PubMed Health⌕ Search

Biomedical subjects

P Turner

Publications and source records attributed to P Turner.

At least 73 records · Page 4Linked to original sources
PubMed1995

Antipyrine repeatability and comparison of the powder and capsule formulations.

Twelve healthy subjects (6 females), who were drug-free and non alcoholic, age 21-40 years and weight 43-80 kg took part in the study which lasted about 4 weeks. The subjects were randomly assigned into 2 panels (of 6 subjects each) and took antipyrine (1,050 mg) orally either as powder made into solution or gelatin capsules on 3 consecutive trial occasions separated by 2-week intervals. Panel A had powder, powder and capsule formulations on trials 1, 2 and 3, respectively, and panel B had capsule, capsule and powder formulations on trials 1, 2 and 3, respectively. There were no significant differences in the saliva pharmacokinetic parameters of antipyrine in the 3 trials for both panels of subjects, except the half-lives in panel B which was significantly different at the 5% level. There were no significant differences in the amounts of antipyrine and its metabolites excreted in urine in the 3 trials. The saliva concentrations of antipyrine in the 3 trials were relatively comparable. The relative bioavailability of the capsule formulation of antipyrine was 97%. This study shows that the saliva pharmacokinetic parameters of antipyrine and the amounts of antipyrine metabolites excreted in urine are highly reproducible following repeated oral administration, either in solution or as capsules. The capsule formulation is fully bioavailable and should be suitable for oral administration in assessing the influence of drugs and environmental factors on antipyrine metabolism.

Adult↗
PubMed1994

Linkage of the angiotensinogen gene to essential hypertension.

BACKGROUND: The renin-angiotensin system is a powerful pressor system with a major influence on salt and water homeostasis. Angiotensinogen (also called renin substrate) is a key component of this system; it is cleaved by renin to yield angiotensin I, which is then cleaved by angiotensin-converting enzyme to yield angiotensin II. The observation that plasma angiotensinogen levels correlate with blood pressure and track through families suggests that angiotensinogen may have a role in essential hypertension. We therefore investigated whether there is linkage between the angiotensinogen gene on chromosome 1q42-43 and essential hypertension. METHODS: Samples of DNA from 63 white European families in which two or more members had essential hypertension were tested for linkage of the angiotensinogen gene to this disorder. Affected cousins, nephews, nieces, and half-siblings were included when possible. To test for linkage, we used as a marker a dinucleotide-repeat sequence flanking this gene, and we employed the affected-pedigree-member method of linkage analysis. Two molecular variants of the angiotensinogen gene, one encoding threonine instead of methionine at position 235 (M235T) and the other encoding methionine rather than threonine at position 174 (T174M), were also tested for possible association with essential hypertension. RESULTS: We found significant linkage (t = 5.00, P < 0.001) and association (chi-square = 53.3, P < 0.001) of the angiotensinogen-gene locus to essential hypertension in the 63 multiplex families. This linkage was consistently maintained in the subgroup of subjects with diastolic pressure above 100 mm Hg and in the subgroups classified according to sex. It has been proposed previously that T174M and M235T are associated with essential hypertension. However, we found no association in our population between either polymorphism and this disorder. CONCLUSIONS: This study provides strong and consistent support for the linkage to essential hypertension of regions within or close to the angiotensinogen gene. Precisely how mutations in this region may result in hypertension remains to be determined.

Aged↗
PubMed1994

Views of hospital staff on the management of hypertension.

A questionnaire concerning the detection and management of hypertension was presented to 265 hospital doctors, 114 medical students and 59 student nurses. Of these 75% were completed. Although only 76% thought that routine measurement was necessary in outpatients, 92% of respondents thought that blood pressure (BP) should be measured routinely in all in-patients. A total of 17% of all doctors and 11% of physicians indicated that they would not use drug treatment until the diastolic BP exceeded 105 mmHg. Thirty-four per cent of respondents still use diastolic phase IV and 84% felt that BP should be measured 2-4 times before deciding on treatment but the posture of the patient (lying, sitting or standing) during recording was inconsistent. Seventy-seven per cent of respondents indicated that they recorded BP to the nearest 5 mmHg and 4% to the nearest 10 mmHg. Despite the literature on the subject, there are still widely differing opinions amongst medical staff on how to record BP and at what level it should be treated.

Attitude of Health Personnel↗
PubMed1994

Pharmacokinetics of naftopidil, a novel anti-hypertensive drug, in patients with hepatic dysfunction.

