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Biomedical subjects

R A Moore

Publications and source records attributed to R A Moore.

At least 127 records · Page 7Linked to original sources

Morphine responsiveness of chronic pain: double-blind randomised crossover study with patient-controlled analgesia.

There is controversy about whether the lack of response of some chronic pain to opioid treatment is absolute or relative. It is widely believed that nociceptive pain is responsive to opioids whereas neuropathic pain tends not to be. We have used a method of patient-controlled analgesia (PCA) with simultaneous nurse-observer measurement of analgesia, mood, and adverse effects to address these issues. Ten patients with chronic pain were given morphine at two concentrations (10 and 30 mg/ml) by PCA in two separate sessions in a double-blind randomised crossover study. Before the study a clinical judgment was made as to whether each pain was nociceptive or neuropathic. Seven patients showed good analgesic responses (more than 70 mm pain relief on a visual-analogue scale) of pain at rest, two patients poor responses (less than 30 mm pain relief), and one a moderate response with both concentrations (30-70 mm pain relief). The response to morphine was consistent (greater and faster relief with the higher concentration) in nine patients. Two patients had pain on movement that responded moderately to low-concentration morphine and well to the higher concentration. All patients with pains judged to be nociceptive showed good analgesic responses compared with half of those with neuropathic pain. There was no evidence that analgesic responses in patients with neuropathic pain were due to changes in mood. This PCA method is a quick and efficient tool to determine the consistency of the analgesic response. Such consistency can guide the clinician as to whether continued or higher-dose opioid treatment will produce good analgesia. An inconsistent response points to the use of other pain-relieving strategies.

Adult↗

A multiple dose comparison of combinations of ibuprofen and codeine and paracetamol, codeine and caffeine after third molar surgery.

In a randomised, double-blind, double-dummy, multiple dose, crossover study in 30 patients we compared an ibuprofen/codeine combination (400 mg ibuprofen/25.6 mg codeine phosphate) with a paracetamol/codeine/caffeine combination (1 g paracetamol/16 mg codeine phosphate/60 mg caffeine) for pain relief over 6 days after two-stage bilateral lower third molar removal. The ibuprofen combination produced significantly greater analgesia than the paracetamol combination, both on single-dose analysis of the first and second days and on multiple-dose measures for days 1, 2, 3 and 4. The mean incidence of adverse effects over the 6 days was 20% for both combinations. This trial design (crossover with multiple dosing in outpatients) is a sensitive way of testing for analgesia, and is potentially more predictive of adverse effect problems than single-dose studies. It confirms that multiple dosing may show increased efficacy.

Acetaminophen↗

Opioid sensitivity of chronic pain: a patient-controlled analgesia method.

Twenty-two patients with chronic pain of malignant or nonmalignant origin were given intravenous morphine by patient-controlled analgesia. A prestudy judgment was made from the characteristics of the pain as to whether it was nociceptive or neuropathic. Analgesic efficacy was assessed by a nurse-observer; adverse events were noted and plasma morphine and metabolitie concentrations measured. Three categories of opioid response were distinguished. Good responders obtained > 70 mm relief on the visual analogue scale, with minimal or manageable adverse events. Moderate responders obtained < 70 but > 30 mm relief with more problematic adverse events, and poor responders had < 30 mm relief with troublesome adverse events. This method for the study of opioid sensitivity allowed a wide dosage range to be studied. The simultaneous analgesic and adverse event measurements showed that the spectrum of observed response was wide, and response category could be judged for the majority by 4 h. In those with poor or moderate response, adverse event severity limited further dose increment. The relationship between pain characteristics and response showed that some pains judged to be neuropathic had a good response to opioid (5/13), and some pains judged to be nociceptive did not (5/14). The study suggests that the pattern of response is not as black and white as the prediction of good response from nociceptive pain and poor from neuropathic pain would suggest, although nociceptive pain was more likely than neuropathic pain to show a good response. For the moderate responders opioid titration may, in the absence of other effective treatments, be useful, but the analgesic endpoint may not be totally satisfactory. The method provides an operational definition of opioid sensitivity.

Adult↗

Benzydamine cream for the treatment of post-herpetic neuralgia: minimum duration of treatment periods in a cross-over trial.

