyclooxygenase enzyme activity, and may also interact with the lipoxygenase enzyme pathway, and with the release and reuptake of arachidonic acid. Diclofenac is almost completely absorbed, highly protein-bound, penetrates well into synovial fluid, and is extensively metabolized. Comparative studies have shown that diclofenac is at least equivalent in efficacy to aspirin and other NSAID when used for the treatment of rheumatic diseases such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Diclofenac also possesses potent analgesic properties. Clinical trials suggest that diclofenac has a favorable side-effect profile, excellent patient tolerability, and a lower patient dropout rate when compared with aspirin and other NSAID.

Leuprolide: a gonadotropin-releasing hormone analog for the palliative treatment of prostatic cancer.

Leuprolide is the first member of the class of gonadotropin-releasing hormone (GnRH) agonist analog to be released in the U.S. The pharmacology of leuprolide is complex and not yet completely defined. This agonist analog is more potent than natural GnRH and appears to be capable of occupying pituitary GnRH receptors. This results in a "down regulation" of the receptors' activity and gonadotropin release, ultimately decreasing serum testosterone levels to those seen following castration. Leuprolide has been found effective in the palliative treatment of advanced cases of prostatic cancer and is not associated with the cardiovascular and thromboembolic toxicity seen with conventional diethylstilbestrol therapy. Leuprolide is administered by daily subcutaneous injections and has been generally well tolerated. The most common adverse effects are hot flashes and a possible flare-up of prostatic carcinoma symptoms on initial dosing. As clinical experience grows in the use of GnRH agonist analog, GnRH will assume a greater role in the treatment of metastatic prostatic cancer.