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Biomedical subjects

C Taylor

Publications and source records attributed to C Taylor.

At least 109 records · Page 6Linked to original sources

Production of cis-1,2-dihydroxy-3-methylcyclohexa-3,5-diene (toluene cis glycol) by Rhodococcus sp. MA 7249.

An attractive method for producing cis-1,2-dihydroxy-3-methylcyclohexa-3,5-diene (toluene cis glycol) was developed employing a cis dihydrodiol dehydrogenase "deficient" strain of Rhodococcus (MA 7249). The toluene cis glycol produced was found to have optical rotations of [alpha]D25 = +25.8 (c 0.45, CH3OH) and +72.8 (c 0.42, CHCl3) which indicated an absolute configuration of (1S,2R) when compared with previously published values. When cultivated in laboratory fermentor in the presence of toluene vapors, MA 7249 reached a toluene cis glycol concentration up to 18 g/l in 110 h. Culture MA 7249 also accumulated cis (1S,2R) dihydrodiols from dihydronaphthalene, biphenyl, chlorobenzene, and styrene.

Journal Article↗

Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis.

BACKGROUND: Multiple sclerosis results from T-cell-dependent inflammatory demyelination of the central nervous system. Our objective was long-term suppression of inflammation with short-term monoclonal antibody treatment. METHODS: We depleted 95% of circulating lymphocytes in 27 patients with multiple sclerosis by means of a 5-day pulse of the humanised anti-CD52 monoclonal antibody, Campath-1H. Clinical and haematological consequences of T-cell depletion, and in-vitro responses of patients' peripheral-blood mononuclear cells were analysed serially for 18 months after treatment. FINDINGS: Radiological and clinical markers of disease activity were significantly decreased for at least 18 months after treatment. However, a third of patients developed antibodies against the thyrotropin receptor and carbimazole-responsive autoimmune hyperthyroidism. The depleted peripheral lymphocyte pool was reconstituted with cells that had decreased mitogen-induced proliferation and interferon gamma secretion in vitro. INTERPRETATION: Campath-1H causes the immune response to change from the Th1 phenotype, suppressing multiple sclerosis disease activity, but permitting the generation of antibody-mediated thyroid autoimmunity.

Adult↗

The ribonucleotide reductase R2 gene is a non-transcribed target of c-Myc-induced genomic instability.

The c-Myc oncoprotein is highly expressed in malignant cells of many cell types, but the mechanism by which it contributes to the transformation process is not fully understood. Here, we show for the first time that constitutive or activated overexpression of the c-myc gene in cultured mouse B lymphocytes is followed by chromosomal and extrachromosomal amplification as well as rearrangement of the ribonucleotide reductase R2 gene locus. Electron micrographs and fluorescent in situ hybridization (FISH) demonstrate the c-Myc-dependent generation of extrachromosomal elements, some of which contain R2 sequences. However, unlike other genes that have been shown to be targets of c-Myc-dependent genomic instability, amplification of the R2 gene is not associated with alterations in R2 mRNA or protein expression. These data suggest that c-Myc-dependent genomic instability involves a greater number of genes than previously anticipated, but not all of the genes that are amplified in this system are transcriptionally upregulated.

Animals↗

Marine radioactivity assessment of Mururoa and Fangataufa atolls.

The International Atomic Energy Agency (IAEA) carried out an international project. 'The Study of the Radiological Situation at the Atolls of Mururoa and Fangataufa' with the aim of assessing the present and future radiological situation at the atolls and making recommendations for either monitoring or remedial actions if they are deemed necessary. The paper concentrates on marine radioactivity aspects and gives an estimation of present radionuclide concentrations in water, sediment and biota of the Mururoa and Fangataufa lagoons and the surrounding ocean. The dominant radionuclide in both lagoons is Pu in sediments (the total inventory is approximately 30 TBq). A decline in radionuclide concentrations has been observed in recent years in lagoon water, with the exception of 3H and 90Sr, for which a contribution from underground sources is to be expected. Radionuclide concentrations in biota from the lagoons and the surrounding ocean are low and consistent with previous measurements. The observed radionuclide concentrations in both lagoons imply that no radiological risk exists for hypothetical inhabitants of Mururoa and Fangataufa Atolls.

Animals↗

Microbial conversion of indene to indandiol: a key intermediate in the synthesis of CRIXIVAN.