In a double-blind multiple-dose cross-over study benzydamine 3% cream was compared with placebo for the treatment of post-herpetic neuralgia. Pain relief, pain intensity, sleep, escape analgesic consumption and side effects were assessed by diary methods for the 2 week treatment periods, with 1 week run-in and 1 week wash-out. There were no significant differences between the 2 treatments. The implications of the results for other antiprostaglandin remedies recommended for treatment of post-herpetic neuralgia are discussed. An important observation with methodological significance for similar studies of chronic conditions was that short treatment periods may produce false positive results. Patients' expectations are high, and if the first study treatment is ineffective, initial significant benefit may be noted when crossing over to the next treatment; this may not last longer than 1 week. Cross-over studies in which neither treatment is effective may, therefore, produce erroneous results if treatment periods are shorter than 2 weeks.

Administration, Topical↗

Oral morphine in cancer pain: influences on morphine and metabolite concentration.

One hundred fifty-one patients with chronic cancer pain were studied during chronic treatment with oral morphine. Plasma concentrations of morphine and metabolites (M3G and M6G) were measured. The ratio of plasma morphine to metabolites was not affected by dose. Generalized linear interactive modeling analysis using morphine dose, age, sex, renal and hepatic dysfunction, and concomitant medication as explanatory variables accounted for 70% of the variance in plasma concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Increasing morphine dose was a significant factor for increased plasma concentrations of morphine, M3G, and M6G. Other significant factors were: age greater than 70 years (increased M3G and M6G plasma concentrations), plasma creatinine greater than 150 mumol/L (increased M3G and M6G plasma concentrations), male sex (decreased morphine and M6G plasma concentrations), raised creatinine plus coadministration of tricyclic antidepressants (increased M3G plasma concentrations), ranitidine (increased morphine plasma concentrations), and raised creatinine plus coadministration of ranitidine (increased M6G plasma concentrations).

Adult↗

Buprenorphine disposition in patients with renal impairment: single and continuous dosing, with special reference to metabolites.

The disposition of buprenorphine has been studied in two patient groups to assess the influence of impaired renal function on the metabolism of buprenorphine and two of its metabolites, buprenorphine-3-glucuronide (B3G) and norbuprenorphine (NorB). A single i.v. dose of 0.3 mg was given to 15 patients (nine with dialysis-dependent renal failure) undergoing lower abdominal or peripheral body surface surgery. Blood was sampled up to 24 h. Concentrations of buprenorphine, B3G and NorB were assayed by a differential radioimmunoassay technique. There were no differences in buprenorphine kinetics between anaesthetized healthy patients and those with renal impairment: mean elimination half-lives 398 and 239 min; clearance 651 and 988 ml min-1; apparent volume of distribution at steady state 313 and 201 litre, respectively. Both metabolites were undetectable following the single i.v. dose. In a second group of 20 patients (eight with renal impairment), buprenorphine was administered by continuous infusion for provision of analgesia and control of ventilation in the ITU (median infusion rate 161 micrograms h-1 (range 36-230 micrograms h-1) for a median duration of 30 h (2-565 h). Buprenorphine clearance in patients with normal and impaired renal function was similar (934 and 1102 ml min-1, respectively), as were dose-corrected plasma concentrations of buprenorphine. In patients with renal failure, plasma concentrations of NorB were increased by a median of four times, and B3G concentrations by a median of 15 times.

Adolescent↗

The effect of the American Heart Association step one diet on hyperlipidemia following renal transplantation.

Cardiovascular disease is a frequent cause of morbidity and mortality following renal transplantation. The percentage of deaths due to ischemic cardiovascular disease and cerebrovascular accidents nearly equals that caused by infection among patients receiving their first transplant, according to data from the European Dialysis and Transplant Association Registry. Hypercholesterolemia is a risk factor for cardiovascular disease frequently identified following renal transplantation, and diets low in fat and cholesterol have been suggested as treatment. Previous studies have not reported the response of LDL cholesterol to dietary treatment, and it is this form of cholesterol that is most closely related to cardiovascular disease. The American Heart Association has provided nutritionists with guidelines for the treatment of hyperlipidemic patients which include the Step One Diet. Previous dietary studies of renal transplant recipients have allowed a slightly higher intake of fat than that currently recommended by the AHA. We wondered if an easily reproducible diet well known to nutritionists such as the AHA Step One Diet would be effective in lowering cholesterol levels in hyperlipidemic renal transplant recipients. The purpose of our study was not to define the mechanisms of posttransplant hyperlipidemia, but rather to assess the effectiveness of dietary intervention on hyperlipidemia following renal transplantation.

