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Biomedical subjects

E Guy

Publications and source records attributed to E Guy.

At least 19 recordsLinked to original sources
PubMed2001

Multicenter evaluation of strategies for serodiagnosis of primary infection with Toxoplasma gondii.

The diagnostic performance of single-serum assays for toxoplasma-specific immunoglobulin (Ig)M. IgA. IgG, and IgE antibodies and of different combinations of such antibody assays in 20 European reference centers was assessed. A panel of 276 sera, of which 73 came from patients who seroconverted within 3 months (acute infection), 49 from patients who had seroconverted 3-12 months earlier (convalescence), and 154 from subjects who had two IgG-positive samples obtained 12 months apart (past infection), was tested with 20 toxoplasma-antibody assays and 195 combinations. In general, every assay with high diagnostic sensitivity showed low diagnostic specificity, i.e. no assay performed alone could reliably distinguish acute from past infection. Furthermore, no single assay (or combination) could separate convalescence from the other stages of toxoplasma infection. However, excellent diagnostic performances were reached by sequential use of highly sensitive IgM assays and methods examining IgG avidity or stage specificity. IgA or IgM assays were less suitable for confirmation of toxoplasma-IgM positivity. This study documents the strength of test combinations in assessing the stage of toxoplasma infection.

Acute Disease↗
PubMed2001

Polymerase chain reaction for diagnosis of cerebral toxoplasmosis in cerebrospinal fluid in HIV-positive patients.

It is important but sometimes difficult to establish a diagnosis of toxoplasma encephalitis (TE) in an HIV-positive immunodeficient patient. The most promising non-invasive method is polymerase chain reaction (PCR) for Toxoplasma gondii in cerebrospinal fluid (CSF). In a retrospective study PCR was used to analyse CSF for the presence of T. gondii DNA in 5 HIV-infected patients with a clinical suspicion of TE (group 1), 8 patients with other HIV-associated symptoms (group 2) and 7 other patients with neurological disorders (group 3). PCR was positive in 2/4 patients with a final diagnosis of TE and negative in all remaining patients in all 3 groups. The 2 patients with positive PCR had a fulminant course and experienced treatment failure. The albumin index was elevated in 4/5 patients in group 1, of whom 3/4 had a final diagnosis of TE, with suspected TE in 1. This small study confirms earlier data indicating that the PCR test has a low sensitivity but a high specificity.

AIDS-Related Opportunistic Infections↗
PubMed2001

Strategy for diagnosis of congenital toxoplasmosis: evaluation of methods comparing mothers and newborns and standard methods for postnatal detection of immunoglobulin G, M, and A antibodies.

In a study involving 14 laboratories supported by the European Community Biomed 2 program, we evaluated immunologic methods for the postnatal diagnosis of congenital toxoplasmosis (CT). Among babies born to mothers who seroconverted to positivity for toxoplasmosis during pregnancy, we analyzed 55 babies with CT on the basis of persistent anti-Toxoplasma immunoglobulin G (IgG) at 1 year of life and 50 control babies without anti-Toxoplasma IgG at 1 year of life in the absence of curative treatment with pyrimethamine-sulfonamides. We tested in-house methods such as the enzyme-linked immunofiltration assay (ELIFA) or Immunoblotting (IB) for the detection of IgG or IgM; these methods allowed comparison of the immunologic profiles of the mothers and the infants. We compared ELIFA and IB with a commercial enzyme immunoassay (EIA) or in-house immunosorbent agglutination assay (ISAGA) for the detection of IgM or IgA. The performances of combinations of methods were also assessed. A cumulative sensitivity of 98% during a 1-year follow-up was obtained with the ELIFA plus ISAGA combination. Only one case of CT was missed by the ELIFA plus ISAGA combination, whereas three cases were missed by the IB plus ISAGA combination, even though 48% of patients with CT were treated with pyrimethamine-sulfonamides, which are known to inhibit antibody neosynthesis. A similar performance was obtained with either ELIFA or IB in combination with EIA. The difference in performance between ELIFA plus ISAGA and IB plus ISAGA was not statistically significant (P = 0.31), and we conclude that both combinations of tests can be used for the diagnosis of CT in newborns.

Adult↗
PubMed2000

A European multicenter study of immunoblotting in serodiagnosis of lyme borreliosis.

A European multicenter study of immunoblotting for the serodiagnosis of Lyme borreliosis showed considerable variation in results obtained from tests with a panel of 227 serum samples. Six laboratories used different immunoblot methods, and a wide range of bands was detected in all the assays. Multivariable logistic regression analysis of data from individual laboratories was used to determine the most discriminatory bands for reliable detection of antibodies to Borrelia burgdorferi sensu lato. These bands were used to construct individual interpretation rules for the immunoblots used in the six laboratories. Further analysis identified a subset of eight bands, which were important in all the laboratories, although with variations in significance. Possible European rules, all closely related, were formulated from these bands, although there was no single rule that gave high levels of sensitivity and specificity for all the laboratories. This is a reflection of the wide range of methodologies used, especially the use of different species and strains of B. burgdorferi sensu lato. The panel of European rules provides a framework for immunoblot interpretation which may be adapted in relation to the characteristics of Lyme borreliosis in local areas.

