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Biomedical subjects

I Blair

Publications and source records attributed to I Blair.

At least 19 recordsLinked to original sources
PubMed2001

Methicillin-resistant Staphylococcus aureus (MRSA): a community-based prevalence survey.

A prevalence survey of nasal methicillin-resistant Staphylococcus aureus (MRSA) carriage was undertaken on a random sample of adults (aged over 16) resident in the community in Birmingham, UK during 1998. Microbiological samples were taken from the anterior nares at the subjects' general practice or in their home. Information about risk factors for the acquisition of MRSA was obtained via a self-completed questionnaire. A 58% response rate (280/483) was achieved. The prevalence of nasal MRSA colonization was 1.5% [4/274, 95% confidence interval (CI) 0.03-2.9%]. Twenty-three per cent (63/274) of subjects were nasal carriers of S. aureus. Six per cent (4/63) of S. aureus isolates were MRSA and 2 of the 4 MRSA carriers reported previous contact with health facilities. The prevalence of MRSA colonization in the general adult population in Birmingham appears to be low.

Adolescent↗
PubMed2000

Outbreak of tuberculosis associated with a church.

Investigation of an outbreak of tuberculosis (TB) in a West Midlands health district in 1999 revealed spread in an extended family network and to church contacts. Within the family four cases of smear positive TB, four cases of smear negative infection, and 14 cases requiring chemoprophylaxis were identified. One of the infectious cases visited a local church on two occasions, which resulted in a further 16 cases of infection including one case of tuberculous meningitis. DNA fingerprinting of isolates from five culture positive cases indicated that the same strain of Mycobacterium tuberculosis was responsible. This outbreak is a reminder that while outbreaks of TB usually arise within households or family networks, where close contact over extended periods provides more opportunity for exposure, community outbreaks of TB can occur after only causal contact.

Adult↗
PubMed1999

Use of protamine to augment adenovirus-mediated cancer gene therapy.

Improving the therapeutic potential of adenoviral (Ad) suicide gene therapy has become an area of intense investigation since the inception of gene therapy strategies for cancer treatment. Poor efficiency of gene transfer to target tissues has become one of the most important limitations to Ad-based gene therapy. Since polycations have been shown to enhance adenovirus-mediated gene transfer in epithelial cells both in vitro and in vivo, we hypothesized that polycations could augment treatment efficacy in animals with established tumor. To address this hypothesis, protamine sulfate, a polycation already safely administered in humans, was complexed with a recombinant Ad (E1E3-deleted) vector containing the herpes simplex 1 thymidine kinase (HSVtk) suicide gene to treat cancer cell lines in vitro and in animals bearing intraperitoneal tumor. In the presence of 5 microg/ml protamine, the efficiency of gene transfer to a number of cancer cell lines normally resistant to adenovirus was significantly enhanced. Protamine's effect in vitro was found to be inversely proportional to the level of expression of the high affinity Ad binding site, coxsackievirus and adenovirus receptor (CAR), on the sur- face of the various cell lines tested. Ad.tk infected tumor cells were rendered 2.5- to three-fold more sensitive to 20 microM ganciclovir (GCV) in the presence of protamine. Protamine also augmented the in vivo transfer efficiency of the marker gene, LacZ (contained in an Ad vector), on the surface of tumors derived from an intraperitoneal mouse model. Quantitative imaging revealed 50% tumor surface transduced with LacZ when treatment was performed in the presence of 50 microg/ml protamine compared with 12% tumor surface in controls. However, experiments performed utilizing intraperitoneal administration of Ad.tk/GCV in the presence or absence of 50 microg/ml protamine demonstrated no significantly improved median survival in mice bearing established intraperitoneal tumors. Similarly, in Fischer rats bearing intrapleural tumor, no improvement in anti-tumor response was observed when Ad treatment was performed intrapleurally in the presence of protamine. Thus, although protamine induced an enhancement of Ad-mediated gene transfer in vitro and in vivo, its use as an adjunct to intracavitary Ad-based cancer gene therapy in vivo appears to be limited.

Adenoviridae↗
PubMed1999

Homologous DNA exchanges in humans can be explained by the yeast double-strand break repair model: a study of 17p11.2 rearrangements associated with CMT1A and HNPP.

Rearrangements in 17p11.2, responsible for the 1.5 Mb duplications and deletions associated, respectively, with autosomal dominant Charcot-Marie-Tooth type 1A disease (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are a suitable model for studying human recombination. Rearrangements in 17p11.2 are caused by unequal crossing-over between two homologous 24 kb sequences, the CMT1A-REPs, that flank the disease locus and occur in most cases within a 1.7 kb hotspot. We sequenced this hotspot in 28 de novo patients (25 CMT1A and three HNPP), in order to localize precisely, at the DNA sequence level, the crossing-overs. We show that some chimeric CMT1A-REPs in de novo patients (10/28) present conversion of DNA segments associated with the crossing-over. These rearrangements can be explained by the double-strand break (DSB) repair model described in yeast. Fine mapping of the de novo rearrangements provided evidence that the successive steps of this model, heteroduplex DNA formation, mismatch correction and gene conversion, occurred in patients. Furthermore, the model explains 17p11.2 recombinations between chromosome homologues as well as between sister chromatids. In addition, defective mismatch repair of the heteroduplex DNA, observed in two patients, resulted in two heterozygous chimeric CMT1A-REPs which can be explained, as in yeast, by post-meiotic segregation. This work supports the hypothesis that the DSB repair model of DNA exchange may apply universally from yeasts to humans.

