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Biomedical subjects

R Dixon

Publications and source records attributed to R Dixon.

At least 73 records · Page 4Linked to original sources
PubMed1997

HM-PAO (CERETEC) SPECT brain scanning in the diagnosis of Alzheimer's disease.

OBJECTIVE: To evaluate the accuracy of Single Photon Emission Computed Tomography (SPECT) scanning in the diagnosis of Alzheimer's Disease (AD) and its capacity to improve the diagnostic accuracy of conventional clinical evaluation. DESIGN: Comparison of SPECT scanning of AD and normal subjects with the criterion standard of clinical diagnosis confirmed by 1-year repeated evaluation. SETTING: A memory clinic in a tertiary care university hospital. PATIENTS: One hundred twenty patients were evaluated upon entering the Jewish General Hospital (McGill University) Memory Clinic. Fifty-eight patients were diagnosed as having AD and 17 as having vascular dementia. Twenty unmatched controls (recruited mainly through newspaper advertisements) were normal, and 25 had cognitive impairment without dementia (not included in the statistical analysis). MAIN OUTCOME MEASURES: Comparison of visual inspection of SPECT, based on the system of classification developed by Holman et al., using B pattern alone as positive or B (bilateral posterior temporal and/or parietal cortex deficits) or C (bilateral posterior temporal and/or parietal deficits with additional defects) pattern and B or C or D (unilateral posterior temporal and/or parietal defects with or without additional defects) as positive compared with clinical diagnosis after repeated evaluations. Sensitivity and specificity, as well as positive predictive value (PPV) and negative predictive value (NPV) based on the prevalence of AD in a memory clinic setting of 30% or 50%, were calculated. RESULTS: With B pattern as positive, the sensitivity of SPECT was 21% whereas the specificity was 80%. With B or C as positive, the sensitivity was 29% and the specificity was 75%. With B or C or D as positive, the sensitivity was 55% and the specificity was 65%. With a 30% prevalence, the PPV with B pattern as positive was 31% whereas the NPV was 30%. The PPV with B or C as positive was 33% while the NPV was 29%, and the PPV with B or C or D as positive was 40% whereas the NPV was 23%. With a 50% prevalence, the PPV with B pattern as positive was 51% and the NPV 49.6%; the PPV with B or C as positive was 54% and the NPV 48.6%; the PPV with B or C or D as positive was 61% while NPV was 41%. CONCLUSION: The sensitivity and specificity were too low for SPECT to be useful as a diagnostic test for AD. The poor positive and negative predictive values in our tertiary care clinic mean that SPECT is not useful in "ruling-in" or "ruling-out" AD in that setting. In fact, clinical evaluation is more accurate.

Aged↗
PubMed1997

The clinical pharmacokinetics of zolmitriptan.

Zolmitriptan (Zomig, formerly 311C90) is a novel, oral, acute treatment for migraine. In healthy volunteers it is rapidly and extensively absorbed and has favorable oral bioavailability (approximately 40%) which is not affected by concomitant food intake. On average, 75% of its eventual Cmax is achieved within 1 h of dosing. Plasma concentrations are sustained for 4 to 6 h after dosing with single or multiple peaks in the plasma concentration-time profile, reflecting continued absorption down the gastrointestinal tract. The pharmacokinetics of zolmitriptan indicate dose proportionality over the dose range of 2.5 to 50 mg and there are no significant changes on multiple dosing. Zolmitriptan is cleared by metabolism followed by urinary excretion of the metabolites. There are three major metabolites, one of which, the N-desmethyl metabolite, is active as a 5HT1D agonist and has mean plasma concentrations approximately two thirds those of the parent compound. The other two metabolites, the N-oxide and indoleacetic acid, are inactive. The elimination half lives of zolmitriptan and its metabolites are similar, approximately 3 h. Zolmitriptan and its active metabolite are minimally protein bound in the plasma (approximately 25%). In migraine patients, plasma concentrations of zolmitriptan and its metabolites are lower during a migraine attack than outside an attack. In summary, the pharmacokinetics of zolmitriptan are simple, predictable and appropriate to an acute oral treatment for migraine.

