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M Leach

Publications and source records attributed to M Leach.

At least 19 recordsLinked to original sources
PubMed2006

Is the cultural context of MMR rejection a key to an effective public health discourse?

OBJECTIVES: (1) To explore the social and cultural influences, and health beliefs associated with low uptake of MMR (measles, mumps and rubella vaccine). (2) To describe and explore the prevalence of health beliefs associated with non-compliance with MMR, with a view to improving the personal relevance and impact of information for parents, in the context of persisting low uptake following public controversy. METHODS: We undertook a survey of mothers' experiences of and attitudes to the MMR, developed through ethnographic study, which was linked to maternal and child information on the Child Health Database in Brighton, England. RESULTS: Mothers interpret MMR risk through concepts of child health embedded in family health history, with a majority both of compliers and non-compliers holding that each child's immune system is unique. Cultural 'risk factors' for non-compliance relate strongly to the use of complementary healthcare, such as homeopathy, with evidence that rejection of vitamin K is associated with MMR non-compliance. Forty per cent, both of compliers and non-compliers, did not consider the possible benefits to other children of MMR. CONCLUSIONS: These findings have paradoxical and challenging consequences for the promotion of immunization in the policy context of increasing emphasis on healthy choices. They demonstrate the need for immunization information that acknowledges and addresses lay concepts of immunity.

Adolescent↗
PubMed2006

The social shaping of childhood vaccination practice in rural and urban Gambia.

Improving childhood vaccination coverage is a key health policy objective in Africa, and as availability increases, it will depend on addressing issues of demand and timely schedule completion. This paper explores vaccination demand in urban and rural areas of The Gambia as shaped by prevailing local vaccination cultures (comprising maternal knowledge and understandings, socio-cultural contexts and interactions with health providers). A survey of 1,600 mothers constructed on the basis of prior ethnography finds a high level of social demand for vaccination, based on lay theories of the general value of immunization in complementing traditional child protection practices. For most rural mothers, strong social networks encourage routine clinic attendance and vaccination 'default' arises only through day-to-day problems and contingencies. However, more pervasive patterns of schedule non-completion are found amongst poorer urban mothers, including recent immigrants, who experience social exclusion at infant welfare clinics. These findings point to the need for health education dialogue grounded in mothers' own understandings and for particular policy attention to improving the clinic experiences of vulnerable social groups in rapidly expanding urban areas.

Data Collection↗
PubMed2005

A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points.

SU5416 (Z-3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone; semaxanib) is a small molecule inhibitor of the vascular endothelial growth factor receptor (VEGFR2). A Phase I dose escalation study was performed. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used as a pharmacodynamic assessment tool. In all, 27 patients were recruited. SU5416 was administered twice weekly by fixed rate intravenous infusion. Patients were treated in sequential cohorts of three patients at 48, 65, 85 110 and 145 mg m-2. A further dose level of 190 mg m-2 after a 2-week lead in period at a lower dose was completed; thereafter, the cohort at 145 mg m-2 was expanded. SU5416 showed linear pharmacokinetics to 145 mg m-2 with a large volume of distribution and rapid clearance. A significant degree of interpatient variability was seen. SU5416 was well tolerated, by definition a maximum-tolerated dose was not defined. No reproducible changes were seen in DCE-MRI end points. Serial assessments of VEGF in a cohort of patients treated at 145 mg m-2 did not show a statistically significant treatment-related change. Parallel assessments of the impact of SU5416 on coagulation profiles in six patients showed a transient effect within the fibrinolytic pathway. Clinical experience showed that patients who had breaks of therapy longer than a week could not have treatment reinitiated at a dose of 190 mg m-2 without unacceptable toxicity. The 145 mg m-2 dose level is thus the recommended dose for future study.

Adolescent↗
PubMed2004

The dose distribution of low dose rate Cs-137 in intracavitary brachytherapy: comparison of Monte Carlo simulation, treatment planning calculation and polymer gel measurement.

