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Biomedical subjects

S McGregor

Publications and source records attributed to S McGregor.

At least 19 recordsLinked to original sources

Can primary care be both patient-centred and community-led?

Examines the relationships between the macro-, meso-, and micro-levels in the NHS at the end of the fundholding period and considers their contemporary implications for primary care groups (PCGs) and local health care co-operatives (LHCCs). Fundholding achieved some success in challenging the way in which services were provided at the micro-level (the practice), but had a less marked effect in terms of changing service provision at the health authority (meso-) level or in developing collaborative working with trusts and health authorities in strategic decision making. The health authorities prioritized alternative models of devolved commissioning. Trusts regarded fundholders as a distraction who exerted influence and commanded trust management time disproportionate to their "market share". PCGs and LHCCs represent a shift back to the meso-level in service planning and purchasing. As such there is a risk that the micro-level benefits of fundholding and other forms of devolved commissioning will be lost, while uncertainties remain regarding the capacity of PCGs and LHCCs to incorporate GPs into a collaborative approach to strategic decision making.

Community Health Planning↗

Cellular origin and procoagulant properties of microparticles in meningococcal sepsis.

Patients with meningococcal sepsis generally suffer from disseminated intravascular coagulation (DIC). The aim of this study was to address whether these patients have elevated numbers of circulating microparticles that contribute to the development of DIC. Plasma samples from 5 survivors, 2 nonsurvivors, and 5 healthy volunteers were analyzed for the presence of microparticles by flow cytometry. Ongoing coagulation activation in vivo was quantified by enzyme-linked immunosorbent assay of plasma prothrombin fragment F(1 + 2), and procoagulant properties of microparticles in vitro were estimated by thrombin-generation assay. On admission, all patients had increased numbers of microparticles originating from platelets or granulocytes when compared with controls (P =.004 and P =.008, respectively). Patients had elevated levels of F(1 + 2) (P =.004), and their microparticles supported thrombin generation more strongly in vitro (P =.003) than those of controls. Plasma from the patient with the most fulminant disease course and severe DIC contained microparticles that expressed both CD14 and tissue factor, and these microparticles demonstrated extreme thrombin generation in vitro. We conclude that patients with meningococcal sepsis have elevated numbers of circulating microparticles that are procoagulant. These findings may suggest a novel therapeutic approach to combat clinical conditions with excessive coagulation activation.

Adolescent↗

Randomised trial of personalised computer based information for cancer patients.

OBJECTIVE: To compare the use and effect of a computer based information system for cancer patients that is personalised using each patient's medical record with a system providing only general information and with information provided in booklets. DESIGN: Randomised trial with three groups. Data collected at start of radiotherapy, one week later (when information provided), three weeks later, and three months later. PARTICIPANTS: 525 patients started radical radiotherapy; 438 completed follow up. INTERVENTIONS: Two groups were offered information via computer (personalised or general information, or both) with open access to computer thereafter; the third group was offered a selection of information booklets. OUTCOMES: Patients' views and preferences, use of computer and information, and psychological status; doctors' perceptions; cost of interventions. RESULTS: More patients offered the personalised information said that they had learnt something new, thought the information was relevant, used the computer again, and showed their computer printouts to others. There were no major differences in doctors' perceptions of patients. More of the general computer group were anxious at three months. With an electronic patient record system, in the long run the personalised information system would cost no more than the general system. Full access to booklets cost twice as much as the general system. CONCLUSIONS: Patients preferred computer systems that provided information from their medical records to systems that just provided general information. This has implications for the design and implementation of electronic patient record systems and reliance on general sources of patient information.

Attitude to Computers↗

Mucosal immunity in extrinsic allergic alveolitis: salivary immunoglobulins and antibody against inhaled avian antigens among pigeon breeders.

