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Biomedical subjects

J Vincent

Publications and source records attributed to J Vincent.

At least 91 records · Page 5Linked to original sources
PubMed1990

Familial defective apolipoprotein B-100: detection in the United Kingdom and Scandinavia, and clinical characteristics of ten cases.

Familial defective apolipoprotein B-100 (FDB) is a recently identified, dominantly inherited genetic disorder, which leads to increased serum concentration of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. This disorder is associated with a G to A mutation in exon 26 of the apolipoprotein B (apo B) gene which creates a substitution of glutamine for arginine in the codon for amino acid 3500. We have searched for this mutation in 374 unrelated individuals with hyperlipidaemia from the United Kingdom, and in 371 unrelated individuals with a primary clinical diagnosis of atherosclerosis from the United Kingdom and Scandinavia. Ten individuals, 9 from the U.K. and 1 from Denmark, were identified. The frequency of the mutation was 3% in individuals classified clinically as having familial hypercholesterolaemia (FH) and 3% in individuals with type IIa hyperlipidaemia without FH, and was not found in patients with types IIb and III hyperlipidaemia. The mutation was rare in individuals with a primary clinical diagnosis of atherosclerosis. Plasma lipid levels and clinical characteristics of the ten patients identified in the present study are similar to those reported for heterozygous FH. Thus, in our study, FDB is associated with moderate to severe hypercholesterolaemia, and appears to be a serious disorder causing premature cardiovascular disease. Individuals with this mutation can be identified unambiguously using routine molecular screening techniques.

Adult↗
PubMed1990

Effects of methylphenidate on early adolescent growth.

Thirty-one hyperactive adolescents treated with methylphenidate for at least 6 months demonstrated no significant deviation from expected height and weight growth velocities. In contrast to findings in prepubertal children, these results suggest that early adolescent growth is insensitive to methylphenidate.

Adolescent↗
PubMed1990

Protection against membrane-mediated cytotoxicity by calcium and zinc.

Injection of S. aureus alpha toxin or ultraviolet-inactivated Sendai virus into the mammary gland of lactating mice leads to cytopathic changes in the alveolar cells compatible with a breakdown of their permeability barrier. Simultaneous administration of Ca2+ or Zn2+ prevents such changes, as it does when added to alveolar cells in vitro. It is concluded that increased levels of Zn2+ (and under certain conditions of Ca2+) may exert a protective role that is clinically significant.

Animals↗
PubMed1989

Biochemical and biological profile of a new enzyme preparation from Antarctic krill (E. superba) suitable for debridement of ulcerative lesions.

A protease extract from Antarctic krill (E. superba) intended as a new enzymatic debrider for necrotic ulcers has been characterized by sodium dodecyl sulphate polyacrylamide gradient gel electrophoresis and fast protein liquid chromatography. The predominant enzymes in the preparation represent trypsin-like activity associated with three serine proteinases. In addition two carboxypeptidases A and B are present as cooperative enzymes for a more complete breakdown of complex proteinaceous substrates. Biological studies on a well-defined substrate (fibrin) originating from leg ulcers, demonstrated more effective degradation by krill enzymes than bovine trypsin, a common component in marketed enzymatic debriders. These findings support previously in vitro/in vivo studies in an animal model (rat) using excised rat skin as "necrotic" tissue.

Animals↗
PubMed1989

Comparative field evaluation of the fluorescent-antibody test, virus isolation from tissue culture, and enzyme immunodiagnosis for rapid laboratory diagnosis of rabies.

The rabies tissue culture infection test (RTCIT) and rapid rabies enzyme immunodiagnosis (RREID) were compared to the fluorescent-antibody test (FAT) with field specimens. At the French National Reference Center for Rabies, 15,248 specimens were analyzed by FAT and RTCIT, and 2,290 of those specimens were also tested by RREID; 818 other specimens were tested by FAT and RREID in 12 laboratories located in Africa, Asia, and Latin America. The sensitivities and specificities of RREID and RTCIT were comparable. This study showed that both tests can be used as backup procedures to confirm FAT. RREID is also strongly recommended for epidemiological studies and for laboratories which are not equipped for performing FAT.

Africa↗
PubMed1988

Privatising residential care for elderly people: the geography of developments in Devon, England.

