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Biomedical subjects

R Coker

Publications and source records attributed to R Coker.

At least 37 records · Page 2Linked to original sources

A study of the variation in tuberculosis incidence and possible influential variables in Manchester, Liverpool, Birmingham and Cardiff in 1991-1995.

SETTING AND OBJECTIVE: The reversal of the decline in United Kingdom tuberculosis rates has sparked a resurgence of interest in the epidemiology and prevention of tuberculosis in the UK. In this paper we quantify the primary factors explaining the variability in the electoral ward level relative risk of tuberculosis in Manchester, Liverpool, Birmingham and Cardiff. DESIGN: Ecological analysis of the incidence of tuberculosis in 397 wards using hospital admissions data as a proxy for tuberculosis incidence. Admissions were evaluated from the financial years 1991/1992 to 1994/1995. Ward level covariates included measures of country of birth, ethnicity and various socio-economic measures. RESULTS: Separate analyses were carried out for pulmonary and non-pulmonary tuberculosis. For pulmonary tuberculosis the final model included measures of the ward population born in India and Pakistan, overcrowded housing and not-owner-occupied housing. For non-pulmonary tuberculosis the covariates were ward population born in India and Pakistan, overcrowded housing and the proportion of households with no car. CONCLUSIONS: The country of birth of the ward population is the single most influential explanatory factor in the variability of the ward rates for both pulmonary and non-pulmonary tuberculosis in these four cities. Measures of poverty are of secondary importance.

Adolescent↗

HIV associated culture proved tuberculosis has increased in north central London from 1990 to 1996.

OBJECTIVES: To examine rates of culture proved tuberculosis in HIV infected patients in three specialist centres in north central London. METHODS: Cases of tuberculosis in patients with previously documented HIV infection from 1990 to 1996 were identified retrospectively from microbiological/clinical records at Chelsea and Westminster, St Mary's, and University College London Hospitals. RESULTS: Between 1990 and 1996 202 cases of culture proved tuberculosis were identified at the three centres. Of these, 132/202 (65.3%) occurred in homosexual/bisexual men, 41/202 (20.3%) were in patients with heterosexual contact in sub-Saharan Africa, and 29/202 (14.4%) were in "others." Overall 148/202 (73.3%) had pulmonary tuberculosis. The total number of HIV infected individuals seen at the three centres increased from 4298 in 1990 to 5048 in 1996. Rates of tuberculosis in the three centres increased from 0.46% in 1990 to 0.83% in 1996. Part of this increase was due to an increase in tuberculosis among Africans from 1993 to 1996. CONCLUSIONS: Rates of HIV associated tuberculosis increased in these three centres in north central London between 1990 and 1996. In part this was due to an increase in the number of African patients with HIV infection attending the three centres. In addition, there was circumstantial evidence of recent transmission among homosexual men with HIV infection. Prospective "real time" surveillance of tuberculosis in HIV infected patients is needed in order to detect case clustering and to improve tuberculosis control.

Africa↗

A novel colorimetric yeast bioassay for detecting trichothecene mycotoxins.

A novel colorimetric microbial bioassay for toxicity has been developed; it shows particular sensitivity to trichothecene mycotoxins. The assay uses inhibition of expression of beta-galactosidase activity within the yeast Kluyveromyces marxianus as a sensitive toxicity indicator, cultures remaining yellow, rather than turning deep green-blue, in the presence of X-gal, a chromogenic substrate. The assay is conducted in standard microtitre plates, permitting small volumes (160 microl) and many replicates, and can be scored either automatically by a plate-reader, or by eye. Factors likely to affect the efficacy of the bioassay, including carbon source, solvents, inoculum cell density, and the use of membrane-modulating agents (MMAs), were assessed. Polymyxin B nonapeptide was the most effective toxicity-enhancing MMA tested, enabling the trichothecene mycotoxin, verrucarin A, to be detected at a concentration of about 1 ng/ml. The assay's reproducibility was examined using polymyxin B sulfate, a cheaper MMA, and another trichothecene mycotoxin, T2 toxin: reproducibility and sensitivity were better for the beta-galactosidase X-gal endpoint than for an alternative chromogenic toxicity indicator, the respiratory substrate 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT).

Biological Assay↗

Inhibition of human immunodeficiency virus replication and growth advantage of CD4+ T cells from HIV-infected individuals that express intracellular antibodies against HIV-1 gp120 or Tat.

Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection often involve the ex vivo transduction and expansion of CD4+ T cells derived from HIV-positive patients at a late stage in their disease (CD4 count <400). These protocols involve the transduction of T cells by murine leukemia virus (MLV)-based vectors encoding antiviral constructs such as the rev m10 dominant negative mutant or a ribozyme directed against the CAP site of HIV-1 RNA. We examined the efficiency and stability of transduction of CD4+ T cells derived from HIV-infected patients at different stages in the progression of their disease, from seroconversion to AIDS. CD4+ T cells from HIV-positive patients and uninfected donors were transduced with MLV-based vectors encoding beta-galactosidase and an intracellular antibody directed against gp120 (sFv 105) or Tat. (sFvtat1-Ckappa). The expression of marker genes and the effects of the antiviral constructs were monitored in vitro in unselected transduced CD4+ T cells. Efficiency and stability of transduction varied during the course of HIV infection; CD4+ T cells derived from asymptomatic patients were transducible at higher efficiencies and stabilities than CD4+ T cells from patients with acquired immunodeficiency syndrome (AIDS). Expression of the anti-tat intracellular antibody was more effective at stably inhibiting HIV-1 replication in transduced cells from HIV-infected individuals than was sFv 105. The results of this study have important implications for the development of a clinically relevant gene therapy for the treatment of HIV-1 infection.

