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Biomedical subjects

C G Swift

Publications and source records attributed to C G Swift.

At least 37 records · Page 2Linked to original sources
PubMed1997

Stereospecific analysis of the major metabolites of ibuprofen in urine by sequential achiral-chiral high-performance liquid chromatography.

A sequential achiral-chiral HPLC method has been developed for the stereospecific analysis of the two major urinary metabolites of ibuprofen, namely hydroxyibuprofen and carboxyibuprofen. Achiral analysis was carried out using a Partisil column (250x4.6 mm, 5 microm) and a mobile phase of hexane:ethanol (98.2:1.8, v/v) containing trifluoroacetic acid (TFA; 0.05%, v/v) at a flow-rate of 2.0 ml/min. The HPLC eluate containing the two metabolites was separately collected, evaporated under nitrogen and the residue dissolved in the mobile phase used for chiral chromatography. Chiral-phase analysis was carried out using a Chiralpak AD CSP (250x4.6 mm, 10 microm) with a mobile phase of hexane:ethanol (92:8, v/v) containing TFA (0.05%, v/v) at a flow-rate of 1.0 ml/min. In both assays the analytes were quantified by ultraviolet detection at a wavelength of 220 nm. Modification of the mobile-phase composition allowed the resolution of all six analytes in a single chromatographic run but with an increase in run time and consequent band broadening. The analytical method described allows the direct quantitation of the stereoisomers of both metabolites of ibuprofen in urine following the administration of therapeutic doses of the racemic drug to man.

Adult↗
PubMed1997

ACE inhibition: postsynaptic adrenergic sympatholytic action in men.

BACKGROUND: The mechanisms by which ACE inhibitors produce a sustained clinical benefit are not entirely clear but may involve the sympathetic nervous system. We compared the effect of local brachial artery infusions of an ACE inhibitor (perindoprilat) with the effect of placebo (0.9% NaCl) on endogenously mediated (lower body negative pressure [LBNP]) and exogenously mediated (brachial artery infusions of norepinephrine) sympathetic vasoconstriction. METHODS AND RESULTS: Eight healthy, normotensive male volunteers (20 to 32 years) were studied on one occasion. Forearm blood flow (FABF; mL x dL forearm(-1) x min(-1)) responses to LBNP (-20 cm H2O) and increasing increments of norepinephrine (60, 120, and 240 pmol/min) were compared when coinfused with placebo and perindoprilat (5 nmol/mL). FABF was measured simultaneously in both arms by venous occlusion plethysmography with mercury-in-Silastic strain gauges with drugs infused locally at the left brachial artery. The right arm served as a control. Baseline FABFs did not differ between the infused and control arms (3.04+/-0.52 versus 3.05+/-0.42 mL x dL forearm(-1) x min(-1); P=.98). Perindoprilat did not alter FABF when infused alone, but the FABF response to LBNP in the infused arm was attenuated during the perindoprilat infusion compared with placebo (-17.8+/-4.3% versus -33.8+/-3.1%, respectively; P=.015). The FABF response to the maximum dose of norepinephrine was also attenuated during the perindoprilat infusion compared with placebo (-28.3+/-1.4% versus -36.9+/-2.8%, respectively; P=.015). The mean slope of the FABF (log transformed) versus norepinephrine dose-response curve was significantly attenuated by perindoprilat compared with placebo (-0.11+/-0.019 versus -0.02+/-0.02; P=.001). CONCLUSIONS: We conclude that ACE inhibition has a significant postsynaptic sympatholytic effect in the forearm circulation of men.

Adult↗
PubMed1997

Impaired nitric oxide-mediated vasodilatation and total body nitric oxide production in healthy old age.