The growth in numbers of very elderly people is becoming a trend in many Western societies. Often, these people may come to require some kind of assisted living environment. In Britain during the 1980s the overwhelming growth of residential accommodation has been in the private rather than the public sector. This has links with a number of other trends in health care and other sectors of the economy which are moving towards privatisation. The reasons for this are discussed and a case study of the county of Devon introduced. A survey of about one-quarter of all 450 homes in the county in mid-1984 revealed that they had important characteristics as small businesses. Countywide, a marked concentration of private residential homes has developed in some coastal 'holiday' locations. However, there have recently been changes in this pattern and growth of numbers of homes in some main towns also. There have been certain adverse reactions to the growth of homes and in a few areas, planning authorities have attempted to prevent the development of local concentrations of homes. This has been related to other policies elsewhere to prevent the concentration and ghettoisation of service-dependent groups. The nature and results of such planning policies are briefly considered. The paper addresses the overall questions of the type of care we wish to provide for our elderly people and whether privatisation of this aspect of health and welfare services is justified. This poses an important area of research for medical geographers interested in service delivery and aspects of equity in health care provision.

Aged↗
PubMed1988

Relationship between plasma prazosin concentration and alpha-antagonism in humans: comparison of conventional and rate-controlled (Oros) formulations.

A single-dose comparative evaluation in young normotensive men of the plasma concentrations and alpha-adrenoceptor antagonism after conventional prazosin and a new slow-release formulation (Oros) is described. Whereas conventional prazosin (2 mg) produced a maximum reduction in erect blood pressure at 3 hours (80/46 mm Hg compared with 110/65 mm Hg with placebo), the lowest blood pressure of 94/48 mm Hg with Oros prazosin (5.5 mg) was not observed until 8 hours after administration. Twenty-four hours after Oros prazosin, prazosin was still detectable in plasma and erect blood pressure was reduced to 107/58 mm Hg compared with 110/71 mm Hg after placebo. alpha 1-Antagonism (assessed by the pressor responses to intravenous phenylephrine) was maximal, with a 4.8-fold shift in dose-response 24 hours after Oros prazosin, and persisted at least until 30 hours after administration, with a 2.3-fold shift. There were significant correlations between alpha 1-antagonism and plasma prazosin concentrations for both Oros and conventional prazosin. The slopes of these relationships were significantly different, but this is thought to be consistent with the differences in the rates of drug release from the two formulations. Overall this study provides further evidence in humans that the duration and extent of the alpha 1-antagonism and the blood pressure response reflect the plasma prazosin concentrations. Additionally these data suggest the potential suitability of this type of a slow-release formulation for single daily administration.

Adult↗
PubMed1988

The pharmacokinetics, antihistamine and concentration-effect relationship of ebastine in healthy subjects.

1. The kinetics and effects of ebastine 10 and 50 mg were studied after oral dosing in healthy subjects. 2. The parent drug was extensively metabolised during the first pass to its carboxylic acid derivative, carebastine. 3. The pharmacokinetics of carebastine were linear over the dose range studied and the terminal elimination half-life was 10.6 +/- 2.6 and 12.5 +/- 1.9 h respectively after 10 and 50 mg of ebastine. 4. Antihistamine (H1-receptor) activity was examined with intradermal histamine (2 micrograms). Oral ebastine reduced the histamine wheal area for up to 24 h and also reduced subjective local pain. 5. Antihistamine activity correlated well with plasma levels of carebastine in individual subjects. 6. Ebastine appears to have potential as an antihistamine for once a day dosing.

Adult↗
PubMed1988

Ebastine: the effect of a new antihistamine on psychomotor performance and autonomic responses in healthy subjects.

1. Ebastine, through its carboxylic acid metabolite has antihistamine (H1-receptor) activity in man. 2. We have examined in a single blind placebo controlled study the effects of 10 mg and 50 mg of ebastine on cardiovascular, autonomic and psychomotor function in healthy subjects. 3. Ebastine had no effect on blood pressure or heart rate and there was no evidence of any anticholinergic activity on circulatory reflexes or salivation. 4. Ebastine did not impair psychomotor performance as assessed by critical flicker fusion at either dose. 5. Ebastine 10 mg had no effect on sedation measured by visual analogue scale or direct questioning, however ebastine 50 mg did cause a modest increase in indices of sedation. 6. Ebastine did not have detectable sedative properties at the 10 mg dose where long-lasting antihistamine effects can be demonstrated.

Adult↗
PubMed1988

Monoclonal antibodies to Mokola virus for identification of rabies and rabies-related viruses.

