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Biomedical subjects

R A Moore

Publications and source records attributed to R A Moore.

At least 163 records · Page 9Linked to original sources

Analysis of morphine and its major metabolites by differential radioimmunoassay.

The analysis of morphine, morphine-3-glucuronide (M-3-G) morphine-6-glucuronide (M-6-G) by differential radioimmunoassay using iodinated label and three different antisera is described. These methods were used to measure concentrations of morphine and its conjugated metabolites in human plasma, over a 3-h period, following a single 10 mg intravenous dose. In 13 patients peak concentrations of M-3-G (739 nmol/L +/- 73.7 SEM) were approximately 10 times greater than those of M-6-G (71.3 nmol/L +/- 8.6 SEM). Times to reach these peaks were similar for both metabolites. Decay of morphine from plasma followed a biexponential pattern with a mean terminal half-life of 59.3 min (+/- 8.1 SEM, n = 11). Accurate determination of the half-lives of the glucuronides was not possible due to the short sampling period, but M-6-G seemed to have a similar half-life to morphine, while M-3-G was eliminated more slowly.

Aged↗

Influenza vaccine: the effects of the 1986/1987 viral strains.

One hundred and twenty healthy volunteers were recruited for a study to evaluate the reactogenicity and serological response of differing doses of the 1986/87 World Health Organization-recommended influenza viral strains. Each vaccine was prepared by Institut Merieux and contained A/Mississippi/1/85, A/Chile/1/83 and B/Ann Arbor/1/86. One vaccine was formulated as a 10/10/10 micrograms HA and the other as a 15/10/15 micrograms HA. No significant advantage could be found with the 15/10/15 micrograms HA combination and it was recommended, therefore, that a 10/10/10 micrograms HA formulation was to be preferred. This vaccine demonstrated a minimal cross-sensitivity to the A/Singapore/6/86 influenza strain. In view of the prevalence of the A/Singapore strain, a second study was subsequently undertaken with a monovalent A/Singapore/6/86-like vaccine in a further 62 volunteers. This demonstrated an overall sero-conversion rate of 90%. Local side-effects with both vaccines were lower than in a similar study in 1984 and this may reflect a reduction in endotoxin levels achieved by a minor modification in the manufacturing technique. These studies confirmed the efficacy of a trivalent A/Mississippi, A/Chile, B/Ann Arbor influenza vaccine and the efficacy of, and necessity for, an additional A/Singapore vaccine.

Adult↗

Role of spinal noradrenergic system in transmission of pain in patients with spinal cord injury.

15 patients with deafferentation pain due to spinal cord injury were investigated for a spinal mechanism of pain transmission. Epidural morphine 5 mg in 5 ml of water had an analgesic effect in 5 patients, 3 of whom also had pain relief with epidural clonidine. Epidural clonidine 150 micrograms in 5 ml of saline had an analgesic effect in 7 patients who did not respond to epidural morphine. Neither epidural morphine nor clonidine was effective in the other 3 patients, 2 of whom obtained relief with epidural buprenorphine 0.3 mg in 5 ml of saline. 1 patient did not find relief with any of the injections. These data suggest that a spinal noradrenergic system may be as important as the opioid system in the transmission of pain in patients with spinal cord injury.

Adult↗

Mediation of hidradenitis suppurativa by androgens.

Forty two women with hidradenitis suppurativa were assessed clinically and biochemically for evidence of androgen excess. Thirteen had irregular menses; 22 of 36 experienced exacerbation of hidradenitis suppurativa premenstrually; 19 had or had had acne vulgaris; and seven were hirsute. Comedones (blackheads) were found in apocrine sites in 37, but also in retroauricular sites in 18 and were considered to be an important physical sign for early diagnosis. Eight had evidence of pilonidal (postanal) sinus. The patients had a higher concentration of total testosterone (p less than 0.01) and free androgen index (testosterone to sex hormone binding globulin concentrations) (p less than 0.01) than normal controls. Patients with hidradenitis suppurativa appear to have endocrine abnormalities sufficient to suggest an androgenic basis for the disease.

Adolescent↗

Performance of a new enzyme-linked immunoassay urine pregnancy test for the detection of ectopic gestation.