In this study, the dose distribution delivered by low dose rate Cs-137 brachytherapy sources was investigated using Monte Carlo (MC) techniques and polymer gel dosimetry. The results obtained were compared with a commercial treatment planning system (TPS). The 20 mm and the 30 mm diameter Selectron vaginal applicator set (Nucletron) were used for this study. A homogeneous and a heterogeneous-with an air cavity-polymer gel phantom was used to measure the dose distribution from these sources. The same geometrical set-up was used for the MC calculations. Beyond the applicator tip, differences in dose as large as 20% were found between the MC and TPS. This is attributed to the presence of stainless steel in the applicator and source set, which are not considered by the TPS calculations. Beyond the air cavity, differences in dose of around 5% were noted, due to the TPS assuming a homogeneous water medium. The polymer gel results were in good agreement with the MC calculations for all the cases investigated.

Body Burden↗
PubMed2003

A protein interaction map of Drosophila melanogaster.

Drosophila melanogaster is a proven model system for many aspects of human biology. Here we present a two-hybrid-based protein-interaction map of the fly proteome. A total of 10,623 predicted transcripts were isolated and screened against standard and normalized complementary DNA libraries to produce a draft map of 7048 proteins and 20,405 interactions. A computational method of rating two-hybrid interaction confidence was developed to refine this draft map to a higher confidence map of 4679 proteins and 4780 interactions. Statistical modeling of the network showed two levels of organization: a short-range organization, presumably corresponding to multiprotein complexes, and a more global organization, presumably corresponding to intercomplex connections. The network recapitulated known pathways, extended pathways, and uncovered previously unknown pathway components. This map serves as a starting point for a systems biology modeling of multicellular organisms, including humans.

Animals↗
PubMed2001

IL-4 exacerbates disease in a Th1 cell transfer model of colitis.

IL-4 is associated with Th2-type immune responses and can either inhibit or, in some cases, promote Th1-type responses. We tested the effect of IL-4 treatment on the development of inflammation in the CD4(+)CD45RB(high) T cell transfer model of colitis, which has been characterized as a Th1-dependent disease. IL-4 treatment significantly accelerated the development of colitis in immunodeficient recipients (recombinase-activating gene-2 (Rag2)(-/-)) of CD4(+)CD45RB(high) T cells. Quantitative analysis of mRNA expression in the colons of IL-4-treated mice showed an up-regulation of both Th1- and Th2-associated molecules, including IFN-gamma, IP-10, MIG, CXCR3, chemokine receptor-8, and IL-4. However, cotreatment with either IL-10 or anti-IL-12 mAb effectively blocked the development of colitis in the presence of exogenous IL-4. These data indicate that IL-4 treatment exacerbates a Th1-mediated disease rather than induces Th2-mediated inflammation. As other cell types besides T cells express the receptor for IL-4, the proinflammatory effects of IL-4 on host cells in Rag2(-/-) recipients were assessed. IL-4 treatment was able to moderately exacerbate colitis in Rag2(-/-) mice that were reconstituted with IL-4Ralpha-deficient (IL-4Ralpha(-/-)) CD4(+)CD45RB(high) T cells, suggesting that the IL-4 has proinflammatory effects on both non-T and T cells in this model. IL-4 did not cause colitis in Rag2(-/-) mice in the absence of T cells, but did induce an increase in MHC class II expression in the lamina propria of the colon, which was blocked by cotreatment with IL-10. Together these results indicate that IL-4 can indirectly promote Th1-type inflammation in the CD4(+)CD45RB(high) T cell transfer model of colitis.

Adjuvants, Immunologic↗
PubMed2000

Genetic analysis, phenotypic diagnosis, and risk of venous thrombosis in families with inherited deficiencies of protein S.

Protein S deficiency is a recognized risk factor for venous thrombosis. Of all the inherited thrombophilic conditions, it remains the most difficult to diagnose because of phenotypic variability, which can lead to inconclusive results. We have overcome this problem by studying a cohort of patients from a single center where the diagnosis was confirmed at the genetic level. Twenty-eight index patients with protein S deficiency and a PROS1 gene defect were studied, together with 109 first-degree relatives. To avoid selection bias, we confined analysis of total and free protein S levels and thrombotic risk to the patients' relatives. In this group of relatives, a low free protein S level was the most reliable predictor of a PROS1 gene defect (sensitivity 97.7%, specificity 100%). First-degree relatives with a PROS1 gene defect had a 5.0-fold higher risk of thrombosis (95% confidence interval, 1. 5-16.8) than those with a normal PROS1 gene and no other recognized thrombophilic defect. Although pregnancy/puerperium and immobility/trauma were important precipitating factors for thrombosis, almost half of the events were spontaneous. Relatives with splice-site or major structural defects in the PROS1 gene were more likely to have had a thrombotic event and had significantly lower total and free protein S levels than those relatives having missense mutations. We conclude that persons with PROS1 gene defects and protein S deficiency are at increased risk of thrombosis and that free protein S estimation offers the most reliable way of diagnosing the deficiency. (Blood. 2000;95:1935-1941)

Adult↗
PubMed2000

Autoimmune thrombocytopenia: a complication of fludarabine therapy in lymphoproliferative disorders.