Rabies and rabies-related virus strains were studied by using a panel of monoclonal antibodies directed against either nucleocapsid proteins or cell surface antigens of Mokola virus (Mok-3). Each strain was used in parallel to infect cultured cells and mice. Then, the patterns of reactivity of the different monoclonal antibodies were determined by the immunofluorescent-antibody staining procedure. On cells, the monoclonal antibodies differentiated fixed rabies virus strains (serotype 1) from rabies-related virus strains. The seven fixed strains (CVS, PV4, PM, Flury LEP and HEP, ERA, and SAD) reacted identically. The previous serotype groupings (serotype 2, Lagos-bat virus; serotype 3, Mokola virus; serotype 4, Duvenhage virus) established with anti-rabies monoclonal antibodies were confirmed, except for that of Lagos-bat Kindia, which appeared to be related to the African subtype of the Duvenhage serotype (Duv-2). Within the Mokola (Mok-1, -2, -3, and -5 and Umhlanga) and the Lagos-bat (Lag-1 and -2, Zimbabwe, Pinetown, and Dakar) serotypes, each strain appeared to be distinct. The African subtype of the Duvenhage serotype reacted differently from the European subtype. Within the Duvenhage serotype, subtypes Duv-4, -5, and -6 and Denmark reacted identically, while subtypes Duv-1, -2, and -3 and German Democratic Republic appeared to be distinct. The monoclonal antibodies specific for the cell surface antigens were also used in neutralization tests with all the strains. Two of them neutralized the infectivity of Mokola virus.

Africa↗
PubMed1988

Pharmacokinetic and pharmacodynamic modelling of the alpha adrenoceptor antagonist doxazosin.

1. The pharmacokinetic and pharmacodynamic profiles of intravenous and oral doxazosin were investigated in 6 normotensive volunteers. 2. The pharmacokinetics of i.v. and oral doxazosin were fitted simultaneously and independently. The parameters derived were in good agreement with a mean elimination half-life of 539 +/- 75 min, bioavailability of 0.65 +/- 0.11 and clearance of 140 +/- 26 ml/min. 3. Pharmacokinetic-pharmacodynamic modelling indicated that the sensitivities to oral and i.v. doxazosin in individual subjects were in good agreement. 4. Based on these findings it is unlikely that doxazosin metabolites contribute significantly to the pharmacodynamic profile of doxazosin.

Administration, Oral↗
PubMed1987

Clinical pharmacology of selective alpha blockers. Hemodynamics and effects on lipid levels.

Selective alpha 1 antagonists decrease blood pressure by reducing elevated peripheral resistance and preserving normal cardiac reflexes. They have also been reported to usually decrease total cholesterol and low-density lipoprotein cholesterol levels, and, in some studies, to increase high-density lipoprotein cholesterol levels. Prazosin, a quinazoline derivative, is well tolerated and is not associated with chronic toxicity. Prazosin has been successfully used in the treatment of hypertension for more than 10 years. Its short plasma half-life requires twice-daily dosing. Although the hypotensive response to an initial dose of prazosin is usually greater than to subsequent doses during long-term therapy, the initial response is an accurate predictor of the hypotensive response in patients during long-term therapy. The vasodilatory action of prazosin is largely due to its blockade of vascular postjunctional alpha 1 receptors. The mechanism involved in its effect on lipid levels is currently under investigation and is an important consideration since hypercholesterolemia, as well as hypertension, is an independent risk factor for stroke and coronary heart disease. Reduction of blood pressure with conventional agents, such as beta blockers or diuretics, has not had the expected impact on coronary heart disease. However, since alpha 1 blockers may influence both hemodynamics and lipids, they warrant evaluation as first-line treatment of hypertension to confirm that they also have an effect on coronary heart disease.

Hemodynamics↗
PubMed1987

A pragmatic approach to the pressor dose-response as an index of vascular reactivity and adrenoceptor function in man.

In clinical pharmacological studies, where it is not possible to describe the full dose-response curve, the construction of dose-response relationships ideally depends upon achieving a reproducible and readily measurable response for each dose administered. This study investigates in normotensive males the technique of dose-response analysis for the blood pressure and heart rate increases with constant infusions of incremental doses of vasoactive drugs, particularly catecholamines. Steady state responses could be adequately obtained using 5 min infusion periods (at each dose level) for noradrenaline and alpha-methyl noradrenaline. At least 7 min was required for phenylephrine and 8 min for isoprenaline. There was an approximate correlation between the time to achieve the steady state response and the half-life of the offset of the agonist effect. For interindividual comparisons it is desirable to compare steady state responses and so the time at each dose level will vary according to which agonist is being used. For intraindividual comparisons it may not be essential that steady state responses are achieved. For example, assessment of the effect of prazosin on the responses to phenylephrine, by calculation of dose ratios, indicated that 5 min dose intervals were adequate.

Adult↗
PubMed1986

Proteases of Antarctic krill--a new system for effective enzymatic debridement of necrotic ulcerations.

The Antarctic krill (Euphausia superba) possesses an "over-dimensioned' digestive system, which is of vital importance for the survival of this euphaucean shrimp in the extreme marine environment. The isolated enzymes contain a well-balanced mixture of both endo- and exopeptidases, assuring fast and complete breakdown of proteinaceous material. These unique properties have now been shown to be extremely valuable for the effective removal of necrotic debris, fibrin or blood crusts in vitro. Therefore the krill enzymes should be considered as an important resource in the future management of necrotic wounds.

Animals↗