An enzyme-linked immunoassay urine pregnancy test was used on a group of patients suspected of having an ectopic pregnancy. Patients were seen in the county hospital emergency department and had the urine test correlated with a serum beta-hCG level determined by radioimmunoassay. There were 884 patients with urine ICON-serum beta-hCG correlations. The ICON was positive in each of the 247 patients whose serum value was over 50 mIU/mL, and was negative in each of the 619 patients whose serum level was below 5 mIU/mL. Eighteen patients had a serum level between 10 and 50 mIU/mL and the ICON was positive in 13. The five patients with a low serum beta-hCG level and a negative ICON had dilute urine when tested. Using a modified testing procedure, each of these produced a positive ICON. Of the 27 patients with an ectopic pregnancy the urine ICON was positive in 26. The urine ICON is an improved assay for hCG in patients suspected of having an ectopic pregnancy, and is ideally suited for ED use.

Chorionic Gonadotropin↗

Ketorolac and acetaminophen for orthopedic postoperative pain.

In a double-blind, single-dose, parallel-group study, ketorolac (5, 10, or 20 mg) was compared with acetaminophen (500 or 1000 mg) when taken by mouth for postoperative orthopedic pain. Analgesic measurements were made by trained nurse observers who used standard verbal rating and visual analog scales. Acetaminophen, 1000 mg, was statistically superior to 500 mg acetaminophen, demonstrating assay sensitivity. Ketorolac, 20 mg, was distinguished from 500 mg acetaminophen, 5 mg ketorolac, and 10 mg ketorolac, but not from 1000 mg acetaminophen. The higher doses of ketorolac induced a longer lasting peak analgesic effect than did acetaminophen, but the magnitude of the peak pain relief was changed little by an increased ketorolac dose. Overall, 10 mg ketorolac appeared equivalent to 1000 mg acetaminophen. Acetaminophen, 500 mg, induced less sedation than the higher doses of ketorolac, but neither drug caused untoward side effects.

Acetaminophen↗

Prophylactic nitroglycerin infusions during coronary artery bypass surgery.

The effects of prophylactic infusion of 1 microgram X kg-1 X min-1 nitroglycerin (NTG) on the incidence of ischemia, hypertension, hypotension and perioperative myocardial infarction were studied in 81 patients during coronary artery bypass grafting (CABG). Forty-one patients (Group 1) received NTG and 40 patients (Group 2) received placebo. All patients received fentanyl for anesthesia and pancuronium. Mean arterial pressure (MAP), pulmonary capillary wedge pressure (PCWP), heart rate (HR), and cardiac output (CO) were measured before and after induction of anesthesia, after intubation, before and after chest incision, after sternotomy, after the pericardium was opened, and during normothermic cardiopulmonary bypass. Myocardial ischemia and infarction were diagnosed from the ECG, hypertension was defined as a 20% increase in MAP, and hypotension was defined as a 20% decrease in MAP compared with preinduction values. No significant differences between Groups 1 and 2 in HR, PCWP, or CO were seen. MAP was significantly lower in Group 1 than Group 2 (P less than 0.05) before chest incision, but increased to levels equal to Group 2 after sternotomy. Hypertension occurred in 32 Group 2 patients and 25 Group 1 patients (0.05 less than P less than 0.1). Group 1 patients had 0.95 +/- 0.14 episodes per patient of hypertension, while Group 2 patients had 2.10 +/- 0.31 episodes (P less than 0.05). Hypotension occurred in 20 Group 1 patients but only six Group 2 patients (P less than 0.05). There was no difference in the incidence of ischemia. In Group 1, nine patients (22%) had ECG changes of ischemia, while 12 patients in Group 2 (30%) had ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

A double-blind controlled cross-over trial of cyproterone acetate in females with hidradenitis suppurativa.

In order to examine whether anti-androgen therapy was effective in hidradenitis suppurativa (HS), ethinyloestradiol 50 micrograms/cyproterone acetate 50 mg in a reverse sequential regimen was compared with ethinyloestradiol 50 micrograms/norgestrel 500 micrograms (Eugynon 50) in 24 female patients. Both treatments produced substantial improvement in disease activity. Seven patients cleared and have remained free of disease for 18 months, five patients improved, four remained unchanged, while two deteriorated. Cyproterone acetate was not clinically significantly more effective than E50, and both gave a similar reduction in free androgen index. Anti-androgen therapy appears to be beneficial in the treatment of hidradenitis suppurativa.

Adult↗

Interaction of polycationic antibiotics with Pseudomonas aeruginosa lipopolysaccharide and lipid A studied by using dansyl-polymyxin.

