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Biomedical subjects

A Woodhouse

Publications and source records attributed to A Woodhouse.

14 recordsLinked to original sources
PubMed1998

Pulmonary administration of aerosolised fentanyl: pharmacokinetic analysis of systemic delivery.

AIMS: Pulmonary drug delivery is a promising noninvasive method of systemic administration. Our aim was to determine whether a novel breath-actuated, microprocessor-controlled metered dose oral inhaler (SmartMist, Aradigm Corporation) could deliver fentanyl in a way suitable for control of severe pain. METHODS: Aersolised pulmonary fentanyl base 100-300 microg was administered to healthy volunteers using SmartMist and the resultant plasma concentration-time data were compared with those from the same doses administered by intravenous (i.v.) injection in the same subjects. RESULTS: Plasma concentrations from SmartMist were similar to those from i.v. injection. Time-averaged bioavailability based upon nominal doses averaged approximately 100%, and was > 50% within 5 min of delivery. Fentanyl systemic pharmacokinetics were similar to those previously reported with no trends to dose-dependence from either route. Side-effects (e.g. sedation, lightheadedness) were the same from both routes. CONCLUSIONS: Fentanyl delivery using SmartMist can provide analgetically relevant plasma drug concentrations. This, combined with its ease of noninvasive use and transportability, suggests a strong potential for field and domicilliary use, and for patient controlled analgesia without the need for i.v. cannulae.

Administration, Inhalation↗
PubMed1998

The effect of duration of dose delivery with patient-controlled analgesia on the incidence of nausea and vomiting after hysterectomy.

AIMS: Postoperative nausea and vomiting (PONV) may be exacerbated by postoperative opioid analgesics and may limit patients' successful use of these medications when used with patient controlled analgesia (PCA). We tested the hypothesis that the rapid change in blood morphine concentration associated with PCA bolus delivery contributed to PONV, and that prolonging its delivery to a brief infusion would result in decreased PONV. METHODS: Patients, who were receiving morphine for pain relief via patient-controlled analgesia (PCA) after total abdominal hysterectomy, received 1 mg morphine sulphate incremental doses either over 40 s with a 5 min lockout interval or over 5 min delivery with a 1 min lockout interval. Episodes of nausea, retching and vomiting, along with the use of morphine and the pain relief obtained, were recorded. RESULTS: Data from 20 patients in each group were analysed. Contrary to expectations, most patients in both groups reported nausea postoperatively. Those patients receiving morphine over 5 min experienced more episodes of emesis (36) than those receiving the dose over 40 s (17). Most patients receiving the 40 s doses vomited in the first 12 h (median time 8 h), while those receiving the 5 min doses vomited between 12 and 24 h (median time 19 h) (P = 0.01). There were no differences between groups in the visual analogue pain scores or use of morphine between groups. CONCLUSIONS: Reasons for these unexpected findings remain speculative. The high incidence of PONV appears to be inherently high in gynaecological surgery patients and standard antiemetic medication regimens appear to be poorly efficacious. Reasons for the differences in the time-course of emetic episodes between the two groups may be related to differences in the time-course of central opioid receptor occupancy.

Adult↗
PubMed1998

Pain description and severity of chronic orofacial pain conditions.

A multidisciplinary pain centre study of 120 consecutive chronic orofacial pain patients assessed pain description and intensity ratings, gender differences, prevalence of concurrent conditions, and interinstrument relationships of the McGill Pain Questionnaire and visual analogue scale. Pain words chosen by patients to describe conditions were predominantly sensory words, and patients with concurrent conditions often listed words indicating a substantial affective component. Results showed pain intensity ratings of chronic orofacial pain conditions have similar or higher pain ratings when compared with other medical chronic pain conditions such as back pain, cancer pain and arthritis. There was a significantly higher female: male ratio (88:32) with gender playing an important but poorly understood causal role. The most frequent condition diagnosed was atypical facial pain (n = 40), followed by temporomandibular disorder (n = 32), atypical odontalgia (n = 29) and pathology of the orofacial region (n = 19). Temporomandibular disorder was present in 75 of the 120 subjects, as the sole pain complaint (n = 32) or as an associated secondary condition (n = 43), indicating concurrent pain conditions exist and may be related. There were significantly higher total pain scores of the McGill Pain Questionnaire in patients with multiple conditions compared with patients with a single condition. The visual analogue scale showed a significant correlation to the number of words chosen index of the McGill Pain Questionnaire for orofacial pain.

Adolescent↗
PubMed1997

Determination of subnanogram concentrations of fentanyl in plasma by gas chromatography-mass spectrometry: comparison with standard radioimmunoassay.