Antibodies, Bacterial↗
PubMed1998

A second European collaborative study on polymerase chain reaction for Toxoplasma gondii, involving 15 teams.

In order to investigate the accuracy and practicability of the polymerase chain reaction (PCR) in the antenatal diagnosis of congenital toxoplasmosis, a collaborative study involving 15 European laboratories was performed under the auspices of the Biomed 2 Programme of the European Community. Each team received 12 aliquots (four negative, eight positive) of 'artificial samples' made of amniotic fluid spiked with tachyzoites of the RH strain of Toxoplasma gondii. Each team performed its own PCR protocol (all were different). Nine of the 15 laboratories were able to detect a single parasite, but two of the 15 found all samples negative. Four of the 15 laboratories found one or more control samples to be falsely positive. This study highlights the lack of homogeneity between PCR protocols and performance and underlines the need for an external quality assurance scheme which could provide 'reference' samples that could be used by any laboratory wanting to establish and maintain an accurate diagnostic test based on PCR.

Amniotic Fluid↗
PubMed1998

Detection of the agent of human granulocytic ehrlichiosis (HGE) in UK ticks using polymerase chain reaction.

Nymphal Ixodes ricinus ticks collected from woodland areas in South Wales, UK, were tested using the polymerase chain reaction for the presence both of the causative agent of human granulocytic ehrlichiosis (HGE) and Borrelia burgdorferi. Twenty-two of 60 (37%) ticks were found positive in the PCR for B. burgdorferi and 4/60 (7%) for the HGE agent. One tick was found positive both for B. burgdorferi and HGE agent. Our findings imply the presence of the HGE agent in UK ticks and the finding of a tick apparently containing both pathogens underlines the potential for concurrent infection with HGE agent and B. burgdorferi to occur after a single tick-bite. Based on our observations, we conclude that there may be a need to consider a range of pathogens both in laboratory investigation and clinical management of suspected tick-borne disease in the UK, particularly where there is a clinical presentation atypical of Lyme borreliosis alone.

Animals↗
PubMed1996

European Union Concerted Action on Risk Assessment in Lyme Borreliosis: clinical case definitions for Lyme borreliosis.

The EU Concerted Action on Risk Assessment in Lyme Borreliosis (EUCALB) has consulted other clinicians and scientists in Europe to produce case definitions of the principal manifestations of European Lyme borreliosis. These case definitions will not only be helpful in supporting its own research interests, but are also intended to assist other clinicians in appropriate management and to support further studies aimed at determining the full clinical spectrum of the disease. The case definitions were achieved after a series of meetings organised by EUCALB with other expert clinicians and scientists from twelve European countries. The definitions and the diagnostic criteria presented thus represent the consensus reached at these meetings. The proposed case definitions consider skin, nervous system, cardiac and musculoskeletal presentations and the role of laboratory investigation in supporting diagnosis.

Acrodermatitis↗
PubMed1995

The spatial distribution of Borrelia burgdorferi-infected Ixodes ricinus in the Connemara region of County Galway, Ireland.

Studies were carried out in the Connemara area of County Galway in the west of Ireland in order to determine the abundance and distribution of the tick, Ixodes ricinus and the prevalence of its infection with Borrelia burgdorferi. The tick was very abundant locally, in particular when associated with cattle, sheep and enclosed red deer. Large numbers of ticks not only occurred on the pastures, but also on adjacent roadside verges. No infections with B. burgdorferi could be demonstrated when nymphal ticks were sampled from central areas of the pastures, suggesting that livestock and red deer are probably not significant reservoirs of the spirochaete. Small numbers of infected nymphal and adult ticks were associated with hedges, dry stone walls, the margins of woodland adjoining infested pastures and in woodland from which livestock were excluded. Woodmice (Apodemus sylvaticus) were most numerous in such habitats and the majority were infected with B. burgdorferi.

Animals↗
PubMed1994

Acquisition of Borrelia burgdorferi by Ixodes ricinus ticks fed on the European hedgehog, Erinaceus europaeus L.

A hedgehog, Erinaceus europaeus, was found to be heavily infested with larval and nymphal Ixodes ricinus in a forest park in Co. Galway, Ireland. A large proportion of the ticks that engorged and detached were infected with the spirochaete, Borrelia burgdorferi, the causative agent of human Lyme borreliosis. The identity of these spirochaetes was confirmed by immunofluorescent assay with B. burgdorferi-specific monoclonal antibody and by polymerase chain reaction test and they were transmitted from the hedgehog to laboratory-reared ticks and from the ticks obtained from the hedgehog to gerbils (Meriones unguiculatus). The high infection rate of the larvae that fed on the hedgehog in comparison with unfed larvae from the same habitat was interpreted as strong evidence that this host species is reservoir competent. Since hedgehogs can evidently feed adult ticks as well as many immature stages, they may well have an important role in the ecology of Lyme borreliosis in some habitats.

