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Biomedical subjects

L Taylor

Publications and source records attributed to L Taylor.

At least 19 recordsLinked to original sources

Microarray and phosphokinase screenings leading to studies on ERK and JNK regulation of connective tissue growth factor expression by angiotensin II 1a and bradykinin B2 receptors in Rat1 fibroblasts.

Rat1 fibroblasts stably transfected with the rat angiotensin II (AngII) AT1a and bradykinin (BK) B2 receptor cDNAs gained the ability to bind Ang II and BK. Wild-type Rat1 cells bound neither ligand. Exposure to either effector led to characteristic Galphai and Galphaq signal cascades, the release of arachidonic acid (ARA), and the intracellular accumulation of inositol phosphates (IP). Microarray analyses in response to BK or AngII showed that both receptors markedly induce the CCN family genes, CTGF (CCN2) and Cyr61 (CCN1), as well as the vasculature-related genes, Cnn1 and Egr1. Real time PCR confirmed the increased expression of connective tissue growth factor (CTGF) mRNA. Combined sequence-based analysis of gene promoter regions with statistical prevalence analyses identified CREB, SRF, and ATF-1, downstream targets of ERK, and JNK, as prominent products of genes that are regulated by ligand binding to the BK or AngII receptors. The binding of AngII or BK markedly stimulated the phosphorylation and thus the activation of ERK2, JNK, and p38MAPK. A BKB2R and an AT1aR chimera which displayed only negligible G-protein-related signaling were constructed. Both mutant receptors continued to activate these kinases and stimulate CTGF expression. Inhibitors of ERK1/2 and JNK but not p38MAPK inhibited the BK- and AngII-stimulated expression of CTGF in cells expressing either the WT or mutant receptors, illustrating that ERK and JNK participate in the control of CTGF expression in a manner that appears to be independent of G-protein. Conversely, addition of BK or AngII to the cell line expressing WT AT1aR and BKB2R downregulated the expression of collagen alpha1(I) (COL1A1) mRNA. However, these effectors did not have this effect in cells expressing the mutant receptors. Thus, a robust G-protein related response is necessary for BK or AngII to affect COL1A1 expression.

Animals↗

Comparison of throat swabs and nasopharyngeal suction specimens in non-sputum-producing patients with cystic fibrosis.

Both throat swabs and nasopharyngeal suction (NPS) specimens are used for microbiological assessment in non-sputum-producing patients with cystic fibrosis (CF), but studies comparing their diagnostic yield are lacking. We, therefore, conducted a prospective study in young CF patients, in which both techniques were performed in random order. Forty-seven consecutive CF children aged 6 months to 10 years were studied during routine visits to the clinic. CF relevant pathogens were found in the majority of patients with no significant differences in the rate of positive cultures for Staphylococcus aureus, Haemophilus influenzae, or Pseudomonas aeruginosa. A statistically significant difference was observed in the rate of detection of other organisms with only 9/47 (19%) of throat swab specimens and 27/47 (57%) of NPS specimens being positive (P = 0.0004). This included 12 positive cultures for Streptococcus pneumoniae and 11 cultures that were positive for Moraxella catarrhalis, both of which are frequent colonizers of the upper airway. Therefore, the most common bacterial pathogens affecting the CF lung appear to be detected in similar frequency by throat swab as by nasopharyngeal suction. There is evidence that nasopharyngeal suction yields more specimens of Streptococcus pneumoniae and Moraxella catarrhalis, which may reflect upper airway colonization rather than lower airway infection. We conclude that nasopharyngeal suction is not routinely warranted as there is no benefit over throat swab in detection of CF pathogens in infants and young children with CF.

Bacteria↗

Clinical governance in practice: closing the loop with integrated audit systems.

Clinical governance has been acknowledged as the driving force behind National Health Service (NHS) reform since the government white paper outlined a new style of NHS in the UK in 1997. The framework of clinical governance ensures that NHS organizations are accountable for continually improving the quality of their services and safeguarding high standards of care by creating an environment in which excellence in clinical care will develop. A major component of a clinical governance framework requires utilizing audit procedures, which assess the effectiveness of current systems and ultimately direct continual quality improvement. This paper describes the audit component of a local clinical governance framework designed for a unit based within an NHS trust, which has utilized a multidisciplinary approach to assess the effectiveness of a newly commissioned service and its impact on the residents and staff. The unit is a 12-bedded, low-secure-intensive rehabilitation unit for clients with severe and enduring mental illness. Using recognized and standardized psychometric outcome measures, information was collected on clinical symptoms, social functioning, social behaviour, quality of life, relationship quality with named nurses and medication side-effects. Additionally, confidential staff measures were included to assess levels of burnout, identify expressed emotion and assess staff perception of models of illness. The paper includes a comprehensive account of how managerial commitment, teaching processes and application of technology ensured prompt data collection and maintained the momentum through the audit timescale. Data analysis and presentation of data in both clinical reviews and in senior management meetings within the unit are discussed. Findings highlight the full integration of the audit system into the processes of the unit. Clinically, the paper highlights the enhancement of the knowledge base of the client group and the influence on clinical decision-making processes and care delivery as a result of the audit. Brief clinical examples are given. In conclusion, the impact of the audit on unit strategy and organizational efficiency are discussed to highlight the importance of closing the audit loop and completing the cycle of clinical governance. The audit system has positive implications for replication in other services.