Absorption↗
PubMed1997

The principles of quality-associated costing: derivation from clinical transfusion practice.

As clinical transfusion practice works towards achieving cost-effectiveness, prescribers of blood and its derivatives must be certain that the prices of such products are based on real manufacturing costs and not market forces. Using clinical cost-benefit analysis as the context for the costing and pricing of blood products, this article identifies the following two principles: (1) the product price must equal the product cost (the "price = cost" rule) and (2) the product cost must equal the real cost of product manufacture. In addition, the article describes a new method of blood product costing, quality-associated costing (QAC), that will enable valid cost-benefit analysis of blood products.

Accounting↗
PubMed1997

The practice of quality-associated costing: application to transfusion manufacturing processes.

This article applies the new method of quality-associated costing (QAC) to the mixture of processes that create red cell and plasma products from whole blood donations. The article compares QAC with two commonly encountered but arbitrary models and illustrates the invalidity of clinical cost-benefit analysis based on these models. The first, an "isolated" cost model, seeks to allocate each whole process cost to only one product class. The other is a "shared" cost model, and it seeks to allocate an approximately equal share of all process costs to all associated products.

Accounting↗
PubMed1997

Quantification of infectious duck hepatitis B virus by radioimmunofocus assay.

A simple method is described for the precise quantification of infectious duck hepatitis B virus (DHBV) in cell culture, using a radioimmunofocus assay (RIFA). Primary duck hepatocyte cell cultures were infected with serial dilutions of viral samples as for a plaque assay, but then maintained with liquid overlay medium. After incubation for up to 14 days, cell monolayers were fixed with acetone, then stained with a monoclonal antibody to DHBV L protein followed by secondary antibody labelled with 125I. Foci of infection (representing individual infectious particles in the inoculum) were detected by autoradiography. The number of foci recovered was increased by addition of dimethyl sulphoxide to culture medium, but was not appreciably altered by the use of semi-solid medium. The titre of virus suspensions determined by RIFA correlated well with titration in ducklings. The RIFA is a useful method for titration of DHBV, as it has a wide dynamic range and is well suited to parallel titration of large numbers of samples. This assay will have wide use for the analysis of DHBV growth kinetics, antiviral efficacy, and virus inactivation procedures.

Animals↗
PubMed1996

Spectrophotometric determination of the cardioprotective drug GP531 in human plasma.

A simple spectrophotometric assay has been developed for determining concentrations of the new cardioprotective agent, GP531, in human plasma. The method is adapted from the Bratton-Marshall assay (BMA) for the detection of primary aromatic amines. The assay can be used to measure plasma concentrations of the drug during i.v. infusion administration to patients. The limit of quantitation of the assay is 1 microgram/ml using a 0.8 ml sample ultrafiltrate of plasma. The colorimetric assay correlates well with a previously described high performance liquid chromatographic (HPLC) procedure.

Aminoimidazole Carboxamide↗
PubMed1996

Defining and implementing a 'no lifting' standard.

Following the launch this spring of the RCN's campaign to reduce injuries from manual lifting of patients, this article describes the main policies and guidelines relating to lifting and handling, and tells how these were used to develop and implement a 'no lifting' standard on an elderly care ward.

Back Pain↗
PubMed1996

Azotobacter vinelandii NIFL is a flavoprotein that modulates transcriptional activation of nitrogen-fixation genes via a redox-sensitive switch.