BACKGROUND: Inhaled antigens from pigeons can cause extrinsic allergic alveolitis (EAA); a model disease of pulmonary inflammation. Among pigeon breeders, serum antibody and sensitized lymphocytes specific for these antigens have been described primarily, but not always, with disease. Antibody activity within the lung may have a closer association with disease, however, sampling by alveolar lavage at bronchoscopy is impractical for screening, therefore we used saliva to quantify the mucosal antibody response. OBJECTIVE: To establish: (a) if antibody activity against inhaled avian antigens was detectable in the saliva of pigeon breeders, (b) if the distribution of saliva antibody and total immunoglobulin levels were quantitatively or qualitatively different from serum, and (c) whether the hypersensitivity symptoms of EAA were associated more with the mucosal or the systemic humoral immune response. MEASURES: Saliva and serum total and avian antigen-specific IgG, IgA (IgA1 and IgA2) antibody activity in 87 pigeon breeders and 24 control subjects with no avian exposure. Albumin levels were used as a protein reference and cotinine levels confirmed smoking status. Specific hypersensitivity symptoms and various exposure indices to pigeons were established by interview. RESULTS: Absolute levels and relative proportions (vs albumin) of IgG, IgA and IgA1 in saliva, and IgG in serum, were significantly higher in pigeon breeders compared with controls, suggesting mucosal inflammation. Avian antigen-specific antibody of all isotypes was readily demonstrable in saliva (predominantly IgA) and serum (predominantly IgG) from pigeon breeders, and there were no significant titres in controls. The levels of IgG antibody in saliva and in serum correlated significantly (r = 0.52, P < 0.001), and both correlated with the raised immunoglobulin levels. In both saliva and serum the IgG rather than the IgA antibody activity was associated with symptoms of EAA. CONCLUSIONS: Antibody activity in saliva and serum, representing the mucosal and systemic responses, respectively, were both strongly stimulated by inhaled antigens. The IgG antibody titres of saliva and serum correlated significantly and were a useful index of inflammation, as measured by the raised total immunoglobulin levels, and symptoms. This suggests that IgG antibody in serum may reflect clinical and immunological sensitization of the lung mucosa. Collecting saliva is noninvasive, and saliva antibody measurement is a convenient method for monitoring EAA, especially in children, and will facilitate sampling for example in epidemiological studies of antibody prevalence.

Albumins↗

The accessibility of information systems for patients: use of touchscreen information systems by 345 patients with cancer in Scotland.

AIM: To examine cancer patients' use, and satisfaction with touchscreen information systems. By examining the experience of subgroups, to address issues of equality of access. PATIENTS: 345 patients starting radiotherapy at the Beatson Oncology Centre (BOC), Glasgow. METHODS: Patients were invited to use a touchscreen computer at the start of treatment. They were sent a printout of what they saw on screen. Patients had open access to the system. Data were collected at recruitment, intervention, 3 weeks and 3 months. Predictor variables included: patients' demographics, information preferences, technology use, and psychological state. Outcome variables included: use and views of the computer and printout. RESULTS: Younger, broadsheet readers with previous computer use were more likely to find the system easy to use. Older, tabloid readers were more likely to find the content new and relevant. DISCUSSION: We need to make systems adapt to users' different needs. More effort should be made to provide affordable information for older, generally less literate and technologically less literate groups in suitable locations.

Age Factors↗

Iron uptake in aluminium overload: in vivo and in vitro studies.

In this study we have evaluated the haematological consequences of chronic aluminium (Al) overload. We have also investigated 'in vivo' whether aluminium overload may modulate gastrointestinal iron (Fe) absorption and 'in vitro' whether the presence of aluminium may influence the cellular uptake of iron. The in vivo studies were performed in rats with normal renal function and the in vitro experiments were done using the rat intestinal epithelial cell line RIE-1. The results demonstrate that aluminium deposit in tissues even with normal renal function. The intraperitoneal aluminium loading resulted in serum and tissue aluminium increases comparable with concentrations found in aluminium-intoxicated renal patients. The aluminium intoxication was accompanied by a microcytic anaemia with a haematological pattern similar to that observed in iron-deficiency anaemia. Nevertheless, iron absorption was significantly reduced despite an increased total iron binding capacity (TIBC). In addition, aluminium was also able to reduce in vitro cellular uptake of iron in the RIE-1 intestinal cell line. These experimental results demonstrate that aluminium interferes with iron absorption and iron transfer, and suggest that these mechanisms may be responsible for maintaining and even increasing the anaemia observed in aluminium overload.

Aluminum↗

Evolution to predominance of swine influenza virus hemagglutinin mutants of predictable phenotype during single infections of the natural host.

L and H2 mutants of the A/NJ/11/76 H1N1 strain of swine influenza virus differ by having either a lysine or a glutamic acid at position 153 of the hemagglutinin glycoprotein of the virus. In two separate experiments, experimental infection of swine with various doses of the H2 mutant resulted in the emergence in 11 of 20 animals of virus with the L phenotype. All evidence indicates that the H2----L mutation, selection, and evolution to predominance occurred within the 7-day span of individual infections. L and H2 mutations appear to act as alleles in the adaptation of virus, respectively, to natural and laboratory hosts. Although the gradual evolution of mutants during sequential infections is commonplace, the present recognition of rapid and predictable evolution of mutants of increased replication efficiency and specific phenotype in the natural host, to our knowledge, is unprecedented.