Indene is oxidized to mixtures of cis- and trans-indandiols and related metabolites by Pseudomonas putida and Rhodococcus sp. isolates. Indene metabolism is consistent with monooxygenase and dioxygenase activity. P. putida resolves enantiomeric mixtures of cis-1,2-indandiol by further selective oxidation of the 1R, 2S-enantiomer yielding high enantiomeric purity of cis-(1S, 2R)-indandiol, a potential intermediate in the synthesis of indinavir sulfate (CRIXIVAN), a protease inhibitor used in the treatment of AIDS. Molecular cloning of P. putida toluene dioxygenase in Escherichia coli confirmed the requirement for the dihydrodiol dehydrogenase in resolving racemic mixtures of cis-indandiol. Rhodococcus sp. isolates convert indene to cis-(1S, 2R)-indandiol at high initial enantiomeric excess and one isolate also produces trans-(1R, 2R)-indandiol, suggesting the presence of monooxygenase activity. Scale up and optimization of the bioconversions to these key synthons for chiral synthesis of potential intermediates for commercial manufacture of indinavir sulfate are described.

Drug Design↗

Accuracy of the EASI 12-lead electrocardiogram compared to the standard 12-lead electrocardiogram for diagnosing multiple cardiac abnormalities.

This study was performed to compare a derived 12-lead electrocardiogram (ECG) using a simple 5-electrode lead configuration (EASI 12-lead) with the standard ECG for multiple cardiac diagnoses. Accurate diagnosis of arrhythmias and ischemia often require analysis of multiple (ideally, 12) ECG leads; however, continuous 12-lead monitoring is impractical in hospital settings. EASI and standard ECGs were compared in 540 patients, 426 of whom also had continuous 12-lead ST segment monitoring with both lead methods. Independent standards relative to a correct diagnosis were used whenever possible, for example, echocardiographic data for chamber enlargement-hypertrophy, and troponin levels for acute infarction. Percent agreement between the 2 methods were: cardiac rhythm, 100%; chamber enlargement-hypertrophy, 84%-99%; right and left bundle branch block, 95% and 97%, respectively; left anterior and posterior fascicular block, 97% and 99%, respectively; prior anterior and inferior infarction, 95% and 92%, respectively. There was very little variation between the 2 lead methods in cardiac interval measurements; however, there was more variation in P, QRS, and T-wave axes. Of the 426 patients with ST monitoring, 138 patients had a total of 238 ST events (26, acute infarction; 62, angioplasty-induced ischemia; 150, spontaneous transient ischemia). There was 100% agreement between the 2 methods for acute infarction, 95% agreement for angioplasty-induced ischemia, and 89% agreement for transient ischemia. EASI and standard 12-lead ECGs are comparable for multiple cardiac diagnoses; however, serial ECG changes (eg, T-wave changes) should be assessed using one consistent 12-lead method.

Aged↗

A bench-scale investigation of land treatment of soil contaminated with diesel fuel.

A bench-scale investigation (soil pan testing) was conducted with the objective of studying degradation rates of diesel contaminated soil (2500 and 10,000 ppm by weight of total petroleum hydrocarbons (TPH) to dry weight of soil) under different treatment conditions over a 17 week testing period. The greatest degradation of the diesel contaminated soil was obtained with the addition of nutrients (Co = 10,000 ppm of TPH; k = 0.19 week-1). 'k' for soil not amended with nutrients was 0.07 week-1. The control cell (C0 = 2500 ppm TPH), with sodium azide (to suppress degradation) was compared with an experimental cell of 2500 ppm initial concentration of TPH without nutrient amendment. The control cell exhibited a relatively low uniform degradation (k = 0.08 week-1) of TPH over the duration of the experiment with reasonable first-order kinetic regression statistics.

Biodegradation, Environmental↗

Sharps injuries: defining prevention priorities.

OBJECTIVE: An institutional review of sharps injuries was conducted to assist in establishing priorities for resource allocation in a sharps prevention program. DESIGN: A retrospective review of 221 sharps injuries occurring during a 1-year period was conducted by a 4-member multidisciplinary team. Each injury was categorized as either moderate/high, low, or unknown risk for acquisition of bloodborne diseases by using modified provincial definitions of occupational risk for exposure to bloodborne pathogens. RESULTS: A total of 119 injuries were considered to be moderate/high risk, and 93 were at low risk for acquisition of bloodborne disease. Nine injuries could not be categorized. In 59% of high-risk injuries, education or changes in technique were identified as the primary preventive intervention. Passive devices such as needleless intravenous administration sets could theoretically address prevention of the majority of low-risk injuries. Known available safety devices could have prevented 33 (28%) high-risk injuries. CONCLUSION: Disposition of resources must take into consideration the risk of bloodborne disease acquisition and the efficiency and expense of the preventable methods employed. Institutional review of injuries combined with a cost analysis revealed that resources were best allocated to protective devices at source (eg, safety syringes) and on a comprehensive, multidisciplinary, and sustained educational program. Needleless intravenous infusion sets would mainly prevent low-risk injuries at significant cost.