Commission on Professional and Hospital Activities↗

A pilot study on a cognitive-behavioral asthma self-management program for adults.

The purpose of our research was to design, implement and evaluate a cognitive-behavioral asthma self-management program for adults. Seventeen adults with asthma completed an eight-week course (two hours, once a week) that consisted of interactive small group discussions and a behavior change procedure. The group discussions were led by a multi-disciplinary faculty (nurse, respiratory therapist, allergist, social worker, psychologist). Following each weekly discussion, participants would attempt to change a behavior related to the discussion. At the following meeting, participants would share their results and get feedback from the group; subsequently a new topic was introduced for discussion and a new behavioral change goal was added at the end of the meeting. Primary outcome measurements included asthma related quality of life, peak flow rate and frequency of key lifestyle behaviors. Outcome analyses indicated statistically significant improvements in frequency of: 1) peak flow monitoring; 2) practicing relaxation; 3) drinking 64 ounces of water a day (P < 0.05). Outcome analyses also indicated statistically significant improvements in quality-of-life (QOL) and asthma knowledge (P < 0.05). These results provide evidence that a cognitive-behavioral asthma education program that incorporates a behavior change procedure with interactive group discussions can lead to both knowledge acquisition and behavioral changes. Such outcomes are essential for reducing asthma morbidity and asthma mortality.

Adult↗

Evaluation of urinary PrPSc as a diagnostic test for sporadic, variant, and familial CJD.

Previously collected urine specimens from 100 patients referred to the UK National CJD Surveillance Unit as suspected cases of Creutzfeldt-Jakob disease (CJD) were analyzed, testing for abnormal prion protein (PrP(Sc)). In this context, the test had a low sensitivity and was not completely specific for CJD. Additionally, the proteins detected by this assay were not PrP(Sc) but appeared to be immunoglobulins.

Antibody Specificity↗

Patterns of morbidity and rehospitalisation following spinal cord injury.

STUDY DESIGN: Longitudinal, descriptive design. OBJECTIVES: The aim of this study was to investigate the frequency, cause and duration of rehospitalisations in individuals with spinal cord injury (SCI) living in the community. SETTING: Australian spinal cord injury unit in collaboration with State Health Department. METHODS: A data set was created by linking records from the NSW Department of Health Inpatient Statistics Collection between 1989-1990 and 1999-2000 with data from the Royal North Shore Hospital (RNSH) Spinal Cord Injuries Database using probabilistic record linkage techniques. Records excluded were nontraumatic injuries, age <16 years, spinal column injury without neurological deficit, full recovery (ASIA Grade E) and index admission not at RNSH. Descriptive statistics and time to readmission using survival analysis, stratified by ASIA impairment grade, were calculated. RESULTS: Over the 10-year period, 253 persons (58.6%) required one or more spinal-related readmissions, accounting for 977 rehospitalisations and 15,127 bed-days (average length of stay (ALOS) 15.5 days; median 5 days). The most frequent causes for rehospitalisation were genitourinary (24.1% of readmissions), gastrointestinal (11.0%), further rehabilitation (11.0%), skin-related (8.9%), musculoskeletal (8.6%) and psychiatric disorders (6.8%). Pressure sores accounted for only 6.6% of all readmissions, however, contributed a disproportionate number of bed-days (27.9%), with an ALOS of 65.9 (median 49) days and over 50% of readmissions (33 out of 64) occurred in only nine individuals aged under 30 years. Age, level and completeness of neurological impairment, all influenced differential rates of readmission depending on the type of complication. Overall rehospitalisation rates were high in the first 4 years after initial treatment episode, averaging 0.64 readmissions (12.6 bed-days) per person at risk in the first year and fluctuating between 0.52 and 0.61 readmissions (5.1-8.3 bed-days) per person at risk per year between the second to fourth years, before trending downwards to reach 0.35 readmissions (2.0 bed-days) as 10th year approaches. Time to readmission was influenced by degree of impairment, with significantly fewer people readmitted for ASIA D (43.2%) versus ASIA A, B and C (55.2-67.0%) impairments (P<0.0001). The mean duration to first readmission was 46 months overall, however, differed significantly between persons with ASIA A-C impairments (26-36 months) and ASIA D impairment (60 months). CONCLUSION: Identifying rates, causes and patterns of morbidity is important for future resource allocation and targeting preventative measures. For instance, the late complication of pressure sores in a small subgroup of young males, consuming disproportionately large resources, warrants further research to better understand the complex psychosocial and environmental factors involved and to develop effective countermeasures.

