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Biomedical subjects

S Oliver

Publications and source records attributed to S Oliver.

At least 55 records · Page 3Linked to original sources
PubMed1998

Bioavailability of repaglinide, a novel antidiabetic agent, administered orally in tablet or solution form or intravenously in healthy male volunteers.

OBJECTIVE: Repaglinide is a novel prandial glucose regulator (PGR) for the treatment of type 2 diabetes. In order to investigate subject variability following oral administration of repaglinide, and to determine the relative and absolute bioavailabilities of repaglinide following oral or intravenous administration, two single-centre, open-label, randomized, crossover clinical studies were conducted. SUBJECTS AND METHODS: Study 1 was conducted in 24 healthy male subjects (aged 18 to 49 years), who received repaglinide 2 mg, as either tablet or oral solution, twice each on 4 separate occasions at least 7 days apart. Study 2 was conducted in 12 healthy male subjects (aged 18 to 45 years), who received repaglinide 2 mg, either as a tablet or as an intravenous infusion over 15 minutes, once each on 2 separate occasions, with a washout period of 7-10 days. RESULTS: In study 1 there was no significant difference between administration of repaglinide 2 mg, in either tablet or oral solution form with regard to intrasubject variation in AUC and Cmax. However, the intrasubject variation in t(max) and mean residence time (MRT) was significantly (p = 0.001) larger for the tablets than for the oral solution. Intersubject variation (CV) in AUC ranged from 44.7% to 62.1% after oral administration. The relative bioavailability of repaglinide (AUC(tablet)/AUC(oral solution)) was 110% (95% CI, 103%-117%). In study 2 the absolute bioavailability of repaglinide administered as a tablet was 62.5% (95% CI, 49.2%-79.5%) relative to an intravenous infusion of the same dose. CONCLUSION: There was no evidence from either study that the tablet formulation led to greater variation in serum profiles of repaglinide. It was concluded that repaglinide is rapidly absorbed and eliminated in healthy subjects when administered orally or intravenously under fasting conditions, and that the total availability of repaglinide is similar in the tablet and oral solution formulations, though that the rate of absorption is slower for the tablet formulation.

Administration, Oral↗
PubMed1997

The value of including broth cultures as part of a routine culture protocol.

Three hundred seventeen clinical specimens from both superficially and deeply infected sites were prospectively examined to assess the true value of including liquid media as part of the routine culture procedure. All broth cultures were subcultured after overnight incubation onto plate media. The isolates obtained from the broth cultures were then compared with the isolates obtained on primary solid media. The isolates obtained from the broth cultures only were evaluated for clinical relevance by review of the patients' records. Twenty-two clinically relevant isolates were obtained from the broth cultures only, but the isolation of these additional organisms altered patient management for only two patients. It would appear from these results that the additional expense and time involved in culturing clinical specimens in fluid media is unwarranted.

Bacterial Typing Techniques↗
PubMed1997

Inhaler use in chronic obstructive pulmonary disease.

Inhaler technique is a common problem, particularly in the elderly. We have assessed the ability to use seven common inhaler devices in 20 patients with chronic obstructive pulmonary disease (COPD). Techniques were taught in a standard fashion in random order and assessed immediately and one hour later by two observers. Fourteen patients had a fault that would result in no drug delivery at some time during the study, and such a fault occurred at some point for each inhaler device. These faults were most common with the diskhaler. Accuhaler, autohaler and turbohaler scored highest and diskhaler lowest. Overall scores declined by one hour after instruction. Patients ranked the metered dose inhaler and accuhaler highest for ease of use and preference. These results show that it is useful to have a small range of devices for patients with COPD and that it is important to review inhaler technique regularly.

Administration, Inhalation↗
PubMed1996

Informed choice for users of health services: views on ultrasonography leaflets of women in early pregnancy, midwives, and ultrasonographers.

With the aim of promoting the informed choice of pregnant women, staff and pregnant women at two urban hospitals were offered leaflets summarising the best available evidence about the effectiveness of routine ultrasonography in early pregnancy. Ultrasonographers doubted the credibility of the evidence and were concerned that the leaflets would raise women's anxiety, reduce uptake of scans, disrupt hospital organisation, and reinforce media messages about the poor safety record of ultrasonography. Midwives thought that the leaflets would inform women, help them to talk about their care with health professionals, and help them to get better care. Women were shocked at some of the contents but thought that it was appropriate to include both advantages and disadvantages of routine scanning in the leaflet. This case study highlights the resistance of some health professionals to evidence based health care; underlying conflicts with the principle of professional autonomy; concern that informed choice may create anxiety; and professional and organisational barriers to allowing informed choice.

Attitude of Health Personnel↗
PubMed1996

Effects of phosphatidylethanolamines on the activity of the Ca(2+)-ATPase of sarcoplasmic reticulum.

