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Biomedical subjects

J McEwen

Publications and source records attributed to J McEwen.

At least 19 recordsLinked to original sources
PubMed1995

Needs assessment in Scotland: collaboration in public health.

The National Health Service reforms revitalized the national emphasis on the public's health and health needs assessment. In Scotland, in contrast with England, there was no central investment in the development of methods and programmes for needs assessment in the context of the new NHS. To achieve a concerted effort, therefore, a self-help network--the Scottish Needs Assessment Programme (SNAP)--was created by the Scottish Forum for Public Health Medicine. This paper describes its evolution to the point where it is now supported as part of a national network of information for purchasing.

Health Care Reform↗
PubMed1995

Prospective study of the quality of life in patients assessed for liver transplantation: outcome in transplanted and not transplanted groups.

The quality of life in adult patients with chronic liver disease who were considered for transplantation was assessed prospectively over a 2 year period, for both those who did and did not subsequently receive transplants. The main outcome measures were the Nottingham Health Profile and survival. Of the 109 patients who completed an entry profile, 27 were transplanted, 71 not transplanted during the study period, and 11 rejected for transplant. Quality of life and severity of liver disease at entry was worse for the transplant group, whose survival at 15 months from entry was 81% compared with 78% for those not transplanted. Among transplant survivors there were marked improvements in quality of life, whilst amongst those not receiving transplants there was little change. In conclusion, liver transplantation was effective in improving quality of life in patients with chronic liver disease, but comparison between transplant and non-transplant patients is difficult because of differences between the groups.

Activities of Daily Living↗
PubMed1992

Synthetic recombinant vaccine expressing influenza haemagglutinin epitope in Salmonella flagellin leads to partial protection in mice.

The influenza virus haemagglutinin epitope 91-108, which is a conserved amino acid sequence in all type A H3 strains, was expressed in Salmonella flagellin, to evaluate its potential as a vaccine. For that purpose, a synthetic oligonucleotide comprising 54 bases coding for the corresponding sequence was inserted into the plasmid pLS408 and transformed into Escherichia coli JM101. Colonies containing the recombinant plasmid were used to transform Salmonella typhimurium LB5000 and were then transduced to a flagellin negative 'live vaccine' aroA mutant of Salmonella dublin. Rabbits immunized either with the live recombinant S. dublin or with the flagellin isolated from it, showed significant levels of IgG response against the synthetic peptide 91-108 as well as against the intact A/Texas/77 influenza virus. Mice immunized with the same preparations developed influenza-specific IgG antibodies in the blood and secreted IgA antibodies in their lungs. Furthermore, these mice showed about 50% protection against challenge infection with the virus. The most successful results were achieved by intranasal immunization with the isolated recombinant flagellin, when employed without the aid of adjuvant.

Amino Acid Sequence↗
PubMed1992

Ethanol kinetics: extent of error in back extrapolation procedures.

1. Plasma ethanol concentrations were measured in 24 male volunteers for 9 h after a single oral dose of 710 mg kg-1. 2. The rate of decline of the plasma ethanol concentration (k0; mean +/- s.d.), was 186 +/- 26 mg l-1 h-1. 3. In each individual, three elimination rates were used to back-extrapolate plasma ethanol concentrations over 3 and 5 h periods from observed values at 4 h and 6 h post-dosing assuming zero-order kinetics. The extrapolated values were then compared with the observed concentrations. 4. Using the mean k0 values for the subjects the mean error in back extrapolation was small but highly variable. The variability in the error increased with the length of the extrapolation period. 5. When a k0 value of 150 mg l-1 h-1 (a value often cited as a population mean) was used for back extrapolation this resulted in significant under-estimation of actual values whereas the use of a k0 value of 238 mg l-1 h-1 (the highest value observed in the present study) resulted in significant over-estimation of actual values. 6. These results indicate that because the kinetics of ethanol are associated with substantial inter-subject variability the use of a single slope value to back calculate blood concentrations can give rise to considerable error.

Adult↗
PubMed1992

Antibodies to shiga holotoxin and to two synthetic peptides of the B subunit in sera of patients with Shigella dysenteriae 1 dysentery.