Adult↗

Construction and Use of a Nonradioactive DNA Hybridization Probe for Detection of Pseudomonas syringae pv. Tomato on Tomato Plants.

Pseudomonas syringae pv. tomato, the causal agent for bacterial speck of tomato, produces the phytotoxin coronatine. A 5.3-kilobase XhoI fragment from the chromosomal region controlling toxin production was cloned into the plasmid pGB2, and the resulting recombinant plasmid, pTPR1, was tested for its ability to serve as a diagnostic probe for P. syringae pv. tomato. In a survey of 75 plant-associated bacteria, pTPR1 hybridized exclusively to those strains that produced coronatine. The detection limit for this probe, which was labeled with the Chemiprobe nonradioactive reporter system, was approximately 4 x 10 CFU of lesion bacteria. During the 1989 growing season, a total of 258 leaf and fruit lesions from nine tomato fields were screened for P. syringae pv. tomato by using pTPR1 and the culture method of detection. The best agreement between the two methods, 90%, occurred early in the season with samples taken from relatively young (5-week-old) plants. Young plants also had a higher percentage of P. syringae pv. tomato-positive lesions. P. syringae pv. tomato was the only coronatine producer recovered from the nine tomato fields. All 244 P. syringae pv. tomato strains isolated during this study reacted strongly with the probe. The P. syringae pv. tomato population of healthy field tomato leaves was determined by a pTPR1 colony hybridization procedure. Every probe-positive colony that was isolated and characterized was identified as P. syringae pv. tomato. The pTPR1 probe should expedite disease diagnosis and facilitate epidemiological studies of this pathogen. It also should aid in screening transplant seedlings for bacterial speck infestation.

Journal Article↗

Use of a personal computer to support an investigational drug service.

A description of the rationale for the computerization of an Investigational drug service, (IDS) including the potential for benefits in three major areas: (1) policy & procedure, (2) financial analysis, and (3) drug accountability. Through the use of readily available computer software, dispensing, and billing procedures have been streamlined. Software with spreadsheet capability facilitates analysis of the financial status of the IDS. A specially designed software package allows maintenance of the drug account-ability records for investigational protocols.

Accounting↗

Codeine 20 mg increases pain relief from ibuprofen 400 mg after third molar surgery. A repeat-dosing comparison of ibuprofen and an ibuprofen-codeine combination.

A combination of 20 mg codeine base and ibuprofen 400 mg was compared with ibuprofen 400 mg in a randomised double-blind cross-over study of multiple doses in 25 patients after 2-stage bilateral third molar removal. The combination produced significantly greater pain relief and doubled the hours of minimum pain intensity and maximal relief on the day of surgery. The patients rated the combination significantly better than ibuprofen alone, and the combination was preferred by 16 of the 22 patients expressing a preference. There was no significant increase in side-effect incidence with the combination. The 30% increase in analgesic effect may be of clinical benefit, and this trial design, cross-over with multiple dosing in out-patients, may be a sensitive test for analgesics, potentially more predictive of side-effect problems than single-dose studies.

Adult↗

Studies on morphine disposition: plasma concentrations of morphine and its metabolites in anesthetized middle-aged and elderly surgical patients.

The effects of aging on the disposition of morphine and its metabolites have been investigated in 10 middle-aged patients (36 to 55 years of age) undergoing lower abdominal or body surface surgery, and compared with 10 elderly patients (65 to 83 years of age) undergoing similar surgery. All patients received 10 mg morphine sulphate pentahydrate IV over 30 seconds as part of a balanced anesthetic technique. Peripheral venous blood samples were collected to 180 min, and plasma concentrations of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) were assayed by differential radioimmunoassay. There were no differences between the two groups for morphine elimination half-life (middle-aged patients, 129 min; elderly patients, 162 min), mean residence time (154 and 207 min), and apparent volume of distribution at steady state (116 and 107 l). However, clearance was significantly greater in the younger patients (853 vs. 559 ml/min; p less than 0.02). The area under the curve (AUC0-180) for M3G and M6G were similar in the two patient groups, as were the peak metabolite concentrations and times to peak concentrations. M6G has been shown in both animals and humans to exert analgesic properties. Despite the reduced clearance of the parent drug, there was an unaltered AUC for M6G, presumed due to the greater decrease in glomerular filtration rate seen during anesthesia in the elderly patient. This phenomenon may result in enhanced analgesic efficacy from a given dose of morphine in the elderly patient.

