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Biomedical subjects

R J Orr

Publications and source records attributed to R J Orr.

16 recordsLinked to original sources
PubMed2004

Dietary preference of dairy cows grazing ryegrass and white clover.

The dietary preference of lactating dairy cows grazing perennial ryegrass (Lolium perenne L.) and white clover (Trifolium repens L.) was studied. Twelve groups of 2 lactating, Holstein-Friesian dairy cows grazed 1.2-ha plots containing conterminal monocultures of clover and grass. Half of the groups grazed a plot containing 75% clover and 25% grass (by ground area), with the remaining groups grazing a plot containing 25% clover and 75% grass. The intake rates of clover were higher than those of grass, and intake rates were higher in the evening than in the morning. During daylight hours, clover formed 63.2% of the diet of the groups offered 25% clover, which was higher than the 25% offered but lower than preference for 100% clover. This indicated that cows showed a partial preference for clover, with an overall value (i.e., the mean of the 75% and 25% clover groups) of 73.8%. There was a diurnal pattern to preference, with a stronger preference for clover in the morning and with the preference for grass increasing during the day. The basis for partial preference remains unclear and warrants further research.

Animals↗
PubMed2001

Polyinosinic acid and polycationic liposomes attenuate the hepatic clearance of circulating plasmid DNA.

DNA that enters the circulation is rapidly cleared both by tissue uptake and by DNase-mediated degradation. In this study, we have examined the uptake of linear plasmid DNA in an isolated perfused liver model and following intra-arterial administration to rats. We found that the DNA was rapidly taken up by the isolated perfused liver without degradation. The single-pass extraction ratio was 0.76 +/- 0.05, the mean transit time was 15.3 +/- 3.6 s, and the volume of distribution was 0.29 +/- 0.07 ml/g. Hepatic uptake was saturable and was inhibited by polyinosinic acid or polycationic liposomes but not by condensation of the DNA with polylysine. When the linear plasmid DNA was administered in vivo, plasma half-life was 3.1 +/- 0.2 min, volume of distribution was 670 +/- 85 ml/kg, and clearance was 32 +/- 4 ml/min. Coadministration of cationic liposomes decreased the volume of distribution to 180 +/- 28 ml/kg as well as the half-life (2.6 +/- 0.2 min). By contrast, polyinosinic acid significantly increased the circulating half-life (7.7 +/- 0.5 min), decreased the volume of distribution (95 +/- 17 ml/kg), and partially inhibited DNA degradation. When administered along with the liposomes and the polyinosinic acid, the distribution of plasmid-derived radioactivity decreased in the liver and increased in most other peripheral tissues. This study shows that pharmacological manipulation of the uptake and degradation of DNA can alter its distribution and clearance in vivo. These results may be useful in optimizing gene delivery procedures for in vivo gene therapy.

Animals↗
PubMed2000

A randomized, double-blinded study of remifentanil versus fentanyl for tonsillectomy and adenoidectomy surgery in pediatric ambulatory surgical patients.

UNLABELLED: We compared, in a double-blinded manner, the anesthetic maintenance and recovery properties of remifentanil with a clinically comparable fentanyl-based anesthetic technique in pediatric ambulatory surgical patients. Anesthesia was induced with either halothane or sevoflurane and nitrous oxide and oxygen. Patients were randomized (computer generated) to receive either remifentanil or fentanyl in a blinded syringe with nitrous oxide and oxygen in one of four possibilities: halothane/remifentanil, halothane/fentanyl, sevoflurane/remifentanil or sevoflurane/fentanyl. In patients receiving remifentanil, a placebo bolus was administered, and a continuous infusion (0.25 microg. kg(-1). min(-1)) was begun. In patients receiving fentanyl, a bolus (2 microg/kg) was administered followed by a placebo continuous infusion. The time from discontinuation of the anesthetic to extubation, discharge from the postanesthesia care unit (PACU), and discharge to home, as well as pain scores, were assessed by a blinded nurse observer. Systolic blood pressure and heart rate were noted at selected times, and adverse events were recorded. Remifentanil provided faster extubation times and higher pain-discomfort scores. PACU and hospital discharge times were similar. There were no statistical differences among the groups for adverse events. There were statistically, but not clinically, significant differences in hemodynamic variables. We noted that continuous infusions of remifentanil were intraoperatively as effective as bolus fentanyl. Although patients could be tracheally extubated earlier with remifentanil, this did not translate to earlier PACU or hospital discharge times. In addition, remifentanil was associated with higher postoperative pain scores. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanil's use as an anesthetic for children. IMPLICATIONS: This is a study designed to examine the efficacy and safety of a short-acting opioid, remifentanil, when used in pediatric patients. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanil's use as an anesthetic for children.

Adenoidectomy↗
PubMed1999

The pharmacology of gene therapy.

The objective for human gene therapy is to express exogenous DNA at a site in vivo for long enough, and at sufficient levels to produce a therapeutic response. The obstacles to this objective are numerous and include the formulation or packaging of the DNA, in vivo delivery, penetration of biological barriers, DNA elimination within the cell and from the tissue compartments of the whole body, control of product expression and overt toxicity. The current challenge is to resolve each of these obstacles to produce a practical and efficient gene therapy. In doing so, it is vital to understand the disposition of DNA vectors in vivo, and to know how conventional medicines may be used to modulate this disposition and to enhance the therapeutic effect of these vectors. Many of the general concepts of human gene therapy have been reviewed extensively in the literature. This review discusses some of the pharmacological aspects of gene delivery and the fate of vectors in vivo, and then highlights how drugs are being used to modulate gene therapy.