Adolescent↗

Root and stem hydraulic conductivity as determinants of growth potential in grafted trees of apple (Malus pumila Mill.).

The anatomy of the graft tissue between a rootstock and its shoot (scion) can provide a mechanistic explanation of the way dwarfing Malus rootstocks reduce shoot growth. Considerable xylem tissue disorganization may result in graft tissue having a low hydraulic conductivity (k(h)), relative to the scion stem. The graft may influence the movement of substances in the xylem such as ions, water and plant-growth-regulating hormones. Measurements were made on 3-year-old apple trees with a low-pressure flow system to determine k(h) of root and scion stem sections incorporating the graft tissue. A range of rootstocks was examined, with different abilities of dwarfing; both ungrafted and grafted with the same scion shoot cultivar. The results showed that the hydraulic conductivity (k(hroot)) of roots from dwarfing rootstocks was lower compared with semi-vigorous rootstocks, at least for the size class of root measured (1.5 mm diameter). Scion hydraulic conductivity (k(hs)) was linked to leaf area and also to the rootstock on to which it was grafted, i.e. hydraulic conductivity was greater for the scion stem on the semi-vigorous rootstock. Expressing conductivities relative to xylem cross-sectional areas (k(s)) did not remove these differences suggesting that there were anatomical changes induced by the rootstock. The calculated hydraulic conductivity of the graft tissue was found to be lower for grafted trees on dwarfing rootstocks compared to invigorating rootstocks. These observations are discussed in relation to the mechanism(s) by which rootstock influences shoot growth in grafted trees.

Biological Transport↗

Issues and experience around the Paediatric Register of Inflammatory Bowel Disease.

Accurate epidemiological data is one of the most important tools to elucidate disease aetiology and natural history. Disease registers are the cornerstone of this process. The importance of registers in facilitating an efficient health service is clear. We have been engaged in the development of a register of paediatric inflammatory bowel diseases, and in this article we present a general overview of registers and of lessons we have learnt along the way.

Child↗

The funding and organization of infection control in NHS hospital trusts: a study of infection control professionals' views.

The problems associated with hospital-acquired infection have been causing increasing concern in England in recent years. This paper reports the results of a nationwide survey of hospital infection control professionals' views concerning the organizational structures used to manage and obtain funding for control of infection. A complex picture with significant variation between hospitals emerges. Although government policy dictates that specific funding for hospital infection control is formally made available, it is not always the case that infection control professionals have adequate resources to undertake their roles. In some cases this reflects the failure of hospitals' infection control budgetary mechanisms; in others it reflects the effects of decentralizing budgets to directorate or ward level. Some use was made of informal mechanisms either to supplement or to substitute for the formal ones. But almost all infection control professionals still believed they were constrained in their ability to protect the hospital population from the risk of infectious disease. It is clear that recent government announcements that increased effort will be made to support local structures and thereby improve the control of hospital acquired infection are to be welcomed.

Attitude of Health Personnel↗

Identification of a soluble OX40 isoform: development of a specific and quantitative immunoassay.

OX40 (CD134) is a member of the TNF receptor family and is expressed selectively on activated T lymphocytes. Through interactions with OX40 ligand, OX40 delivers potent costimulatory signals to T cells. Here, we describe a sandwich ELISA method for the detection and quantification of OX40 using the monoclonal anti-OX40 antibodies ACT35 and L106 as capture and detecting antibodies, respectively. With this ELISA, the existence of naturally occurring soluble forms of OX40 (sOX40) could be demonstrated for the first time. Soluble OX40 is detectable in serum of subpopulations of healthy donors and patients with autoimmune disease and cancer. Among the five diseases that were investigated, chronic lymphocytic leukemia was identified as the one with the highest frequency of sOX40-positive sera and with the highest mean sOX40 serum concentration. The stability of sOX40 is not affected by repeated freeze/thaw cycles nor by prolonged storage at -20 degrees C, allowing studies on the potential diagnostic significance of sOX40 using existing banks of sera.