Animals↗
PubMed1993

Vascular clearance of Borrelia burgdorferi in rats.

Radiolabeled Borrelia burgdorferi, the etiologic agent of Lyme disease, injected intravenously into rats are cleared from the vasculature within 1 h of injection. One low passage isolate showed trafficking between the circulation and possibly the vessel walls for the first 2 h after injection. All strains used were resistant to the effects of normal and heat-inactivated rat serum. During the first 2 h after injection, B. burgdorferi can be visualized in, and recovered from, the platelet-rich plasma. B. burgdorferi can adhere to both human and rat platelets in in vitro assays, but an in vivo association with these cells was not apparent. Similarly, none of the strains of B. burgdorferi used induced platelet aggregation. Removal from the circulation into the organs was measured in perfused rats by polymerase chain reaction and autoradiography and in non-perfused rats by organ cultures. These organisms invade organs (heart, kidneys, bladder, liver, spleen, brain) within 1-6 h after injection. Invasion of organs occurred in an apparent random manner; a large amount of radiolabel but no live organisms was excreted in the urine during the first 24 h, suggesting degradation of the inoculum.

Animals↗
PubMed1986

Profound reduction in morphine clearance and liver blood flow in shock.

In six patients with septic shock apparent liver blood flow was significantly reduced compared with two patients restudied on recovery from shock and a group of four matched unshocked patients undergoing intensive care (287 +/- 23 ml/min vs 870 +/- 164 ml/min; mean +/- SEM). In the shocked patients the elimination half-life of morphine was significantly prolonged (13.2 +/- 3.5 h vs 5.9 +/- 1.4 h; mean +/- SEM) and the systemic clearance of morphine reduced by 53%, in comparison with the non-shocked patients. In both groups, morphine elimination was markedly delayed compared with previously reported observations in normal subjects and surgical patients. Care should be exercised with the use of drugs with a high hepatic extraction ratio in shocked patients.

Aged↗
PubMed1984

Factors affecting the response to inhibition of drug metabolism by cimetidine--dose response and sensitivity of elderly and induced subjects.

The effect of cimetidine on oxidative drug metabolism was characterised using antipyrine clearance in a group of healthy volunteers. In six subjects cimetidine produced a dose dependent reduction of antipyrine clearance: 400 mg/day (16.8 +/- 2.2%, mean +/- s.e. mean), 800 mg/day (26.3 +/- 1.5%) and 1600 mg/day (33.5 +/- 2.4%). The effect of cimetidine (800 mg/day) was of similar magnitude (approximately 25%) in two groups of six young (21-26 years) and six elderly (65-78 years) subjects. The effect of pretreatment begun just 1 h before administration of antipyrine was similar to that of 24 h pretreatment and that reported for chronic cimetidine pretreatment. The percentage reduction in antipyrine clearance produced by cimetidine 800 mg/day was greater (44 +/- 5 vs 24 +/- 3%; P less than 0.05) in six subjects who had been pretreated with the hepatic enzyme inducer rifampicin (600 mg/day for 21 days) than in the control uninduced state. Although cimetidine was capable of rapidly reversing the effect of rifampicin on antipyrine clearance, following withdrawal of both rifampicin and cimetidine there was still evidence of enzyme induction. These results suggest that the effect of cimetidine on oxidative metabolism is dose dependent, is more marked in enzyme induced subjects, is independent of the duration of pretreatment and is of similar magnitude in young and elderly subjects.

Adult↗
PubMed1983

Lack of effect of ranitidine on the disposition of lignocaine.

Cimetidine has been shown to alter the disposition of lignocaine and other drugs that are highly extracted by the liver. In a placebo controlled study ranitidine (150 mg twice daily) did not alter the elimination half-life, systemic clearance or distribution of lignocaine (mg/kg) in six healthy subjects. The interaction with cimetidine appears to be unrelated to histamine H2-receptor antagonism.

Adult↗
PubMed1983

Enzyme induction with rifampicin; lipoproteins and drug binding to alpha 1-acid glycoprotein.

Hepatic enzyme induction has been reported to increase lignocaine binding, alpha 1-acid glycoprotein concentration and high density lipoprotein (HDL) cholesterol. In eight volunteers treated with rifampicin for 3 weeks there was no significant alteration in these three variables although their antipyrine clearance was significantly increased. In 10 patients with pulmonary tuberculosis treated with rifampicin (mean 5 months) the degree of serum protein binding of lignocaine, alpha 1-acid glycoprotein and HDL-cholesterol concentration was not different from that of matched control patients. These results suggest that differential induction of these variables may occur.

Adult↗