British Columbia↗

Taking on the student role: how can we improve the experience of registered nurses returning to study?

Regardless of the number of nurses who undertake graduate certificate courses in critical care nursing in Victoria, Australia, there is still a shortage of skilled nurses in the critical care areas. Preparation for practice in this specialist field has moved from hospital-based programs to tertiary-based courses during the past decade. As a consequence, there has been scrutiny of the clinical ability of graduates to perform the role function. Although this is understandable, anecdotal evidence to date indicates that students in these courses experience many difficulties, yet very little is written about the stressors they encounter. As the future of the critical care work force depends on a constant supply of students undertaking courses, it is essential to gain insight into the student experience, with a view to optimising it for future students and perhaps preventing attrition from courses. This paper describes a qualitative research study involving 14 students undertaking a graduate certificate course in critical care nursing. The aim of the study was to document the students' experience in relation to factors they identified as helping or hindering their progress on the course. Data were obtained at three points during the academic component of the course: on entry, at the end of semester 1 and at the end of semester 2. Interviews and questionnaires were used as the data collection methods. Results indicate that for this group of students, the experience of undertaking the course was adversely affected by stress related to three factors: change of role from clinician back to student; unmet expectations, and exhaustion. Recommendations related to preparation for study, curriculum timelines and peer support are included in this paper.

Attitude of Health Personnel↗

Estimating the prevalence of problem drug use in inner London: a discussion of three capture-recapture studies.

AIMS: To provide an evidence base of estimates of the prevalence of problem drug use in inner London. DESIGN: Re-analysis of three capture-recapture studies using subjects aged 15-49 years, that aim to estimate the hidden population from analysing the overlaps between three data sources. SETTING: Newham (1995) Camden and Islington (C&I) (1993/4) and Lambeth, Southwark and Lewisham (LSL) (1992). PARTICIPANTS: Each study collected data from three sources of problem drug users including: the Regional Drug Misuse Database, specialist drug agencies, HIV tests, social services, police arrests and court records. In LSL opiate users were analysed separately. The studies identified 1832 individuals in LSL, 543 in Newham, and 1321 in C&I. MEASUREMENTS: Poisson models were fitted to the data testing different interactions between the data sources representing potential dependencies. The simplest model was selected on the basis of its AIC score and log-likelihood ratio tests. FINDINGS: The number of hidden problem drug users were estimated to be 12,500 (95% CI 9600-16,100) in LSL with 4400 (3200-6100) opiate users; 7000 (5000-10,000) in C&I and 3800 (2000-7200) in Newham. The prevalence of problem drug use in those aged 15-49 was estimated to be 3.1% (2.5-3.9%) in LSL with 1.3% (1.0-1.6%) opiate users; and 3.6% (2.7-4.9%) and 3.3% (1.9-5.7%) in C&I and Newham, respectively. CONCLUSIONS: Despite the inherent problems with capture-recapture methods, our three studies establish an evidence base for estimates of problem drug use in London. It is important that a larger study is carried out in London.

Adolescent↗

Preventing opiate overdose fatalities with take-home naloxone: pre-launch study of possible impact and acceptability.