ATPase activities for the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum reconstituted into dioleoylphosphatidylethanolamine [di(C18:1)PE] are, at temperatures higher than 20 degrees C, lower than in dioleoylphosphatidylcholine [di(C18:1)PC], whereas in egg yolk phosphatidylethanolamine the activities are the same as in di(C18:1)PC up to 25 degrees C, suggesting that low ATPase activities occur when the phosphatidylethanol-amine species is in the hexagonal H11 phase. ATPase activities measured in mixtures of di(C18:1)PC and di(C18:1)PE do not change with changing di(C18:1)PE content up to 80%. It is concluded that curvature frustration in bilayers containing di(C18:1)PE has no effect on ATPase activity. The rates of phosphorylation and of Ca2+ transport are identical for the native ATPase and for the ATPase in di(C18:1)PE. Dephosphorylation of the phosphorylated ATPase in di(C18:1)PE at 25 degrees C is, however, slower than for the native ATPase, explaining the lower steady-state rate of ATP hydrolysis; in egg yolk phosphatidylethanolamine at 25 degrees C the rate of dephosphorylation is equal to that for the unreconstituted ATPase. Phosphorylation of the ATPase by P1 in the absence of Ca2+ is unaffected by reconstitution in di(C18:1)RE. The stoichiometry of Ca2+ binding to the ATPase is also unaltered. Studies of the effect of di(C18:1)PE on the fluorescence intensity of the ATPase labelled with 7-chloro-4-nitro-2,1,3-benzoxadiazole are consistent with an increase in the E1/E2 equilibrium constant, where E1 is the conformation of the ATPase with two high-affinity binding sites for Ca2+ exposed to the cytoplasm, and E2 is a conformation unable to bind cytoplasmic Ca2+. A slight increase in affinity for Ca2+ can be attributed to the observed increase in the E1/E2 equilibrium constant.

Calcium-Transporting ATPases↗
PubMed1996

Characterization of the soluble, secreted form of urinary meprin.

A soluble form of the kidney membrane metalloendopeptidase, meprin, is present in urine. Urinary meprin is expressed in BALB/C mice with the Mep-1 alpha/alpha genotype (high meprin, expressing meprin-alpha and meprin-beta ) but not in BALB.K mice of the Mep-1b/b genotype (that only express meprin-beta ). Western blotting with antisera specific to the meprin-alpha and the meprin-beta subunits established that the only form of meprin present in urine samples was derived from meprin-alpha. This form of meprin is partially active, and comprises at least three variants by non-reducing SDS/PAGE and by zymography and two protein bands on reducing SDS/PAGE. Sequencing of these two bands established that the N-terminus of the larger protein band begins with the pro-peptide sequence of the alpha-subunit (VSIKH..), whereas the smaller band possessed the mature meprin N-terminal sequence (NAMRDP..). Trypsin is able to remove the pro-peptide, with a concomitant activation in proteolytic activity. After deglycosylation, the size of the pro- and mature forms of urinary meprin are consistent with cleavage in the region of the X-I boundary. There is a pronounced sexual dimorphism in urinary meprin expression. Females secrete a slightly larger form, and its proteolytic activity is about 50% of that released by males. The urinary meprin is therefore a naturally occurring secreted form of this membrane-bound metalloendopeptidase and is more likely to be generated by alternative processing pathways than by specific release mechanisms.

Amino Acid Sequence↗
PubMed1996

Glycerol and ichthammol: medicinal solution or mythical potion?

Glycerol and ichthammol (G & I) has been used for generations by otologists. However, there is a paucity of information on both its mode of action and its anti-bacterial properties. The aim of this paper was to ascertain firstly, what the most common organisms found in discharging ears were and secondly, what antibacterial activity G & I had against these organisms. All ear swabs from 1992-1994 in our unit were reviewed to ascertain the prevalence of the commonly isolated organisms. Fresh isolates of these organisms were collected and plated onto agar with wells of glycerol, ichthammol and a combination of both as used in clinical practice. The diameters of the zones of inhibition observed after incubation were measured in millimetres. Common isolates were: Pseudomonas aeruginosa, Staphylococcus aureus, Proteus mirabalis, Streptococcus pyogenes in descending order of frequency. Pure glycerol showed no significant zones of inhibition against any of the organisms tested. The average zones of inhibition for G & I and ichthammol alone were for Staphylococcus aureus 15 mm and 18 mm and for Streptococcus pyogenes: 16 mm and 23 mm. Ichthammol alone was significantly more effective than G & I (p < 0.001). There was no significant activity against Proteus mirabalis and Pseudomonas aeruginosa. The therapeutic benefit of G & I is due in part to the inherent anti-bacterial activity of ichthammol against the Gram positive organisms as well as its anti-inflammatory action and the dehydrating effect of the glycerol.