The NIFL regulatory protein controls transcriptional activation of nitrogen fixation (nif) genes in Azotobacter vinelandii by direct interaction with the enhancer binding protein NIFA. Modulation of NIFA activity by NIFL, in vivo occurs in response to external oxygen concentration or the level of fixed nitrogen. Spectral features of purified NIFL and chromatographic analysis indicate that it is a flavoprotein with FAD as the prosthetic group, which undergoes reduction in the presence of sodium dithionite. Under anaerobic conditions, the oxidized form of NIFL inhibits transcriptional activation by NIFA in vitro, and this inhibition is reversed when NIFL is in the reduced form. Hence NIFL is a redox-sensitive regulatory protein and may represent a type of flavoprotein in which electron transfer is not coupled to an obvious catalytic activity. In addition to its ability to act as a redox sensor, the activity of NIFL is also responsive to adenosine nucleotides, particularly ADP. This response overrides the influence of redox status on NIFL and is also observed with refolded NIFL apoprotein, which lacks the flavin moiety. These observations suggest that both energy and redox status are important determinants of nif gene regulation in vivo.

Adenosine Diphosphate↗
PubMed1996

The effect of renal insufficiency and hemodialysis on the pharmacokinetics of nalmefene.

The disposition of nalmefene, an opioid antagonist intended for the reversal of opioid-induced respiratory depression, and its primary metabolite nalmefene glucuronide, were characterized in adult volunteers with normal renal function and in patients with end-stage renal disease (ESRD). The effect of hemodialysis on the elimination of nalmefene and nalmefene glucuronide also was assessed. Participants with normal renal function received a single intravenous dose of 2 mg, and patients with ESRD received two separate doses of 1 mg nalmefene hydrochloride. Terminal elimination half-life (t1/2) of both nalmefene and nalmefene glucuronide was prolonged in patients with ESRD compared with that in participants with normal renal function. The steady-state volume of distribution (Vdss) of nalmefene was significantly higher and total body clearance lower in patients with ESRD than in participants with normal renal function. Hemodialysis clearance of nalmefene was approximately 3.3% of total body clearance. Although the hemodialysis clearance of nalmefene glucuronide was 179.3 +/- 24.1 mL/min and its t1/2 was significantly reduced during dialysis to 5.2 +/- 2.3 hours, a dramatic rebound of nalmefene glucuronide concentrations of 75.7% was observed 7.7 +/- 5.4 hours after the end of hemodialysis. Thus, hemodialysis does not result in clinically significant alterations in the disposition of nalmefene or its primary metabolite, nalmefene glucuronide. These data suggest that there is no pharmacokinetic basis for modification of the initial dosage, but maintenance doses, if needed, should be administered less frequently due to the prolonged elimination of the active moiety, nalmefene.

Adult↗
PubMed1996

A sensitive assay for the aminoimidazole-containing drug GP531 in plasma using liquid chromatography with amperometric electrochemical detection: a new class of electroactive compounds.

Aminoimidazole-containing compounds have been found to be electroactive and can be detected by amperometric electrochemical detection (ECD) with a high degree of sensitivity. A liquid chromatography (LC) method using ECD was developed for measuring plasma concentrations of the aminoimidazole-containing drug GP531, a potent adenosine-regulating agent. Plasma samples were extracted with 2-propanol and analyzed by LC under isocratic conditions using a mobile phase of methanol-sodium phosphate (pH 6.3; 3.3 mM) (32:68, v/v). The potential of the glassy carbon working electrode was set at +800 mV. The limit of quantitation was 12.5 ng ml-1 of GP531 using 100 microliters of plasma. The method was used to define the pharmacokinetics of GP531 in monkey following i.v. administration.

Aminoimidazole Carboxamide↗
PubMed1996

Kinetic disposition of an aqueous formulation of alphacypermethrin applied to the dorsal mid-line of sheep with long wool and its effect on lice.