A fluorescent derivative of polymyxin B (dansyl-polymyxin) was used to study the interaction of polycations with lipopolysaccharide (LPS) and lipid A from Pseudomonas aeruginosa. Dansyl-polymyxin became bound to LPS and lipid A sites, including Mg2+-binding sites, resulting in a 20-fold enhancement of fluorescence. A Hill plot of the binding data showed that the binding of dansyl-polymyxin to LPS was cooperative (n = 1.98) and of high affinity (S0.5 = 0.38 microM). The maximal binding capacity of LPS was approximately four molecules of dansyl-polymyxin per mol of LPS. The dansyl-polymyxin interaction with lipid A displayed similar kinetics (n = 2.26; S0.5 = 0.38 microM), and the maximal binding capacity was approximately 2 mol of dansyl-polymyxin per mol of lipid A. A variety of polycationic compounds, including gentamicin, streptomycin, and polymyxin B, as well as Mg2+, were able to displace dansyl-polymyxin bound to LPS or to lipid A. Marked differences both in terms of the degree of displacement and in terms of the amount of competing polycation required to displace a given amount of dansyl-polymyxin were observed. Addition of excess polymyxin B resulted in displacement of all of the dansyl-polymyxin, demonstrating that only polymyxin-binding sites were being probed. Our data demonstrate that polymyxin B binds to multiple sites on LPS, including sites which bind aminoglycoside antibiotics and other polycationic compounds.

Anti-Bacterial Agents↗

Involvement of outer membrane of Pseudomonas cepacia in aminoglycoside and polymyxin resistance.

Pseudomonas cepacia was found to be resistant to the outer membrane-permeabilizing effects of aminoglycoside antibiotics, polymyxin B, and EDTA. Permeabilization of P. cepacia to the fluorescent probe 1-N-phenylnaphthylamine was not achieved at concentrations 100- to 1,000-fold above those required to permeabilize Pseudomonas aeruginosa. Furthermore, in contrast to P. aeruginosa cells, intact cells of P. cepacia did not bind the fluorescent probe dansyl-polymyxin. However, purified lipopolysaccharide (LPS) from P. cepacia bound dansyl-polymyxin with approximately the same affinity as did LPS from P. aeruginosa. Also, binding of dansyl-polymyxin to P. cepacia (and P. aeruginosa) LPS was inhibited by polymyxin B, streptomycin, gentamicin, and Mg2+. These data suggest that P. cepacia does not utilize the self-promoted pathway for aminoglycoside uptake and that the outer membrane is arranged in a way that conceals or protects cation-binding sites on LPS which are capable of binding polycations such as aminoglycosides or polymxyin.

Aminoglycosides↗

Radioimmunoassay of buprenorphine with iodine label: analysis of buprenorphine and metabolites in human plasma.

Quantitative analysis of potent opiate drugs in plasma by radioimmunoassay is potentially inaccurate because of the occurrence of cross-reacting metabolites. This paper describes the chemical synthesis of buprenorphine-3-O-glucuronide, a metabolite of buprenorphine, and an extraction procedure coupled with radioimmunoassay which allows the sensitive and specific measurement of buprenorphine using an iodinated buprenorphine derivative. The measurement of extracted and unextracted samples using two different antisera allowed investigation of the metabolism of buprenorphine. In four patients who had taken sublingual buprenorphine for at least one month, N-dealkyl buprenorphine was present in similar concentrations to those of buprenorphine, while buprenorphine-3-O-glucuronide was present in two to three times those concentrations.

Administration, Oral↗

Intrathecal morphine and heroin in humans: six-hour drug levels in spinal fluid and plasma.

Lumbar spinal fluid and plasma concentrations of morphine were measured by radioimmunoassay after intrathecal administration of 1 mg of morphine (n = 13) or heroin (n = 10). Plasma levels of morphine were measured regardless of 'whether heroin or morphine was injected intrathecally, because of the rapid biotransformation of heroin to morphine in plasma. Significant drug concentrations appeared in plasma after intrathecal heroin (peak concentration 47.8 +/- 9.0 nmol/L, time to peak concentration 10 +/- 2.4 min); after intrathecal morphine plasma drug concentrations were significantly lower (8.1 +/- 1.0 nmol/L; P less than 0.002) and significantly later (216 +/- 39 min; P less than 0.002). Elimination half-life of heroin from spinal fluid (43 +/- 5 min) was significantly shorter than for morphine (73 +/- 5 min; P less than 0.02).