A method was devised to determine fentanyl plasma concentrations by GC-MS using selected-ion monitoring (SIM) with sufentanil as internal standard. This was compared with a commonly used commercial radioimmunoassay (RIA). Sample preparation for GC-MS involved basification of plasma then extraction using n-butyl chloride followed by concentration to dryness and reconstitution in toluene for chromatography. Using 1-ml plasma samples, the estimated limit of detection of fentanyl was 20 pg/ml. Blood samples for pharmacokinetic studies were split and assayed by GC-MS and RIA which had a limit of detection of 200 pg/ml. Pearson's r (r - 0.80, p < 0.0001) indicated the methods were highly correlated at all plasma concentrations. Owing to the greater sensitivity of the method, GC-MS is recommended over RIA for subnanogram determination of fentanyl in plasma.

Analgesics, Opioid↗
PubMed1997

Morphine pharmacokinetics after pulmonary administration from a novel aerosol delivery system.

BACKGROUND: Successful pharmacotherapy of pain often depends on the mode of drug delivery. A novel, unit dose, aqueous aerosol delivery system (AERx Pulmonary Drug Delivery System) was used to examine the feasibility of the pulmonary route for the noninvasive systemic administration of morphine. METHODS: The study had two parts: (1) a dose-ranging study in four subjects with three consecutive aerosolized doses of 2.2, 4.4, and 8.8 mg (nominal) morphine sulfate pentahydrate at 40-minute intervals, and (2) a crossover study, on separate days, in six subjects with 4.4 mg (nominal) aerosolized morphine sulfate administered over 2.1 minutes on three occasions and intravenous infusions of 2 and 4 mg over 3 minutes. Subjects were healthy volunteers from 19 to 34 years old. Arterial blood was sampled for a total of 6 hours and plasma morphine concentrations were measured by gas chromatography-mass spectrometry. RESULTS: In part 1, plasma morphine concentrations were proportional to dose. In part 2, the mean +/- SD peak plasma concentration (Cmax) occurred at 2.7 +/- 0.8 minutes after the aerosol dose, with mean values for Cmax of 109 +/- 85, 165 +/- 22, and 273 +/- 114 ng/ml for the aerosol and 2 and 4 mg intravenous doses, respectively. The bioavailability [AUC(0-360 min)] of aerosol-delivered morphine was approximately 100% relative to intravenous infusion, with similar intersubject variability in AUC for both routes (coefficient of variation < 30%). CONCLUSION: The time courses of plasma morphine concentrations after pulmonary delivery by the AERx system and by intravenous infusions were similar. This shows the utility of the pulmonary route in providing a noninvasive method for the rapid and reproducible systemic administration of morphine if an appropriate aerosol drug delivery system is used.

Administration, Inhalation↗
PubMed1997

Using cross-check questions to address the problem of mis-reporting of specific food groups on Food Frequency Questionnaires. UKWCS Steering Group. United Kingdom Women's Cohort Study Steering Group.

OBJECTIVE: To explore the potential mis-reporting of specific food groups from food frequency questionnaire (FFQ) data and to examine the effect of using a weighting factor on estimated nutrient intake and ranking of subjects within the cohort according to nutrient intake. DESIGN AND SUBJECTS: A weighting factor was calculated for each of the individual 6572 women aged 35-69 y for four food groups, fish, meat, vegetables and fruit, using FFQ data and cross-check responses. RESULTS: The vegetables weighting had most effect on median intakes, particularly of fibre, vitamins A, C and E and folate. When all the weightings were applied, the median intakes of vitamins A and E were reduced by 35% and 27% respectively and the vitamin C intake was reduced by 44%. Ranking of subjects within the cohort according to nutrient intake was barely affected by the fish and meat weightings. The vegetable weighting had most effect on vitamin A with a rank correlation coefficient of 0.88. When all the weightings were applied the rank correlations for vitamins A, C and E and folate were all less than 0.90. CONCLUSION: Inclusion of cross-check questions in FFQs can provide an additional source of information on food group intake. This can be compared with FFQ data to help identify possible over-reporting and then to adjust frequency of intake accordingly.

Adult↗
PubMed1997

Nausea and vomiting in the postoperative patient-controlled analgesia environment.

Despite common clinical opinion that patient-controlled analgesia should be renamed 'patient-controlled nausea', there is little evidence in support of the notion that postoperative nausea and vomiting are exacerbated by the method. Indeed, data indicate that opioid-sparing techniques are not associated with less postoperative nausea and vomiting. Although some evidence suggests that certain opioids are less emetogenic than others, this too does not stand scrutiny when compared across patients, although research is still required to find whether individual patients are better treated with a particular opioid. Similarly, the emerging practice of combining anti-emetics with patient-controlled analgesia needs wider study before it can be supported.

Analgesia, Patient-Controlled↗
PubMed1997

The influence of age upon opioid analgesic use in the patient-controlled analgesia (PCA) environment.