Acute- and convalescent-phase sera from 18 Thai patients and convalescent-phase sera from two Israeli patients and one Bangladeshi patient with Shigella dysenteriae 1 (Shiga) dysentery were tested by enzyme-linked immunosorbent assay to detect antibodies that bind S. dysenteriae lipopolysaccharide (LPS), Shiga holotoxin, or two synthetic peptides representing epitopes from the B subunit of Shiga toxin. Paired sera from 24 Maryland adults with Shigella flexneri 2a or Shigella sonnei diarrhea served as negative controls. Of the 16 paired Thai serum samples tested for immunoglobulin G LPS antibody, 10 had greater than or equal to 4-fold rises (the two subjects with the highest convalescent-phase titers exhibited toxin-neutralizing activity); acute-phase specimens from four of the remaining six individuals already had elevated Shiga LPS titers in their acute specimens ranging from 1:800 to 1:12,800. Similarly, convalescent-phase sera from the two Israeli patients and the Bangladeshi patient revealed LPS titers of 1:800 to 1:3,200. In contrast, none of the Maryland volunteers with S. flexneri or S. sonnei diarrhea manifested rises in Shiga anti-LPS (P less than 0.00001 versus 10 of 16 Thai patients). Only 4 of the 18 Thai patients had significant rise in antibody to purified Shiga toxin, while one of the two Israeli patients and the one Bangladeshi patient had elevated convalescent-phase titers. None of the sera that reacted with Shiga holotoxin had antibody that bound to the peptides. This report, which describes a search for serum antibodies that bind Shiga toxin in patients with Shiga dysentery, demonstrates such antibodies in only a minority of patients with bacteriologically confirmed disease. During Shiga dysentery, Shiga toxin may be elaborated in such small quantities in vivo that it fails to elicit an immune response in most patients even though it may exert biological effects. In this behavior Shiga toxin resembles tetanus toxin, another potent exotoxin that fails to elicit antitoxic responses in people who recover from clinical tetanus.

Adolescent↗
PubMed1991

The pharmacokinetics of dermatan sulphate MF701 in healthy human volunteers.

1. The pharmacokinetics of dermatan sulphate MF701 were studied in 12 healthy males after administration of single intravenous bolus (200 mg), intramuscular (100 and 300 mg) and oral (1 g) doses. The study was conducted according to a within-subject crossover design in two paired blocks. 2. Plasma drug concentrations were measured using a competitive binding assay and a range of biological activity assays, including a sensitive catalysed thrombin inhibition test. 3. Following intravenous administration, plasma concentrations of dermatan sulphate determined by competitive binding assay were described by a two-compartment open model with an initial t1/2, in of 0.6 h and a t1/2,z of 7.5 h. Biological activity assays were insufficiently sensitive to detect the second phase, and therefore yielded apparent monoexponential kinetics. 4. After intramuscular injection the apparent bioavailability of dermatan sulphate was 16-20%. Plasma drug concentrations increased in proportion to dose when measured by competitive binding assay. Low concentrations persisted for more than 24 h at the higher dose, and these may prove therapeutically relevant on chronic administration. 5. We confirm that dermatan sulphate is the only glycosaminoglycan known to generate significant plasma concentrations following oral administration. Oral bioavailability was estimated to be 7%.

Adolescent↗
PubMed1991

Magnesium deficiency may be an important determinant of ventricular ectopy in digitalised patients with chronic atrial fibrillation.

Digitalised patients with chronic atrial fibrillation (AF) have a high prevalence of ventricular premature beats (VPB); magnesium deficiency may be a contributory factor. We have used a magnesium loading-test to examine the relationship between ventricular ectopy and magnesium status in 14 digitalised patients with chronic AF. Among seven patients with infrequent VPB (less than 250 24 h-1; mean 107 24 h-1) mean magnesium retention was 10.1% and four subjects retained no significant quantities of magnesium, indicating magnesium repletion. Among the remaining seven patients, mean magnesium retention was significantly higher (33.1%, P less than 0.02) and all patients retained 20% or more of the load given. There was an overall relationship between Mg retention and numbers of VPB (rs = 0.54; P less than 0.05). Magnesium deficiency may be determinant of ventricular ectopy in digitalised patients with chronic AF.

Aged↗
PubMed1991

Kinetics of idaverine in healthy male subjects after single dose oral and intravenous administration.

The kinetics of idaverine was studied in an open, cross-over, partially randomized design after single oral (2 mg) and intravenous (1 and 2 mg doses to 12 healthy male subjects. In the first session, the volunteers were administered 1 mg idaverine by constant intravenous infusion during 45 min. The treatments in the second and third sessions were given according to a cross-over design, randomized in blocks of six for each session (2 mg either orally or by intravenous infusion during 45 min). The washout period between the sessions was at least 1 week. Plasma, urine and faeces were analysed for idaverine and its pharmacologically active metabolite N-desmethylidaverine by gas chromatography with nitrogen flame ionisation detection. After intravenous administration, the MRT was on average 2 hours and the mean CLS was about 900 ml.min-1. CLR is about twice the glomerular filtration rate, suggesting net tubular secretion of idaverine. The AUC and the cumulative urinary and faecal excretion values gave no indication of dose-disproportionality within the range of 1 and 2 mg administered intravenously. Maximum plasma levels of 1-3 ng.ml-1 were reached between 0.5 hours and 3 hours after oral dosing. The MRT was 4.4 hours. Systemic availability was about 29%. N-desmethylidaverine was barely detectable in plasma after all doses. Idaverine was well tolerated, only a small increase in heart rate was observed.