1. Basal release of nitric oxide from the vascular endothelium maintains a constant vasodilating tone. Impaired nitric oxide-mediated vasodilatation has been described in hypertension and atheromatous disease. Circulatory diseases account for considerable morbidity and almost half of all deaths in people over the age of 75 years. 2. We have therefore compared nitric oxide-dependent vasorelaxation in 12 healthy elderly subjects with 12 young volunteers matched for blood pressure, cholesterol and glucose, using forearm occlusion venous plethysmography combined with brachial artery infusions of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA; 1, 2 and 4 mumol/min) with noradrenaline (60, 120 and 240 pmol/min) as a control vasoconstrictor. We also measured urinary nitrate excretion after a controlled 48 h low nitrate diet as an index of total body nitric oxide production and correlated these changes with forearm blood flow responses to L-NMMA and noradrenaline in both groups. 3. The mean age and blood pressure of the elderly subjects was 76 (range 66-82) years and 132/76 (SEM 4/3) mmHg respectively, while in the young these were 27 (20-35) years and 131/72 (4/3) mmHg respectively. L-NMMA and noradrenaline produced dose-dependent reductions in forearm blood flow in both groups. L-NMMA (4 mumol/min) produced less vasoconstriction in the elderly than in the young (-37.7 +/- 2.6 versus -48.3 +/- 4.2%; P = 0.017). The mean slope of the L-NMMA dose-response curves in the elderly was significantly less than the younger group (-35.2 +/- 3.1 versus -63.7 +/- 10.6; P = 0.041). Noradrenaline, 240 pmol/min, also produced less vasoconstriction in the elderly compared with the young (-22.8 +/- 2.9 versus -35.3 +/- 5.0%; P = 0.029) although the slopes of the dose-response curves did not differ significantly. 4. Urinary nitrate adjusted for creatinine clearance was also significantly higher in the younger group (460.6 +/- 97.7 versus 205.9 +/- 64.8 mumol/day; P = 0.042) and showed a significant correlation with the percentage change in forearm blood flow in response to the maximum dose of L-NMMA (r = 0.5, P = 0.046). 5. We conclude that nitric oxide-mediated vasodilatation in the forearm vascular bed is diminished in old age and this reflects a more generalized reduction in nitric oxide production (as measured by urinary nitrate) in the circulation of older people. The blunted response to noradrenaline points to a more generalized reduction in vascular reactivity in the elderly.

Adult↗
PubMed1997

Development of prescribing indicators for elderly medical inpatients.

AIMS: To identify and improve suboptimal prescribing for elderly patients we have developed a number of prescribing indicators which focus on areas of concern and allow evaluation of the benefit of interventions. We report here on fourteen indicators. METHODS: The indicators are of three types: a) purely descriptive with no attempt to define optimal values, e.g. number of items prescribed per patient; b) based on unnecessary or potentially harmful prescribing, e.g. duplication; c) assessing the appropriateness of prescribing specific drugs or combinations e.g. digoxin and warfarin/aspirin in atrial fibrillation (AF). Appropriateness was defined on the basis of objective research findings and involved comparing individual patient clinical records to criteria for appropriate prescribing. Prescribing and personal data were collected for medical inpatients aged 65 years or over in 19 hospitals in England and Wales. A total of 1686 patients were included, median age 81 years, 41% were male. RESULTS: Patients were prescribed 11475 items, mean 4.6 regular items per patient. Completion of drug allergy/sensitivity statements varied from 3 to 93% between units. Use of generic name and specification of a maximum frequency of administration for "as required' medicines were more consistent, ranging from 76-94% and 52-81% respectively. Little duplication of therapy was seen. Benzodiazepines were prescribed for 22% patients, but were appropriate in only approximately one third of these. Of the 2% patients prescribed an angiotensin converting enzyme inhibitor with a potassium-sparing diuretic or potassium supplement, prescription of the combination was appropriate in 84%. Coprescription of steroids with beta 2-adrenoceptor agonists appeared excessive in 67% patients receiving a beta 2-adrenoceptor agonist, as only 51% had documented evidence of steroid responsiveness or another indication for steroids. Stroke prophylaxis in AF was inadequate: 22% patients prescribed digoxin also received warfarin or aspirin 300 mg whereas 64% should have received the coprescription. CONCLUSIONS: These prescribing indicators are sensitive to inappropriate prescribing for elderly medical inpatients and cover a wide range of therapeutic areas. They should enable changes in prescribing quality to be measured objectively. Interhospital variation in casemix resulted in substantial differences in the proportion of patients in whom it would have been appropriate to prescribe specific drugs or combinations and prevented derivation of reference ranges of optimal prescribing for four indicators.

Aged↗
PubMed1997

The use of over-the-counter medication by elderly medical in-patients.

Use of over-the-counter (OTC) medications by elderly patients is often not identified. This survey was performed to study the use of OTCs by medical in-patients aged 65 and over. Data on the use of OTC medications before and during hospital admission were collected by questioning patients and case notes were examined for documentation of their use of OTC medications. OTC medications were used by 44 of 138 (32%) patients interviewed. Patients used a total of 70 OTC medications before admission and six OTC medications were being used during hospital admission. There was no documentation of pre-admission and in-hospital OTC medicine use in the clinical notes and patients had little knowledge of the potential harm some products can cause. As more products become available over the counter, doctors should record their use in patients' notes and patients should be encouraged to seek professional advice before purchasing OTC medicines and to read the product information leaflets.

Aged↗
PubMed1996

Aspartame pharmacokinetics - the effect of ageing.

