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Biomedical subjects

L Donovan

Publications and source records attributed to L Donovan.

At least 19 recordsLinked to original sources

The influence of previous exposure to environmental mycobacteria on the interferon-gamma response to bacille Calmette-Guérin vaccination in southern England and northern Malawi.

We report a large study of the effect of BCG vaccination on the in vitro 6-day whole blood interferon-gamma (IFN-gamma) response to antigens from eight species of mycobacteria among schoolchildren in south-eastern England, where bacille Calmette-Guérin (BCG) vaccination is highly protective against pulmonary tuberculosis, and among young adults in northern Malawi, where BCG vaccination is not protective. In the UK children, BCG induced an appreciable increase in IFN-gamma response to antigens from most species of mycobacteria. The degree of change was linked to the relatedness of the species to Mycobacterium bovis BCG, and provides further evidence of the cross-reactivity of mycobacterial species in priming of the immune system. IFN-gamma responses to purified protein derivatives (PPDs) from M. tuberculosis and environmental mycobacteria were more prevalent in the Malawian than the UK group prior to vaccination; BCG vaccination increased the prevalence of responses to these PPDs in the UK group to a level similar to that in Malawi. There was no evidence that the vaccine-induced change in IFN-gamma response was dependent upon the magnitude of the initial response of the individual to environmental mycobacteria in the United Kingdom or in Malawi. These observations should assist the development and interpretation of human clinical trials of new vaccines against M. tuberculosis in areas of both low and high exposure to environmental mycobacteria.

Adolescent↗

A national survey of genitourinary medicine clinic attenders provides little evidence of sexual transmission of hepatitis C virus infection.

OBJECTIVE: To determine the prevalence and genetic diversity of hepatitis C virus in genitourinary medicine clinic attenders and to assess the extent of sexual transmission of the virus. METHODS: A cross sectional, unlinked, anonymous survey in 14 genitourinary medicine clinics situated in England, Wales, and Northern Ireland. Serum specimens from genitourinary medicine clinic attenders, retained as part of the Unlinked Anonymous Prevalence Monitoring Programme (UAPMP) serum archive, were tested in small pools, for the presence of antibody to hepatitis C virus (anti-HCV). The main outcome measures were prevalence of antibodies to hepatitis C virus and identification of hepatitis C virus genotypes. RESULTS: Testing of 17,586 specimens from 1995 showed an adjusted prevalence of anti-HCV in genitourinary medicine clinic attenders of 1.03% (95% CI: 0.89 to 1.16) overall and 0.65% (95% CI: 0.51 to 0.78) among those who did not report injecting drug use. Prevalence in injecting drug users attending genitourinary medicine clinics was 36.9% in both 1995 and 1996. Heterosexual injecting drug users had a higher prevalence of anti-HCV than homosexual/bisexual injectors. The most common hepatitis C genotypes were types 3a and 1a. There was a high degree of concordance between genotype and serotype. CONCLUSIONS: The low prevalence of anti-HCV in genitourinary medicine clinic attenders who deny injecting drugs suggests that the majority of hepatitis C infections have been acquired in adult life, mostly by injecting drug use, and that the hepatitis C virus is rarely transmitted sexually. The use of needle exchanges may explain the relatively low prevalence observed in the injecting drug users.

Adult↗

Successful engraftment of a second transplant using non-myeloablative conditioning as treatment for graft failure following unrelated donor BMT.

A 32-year-old man with CML in second chronic phase developed primary graft failure following matched unrelated donor transplantation using cryopreserved marrow cells. He was successfully regrafted within 60 days from a second fully matched donor using a non-myeloablative conditioning regimen, with minimal toxicity. He remains in complete haematological, cytogenetic and molecular remission 2 years after second transplant. We believe that reduced intensity or 'mini-transplants' may be preferable for patients requiring second allografts which are usually associated with a high transplant-related mortality.

Adult↗

Prevalence of hepatitis C among injection drug users in England and Wales: is harm reduction working?

OBJECTIVES: This study sought to establish the prevalence of hepatitis C antibodies (anti-HCV) and hepatitis B antibodies (anti-HBc) among injection drug users in England and Wales. METHODS: A voluntary cross-sectional survey collected oral fluid samples and behavioral information; 2203 injectors were recruited through drug agencies, and 758 were recruited in the community. RESULTS: Prevalence was 30% for anti-HCV, 21% for anti-HBc, and 0.9% for HIV antibodies. Anti-HCV prevalence rates were significantly greater among those with longer injecting careers, those in older age groups, those residing in London, those recruited in drug agencies, those positive for anti-HBc, and those with a previous voluntary HIV test. CONCLUSIONS: Anti-HCV prevalence rates among injectors in England and Wales, where comprehensive harm reduction programs exist, are lower than rates in other industrialized countries.