Administration, Oral↗
PubMed1990

Pharmacokinetics and pharmacodynamics of the ace inhibitor benazepril hydrochloride in the elderly.

The pharmacokinetics and pharmacodynamics of a single oral dose benazepril.HCl 10 mg have been studied in 15 healthy volunteers aged 65 to 80 y. The kinetics of unchanged benazepril and its active metabolite benazeprilat did not differ significantly in males and females, so the combined kinetic data from all 15 elderly subjects were compared with a historical control group of 19-32 year-old healthy men treated in the same way. The disposition of benazepril was not affected by age. The time to maximum plasma concentration, tmax (0.5 h) and elimination half-life (0.6 h) in the elderly were the same as in young subjects. The kinetics of benazeprilat was slightly changed in the elderly; although its tmax (1.5 h) was not affected, Cmax and the AUC were 20-40% greater. The elimination half-life of benazeprilat during the first 24 h after dosing in the elderly was increased by about 20% to 3.2 h. The renal plasma clearance of benazeprilat (18.1 ml.min-1) was about 20% smaller than in the young subjects. An average of 18.5% of the dose was recovered as benazeprilat in the 24 h urine from the elderly subjects, which was similar to the recovery in the young subjects. Both benazepril and benazeprilat were highly bound to serum proteins (96 and 95%, respectively). Mean systolic and diastolic blood pressures in the elderly were reduced by a maximum of 37/16 mm Hg at 6 h, in association with a small rise in pulse rate. Treatment was generally well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Comparison of once daily atenolol, nitrendipine and their combination in mild to moderate essential hypertension.

1. The aim of the study was to compare the efficacy and the tolerability of treatment with atenolol (50-100 mg once daily), nitrendipine (20-40 mg once daily) and their combination (atenolol 50 mg + nitrendipine 20 mg) once daily in patients with mild to moderate essential hypertension. 2. The study was a randomised, double-blind, placebo controlled parallel groups design: blood pressures were measured at 'trough' effect (i.e. 24 h after dosing) to assess the adequacy of once-daily treatment. 3. Mean blood pressures (mm Hg) recorded on four occasions over 12 weeks of treatment were significantly lower both with atenolol (155/97 sitting: 155/104 standing) and with the combination of atenolol plus nitrendipine (153/96 sitting: 152/104 standing) than with placebo (169/108 sitting: 169/114 standing). Nitrendipine alone had no significant effect on blood pressure 24 h after dosing (165/104 sitting: 165/110 standing). 4. Withdrawals due to adverse effects were more common during treatment with nitrendipine: 7/32 of the patients experienced adverse effects attributable to intense systemic vasodilatation (e.g., flushing, erythema, headache). 2/37 patients taking atenolol were withdrawn: one because he developed a psoriatic rash and the other because of impaired peripheral circulation. Of the 35 patients taking combination treatment, two were withdrawn: one developed headaches and dyspnoea, and the other asthma. 5. The results suggest that once daily dosing with nitrendipine does not control blood pressure throughout the 24 h period in the majority of patients, and is associated with a considerable burden of adverse effects. Combination treatment was better tolerated but appeared to offer no advantages over atenolol alone in terms either of blood pressure control or adverse effects.

Adolescent↗
PubMed1990

Quality of life following liver transplantation: a preliminary report.

Although the quality of life attained after heart transplantation has been assessed, there is no equivalent information for recipients of liver grafts in this country. In this paper we report a cross-sectional survey of 81 adult patients in the Cambridge/King's College Hospital joint programme using the Nottingham Health Profile which is a validated measurement of the quality of life. The results show the quality of life to be high, and broadly similar to the levels expected in the general population. The data suggest an increase in the problems related to physical mobility (two-fold) and a reduction in problems of emotional reaction (a halving).

Adult↗
PubMed1989

Attendance and non-attendance for breast screening at the south east London breast screening service.

OBJECTIVES: To ascertain the reasons for a low rate of response for breast screening. DESIGN: All relevant aspects of the organisational process examined, including general practitioners' notes. Non-responders visited and interviewed. SETTING: An inner city breast screening service working on the model advocated by the Forrest report. SUBJECTS: 288 Women aged 50-64 registered with several general practices and invited for screening by post. MAIN OUTCOME: Determination of factors important for success of breast screening programmes. RESULTS: After five women were excluded by their general practitioners the response rate was 129 out of 283 (46%), but 99 (35%) of the women did not receive their invitations because of inaccuracies in the family practitioner committee's database and general practitioners failing to check women's addresses completely. CONCLUSIONS: Increased rates of response will depend on enabling general practitioners to check addresses and on an increased awareness of the importance of information.