The pharmacokinetics of naftopidil, a novel alpha-1 adrenoceptor-blocking antihypertensive, were investigated in ten patients (9M/1F) with hepatic dysfunction after oral administration (50 mg, tablet) and after an intravenous infusion of 5.0 mg over 2 minutes. Results were compared to a control group of 12 healthy subjects (6M/6F) of a previous investigation, which was carried out according to the identical study protocol. The pharmacokinetic parameters obtained for the i.v. administration were comparable in both groups (half life 3.6 +/- 3.4 hours in liver-impaired subjects versus 3.3 +/- 2.1 hours in controls; clearance 11.9 +/- 4.7 ml/minute/kg versus 11.0 +/- 1.6 ml/minute/kg). Following oral administration the plasma levels and half-life times of naftopidil were significantly increased in liver impairment (t1/2 16.6 +/- 19.3 hours versus 5.4 +/- 3.2 hours in controls; P = 0.012). Mean values for the absolute bioavailability in patients with hepatic dysfunction were significantly higher (mean 75%, median 53%, range 13.4-211.0%) compared to healthy subjects (mean 17%, median 16%, range 6.7-29.6%, P = 0.001). Reduction of functional hepatic blood flow in chronic liver disease or, as evidenced in one case as a consequence of shunt surgery, is the probable cause of the observed alteration in naftopidil kinetics. This phenomenon occurred only following the oral 50 mg dose whereas the intravenous 5 mg dose obviously still could be normally handled. Naftopidil demethylation and hydroxylation were both less and non-uniformly affected. The pharmacokinetic findings suggest that in patients with severe hepatic impairment or evidence for marked changes in hepatic blood flow the dose of naftopidil may require adjustment to the lower end of the therapeutic range and/or may be limited to once daily. However, before definite conclusions can be drawn, further steady-state studies are required. Despite the pharmacokinetic discrepancies no difference in drug tolerability was seen between patients and healthy subjects.

Administration, Oral↗
PubMed1994

Enalapril pharmacokinetics and ACE inhibition, following single and chronic oral dosing.

Twelve normal volunteers were given 10 mg enalapril maleate by single and 2 weeks multiple dose administration, and blood samples were collected for the determination of enalaprilat concentration and angiotensin converting enzyme (ACE) activity. The mean terminal elimination half-life following a single administration of 10 mg enalapril, was 27 hours. The inhibition of ACE activity paralleled enalaprilat concentrations following both single and multiple dosing and the time of maximum inhibition of ACE activity was associated on both occasions with maximum concentration of enalaprilat. Emax modelling of enalaprilat concentration and ACE activity gave comparable values of Emax for both methods of administration. An accumulation factor of 1.7 was calculated from the area under the concentration time curve (AUC) of enalaprilat within a dosing interval at steady-state and the total AUC following single administration of enalapril. There were no significant differences between males and females in the accumulation factor, half-life and AUCinf.

Administration, Oral↗
PubMed1993

Typing of feline calicivirus isolates from different clinical groups by virus neutralisation tests.

One hundred and thirteen isolates of feline calicivirus originating from seven different clinical groups were typed by virus neutralisation tests using eight different cat antisera. The clinical groups comprised 'healthy' cats, cases of acute oral/respiratory disease, chronic stomatitis, acute febrile lameness syndrome, vaccine reactions (clinical disease seen within 21 days of vaccination) and vaccine breakdowns (clinical disease seen more than 21 days after but within one year of vaccination). Isolates from the vaccine reaction cases were grouped into those associated with acute oral/respiratory disease alone and those associated with the lameness syndrome, and the latter group was further subdivided according to the vaccine used. Two groups appeared significantly different from others with some of the antisera. Thus the lameness vaccine reaction isolates associated with vaccine B were significantly different from the isolates from all the other clinical groups, including other lameness isolates, with a number of the antisera. In addition, the chronic stomatitis isolates were significantly different from those from the 'healthy' and the acute oral/respiratory disease groups with one or two of the antisera. Eighty-five to 88 per cent of the isolates were neutralised by antisera raised against F9 or F9-like vaccine strains at a dilution of 1 in 2. Twenty antibody units of such antisera neutralised 42 to 80 per cent of the isolates. A bivalent antiserum raised against a vaccine F9 strain and field strain LS015 neutralised 96 per cent of the isolates at a dilution of 1 in 2, and 20 antibody units neutralised 68 per cent of isolates. Antisera to field strain F65 neutralised all the remaining isolates at a dilution of 1 in 2 and 44 per cent of the remaining isolates at a dilution of 20 antibody units. Therefore, strains LS015 and F65 may be of use in the production of a polyvalent feline calicivirus vaccine, together with the widely used strain F9.

Animals↗
PubMed1993

Cutaneous blood flow changes and weal induced by intradermal bradykinin following pretreatment with indomethacin and captopril.

The effects of indomethacin and captopril on local cutaneous blood flow changes and weal induced by intradermal injections of bradykinin were assessed in two randomised, double-blind, placebo-controlled studies in healthy volunteers. Alterations in cutaneous blood flow were estimated by laser Doppler flowmetry (LDF) and erythema area. LDF output, erythema area and weal volume increased with incremental bradykinin dose. Single doses of indomethacin 25 mg and 75 mg did not affect these cutaneous responses compared with placebo. Captopril 25 mg significantly potentiated the increase in local cutaneous blood flow measured by LDF, but not erythema area, and weal volume induced by bradykinin. The effects of the combined treatment of indomethacin 75 mg and captopril 25 mg were not significantly different from those due to captopril alone. The enhanced cutaneous effects of bradykinin following administration of captopril are in keeping with effective kininase II inhibition in the tissues. Cyclo-oxygenase products release does not appear to contribute to the cutaneous actions of bradykinin nor the potentiation of these responses by captopril.