A group of 5 adult Merino sheep with fleeces about 70 mm long (7-months growth of wool) was treated with a topical formulation of the synthetic pyrethroid insecticide, alphacypermethrin, applied to the dorsal mid-line. Insecticide concentrations at the tip, middle and base of wool staples collected from meridians along the back, upper and lower flanks were measured at intervals from 1 to 98 days after treatment. Some movement of the alphacypermethrin from the back to the lower body occurred within 24h after treatment, but despite careful application of the insecticide there was wide variation in the concentration between and within meridians. The majority of the alphacypermethrin remained close to the dorsal mid-line and near the tip of the staple. There were significant differences in the concentration between the tip, middle and base segments of the staples in the back and lower flank meridians (P < 0.05). Despite exposure of the sheep to normal weathering, there was no significant difference in the concentration of alphacypermethrin between samples collected at day 1 or day 98 after treatment (P > 0.05). Numbers of pyrethroid-susceptible lice surviving exposure in vitro for 20 h differed significantly between samples collected at different times after treatment, lice survived for 20 h in wool taken from parts of the fleece that contained high (P < 0.05). The numbers of lice surviving in samples collected within 28 days after treatment tended to be lower than in those collected from 28 to 98 days but, in some samples, regardless of time after treatment, concentrations of alphacypermethrin.

Administration, Topical↗
PubMed1996

Parental influences on the dieting beliefs and behaviors of adolescent females in New Zealand.

PURPOSE: To investigate parental influences on the weight perceptions and the dieting beliefs and behaviors of adolescent girls. METHODS: The subjects were 232, 8th and 9th grade girls attending an urban New Zealand secondary school. Data on girls' perceptions of being thinner, beliefs about dieting, and their dieting behavior were obtained via a number of self-report scales. RESULTS: An association was found between girls' perceptions of the impact of being thinner, dieting beliefs, dieting behaviors, and parental encouragements to diet (p < .0001). In general, parental dieting practices did not influence dieting beliefs except that fathers' dieting behavior was associated with some aspects of girls' dieting behaviors. CONCLUSIONS: Parental encouragement to diet was associated with a wide range of weight loss behaviors, including the more extreme measures. In addition, having a father who dieted was associated with participation in a number of the dieting behaviors.

Adolescent↗
PubMed1996

The role of interleukin-15 in T-cell migration and activation in rheumatoid arthritis.

Interleukin 15 (IL-15) is a novel cytokine with interleukin-2-like activity. It is also a potent T-lymphocyte chemoattractant. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the presence of activated T lymphocytes, macrophages and synoviocytes in the synovial membrane. The mechanisms of T-cell activation in RA are currently unclear. We report the presence of high concentrations of IL-15 in rheumatoid arthritis (RA) synovial fluid and have demonstrated its expression in the synovial membrane lining layer by immunohistochemistry. RA synovial fluids were found to contain chemotactic activity, which was attributable in part to the presence of IL-15. Moreover, in a murine model, injection of recombinant IL-15 was found to induce a local tissue inflammatory infiltrate consisting predominantly of T lymphocytes. Synovial fluid T lymphocytes proliferate in response to IL-15, demonstrating that continued responsiveness to IL-15 is a feature of T cells after entry into the synovial compartment. These data suggest that IL-15 can recruit and activate T lymphocytes in the synovial membrane, thereby contributing to RA pathogenesis.

Aged↗
PubMed1996

Atovaquone has no effect on the pharmacokinetics of phenytoin in healthy male volunteers.

The potential pharmacokinetic interaction between atovaquone and phenytoin was investigated in 12 healthy male volunteers. Each volunteer received a single 600 mg oral dose of phenytoin in the two treatment periods. On one occasion phenytoin was taken alone and on the other pre-treatment with 2000 mg atovaquone taken as two doses of 1000 mg as a microfluidized suspension. The mean (+/- s.d.) peak plasma concentrations (Cmax), apparent total clearance (CL/F) and terminal half-life (t1/2) for phenytoin when administered alone were 10.6(1.8) mg 1(-1), 24.3 (7.7) ml min-1 and 25(8) h, respectively. When administered together with atovaquone, phenytoin Cmax, CL/F and t1/2,z were 10.9 (2.0) mg 1(-1), 23.8 ml min-1 and 24(6) h, respectively. There were no statistically significant differences in any of these plasma pharmacokinetic parameters. There were also no statistically significant differences in the fraction of circulating drug not bound to plasma protein or urinary excretion of 5-hydroxyphenyl-phenyl-hydantoin. In conclusion, there was no effect of atovaquone on the pharmacokinetics of phenytoin or its major metabolite after a single dose.