Breast Neoplasms↗
PubMed1989

Hallucinations in children caused by oxolamine citrate.

Twenty reports in Australia, Belgium and The Netherlands have implicated oxolamine-citrate cough-mixtures as a cause of hallucinations in children of less than 10 years of age. Fever is not thought to be a likely alternative explanation. Similar reactions in older children and adults have not been reported and it is possible that the recommended doses for young children are too high. Information about the use of the drug in Australia suggests that such reactions are uncommon, but the information should be interpreted cautiously.

Antitussive Agents↗
PubMed1989

Expression of Shiga toxin epitopes in E. coli immunological characterization.

Synthetic oligodeoxynucleotides encoding for two peptides corresponding to residues 9-21 and 19-31 in the amino acid sequence of the B subunit of Shiga toxin were prepared and inserted into pTOZ plasmid, in phase with the lacZ gene. The resultant vectors were used for transfection of E. coli. The bacteria containing the recombinant DNA expressed the respective peptides in the form of fusion proteins with beta-galactosidase. The N-terminal region of the Shiga toxin B subunit, containing the two peptides, was previously identified as a relevant epitope of the toxin, leading to the induction of neutralizing antibodies. The present study demonstrates that the bacterial extracts containing the fusion proteins as the products of the recombinant vectors, when used for immunization of rabbits, elicited a humoral immune response which was specific toward the respective peptides. Furthermore, the antibodies cross-reacted with the intact Shiga toxin.

Amino Acid Sequence↗
PubMed1989

The pharmacokinetics and bioavailability of cilazapril in normal man.

1. The pharmacokinetics of cilazapril and its active metabolite, cilazaprilat, were investigated in a three-part crossover study in 12 healthy male volunteers aged 19-38 years, excluding one subject who withdrew from the study. 2. Single 2.5 mg oral doses of cilazapril, and equivalent oral and intravenous doses of cilazaprilat were administered as aqueous solutions to the fasted subjects. There was an interval of 1 week between treatments. Concentrations of cilazapril and cilazaprilat in plasma and urine, and activities of angiotensin converting enzyme (ACE) in plasma were measured by radioenzymatic methods. 3. After 10 min infusion of cilazaprilat, the mean plasma concentration was 194 ng ml-1, and ACE inhibition was almost 100%. The decline in concentrations was polyphasic, with mean half-lives for the periods 1-4 h and 24-168 h of 0.90 and 46 h, respectively. Between 4 and 24 h the decline was non-linear, and ACE inhibition decreased from 91% to 67%. Urinary recovery of cilazaprilat averaged 91% of dose. 4. After oral cilazapril, the parent drug was rapidly absorbed and rapidly eliminated, with a mean maximum plasma concentration of 82 ng ml-1 at 0.83 h and a single elimination half-life of 1.3 h. Cilazaprilat peaked at 36 ng ml-1 about 1.7 h after dosing and the decline in concentrations was biphasic, with half-lives of 1.8 h and 45 h. After oral cilazaprilat, plasma concentrations were considerably lower, and the peak later (2.2 h). 5. Urinary recovery data indicated an absolute bioavailability for cilazaprilat of 57% (range 45-75%) from oral cilazapril, but only 19% (range 8-40%) from oral cilazaprilat.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

A pharmacokinetic study of cilazapril in elderly and young volunteers.

1. Cilazaprilat is an inhibitor of angiotensin converting enzyme (ACE) and is the active metabolite of cilazapril. The pharmacokinetics of cilazaprilat, and the inhibition of plasma ACE were investigated in 12 elderly and 12 young healthy volunteers. 2. Single oral 1 mg doses of cilazapril were given to the elderly (age range 65-83 years) and the young (age range 18-31 years) in an open study. Plasma and urinary cilazaprilat concentrations, and plasma ACE activities were measured up to 72 h after dosing by radioenzymatic methods. 3. Cilazapril was well tolerated in both young and elderly subjects. Small falls in blood pressure were observed up to 8-24 h after dosing. 4. The mean peak plasma cilazaprilat concentration in the elderly (11.5 ng ml-1) was significantly greater (P less than 0.02) than the corresponding value in the young (8.3 ng ml-1). Total and renal clearances were significantly lower (both P less than 0.05) in the elderly (12.8 and 5.11 h-1) than in the young (16.0 and 7.21 h-1). Total urinary recovery of cilazaprilat was similar for the two groups at about 43% of dose. 5. Plasma ACE inhibition was slightly greater in the elderly but the mean inhibition in the two groups did not differ by more than 10% at any time-point from 1-72 h. 6. The plasma concentrations of cilazaprilat required for 90% ACE inhibition were similar at 4.7 and 4.8 ng ml-1 in the elderly and young respectively. 7. It is concluded that the age-related changes in cilazaprilat kinetics and in the degree of ACE inhibition are small.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