Enzyme-Linked Immunosorbent Assay↗

Electroconvulsive thresholds of inbred mouse strains.

The electroconvulsive threshold (ECT) test is used commonly in the screening of anti-epileptic drugs in rodent models, but little is known about its genetic or mechanistic basis. Thresholds for minimal clonic, maximal tonic, or psychomotor (partial) seizures were determined in 16 different inbred mouse strains in two different laboratories. A wide range of thresholds was observed, suggesting that a variety of neuroexcitability alleles exist in inbred strains. Although there was generally good cross-strain correlation between the three seizure types, several outlier strains were detected, showing that genetically encoded differences can affect the ability of a particular seizure type to spread through the brain. Furthermore, the relative seizure susceptibility of a strain was comparable between the two laboratories, suggesting that despite different test sites, instrumentation, and personnel, the ECT assay is portable and that common inbred strains can often be relied upon as calibration standards. Last, the ECT paradigm was also sensitive enough to detect single locus differences, laying the groundwork for mutation screens for new neuroexcitability models.

Animals↗

Isolation and characterization of the promoter region of the rat kidney-type glutaminase gene.

A lambdaEMBL3 rat genomic library was screened to clone a phage that contained the promoter region of the kidney-type mitochondrial glutaminase gene. The resulting lambdaGA1 phage contained 13.7 kb of genomic DNA that was mapped by Southern blotting and restriction analysis. The 2.22 kb and 0.83 kb SacI fragments of lambdaGA1 were sequenced and the transcription initiation site was identified by RNase mapping. The reported sequence contains 2287 bp of the promoter, the entire exon 1 (542 bp), and 223 bp of the initial intron of the glutaminase gene. The initial exon contains 141 bp of 5'-nontranslated sequence and 401 bp of coding sequence that encodes the 72-amino acid mitochondrial targeting presequence and 61 amino acids from the N-terminus of the mature 66 kDa glutaminase subunit. Various segments of the GA promoter were cloned into a chloramphenicol acetyltransferase (CAT) expression vector. The resulting GA-CAT constructs were transfected into LLC-PK(1)-F(+) kidney cells to assess the promoter function of the isolated genomic DNA. The GA(-402)CAT construct produced a 10-fold greater CAT activity than the promoter-less pCAT vector. Analysis of various deletion constructs indicated that elements located between -402 and -63 bp must act in synergy with more proximal elements to create a functional promoter. The initial 402 bp segment lacks a TATA sequence but is GC-rich and contains two CCAAT boxes and two Sp1 sites.

Amino Acid Sequence↗

An investigation into the predictive ability of rehabilitation clinicians.

PURPOSE: There is increasing pressure by providers, purchasers and recipients of service within the United Kingdom for a more accurate prediction of rehabilitation outcomes. The purpose of this research was to investigate how accurately clinicians were predicting rehabilitation outcomes. METHOD: The study was carried out among 47 patients admitted to a general rehabilitation unit. The Functional Independence Measure and Functional Assessment Measure (FAM) were used as the outcome measure. RESULTS: The results showed a statistically significant positive correlation between goal scores and discharge scores as a total population using Spearmans correlation co-efficient. When breaking the sample into an orthopaedic and CVA population, the predictive ability for the orthopaedic population was consistently higher than for the CVA population. CONCLUSIONS: The results of this study suggest that the predictive ability of clinicians is good for the rehabilitation population although the prediction is consistently better with the orthopaedic population than the CVA population.

Adult↗

Evaluation of a portable blood lead analyzer with occupationally exposed populations.

BACKGROUND: This project evaluated a portable electroanalytical instrument that is used to rapidly analyze blood lead levels in individuals, using a fresh whole blood sample (venous). METHODS: Samples were obtained from 208 lead-exposed employees who donated two 2 ml venous blood samples into "lead-free" evacuated tubes. One blood sample was analyzed onsite using the portable field instrument while the second sample was analyzed using graphite furnace atomic absorption spectrometry (GFAAS). RESULTS: According to GFAAS results, employee venous blood lead levels ranged from 1 microg/dl to 42 microg/dl. The mean difference between the results from the field instrument and GFAAS was less than 1 microg/dl. Analysis indicates that the results from the field instrument yielded a slight positive bias overall (P value = 0.0213), with less bias for blood lead levels above 10 microg/dl (P value = 0.0738). CONCLUSIONS: Within the blood range evaluated (1-42 microg/dl), the instrument performed adequately according to Clinical Laboratory Improvements Amendments (CLIA) proficiency requirements. The ability of the instrument to perform rapid analysis makes it potentially valuable to occupational health professionals for medical monitoring or on-site investigations.

Adult↗