Bradykinin↗
PubMed1993

Influence of debrisoquine hydroxylation phenotype on the pharmacokinetics of mexiletine.

Marked interindividual variation has been observed in the pharmacokinetics of the antiarrhythmic agent mexiletine. The fact that its urinary excretion is dependent on urinary pH may account, in part, for such variation. The influence that genetic differences in hepatic metabolism of the debrisoquine-type may have on mexiletine pharmacokinetics was considered in this study. The pharmacokinetics and urinary excretion of mexiletine (250 mg administered intravenously) were investigated in 5 rapid extensive metabolisers (EM), 5 slow EM and 5 poor metabolisers (PM) of debrisoquine, under conditions of controlled urinary pH. Mexiletine disposition kinetics was found to be altered in PM individuals. These subjects showed higher total area under the curve (AUC), (15.7 versus 8.16 micrograms.h.ml-1) prolonged elimination half-lives (in serum and urine) (serum: 18.5 versus 11.6 h, urine: 19.2 versus 11.7 h) and lower total clearance values compared with EM (216 versus 450 ml.min-1). In this respect, slow EM individuals generally presented intermediate values of those pharmacokinetic parameters. A higher incidence of adverse-effects was also observed among slow EM and PM subjects. It is concluded that genetic differences in mexiletine oxidation of the debrisoquine-type have an influence on its observed pharmacokinetic variability. The clinical consequences are discussed.

Adult↗
PubMed1993

Activity nursing and the changes in the quality of life of elderly patients: a semi-quantitative study.

In recent years increasing awareness and interest in different approaches to caring for elderly people have produced improvements in their psychological and social care. This paper evaluates the change in the quality of life which was brought about by the introduction of activity nursing into a continuing care unit. Significant changes were observed in cognitive functioning and quality of life. The benefits to both relatives and staff were also considerable.

Aged↗
PubMed1993

A comparison of the effects of captopril and enalapril on skin responses to intradermal bradykinin and skin blood flow in the human forearm.

1. The effects of captopril and enalapril on skin responses to intradermal injections of bradykinin and skin blood flow in the forearm were investigated in this randomised, double-blind, placebo-controlled, cross-over study. 2. Intradermal injections of 0, 1, 2.5 and 5 micrograms of bradykinin in 0.9% sodium chloride were made into the forearm of twelve healthy volunteers before and at 2, 6 and 24 h after single oral doses of 25 mg captopril, 10 mg enalapril or placebo. Forearm skin blood flow was measured by the technique of laser Doppler flowmetry (LDF) before the injections were made and the skin responses evaluated at 15 min after injections of bradykinin by measurement of cutaneous blood flow outside the induced weal, erythema area and weal volume. 3. The bradykinin-induced cutaneous responses measured by LDF, erythema area and weal volume increased with incremental bradykinin dose. Compared with placebo, captopril significantly augmented the cutaneous vasodilator effects of bradykinin, measured by LDF and erythema area, at 2 h and the weal responses at 2 and 6 h. Enalapril enhanced the vasodilator responses to bradykinin at 2 and 6 h and the weal responses at 2, 6 and 24 h. Neither captopril nor enalapril significantly affected forearm skin blood flow. 4. This study showed that captopril and enalapril potentiated the effects of intradermal bradykinin both with respect to blood flow changes and weal formation in keeping with effective kininase II inhibition and the time course of these changes are consistent with enalapril being a longer acting drug than captopril. Captopril and enalapril exerted no influence on forearm skin blood flow measured by LDF.

Adult↗
PubMed1993

Bile duct injury during laparoscopic cholecystectomy: a report of the Standards Sub-committee of the Victorian State Committee of the Royal Australasian College of Surgeons.

A survey of Victorian surgeons performing laparoscopic cholecystectomy was carried out. This report discusses the bile duct injuries identified in the survey. Twelve injuries were recorded, a rate of 0.2%. Three of the 12 required formal repair, the other 9 being treated by T-tube alone. Possible mechanisms of these injuries, the experience of the surgeon, the role of operative cholangiography and delays in recognition of the injury are discussed.

Bile Ducts↗
PubMed1993

Investigating children's knowledge and understanding of AIDS.

Though AIDS education in schools reaches many adolescents, the incidence of adolescent HIV infection has risen dramatically. Reasons for failure to properly educate adolescents include not educating children prior to adolescence and neglecting to assess and address children's varying levels of cognitive development when designing AIDS education programs. Citing examples from a study of more than 600 elementary-age schoolchildren, this paper focuses on the importance of assessing children's understanding of disease processes rather than accepting their use of key phrases in appropriate contexts as reflecting knowledge, and using the level at which they understand disease processes rather than age as the primary determinant of students' readiness for comprehending AIDS-related concepts. Guidelines for assessing how well children understand disease processes, including use of nonleading probes, are presented.

Acquired Immunodeficiency Syndrome↗