Aspartame is an intense sweetener which is increasingly used in the UK. It is registered at an acceptable daily intake (ADI) of 40 mg/kg, although there are no previous data relating to the metabolism of aspartame in older people. Twelve young and 12 elderly volunteers each received a single dose of approximately 40 mg/kg of aspartame. Baseline concentrations of phenylalanine (the main metabolite of aspartame) rose after ingestion with a significantly higher maximum concentration (Cmax) (81.3 vs. 63.3 micromol/1, p<0.01) and area under the plasma concentration-time curve extrapolated to infinity AUC 9(0-infinity)(518.7 vs. 353.5 micromol . h/l, p<0.01) in the elderly group. The higher concentrations reflected a significant fall in volume of distribution (V) from 2.03 to 1.59 1/kg (p <0.05) and clearance (CL) from 7.3 to 4.9 ml/min/kg (p <0.005) in the elderly group. The greater effect on CL than on V resulted in a small but non-significant rise in elimination half life (3.5 to 3.9 hours). The sizes of the differences were modest implying that there is no need on pharmacokinetic grounds for a change in the ADI for older people.

Adult↗
PubMed1995

Twenty-four-hour ambulatory blood pressure monitoring in healthy elderly people: reference values.

One hundred and two healthy elderly volunteers (aged 65-83 years) underwent 24-hour ambulatory blood pressure monitoring. Mean day- and night-time pressures were higher than reported for younger subjects. Removing outlying BP measurements from individual 24-hour recordings only minimally affected mean figures of the group but in some individuals mean day diastolic BP may be up to 5 mmHg lower on editing. Using unedited data, mean day and night pressures were 134/81 mmHg and 119/67 mmHg respectively (corresponding 95th centiles 160/96 mmHg and 146/84 mmHg) and systolic and diastolic BP loads were 36% and 21%. These values may be used as temporary reference values for elderly subjects pending the results of longitudinal studies. Studies quoting ABPM data should specify whether data editing has been employed and, if so, the editing thresholds should be stated.

Aged↗
PubMed1995

Hawksley random zero sphygmomanometer versus the standard sphygmomanometer: an investigation of mechanisms.

There has been recent controversy over the accuracy of the Hawksley random zero sphygmomanometer (RZS). In most instances, there has been a bias towards lower recordings with the RZS. In an attempt to identify the mechanism, we designed a study to test the hypothesis that biased error is due to: (1) the magnitude of the random zero; and (2) the magnitude of the pressure being recorded. A RZS (60 mm Hg zero UK version) was connected via a Y-tube to a standard mercury sphygmomanometer (SMS). The circumference of the cam responsible for the variable reservoir size in the RZS was marked into quarters. Within each 10 mm Hg band from 300 to 60 mm Hg, 12 paired readings were taken randomly: three within each of the four quarters of the cam circumference. The mean SMS value was 148.8 vs. 148.2 mm Hg for the RZS. Although of minimal biological significance this difference was highly significant (t = 6.2; p < 0.0001). Our findings fail to confirm the difference between RZS and SMS previously reported and we did not find any evidence of a relation in the difference between SMS and RZS and either the random zero value or the height of the blood pressure. Our findings suggest that if the RZS does under record BP versus the SMS it may relate to a patient-machine interaction not detectable in our system.

Blood Pressure Determination↗
PubMed1995

Investigation of ambulatory blood pressure monitoring data editing criteria.

Ambulatory blood pressure monitoring (ABPM) allows multiple measurements of BP over a 24h period but often produces a proportion of measurements which are distant from the mean and unlikely to be genuine. The software which accompanies the SpaceLabs 90207 monitor requires criteria to be set which excludes outliers (autoediting) but there is no published data evaluating at what levels these autoediting criteria should be set. This study set out to ascertain whether outlying BP measurements represent true blood pressures or machine error, the determinants of machine error and appropriate autoedit criteria. Twenty subjects, both normotensive and hypertensive, were studied by ABPM with a blinded observer recording BP using a standard mercury sphygmomanometer (SMS) connected via a T-tube during three activity phases: sitting with cuffed arm still, walking but keeping arm still during measurement and sitting but gently moving the arm during measurement. The results show that a high ABPM/SMS discrepancy is associated with arm movement. After studying different autoediting criteria which aimed to eliminate the maximum number of conflicting readings while excluding the minimum number of unconflicting readings, an autoediting threshold of between 1.75 and 2 s.d.s from the mean based separately on sleep and awake measurements is suggested.

Aged↗
PubMed1994

The pharmacokinetics and pharmacodynamics of medifoxamine after oral administration in healthy elderly volunteers.