Animals↗

A multi-infection model for antifungal screening in vivo.

A new in-vivo antifungal screen is described in which each mouse is given a vaginal infection with Candida albicans, a dermal infection with Trichophyton quinckeanum, a systemic infection with Can. albicans and a lung infection with Cryptococcus neoformans. Mice are dosed orally once daily on days 0-3 and infections evaluated on day 6 by visually scoring the dermal lesions and by culturing vaginal samples and kidney and lung homogenates. Mice carrying the multiple infections show no signs of distress at this time. Validation studies with eight antifungal agents show there is no interference between the four infections, and illustrate the different patterns of activity which result from differences in innate sensitivity and pharmacological behaviour of drugs in the host. This screen provides the maximum amount of information for a minimal investment of compound and effort, and naturally uses fewer animals than multiple tests using single infections.

Animals↗

Activity of ICI 195,739--a novel, orally active bistriazole--in rodent models of fungal and protozoal infections.

ICI 195,739 shows superior potency to other azoles in eliminating vaginal candidosis or dermatophyte infections in animal models of infection by both oral dosing and topical application; effective doses are in the range of 0.5-5.0 mg/kg/day or 0.01-0.30% in a topical formulation. ICI 195,739 is likewise effective in models of systemic fungal infection; 1, 10, 25 mg/kg/day will protect animals given a lethal inoculum of C. albicans, C. neoformans, or A. fumigatus, respectively, as long as dosing is continued, showing activity in this respect superior to that of other azoles tested. ICI 195,739 will suppress infections in mice with T. cruzi and prevent mortality with five daily doses of 1 mg/kg; cure rather than suppression of patent infections has been achieved with 35 daily doses of 10 mg/kg.

Animals↗

Quantification of vaginal Candida albicans infections in rodents.

Estradiol-treated mice and estradiol-treated ovariectomized rats support vaginal infections with Candida albicans for several months; low-grade uterine infections occur in around half the animals. A comparison has been made and the relative advantages discussed of quantifying these infections by sampling with a wire loop and plating on BiGGY agar, sampling by vaginal washing, or removal and homogenization of the vagina followed by dilution and plate counting.

Animals↗

Vaccination of swine with thymidine kinase-deficient mutants of pseudorabies virus.

A mutant of pseudorabies virus (PRV) deficient in thymidine kinase (TK-) activity was isolated and characterized. The mutant grew well in cell culture and did not revert to the thymidine kinase-positive phenotype. The PRV-TK- was not virulent when inoculated intranasally into 3-to 4-week-old pigs and could not be reactivated from the ganglia of these pigs by explantation and cocultivation with susceptible cells several weeks after virus inoculation. Pigs that had been exposed to PRV-TK- were immune to challenge exposure with a virulent strain of PRV. Furthermore, the challenge virus was not recovered from the ganglia of most of these pigs, indicating that colonization of the ganglia by a super-infecting virulent PRV strain was considerably reduced by vaccination.

Animals↗

Hemagglutinin mutants of swine influenza virus differing in replication characteristics in their natural host.

In two mutant clones (L and H) of A/NJ/11/76 (Hsw 1N1) influenza viruses which differ slightly antigenically and markedly in replication characteristics in chicken embryos and Madin Darby canine kidney cells, these pleiotropic differences are mediated by mutation in the hemagglutinin gene (E. D. Kilbourne, Proc. Natl. Acad. Sci. U.S.A. 75:6258--6262, 1978). Experimental infection of swine with either the mutant L and H clones or recombinant viruses differing genetically only with respect to the presence of L or H hemagglutinin demonstrated greater infectivity for the natural host of viruses bearing the L hemagglutinin. Introduction of the L but not the H hemagglutinin gene into the human influenza virus A/PR/8/34 rendered it infective for swine. Both L and H variants were isolated from pigs naturally infected with contemporary swine influenza viruses when selective conditions for the suppression of the more prevalent L mutant were employed. The L and H mutants of swine influenza virus are yet another example of viral dimorphism in nature and probably are not mere artifacts of laboratory selection. In any event, the frequent apparent allelic appearance of the two forms suggests frequent mutation and/or reversion involving a point mutation in the hemagglutinin gene. The present studies demonstrate the importance of a single gene in the pathogenesis of an influenza viral infection in its natural host.

Animals↗