AIMS: Before proceeding with the introduction of an overdose fatality prevention programme including teaching in cardio-pulmonary resuscitation and distribution of naloxone, a pre-launch study of treatment and community samples of injecting drug misusers has been undertaken to establish (i) the extent of witnessing overdoses, (ii) the acceptability of naloxone distribution and training; and (iii) the likely impact of such measures. DESIGN AND SETTING: Structured interview of two samples: (a) a community sample of injecting drug misusers recruited by selected privileged access interviewers (PAI) and interviewed by them in community settings and (b) a treatment sample of opiate addicts recruited from our methadone maintenance clinic (interviewed by in-house research staff). PARTICIPANTS: (a) Three hundred and twelve injecting drug misusers with a history of having injected and currently still using injectable drugs; and (b) 142 opiate addicts in treatment at our local catchment area methadone maintenance clinic in South London. FINDINGS: History of personal overdose was found with 38% of the community sample and 55% of the treatment sample--mainly involving opiates and in the company of friends. Most (54% and 92%, respectively) had witnessed at least one overdose (again mostly involving opiates), of whom a third had witnessed a fatal overdose. Only a few (35%) already knew of the existence and effects of naloxone. After explanation to the treatment sample, 70% considered naloxone distribution to be a good proposal. Of the 13% opposed to the proposal, half thought it may lead them to use more drugs. Eighty-nine per cent of those who had witnessed an overdose fatality would have administered naloxone if it had been available. We estimate that at least two-thirds of witnessed overdose fatalities could be prevented by administration of home-based supplies of naloxone. CONCLUSIONS: Substantial proportions of both community and treatment samples of drug misusers have witnessed an overdose death which could have been prevented through prior training in resuscitation techniques and administration of home-based supplies of naloxone. Such a new approach would be supported by most drug misusers. On the basis of these findings, we conclude that it is appropriate to proceed to a carefully constructed trial of naloxone distribution.

Adult↗

Self-reported overdose among injecting drug users in London: extent and nature of the problem.

AIMS: To estimate the extent and nature of overdose and factors associated with overdose among injecting drug users in London. DESIGN: Three hundred and twelve current injecting drug users were recruited and interviewed in community settings by a team of "privileged access interviewers". MEASUREMENTS: A structured questionnaire was used that covered the following areas: demographic characteristics, drug use, injecting behaviour, sharing practices, severity of drug dependence, experience of overdose, injecting-related health problems and treatment history. FINDINGS: The results showed that experience of overdose was common (38%). A majority (54%) had witnessed someone else overdose. Overdosing was not a solitary experience; over 80% of subjects who had overdosed had done so in the presence of someone else, but only 27% reported ambulances having been called. Factors found to be associated with overdose were: age at which injecting began; gender (women being more likely to experience overdose); use of alcohol; and polydrug injection. The overall rate of overdosing was one per 6 years of injecting; however, once an individual had an overdose the chance of having another increased. The risk of experiencing a first overdose fell with years of injecting. CONCLUSIONS: Harm-reduction interventions with drug injectors should educate users on the risk factors associated with overdose and actions that should be taken when someone has overdosed. Interventions designed to reduce the risk of overdose may be more effective if they are differentially targeted on drug injectors who have already experienced an overdose.

Adolescent↗

Comparison of intestinal function in human immunodeficiency virus-seropositive patients in Kampala and London.

BACKGROUND: White homosexual men with human immunodeficiency virus (HIV) show progressive impairment of intestinal function assessed in terms of intestinal permeability and absorptive capacity. In this study we aimed to determine the effects of heterosexually acquired HIV on small-intestinal function in native Africans, among whom there is a high prevalence of tropical enteropathy. METHODS: Intestinal absorptive capacity (using 3-O-methyl-D-glucose, D-xylose, and L-rhamnose) and permeability (differential 5-h urinary excretion of lactulose/L-rhamnose) were assessed in healthy white (n = 57) and black (n = 14) controls in London, apparently healthy black Africans in Kampala, Uganda (n = 26), HIV-infected patients with (n = 9) and without (n = 30) diarrhoea in Kampala, and 39 white homosexual men with HIV in London who were stratified to resemble the African patient group. RESULTS: Intestinal integrity and absorptive capacity were significantly (P < 0.01) impaired in both black controls in London and apparently healthy black Africans, compared with white controls. HIV-infected white and black patients without diarrhoea did not differ significantly from white and black African controls, respectively, with the exception of increased intestinal permeability among the white patients. White and black African patients with HIV/acquired immunodeficiency syndrome (AIDS) and diarrhoea were found to have marked malabsorption and increased intestinal permeability. Although the relative increase in intestinal permeability was similar in the two groups, by far the largest values for intestinal permeability were found among black Africans with HIV/AIDS and diarrhoea. CONCLUSIONS: Whites and blacks differ with regard to intestinal barrier function. HIV-positive black Africans without gastrointestinal symptoms differ insignificantly from white Londoners with homosexually acquired disease, whereas those with gastrointestinal symptoms have markedly abnormal indices of small-intestinal function with severely comprised intestinal integrity.

Acquired Immunodeficiency Syndrome↗