Chemistry, Pharmaceutical↗
PubMed1997

Single-dose ondansetron prevents postoperative vomiting in pediatric outpatients.

UNLABELLED: This randomized, double-blind, parallel-group, multicenter study evaluated the safety and efficacy of ondansetron (0.1 mg/kg to 4 mg intravenously) compared with placebo in the prevention of postoperative vomiting in 429 ASA status I-III children 1-12 yr old undergoing outpatient surgery under nitrous oxide- and halothane-based general anesthesia. The results show that during both the 2-h and the 24-h evaluation periods after discontinuation of nitrous oxide, a significantly greater percentage of ondansetron-treated patients (2 h 89%, 24 h 68%) compared with placebo-treated patients (2 h 71%, 24 h 40%) experienced complete response (i.e., no emetic episodes, not rescued, and not withdrawn; P < 0.001 at both time points). Ondansetron-treated patients reached criteria for home readiness one-half hour sooner than placebo-treated patients (P < 0.05). The age of the child, use of intraoperative opioids, type of surgery, and requirement to tolerate fluids before discharge may also have affected the incidence of postoperative emesis during the 0- to 24-h observation period. Use of postoperative opioids did not have any effect on complete response rates in this patient population. We conclude that the prophylactic use of ondansetron reduces postoperative emesis in pediatric patients, regardless of the operant influential factors. IMPLICATIONS: Postoperative nausea and vomiting often occur after surgery and general anesthesia in children and are the major reason for unexpected hospital admission after ambulatory surgery. Our study demonstrates that the prophylactic use of a small dose of ondansetron reduces postoperative vomiting in pediatric patients.

Anesthesia, General↗
PubMed1996

Induction, recovery, and safety characteristics of sevoflurane in children undergoing ambulatory surgery. A comparison with halothane.

BACKGROUND: Sevoflurane is an inhalational anesthetic with characteristics suited for use in children. To determine whether the induction, recovery, and safety characteristics of sevoflurane differ from those of halothane, the following open-labeled, multicenter, randomized, controlled, phase III study in children undergoing ambulatory surgery was designed. METHODS: Three hundred seventy-five children, ASA physical status 1 or 2, were randomly assigned in a 2:1 ratio to receive either sevoflurance or halothane, both in 60% N2O and 40% O2. Anesthesia was induced using a mask with an Ayre's t piece or Bain circuit in four of the centers and a mask with a circle circuit in the fifth center. Maximum inspired concentrations during induction of anesthesia were 7% sevoflurane and 4.3% halothane. Anesthesia was maintained by spontaneous ventilation, without tracheal intubation. End-tidal concentrations of both inhalational anesthetics were adjusted to 1.0 MAC for at least 10 min before the end of surgery. Induction and recovery characteristics and all side effects were recorded. The plasma concentration of inorganic fluoride was measured at induction of and 1 h after anesthesia. RESULTS: During induction of anesthesia, the time to loss of the eyelash reflex with sevoflurane was 0.3 min faster than with halothane (P < 0.001). The incidence of airway reflex responses was similar, albeit infrequent with both anesthetics. The total MAC.h exposure to sevoflurane was 11% less than the exposure to halothane (P < 0.013), although the end-tidal MAC multiple during the final 10 min of anesthesia was similar for both groups. Early recovery as evidenced by the time to response to commands after sevoflurane was 33% more rapid than it was after halothane (P < 0.001), although the time to discharge from hospital was similar for both anesthetics. The mean ( +/- SD) plasma concentration of inorganic fluoride 1 h after discontinuation of sevoflurane was 10.3 +/- 3.5 microM. The overall incidence of adverse events attributable to sevoflurane was similar to that of halothane, although the incidence of agitation attributable to sevoflurane was almost threefold greater than that attributable to halothane (P < 0.004). CONCLUSIONS: Sevoflurane compared favorably with halothane. Early recovery after sevoflurane was predictably more rapid than after halothane, although this was not reflected in a more rapid discharge from the hospital. The incidence of adverse events was similar for both anesthetics. Clinically, the induction, recovery, and safety characteristics of sevoflurane and halothane are similar. Sevoflurane is a suitable alternative to halothane for use in children undergoing minor ambulatory surgery.

Ambulatory Surgical Procedures↗
PubMed1976

Is continuous transpulmonary pressure better than conventional respiratory management of hyaline membrane disease? A controlled study.

The influence of continuous positive airway pressure (CPAP) and positive end-expiratory pressure (PEEP) on mortality and complication rates in severe hyaline membrane disease (HMD) was evaluated in a randomized, prospective study. Patients were admitted to the study if the Po2 was less than 50 mm Hg with FiO2 greater than 0.6. Twenty-four patients in each of three weight groups were equally divided between treatment and control groups. The treatment regimen included CPAP (6 to 14 cm H2O) for spontaneously breathing patients and PEEP for patients requiring mechanical ventilation for apnea or hypercapnia (Pco2 greater than 65 mm Hg). Control patients received oxygen and were mechanically ventilated if they had apnea, hypercapnia, or Po2 less than 50 mm Hg with FiO2 greater than 0.8. Oxygenation improved after the start of CPAP or PEEP; however, Pco2 rose after CPAP was initiated. There was no significant difference between treatment and control groups in mortality, requirement for mechanical ventilation, or incidence of pulmonary sequelae. The incidence of pulmonary air-leak was increased with Peep. the findings suggest that CPAP and PEEP have not significantly altered the outcome of HMD.

Carbon Dioxide↗