Anti-Infective Agents, Local↗
PubMed1996

Evidence-based consumer health information: developing teaching in critical appraisal skills.

OBJECTIVE: To help people who give health information to the public develop the skills they need to make sense of evidence about effectiveness. DESIGN: Educational approach, preceded by careful planning with representatives of possible participants. SETTING AND STUDY OF PARTICIPANTS: Staff in consumer health information services and members of maternity self-help groups in the UK in summer 1995. INTERVENTIONS: Pairs of half-day workshops introducing participants to randomised controlled trials and systematic reviews and to their critical appraisal. The workshops were run participatively and had at their centre a critical appraisal session in small groups. MAIN OUTCOME MEASURES: Attendance at workshops, satisfaction and enjoyment of workshops; comments at a follow-on event. RESULTS: Four pairs of workshops were held (three for consumer health information services, one for maternity self-help groups), 54 people attended a pair of workshops and a further 34 attended individual workshops. The workshops were enjoyed and found to be a good use of time. CONCLUSIONS: It is feasible to introduce critical appraisal skills to people whose primary role is to give health information to the public. There is a need for comparative evaluation of different approaches.

Community Participation↗
PubMed1996

A journey from bureaucracy to enterprise.

Uses the Business Development Consultancy as a case study to demonstrate how a training and development function responded to the working for patient reforms in the NHS. Offers an example of how change can be managed effectively when moving from a bureaucratic to enterprise culture. Emphasizes dealing with the human side (including the casualties of the change) and obtaining ownership of the change and focuses on how the mind set needs to shift. Highlights that change is more than implementation of a new organizational structure or set of rules. Reinforces that change is continuous and requires continual monitoring and review. Ends by stating that change from bureaucracy to enterprise may be difficult but can be achieved successfully.

Health Services Research↗
PubMed1996

The progress of lay involvement in the NHS Research and Development Programme.

The Central Research and Development Committee is seeking to involve lay perspectives in the NHS R&D Programme. This paper describes some recent examples of lay involvement in each step of the research process from setting the agenda to making use of research findings. Innovative approaches have involved lay people in identifying research need and in the subsequent commissioning process. Lay contributions have given particular emphasis to information and support, whether this is in maternity care, cancer care, HIV prevention, participation in clinical trials or systematically reviewing evidence of effectiveness. Difficulties in identifying appropriate lay people to involve in research, their different skills, their lack of resources and support and their need for time for thought and discussion with their peers have all posed problems. Suggestions for overcoming some of these obstacles are presented, including resources, training and support, and clarification of the role, nature and potential for lay involvement. Lastly this paper considers the urgent need to learn from the efforts made so far, possible approaches to evaluation and how this is being addressed by a newly convened advisory group to the Central R&D Committee.

Community Participation↗
PubMed1995

Caffeine phenotyping of cytochrome P4501A2, N-acetyltransferase, and xanthine oxidase in patients with familial adenomatous polyposis.

Patients with familial adenomatous polyposis (FAP) and age and sex matched controls were tested for cytochrome P4501A2 (CYP1A2), N-acetyltransferase, and xanthine oxidase activities using caffeine urinary metabolites as a discriminator. FAP patients showed significant underactivity of N-acetyltransferase (which inactivates some carcinogens) and significant overactivity of CYP1A2 (which activates some carcinogens). Xanthine oxidase activity, which can generate free radicals and cause cellular damage, was significantly increased in the FAP patients. All but one of the FAP patients had undergone colectomy. A separate group of six patients was therefore assessed before and at an average time of eight weeks after colectomy. No effect on enzyme activity was seen. The differences in enzyme activities detected in this study could produce an excess of active carcinogenic metabolites in the bile of FAP patients and contribute to the high risk for intestinal cancer in FAP.

Acetyltransferases↗
PubMed1994

Kitson's Therapeutic Nursing Function Indicator as a predictor of the quality of nursing care in hospital wards.

This study examines the value of Kitson's (1991) Therapeutic Nursing Function Indicator (TNFI) as a predictor of the quality of nursing care in hospital wards. The TNFI was updated and modified for use in medical and surgical as well as elderly care wards, and was administered to the sister and deputy of 11 wards. Kitson's Therapeutic Nursing Function Matrix (TNFM), which assesses the quality of self-care activities (more precisely, the level of therapeutic nursing), was administered to patients in the first nine wards and was tested for inter-rater reliability. Acceptable reliability was achieved for identification of activities. However, correlations between activity scores were low, although statistically significant. Scores from the modified TNFI were compared with mean TNFM ward scores to test Kitson's finding that the TNFI is a predictor of the quality of nursing; our results did not support this hypothesis. Differences in the design of our study with Kitson's might be responsible for this result. Our analysis, however, suggests that the TNFI has become out of date because of changes in the organisation of nursing work, and that it is no longer a sensitive predictor of the quality of nursing care.

Activities of Daily Living↗