We describe two cases of autoimmune thrombocytopenia precipitated by fludarabine therapy in patients with chronic lymphatic leukaemia. Both were treated with high dose steroids and initially responded with recovery of normal platelet counts. One patient developed recurrent autoimmune thrombocytopenia on two occasions following re-exposure to the drug when his disease had become refractory to all other treatments. A retrospective review of the case notes of 45 patients with lymphoproliferative disorders treated with fludarabine over the past 6 years indicated the development of autoimmune thrombocytopenia in 4.5% (two out of 45) and autoimmune haemolytic anaemia in 6.7% (three of the 45).

Adult↗
PubMed1999

Inhibition and binding studies of coenzyme A and bovine phenol sulfotransferase.

Phenol sulfotransferases (PSTs, EC 2.8.2.1) catalyze sulfonyl group transfer from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to the hydroxyl oxygen of aromatic acceptor substrates. The structural overlap between PAPS and coenzyme A (CoA) suggested a possible role of this common acyl carrier in modulating PST activity. To test this hypothesis, purified recombinant bovine PST was examined by kinetic and affinity chromatographic approaches. After demonstrating PST enzyme inhibition by CoA, systematic variation of CoA and PAPS concentrations indicated simple competitive inhibition with K(i) = 1. 3 microM. PST bound to CoA-agarose, attached via the pantetheinyl thiol group, was eluted with PAP but not by 2-naphthol. This observation was consistent with the pattern of inhibition. Additional members of the sulfotransferase superfamily, as well as acylated CoAs, should be further investigated.

Animals↗
PubMed1999

A perianal ulcer.

Explore the source record for details and available documents.

Amphotericin B↗
PubMed1999

Effect of water content on the physical properties of model dentine primer and bonding resins.

OBJECTIVE: Primers and adhesives containing hydroxyethyl methacrylate (HEMA) are placed on moist dentine even though several studies indicate that water may interfere with the polymerization reaction. The purpose of this study was to evaluate the influence of increasing amounts of water on the physical properties of a model dentine primer resin (HEMA) and model dentine bonding resin (a mixture of HEMA and Bis-GMA). METHODS: Miniature (ca 10 x 0.5 mm (long x thick) hour-glass shaped and parallel-sided specimens were created by casting the monomer or comonomer mixtures into appropriately shaped moulds. The water content was either 0, 5, 9, 17 or 29 vol%. One hour after polymerization, half the specimens were subjected to physical testing under dry conditions. The other half were immersed in water for 24 h and then tested while wet. The ultimate tensile strength (UTS), modulus of elasticity (E), percent elongation at failure, and toughness were calculated. RESULTS: The properties of the dry-stored primer and bonding resins were not altered by water incorporation up to 9 vol%. Higher water content lowered the physical properties (P < 0.05). Immersion of primers polymers in water for 24 h significantly decreased their properties. Water immersion of the bonding resins was unaffected only for specimens containing 0 or 5 vol% water. CONCLUSIONS: The plasticizing effects of extrinsic water are far more important than the effects of intrinsic water in poly-HEMA resin. Hybrid layers composed primarily of poly-HEMA would be expected to be more elastic than those made with bifunctional, cross-linked polymer chains.

Bisphenol A-Glycidyl Methacrylate↗
PubMed1999

Spinal epidural haematoma in haemophilia A with inhibitors--efficacy of recombinant factor VIIa concentrate.

We report the case of a 21-year-old man with severe haemophilia A and factor VIII inhibitors who presented with an extensive spinal epidural haematoma (C2-T12), probably induced by sit-up exercises. The bleed was defined by magnetic resonance imaging of the cervical and thoracic spine and prompt treatment with recombinant factor VIIa concentrate led to complete resolution at 4 weeks. Neurological sequelae were averted and surgical decompression was not necessary. We discuss the difficulties in diagnosis and management of such a case.

Adult↗