Animals↗

Transforming growth factor-beta (TGF-beta).

The TGF-beta family of cytokines are ubiquitous, multifunctional and essential to survival. They play important roles in growth and development, inflammation and repair and host immunity. The mammalian TGF-beta isoforms (TGF-beta 1, beta 2 and beta 3) are secreted as latent precursors and have multiple cell surface receptors of which at least two mediate signal transduction. Autocrine and paracrine effects of TGF-beta's can be modified by extracellular matrix, neighbouring cells and other cytokines. The vital role of the TGF-beta family is illustrated by the fact that approximately 50% of TGF-beta 1 gene knockout mice die in utero and the remainder succumb to uncontrolled inflammation after birth. TGF-beta 2 and TGF-beta 3 gene knockout mice are not yet described. More recently, novel TGF-beta-like molecules have been described which share some of the properties of the mammalian TGF-beta isoforms. The role of TGF-beta in homeostatic and pathogenic processes suggests numerous applications in the diagnosis and treatment of various diseases characterised by inflammation and fibrosis.

Animals↗

Survey of food safety awareness among HIV positive individuals.

A survey was carried out by personal interview to assess the awareness of basic food hygiene and food safety amongst 77 HIV-positive individuals attending a single hospital. There was some confusion and lack of knowledge about aspects of food storage and despite the fact that 74% of subjects had modified their diet since learning their HIV status (mainly for nutritional reasons) only 25% reported receiving information on food safety. Of the subjects interviewed 96%, 66% and 23% were aware of the risks of infection from Salmonella, Listeria monocytogenes and Cryptosporidium, respectively; although most were not aware of the UK Government's advice on the consumption of eggs, soft cheese, pâté and cook-chill foods. Over 40% of those interviewed reported that they did not drink tap water (most drank bottled water instead), but few were aware of infections potentially transmitted through water. Although pets represent a potential source of a wide variety of infectious agents, there was a high level of awareness of this problem. This study highlights the need for improving the availability of information on food hygiene and infections acquired through food and water to HIV-positive individuals.

Awareness↗

Detection of cytomegalovirus (CMV) in HIV+ patients: comparison of cytomorphology, immunocytochemistry and in situ hybridization.

CMV is regarded as an important pathogen in immunocompromised patients. This study compares three cytological methods of diagnosis of CMV in alcohol-fixed smears from bronchoalveolar lavage (BAL) specimens from 40 HIV+ patients, using cytomorphology (CM), immunocytochemical staining (ICC) and in situ hybridization (ISH). The results of CM are compared with virological detection methods using the detection of early fluorescent foci (DEAFF) 48-h culture technique and virus isolation studies (VISO 1). ICC was the most sensitive technique, identifying CMV in 13 cases, six of which were also positive on ISH. Cytomorphology was the least sensitive, with only one case showing diagnostic features of CMV cytopathic effect. One additional case showed morphological features suggesting viral infection but not specific for CMV. Both of these cases were confirmed by ICC and ISH. Virology studies identified CMV in all 13 cases and in an additional five cases. ICC detected two cases which were negative on the DEAFF test but which were later detectable by the VISO 1 technique. These findings support the usefulness of ISH and ICC in confirming CMV in cases where the infection was suspected on cytomorphological features. ISH and ICC also increase the detection of CMV in BAL smears not showing morphological features on CM.

AIDS-Related Opportunistic Infections↗

Patients unaware of their HIV status present to inner city accident and emergency department with respiratory complications.

OBJECTIVE: To examine the clinical presentations and management of patients presenting to an accident and emergency (A&E) department with an AIDS defining illness (ADI). METHODS: Presentations of patients in the A&E department with ADI were reviewed retrospectively. The age, sex, ethnic origin, risk factor for HIV infection, route of referral to hospital, presenting complaint, triage category, referral from A&E, admission under medical specialists, diagnosis, and survival from ADI were noted for each patient. RESULTS: 133 patients were registered at St Mary's Hospital in London with ADI during 1994. A significant minority of these patients (25/133) presented to the hospital without prior knowledge of their HIV positive status. Thirty two patients presented to the A&E department with their ADI. Of these, 13/32 (41%) were unaware of the HIV serostatus. All 13 patients had an acute respiratory disease (Pneumocystis carinii pneumonia or pulmonary tuberculosis). In contrast, patients aware of their HIV positive status (19/32) presented to the A&E department with a wide range of non-pulmonary ADI. CONCLUSIONS: The study emphasises the importance of respiratory complications in patients who present with a ADI to emergency departments but are unaware of their HIV positivity. These patients presented solely with Pneumocystis carinii pneumonia or pulmonary tuberculosis, conditions in which early diagnosis and treatment significantly reduce morbidity and mortality.

AIDS-Related Opportunistic Infections↗