Charcot-Marie-Tooth Disease↗
PubMed1999

Audit of immunization policy and practice of health care workers within National Health Service Trusts in England and Wales.

The purpose of this study was to identify the variation in occupational health immunization policies and practice within NHS Trusts throughout England and Wales. Questionnaires were sent to 440 NHS Trusts and 279 were returned (a response rate of 63%). The results were compared with current Department of Health Guidelines. They highlighted the fact that NHS Trusts do not adopt a consistent approach to immunization practice and that these policies often do not reflect Department of Health Guidance. Of those responding, 249 (89%) stated that they would like additional guidance on immunization practice within the NHS workplace. The production of updated, evidence-based guidelines for immunization practice, may help to ensure that a more consistent approach is taken throughout the NHS. This would benefit both the Trusts and their employees who at present may be confused by being given different advice when moving between Trusts.

Communicable Disease Control↗
PubMed1998

A large outbreak of Q fever in the West Midlands: windborne spread into a metropolitan area?

The largest outbreak of the zoonotic disease Q fever recorded in the United Kingdom (UK) occurred in Birmingham in 1989. One hundred and forty-seven cases were identified, 125 of whom were males, and 130 of whom were between 16 and 64 years of age. Fewer cases of Asian ethnic origin were observed than expected (p < 0.01), and more smokers (p < 0.005). A case control study (26 cases and 52 matched controls) produced no evidence that direct contact with animals or animal products had caused the outbreak. The epidemic curve suggested a point source exposure in the week beginning 10 April. The home addresses of cases were clustered in a rectangle 11 miles (18.3 km) north/south by 4 miles (6.7 km) east/ west, and attack rates became lower towards the north. Directly south of this area were farms engaged in outdoor lambing and calving, a potent source of coxiella spores. A retrospective computerised analysis showed that the geographical distribution of cases was associated with a source in this area (p < 0.00001). On 11 April, unusual southerly gales of up to 78 mph (130 km/h) were recorded. The probable cause of the outbreak was windborne spread of coxiella spores from farmland to the conurbation.

Adolescent↗
PubMed1996

Machado-Joseph disease in east Arnhem Land, Australia: chromosome 14q32.1 expanded repeat confirmed in four families.

Four kindreds of east Arnhem Land Australian aboriginal people from Groote Eylandt and adjacent communities display symptoms of a similar spinocerebellar degeneration (multiple-system degenerative disease). The familial pattern indicates an autosomal dominant inheritance, though with varying penetrance in different families. This condition is clinically and pathologically consistent with Machado-Joseph disease (MJD), and there is the possibility of Portuguese ancestry. These families exhibit anticipation, particularly in the case of paternal inheritance, with those with earlier age of onset presenting a clinical pattern consistent with MJD type I. There was no expansion of the CAG repeat region of the SCA1 gene in these families. The demonstration of expansion of the CAG repeat on chromosome 14q32.1 in all four families confirms the diagnosis of MJD.

Australia↗
PubMed1994

Gonorrhoea in the West Midlands.

The number of cases of gonorrhoea in residents of areas served by district health authorities of the West Midlands has been measured to provide an indicator of this population's sexual health. A detailed data set was collected on all cases of gonorrhoea diagnosed at genitourinary medicine (GUM) clinics in the West Midlands region during a three month period. Consultants in genitourinary medicine and colleagues in public health medicine cooperated, and data collection was complete for all but one clinic. The numbers of new cases of gonorrhea seen at GUM clinics varied widely between districts. The number of cases in the first quarter of 1992 in several districts implied a much higher incidence than the national annual rate of 61 new cases per 100,000 population in 1990. The routine workload statistics (KC60) from GUM clinics do not provide data on cases' area of residence. Further special surveys are needed to monitor trends in particular populations to assist progress towards targets for sexual health.

Adolescent↗
PubMed1994

Tumor cell-derived 12(S)-hydroxyeicosatetraenoic acid induces microvascular endothelial cell retraction.