Aged↗

Halothane metabolism in acyanotic and cyanotic patients undergoing open heart surgery.

The metabolism of halothane was examined in patients with acyanotic and cyanotic congenital heart disease undergoing open heart surgery. Statistically significant (P less than 0.05) pre-surgical differences between acyanotic and cyanotic groups included pH (7.46 +/- 0.02 vs 7.36 +/- 0.02), PaO2 (277 +/- 58 vs 51 +/- 3 torr), O2 saturation (97 +/- 1 vs 74 +/- 4%), and hematocrit (45 +/- 3 vs 58 +/- 2%). Serum fluoride levels were significantly greater in cyanotic than in acyanotic groups 2-4 hours after initial exposure to halothane. Both groups had significant intragroup increases in serum levels of fluoride, bromide, and trifluoroacetic acid. Significant increases in serum levels of lactate dehydrogenase, creatinine phosphokinase, and glutamic oxaloacetate transaminase were observed in both groups, whereas, the cyanotic patients had additional significant increases in blood urea nitrogen and direct bilirubin. The cyanotic group also had higher total and direct serum bilirubin levels than the acyanotic group. Therefore, patients with cyanotic congenital heart disease had greater reductive metabolism of halothane than acyanotics. However, cyanotic and acyanotic patients had essentially similar postoperative derangements in hepatic and renal function.

Cardiopulmonary Bypass↗

Epinephrine reduces systemic absorption of extradural diacetylmorphine.

The effect of epinephrine on the vascular absorption of morphine from the extradural space is uncertain; this study examined the effect of epinephrine on the related but more lipophilic opiate diacetylmorphine (diamorphine, heroin) because any effects of vasoconstriction on diacetylmorphine absorption should be maximally apparent. With this experiment, we hoped to resolve whether epinephrine does or does not alter vascular absorption of extradurally injected opiates. Thirty patients undergoing lumbar laminectomy were given either extradural diacetylmorphine, 5 mg, extradural diacetylmorphine, 5 mg with 1:200,000 epinephrine, or 1:200,000 epinephrine followed 5 min later by 5 mg extradural diacetylmorphine. Plasma morphine concentrations were measured by radioimmunoassay because of the rapid conversion of diacetylmorphine to morphine in plasma; repeated blood samples were obtained the first 30 min after injection into the epidural space. Significantly lower plasma morphine levels occurred between 3 and 20 min when epinephrine was added to diacetylmorphine. Peak plasma morphine levels (mean +/- SEM) were 179 +/- 37 nmol/L with diacetylmorphine alone, 87 +/- 16 nmol/L with diacetylmorphine and epinephrine given together and 44 +/- 11 nmol/L with epinephrine pretreatment, all significantly different from one another. The mean peak plasma morphine concentration was 8.7 +/- 1.1 min for diacetylmorphine alone, but addition of epinephrine (together or sequentially) meant that 15 of 20 patients had no peak level before 120 min. Epinephrine reduced absorption of diacetylmorphine from the extradural site by at least 55% over the first 30 min. The incidence of patients with more than 9 hr analgesic duration was significantly (P = 0.033) greater in patients who had diacetylmorphine and epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Genital injury and implied consent to alleged rape.

A review of 440 cases of reported rape was undertaken to see if sustaining injury to the genital area was an inevitable consequence of being raped. Injuries to areas other than the genital were taken as objective evidence that the victim did not consent to the encounter, while sperm found in her vagina that could not be accounted for by voluntary coitus was taken as objective evidence that penile penetration of the vagina had occurred. Of the 75 victims with objective evidence of both noncompliance and vaginal penetration, 28% sustained genital injury. The absence of genital injury does not imply consent by the victim or the absence of vaginal penetration by the assailant.

Expert Testimony↗

Renal failure and the use of morphine in intensive care.

Intravenous morphine infusions were given to 20 patients in the intensive-care unit to provide sedation and analgesia. In 10 of the patients renal impairment was already present or developed during intensive care. Plasma morphine concentrations for a given dose of morphine and morphine clearance depended on renal function; dose-related plasma morphine concentrations rose as renal function deteriorated. Reduced morphine clearance leads to increased elimination half-life of the drug, and neurological impairment caused by unrecognised high concentrations of morphine could result in an incorrect diagnosis of cerebral damage in patients in intensive care.

Adult↗