Adult↗

The prevalence and genetic diversity of hepatitis C infection in antenatal clinic attenders in two regions of England.

The prevalence and genetic diversity of hepatitis C infection in women attending antenatal clinics in two regions of England was investigated to inform future surveillance and control measures. Women booking into antenatal care are routinely offered a test for immunity to rubella. Serum residues from these tests were unlinked, anonymized and archived as part of the Unlinked Anonymous Prevalence Monitoring Programme (UAPMP). The serum specimens were tested for anti-HCV using a cost-effective pooling strategy. After taking into account differential sampling from the UAPMP serum archive, the adjusted overall prevalence of anti-HCV was 0.43% (95% CI: 0.32-0.53) in London and 0.21% (95% CI: 0.14-0.28) in the Northern and Yorkshire region. Restriction fragment length polymorphism of amplified HCV RNA identified type 3a as the most common HCV genotype in these antenatal women. The prevalence of anti-HCV in antenatal women in the UK is low and consistent with that expected from injecting drug use.

Adolescent↗

Why us? Why me?

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Abnormalities, Multiple↗

Biological variation of lipids and lipoproteins in fingerstick blood.

The biological variability of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and calculated low-density lipoprotein cholesterol (LDL-C) was determined in three serial (monthly) capillary and venous specimens from 83 subjects. The analytes were quantified with a desktop analyzer. We saw no differences in the coefficient of biological variability (CVb) between capillary and venous specimens for any analyte (TC, 5.2%; TG, 14.7%; HDL-C, 7.2%; LDL-C, 5.4%). The average analytical variability (CVa) for each analyte, determined in quality-control pools, was; TC, 5.0%; TG, 5.2%; HDL-C, 5.8%; and LDL-C, 7.5%. Compared with standardized laboratory measurements, the desktop analyzer exhibited a significant (P < 0.001) positive bias for all analytes (average bias: TC, 5%; TG, 16%; HDL-C, 6%; and LDL-C, 2.4%). Thus, the biological variation of lipids and lipoproteins was the same in fingerstick and venous samples, and the desktop analyzer showed inherently greater analytical variability.

Adult↗

Temporal and spatial regulation of a novel gene in barley embryos.

The temporal and spatial pattern of expression of a novel barley gene is described. The gene has been identified through the differential screening of a cDNA library constructed to poly(A)+ RNA of zygotic embryos. Transcripts corresponding to the cDNA, pZE40, become abundant in the non-axial tissues of the developing embryo within 8-10 days after anthesis, when steady-state levels are high in the scutellum, coleoptile and coleorhiza, with the exception of the scutellar epithelium. This expression pattern is maintained throughout maturation of the embryo until levels eventually decline as the grain desiccates. On germination, there is a transient re-appearance of mRNA to pZE40, with accumulation specifically restricted to the scutellum of the seedling. In situ hybridization has enabled the detection of transcripts elsewhere in the barley plant, in highly localized groups of cells. The timing and cell specificity of expression suggests the gene product is involved in the synthesis and/or transport of metabolites.

Base Sequence↗

A novel approach for the evaluation and treatment of psoriasis. Oral or topical use of 1,25-dihydroxyvitamin D3 can be a safe and effective therapy for psoriasis.

We investigated the effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3) on cultured fibroblasts and keratinocytes from patients with psoriasis and treated 17 patients with psoriasis with orally or topically administered 1,25-(OH)2-D3. Cultured fibroblasts from three of five patients showed a normal response to the antiproliferative activity of a physiologic dose of 1,25-(OH)2-D3, whereas fibroblasts from the other two had a partial resistance to the drug. Cultured keratinocytes from two patients with psoriasis possessed nuclear receptors for 1,25-(OH)2-D3 and the drug caused a dose-dependent inhibition of proliferation and induction of terminal differentiation of these cells similar to effects in normal cultured keratinocytes. Ten of 14 patients with moderate to severe psoriasis who received oral 1,25-(OH)2-D3 showed significant clearing of their hyperkeratotic plaques. Three patients had complete clearing that was sustained with maintenance therapy, but four patients received little or no benefit from the therapy. By the administration of 1,25-(OH)2-D3 as a single oral dose at bedtime, larger doses of the drug could be tolerated without evidence of hypercalciuria or hypercalcemia. Three patients who received topical 1,25-(OH)2-D3 showed a rapid response with complete clearing after 6 weeks of therapy. Therefore, these preliminary findings suggest that orally or topically administered 1,25-(OH)2-D3 may be a safe and effective alternative therapy for the treatment of psoriasis.

Administration, Cutaneous↗