Our previous work demonstrated that the 12-lipoxygenase metabolite of arachidonic acid, 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] induced a nondestructive and reversible retraction of cultured endothelial cells. In the current study we tested the hypothesis that tumor cells produce 12(S)-HETE during their interactions with endothelial cells which in turn induces endothelial cell retraction. Coincubation of Lewis lung carcinoma cells or elutriated B16 amelanotic melanoma (B16a) cells but not 3T3 fibroblasts with microvascular endothelial cells (CD3) resulted in a time- and concentration-dependent retraction of the CD3 monolayers as revealed by quantitative binding assays and phase contrast microscopy. Lewis lung carcinoma cell-induced endothelial cell retraction was blocked by specific lipoxygenase inhibitors but not by cyclooxygenase inhibitors, suggesting the involvement of a lipoxygenase metabolite(s). Radioimmunoassay and high-performance liquid chromatography analysis of tumor cell extracts identified 12(S)-HETE as the major lipoxygenase metabolite of arachidonic acid and tumor cell generation of 12(S)-HETE was specifically blocked by a select 12-lipoxygenase inhibitor N-benzyl-N-hydroxy-5-phenyl-pentamide. The identity and stereochemistry of tumor cell-derived 12-HETE was substantiated by gas chromatography-mass spectrometry analysis and chiral phase high-performance liquid chromatography, respectively. Lewis lung carcinoma cell adhesion to CD3 monolayers was accompanied by an enhanced 12(S)-HETE biosynthesis by tumor cells, which paralleled the tumor cell-induced endothelial cell retraction in a cell number-dependent manner. Pretreatment of tumor cells with N-benzyl-N-hydroxy-5-phenylpentamide inhibited both increased 12(S)-HETE biosynthesis and tumor cell-induced endothelial cell retraction. Highly metastatic variants of elutriated B16a cells which had been shown to produce large quantities of 12(S)-HETE induced significant CD3 cell retraction, while low metastatic subpopulations of B16a cells which synthesized no or little 12(S)-HETE did not induce endothelial cell retraction. These results suggest that 12(S)-HETE synthesis during tumor cell-endothelial cell interactions may represent a key contributory factor in cancer metastasis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1993

Tuberculosis in the West Midlands, 1990-1991.

In the late 1980s, notifications of tuberculosis stopped their former steady decline. There has been speculation as to why this should be so, with much interest centred on a possible association with the HIV epidemic. Notification rates are higher in persons of Indian subcontinent ethnic origin compared with the indigenous white population. Changes in the size and structure of the former population subgroup may have contributed to the recent increase in notifications in some areas. The absence of data on ethnic group in routinely collected data has led to the recommendation that special surveys should be conducted to clarify the contribution of ethnic minorities to the occurrence of tuberculosis in the UK. One such survey has been carried out in the West Midlands, where notifications increased by 27% between 1987 and 1989. Notification rates were found to vary widely by age, sex, district of residence and ethnic group; the highest notification rates occurring in older females of Indian subcontinent origin. These differences help to explain the increase in the absolute number of notifications and suggest that certain population subgroups warrant special attention.

Adolescent↗
PubMed1993

Active surveillance of HIV infection in the West Midlands.

We describe a new active surveillance system for human immunodeficiency virus (HIV) infection in the West Midlands region, a National Health Service administrative area in central England serving a population of five million. A detailed, confidential dataset is collected on each case of HIV infection identified through laboratory reporting of positive HIV antibody tests. The consultant in communicable disease control in each district health authority responsible for the surveillance of infectious disease collects and updates the data, which are then shared with staff at the regional health authority (RHA) who maintain a regional database. Regular reports from this database allow local monitoring of the epidemic and the equitable allocation of resources.

England↗
PubMed1993

A large Q fever outbreak in the West Midlands: clinical aspects.

In the spring of 1989 the largest outbreak of acute Q fever recorded in the United Kingdom occurred in Solihull and surrounding areas of the West Midlands. The diagnosis was confirmed in 147 people, mainly males of working age. Windborne spread from farmland to the south of the urban area was the most likely route of infection. Fever was the commonest symptom, seen in 101/102 (99%) cases, followed by weight loss reported by 83/101 (82%). Headache, often severe, was experienced by 69/101 (68%). The commonest respiratory symptom was breathlessness, 65/102 (64%), followed by cough, 52/102 (51%), and chest pain, 46/102 (45%). Neurological features, seen in 23% of cases, were more prominent in this outbreak than is commonly recognized. Persisting ill health 6 months following the acute episode not due to chronic Q fever was also a prominent feature of this largely urban outbreak.

Adolescent↗
PubMed1990

Cytochrome P-450-dependent oxidation of arachidonic acid to 16-, 17-, and 18-hydroxyeicosatetraenoic acids.

Incubation of rat liver microsomal fractions with arachidonic acid in the presence of NADPH results in the formation of three novel monohydroxylated fatty acid metabolites. Utilizing chromatographic and mass spectral techniques, these metabolites have been identified as 16-, 17-, and 18-hydroxyeicosatetraenoic acids. The NADPH-dependent microsomal metabolism of arachidonic acid to 16-, 17-, 18-, and 19-hydroxyeicosatetraenoic acids is induced after animal treatment with beta-naphthoflavone. Reconstitution of the arachidonic acid oxygenase utilizing individual purified cytochrome P-450 enzymes demonstrates regioselectivity, controlled by the protein catalyst, for the hydroxylation of the sp3 carbon atoms adjacent to the methyl end of the fatty acid.

Animals↗