The pharmacokinetics and psychomotor effects of medifoxamine, a 5 HT reuptake inhibitory antidepressant, were studied in healthy elderly volunteers after single and multiple dosing. The elimination half life (t1/2z) after single doses of 300 mg was 2.8 h--almost identical to that found in young volunteers. After seven days of dosing at 100 mg three times daily the mean corrected AUC after 300 mg significantly increased from 1.04 to 1.34 mg.h.l-1 and t1/2z increased to 4.0 h (NS). There were no significant changes in critical flicker fusion frequency, symbol digit substitution, continuous attention or choice reaction times.

Administration, Oral↗
PubMed1994

Pharmacokinetics and prescribing in the elderly.

The use of prescribed medication in general is higher in the elderly than in the young and it is possible that existing patterns of antimicrobial agent prescribing may predispose to suboptimal response, certain adverse drug reactions (ADR) and the emergence of resistant strains of organisms. Age is an important variable affecting the pharmacokinetics of drugs, including many antimicrobials. Changes which may affect Cmax/MIC ratios and/or the time above MIC include reduced first-pass metabolism, altered distribution volume, reduced binding to albumin, reduced metabolic biotransformation and reduced renal elimination. Application of a knowledge of antimicrobial agent pharmacokinetic changes with age and their implications for response may enable more precise determination of dose regimens for older patients, which is probably desirable for the prevention of both ADR and bacterial resistance.

Absorption↗
PubMed1994

Psychomotor performance and antihypertensive treatment.

1. The aim of treatment of hypertension is prevention of cardiovascular complications without adverse drug reactions. Psychomotor performance can be measured objectively yet there remains uncertainty concerning the psychomotor effects of antihypertensive drugs during chronic treatment. This uncertainty is partly due to the confounding adverse effects of cerebrovascular disease and hypertension itself. There are as yet insufficient good quality data on psychomotor effects with which to differentiate between the commonly used agents. However, in general, the beneficial effect of lowering blood pressure tends to more than offset any adverse effects of the agent used.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

The association of age with gastric emptying.

Gastric emptying is important as a rate-limiting step in the absorption of orally administered drugs. Paracetamol absorption kinetics were used to compare gastric emptying in 19 fit elderly and 19 fit young volunteers. The results showed no significant difference in any of the derived parameters (t1/2abs, tlag and tmax) between the two groups. These results suggest that ageing does not impair this rate-limiting step in drug absorption.

Acetaminophen↗
PubMed1993

Computerised psychomotor performance testing: a comparative study of the single dose pharmacodynamics of minaprine and amitriptyline in young and elderly subjects.

The psychomotor and cardiovascular effects of minaprine 100 mg, a novel antidepressant, were compared with amitriptyline 25 mg, as a positive control, and placebo in a single dose randomised double-blind crossover trial using an automated psychomotor test battery (APT), postural sway (PS), blood pressure (BP) and pulse in nine young and nine elderly healthy subjects. Analysis of variance, taking into account baseline values, showed that continuous attention test (CAT), critical flicker fusion threshold (CFFT), decision making test (DMT) and paired word association (PWA) were significantly impaired with amitriptyline compared with minaprine and placebo. Minaprine did not differ from placebo. Amitriptyline significantly lowered supine systolic blood pressure (BP) and all treatments produced significant decreases in heart rate in young and elderly. No age effect on psychomotor performance was seen. Minaprine compared favourably with amitriptyline using the APT with the doses used. The APT is useful in the evaluation of new drugs on psychomotor performance.

Adult↗
PubMed1993

Assessment of changes in psychomotor performance of elderly subjects.

1. The repeatability of a computerised psychomotor test battery on a day-to-day and week-to-week basis was assessed by determining its test-retest reliability and variations in group-means and intraindividual psychomotor performance scores of elderly people. 2. Psychomotor performance was assessed in 50 well-screened elderly subjects (21 males, 29 females; mean age 70.4 +/- 5.0 (s.d.) years) on 5 consecutive days and over 4 weeks in standardised test conditions. 3. The psychomotor test battery consisted of computerised versions of symbol digit substitution test (SDST), continuous attention test (CAT), choice reaction time (CRT), critical flicker fusion test (CFFT), cognitive flexibility test (FLEX), paired word association test (PWAT) and inspection time (INSP). 4. Main outcome measures were test-retest reliability, group variability and intraindividual variability. 5. There was no significant variation in group-means for all components of the test battery over 5 days or 4 weeks on two way analysis of variance. The intraindividual coefficient of variation was low for SDST, CRT, CFFT, FLEX, PWAT and INSP during the period of assessment. Test retest reliability was greater than 0.8 for SDST, CAT, CRT and PWAT. 6. Tests in the Automated Psychomotor Test Battery are reliable and repeatable measures of psychomotor performance on a day-to-day and week-to-week basis.

Aged↗