Adult↗

Studies on morphine disposition: influence of general anaesthesia on plasma concentrations of morphine and its metabolites.

The kinetics of morphine were studied during balanced anaesthesia in 10 patients undergoing lower abdominal or body surface surgery, and compared with those obtained in nine awake patients receiving morphine i.v. for the relief of chronic non-cancer pain. All patients received morphine sulfphate pentahydrate 10 mg i.v. over 30 s. Venous blood samples were collected for up to 180 min, and plasma concentrations of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) assayed by a differential radioimmunoassay technique. There were no differences between groups with respect to the elimination half-life (awake group: 207 min; anaesthetized group: 153 min), volume of distribution at steady state (awake: 147 litre; anaesthetized: 128 litre), or clearance (awake: 587 ml min-1; anaesthetized: 766 ml min-1). Peak concentrations of M3G were similar in the two groups, but the peak concentration of M6G was greater in the anaesthetized patients. The AUC for M3G and M6G (0-180 min) also were greater in the anaesthetized patients, presumably as a result of decreases in renal blood flow and glomerular filtration rate during halothane anaesthesia.

Adult↗

Studies on morphine disposition: influence of renal failure on the kinetics of morphine and its metabolites.

The influence of renal failure on the disposition of morphine and its metabolites was studied in nine patients with end-stage renal failure undergoing transplantation, and compared with five healthy anaesthetized patients. All patients received morphine sulphate pentahydrate 10 mg i.v. over 30 s, as part of a balanced anaesthetic technique. Venous blood samples were collected for up to 24 h, and plasma concentrations of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) assayed by a differential radioimmunoassay method. There were no differences between the two groups for morphine elimination half-life (renal failure: 290 min; anaesthetized controls: 286 min), or clearance (renal failure: 533 ml min-1; controls 741 ml min-1). However, the volume of distribution at steady state was greater in the control group (241 litre v. 141 litre; P = 0.002). The peak concentrations of M3G and M6G were greater in the renal transplant patients (P = 0.001 and P = 0.01, respectively), as were the AUC (0-24 h) (P = 0.002 and P = 0.002). M6G has been shown to possess analgesic properties in both man and experimental animals, and therefore the increased AUC for M6G may contribute to the prolonged effect seen with morphine when given to patients with impaired renal function.

Adult↗

The elderly victim of rape.

A common misconception about sexual assault is that the rapist is motivated by a sexual desire stimulated by a victim seductive in her behavior or dress. A retrospective analysis of 740 reported sexual assaults revealed 21 cases involving a victim between the ages of 60 and 90 years of age. The elderly victim was more often white and the assailant more often black than when younger victims are involved. Also, the data suggest that the rape of elderly women may involve a relatively few rapists, and that their assaults are of a serial nature. This study concludes that these rapists are motivated by anger, possibly racially related, and a need to express power, rather than by sexual desire.

Black or African American↗

Local pulmonary ventilation using nonradioactive xenon-enhanced ultrafast computed tomography.

Using ultrafast computed tomography, we have developed a technique for measuring local ventilation in a volume of 1 cm3 in the normal supine lung. The technique employs the inert gas xenon in its nonradioactive form and makes use of its radiopaque properties. The inhalation of xenon results in changes in density which can be detected and measured in Hounsfield units using ultrafast computed tomography. Using this property and assuming a monoexponential form for the washin curve of the inert gas, it is possible to calculate ventilation at a local level. The methodology also permits measurements of minute ventilation during the procedure, thus permitting standardization. Using this technique, we calculated local ventilation in six normal subjects and have demonstrated a minor gradient in ventilation between the dorsal and ventral regions of the lung while in the supine position.

Adult↗