Adult↗
PubMed1996

311C90 (Zolmitriptan), a novel centrally and peripheral acting oral 5-hydroxytryptamine-1D agonist: a comparison of its absorption during a migraine attack and in a migraine-free period.

The oral absorption of a 10-mg oral dose of the novel 5-hydroxytryptamine (5HT1D) agonist, 311C90, was compared during a moderate or severe migraine headache and in a migraine-free period in an open, two-period study. The safety and efficacy of 311C90 in acute migraine were also assessed. Twenty patients attended the clinics during a moderate or severe migraine attack and 18 patients returned for a second dose in a migraine-free period. 311C90 was less rapidly absorbed during a migraine attack compared to the migraine-free period, consistent with gastric stasis during a migraine attach. The median area under the curve (AUC) was 15.7 ng/mlh lower during a migraine (median AUC: 18.4 ng/ml.h, range: 0-60.8 ng/ml.h) compared to the migraine-free period (median AUC: 33.4 ng/ml.h, range 9.4-79.5 ng/ml.h) (95% confidence interval: 6.9, 25.3) and the time to reach maximum plasma concentration was delayed (n = 18). Eleven out of 20 patients experienced a significant improvement in migraine headache intensity at 2 h post-dose. Plasma 311C90 concentrations were generally higher in those patients who responded to treatment with 311C90 in the plasma, but there was one patient with no quantifiable 311C90 in the plasma whose headache improved. Minor adverse experiences were reported in 11 out of 20 patients during a migraine attack and in 11 out of 18 patients outside an attack. They occurred shortly following drug administration and were of short duration, but their occurrence did not appear to be related to plasma 311C90 concentration. There were no clinically significant changes in blood pressure or 12-lead ECG during the assessment period.

Adolescent↗
PubMed1996

Single-dose and steady-state pharmacokinetics of a novel microfluidized suspension of atovaquone in human immunodeficiency virus-seropositive patients.

The single- and multiple-dose pharmacokinetics of and tolerability to a new microfluidized suspension of atovaquone were studied in human immunodeficiency virus-seropositive patients with CD4 counts of < or = 200 cells per mm3 in order to define a dosing regimen for the treatment of Pneumocystis carinii pneumonia. This was an open study with groups of six patients each. In the first part of the study, six subjects received escalating single doses of 500, 1,000, and 1,500 mg after an overnight fast at weekly intervals. In the second part of the study, groups of six subjects were dosed for 14 days according to three regimens: 1,000 mg twice daily fasting, twice daily with a high-fat meal, or once daily with a high-fat meal. Plasma atovaquone levels were assayed by high-performance liquid chromatography. Pharmacokinetic parameters were determined by noncompartmental methods, and statistical comparison of parameters for single doses was performed by analysis of variance. Plasma drug concentrations increased with single doses from 500 to 1,000 mg but were no higher with a dose of 1,500 mg. Thus, 1,000 mg was selected for multiple administration. A regimen of 1,000 mg twice daily with food resulted in a 93% increase in the average trough steady-state concentration compared with 1,000 mg once daily with food. Food increased the bioavailability of atovaquone 1.4-fold over that in the fasting state. All patients who received 1,000 mg twice daily with food achieved target steady-state concentrations in plasma of 15 to 25 micrograms/ml. Multiple-dose regimens were generally well tolerated, but the higher levels in plasma achieved by 1,000 mg twice daily with food were associated with an increased incidence of rash. In conclusion, target plasma atovaquone concentrations for the treatment of P. carinii pneumonia can be achieved in most patients with 1,000 mg twice daily in a fasting state and in all patients with 1,000 mg twice daily administered with food, but at higher concentrations in plasma, there may be an increased risk of rash.

Adult↗