It is often asserted that older patients are more sensitive to opioid analgesics than younger patients but experimental evidence for this assertion remains sparse. Two studies were conducted investigating the relationship between age and opioid analgesic use in the patient-controlled analgesia environment. In study I, the relationship was analysed subsequent to our publication of a study investigating patients' responses to opioid use with patient-controlled analgesia. Fifty-five postoperative patients, stratified into 'older' and 'younger' patients by median age, received morphine or pethidine or fentanyl patient-controlled analgesia. A strong inverse relationship was found between age and fentanyl and morphine use but not between age and pethidine use. Study II was a retrospective study of the medical records of 199 patient-controlled analgesia patients who had received morphine or pethidine patient-controlled analgesia; there were insufficient patients who had used fentanyl for a reasonable sample. There was a difference in morphine use with the younger patients using significantly more morphine than the older patients (< 60 years). Findings were less clear for patients receiving pethidine but there was an inverse correlation between age and pethidine use as well. Overall, the findings of these two studies supported the common clinical belief that older patients require less opioids than younger patients.

Adult↗
PubMed1993

Painful stimulation of the forehead increases photophobia in migraine sufferers.

Thresholds for visual and auditory discomfort were investigated in 51 migraine sufferers and 27 controls of similar age and sex distribution who rarely suffered from headache. Tests in migraine sufferers were carried out during the headache-free interval. Discomfort thresholds were measured before and during painful stimulation of the forehead with ice. The visual discomfort threshold was lower in migraine sufferers than in controls, and decreased further during painful stimulation of the forehead. In contrast, the auditory discomfort threshold was similar in migraine sufferers and controls, and did not decrease during painful stimulation of the forehead. These findings suggest that trigeminal discharge contributes to photophobia but not phonophobia in migraine sufferers.

Adult↗
PubMed1993

Mechanisms of increased sensitivity to noise and light in migraine headache.

To determine whether phonophobia is a manifestation of loudness recruitment, the hearing and auditory discomfort thresholds to an 8000 Hz tone were measured during the headache-free interval and again during an attack of migraine in 16 migraine sufferers. The visual discomfort threshold was also determined. For comparison, measures were taken in 16 non-headache controls of similar age and sex distribution. Auditory and visual discomfort thresholds decreased substantially during attacks of migraine. Increases (three subjects) or decreases (three subjects) in hearing threshold during attacks of migraine were significantly greater than the variation recorded in control subjects from Session 1 to Session 2. The findings do not support the view that phonophobia in migraine is a manifestation of loudness recruitment, although cochlear disturbances might mediate hearing loss in some cases. Disruption of central sensory processing mechanisms during migraine could increase sensitivity to quiet sounds, and contribute to phono- and photophobia.

Adult↗
PubMed1990

Purification of hamster dihydroorotate synthetase using Procion blue-Sepharose.

Dihydroorotate (DHO) synthetase is a trifunctional protein that catalyzes the first three reactions of de novo pyrimidine biosynthesis. A single-step procedure for purification of DHO synthetase from mutant hamster cells that overproduce this protein has been developed. The synthetase is adsorbed from a postmitochondrial supernatant to a column of Procion blue-Sepharose 4B and, after the column is washed, the synthetase is eluted as a single peak with 0.4 M KCl. Pooled fractions from the trailing side of this peak yield DHO synthetase with a specific activity for aspartate transcarbamylase of 14 mumol/min/mg protein, representing a purification factor of 8.5-fold and a recovery of 28% from the postmitochondrial supernatant. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the DHO synthetase was of high purity. A further 34% of the DHO synthetase from the leading side of the eluted peak contained a minor proportion of a proteolytic fragment. Similar results were obtained with an established four-step purification procedure.

Animals↗
PubMedDate not supplied

The minimum effective concentration of opioids: a revisitation with patient controlled analgesia fentanyl.

BACKGROUND AND OBJECTIVES: Whether patients titrate themselves to an individualized blood or plasma opioid concentration (the so-called minimum effective concentration or [MEC]) has been debated extensively. Nevertheless, there is consistent opinion that during patient controlled analgesia (PCA) patients balance acceptable pain relief against unacceptable side effects. This study sought to characterize fentanyl used by PCA with respect to MEC and factors influencing PCA use. METHODS: An intensive study of 25 patients with observations over the first 24 hours after orthopedic surgery was planned on the premise that this approach would provide a measure of the fentanyl MEC. This necessitated repeated measurements of pain scores and plasma fentanyl concentrations before and 10 minutes after every PCA demand. In addition, a battery of psychological tests was given before and approximately 48 hours after surgery. RESULTS: Logistic difficulties of maintaining a 24-hour study design resulted in its termination after 5 patients. The patients had convincingly distinct MECs (ranging from 0.23 to 0.99 ng/mL). The relationship between plasma fentanyl concentration and pain score was steep, such that small changes in concentration coincided with marked changes in pain relief. Despite preoperative expectations of achieving satisfaction in postoperative analgesia, not all patients titrated themselves to a pain-free state; all but one were satisfied with PCA. Surprisingly few side effects were reported. Unfortunately, the small sample size made systematic analysis of the psychological tests impossible. CONCLUSIONS: This study found evidence to support the concepts of an individual MEC and a therapeutic window of fentanyl used with PCA.

Adult↗