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Biomedical subjects

J Holloway

Publications and source records attributed to J Holloway.

At least 19 recordsLinked to original sources
PubMed2006

MUC7 haplotype analysis: results from a longitudinal birth cohort support protective effect of the MUC7*5 allele on respiratory function.

The mucin MUC7 is a glycoprotein that plays a role in bacterial clearance and has candidacidal activity. There are two common allelic forms with 5 or 6 tandem repeats (TR) of a 23 amino acid motif within the highly glycosylated (mucin) domain. The MUC7*5 allele has previously been shown to be less prevalent in patients with asthma, suggesting a protective role in respiratory function. Here we report the characterisation of other frequent genetic variation within and in the vicinity of the gene MUC7. A total of 26 polymorphisms were identified of which 5 are located in transcribed regions. A subset of 8 polymorphisms was selected to represent the major haplotypes, and allelic association was studied in individuals of Northern European ancestry, including known asthmatics. There was low haplotype diversity and strong association between each of the loci, and the MUC7*5 allele-carrying haplotype remained the one most strongly associated with asthma. Five of these polymorphisms have also been tested in the 1946 longitudinal birth cohort, for whom developmental, environmental and respiratory health data are available. We show that the haplotype carrying MUC7*5 is associated with higher FEV1 at 53 years, reduced age-related decline of FEV1, and also reduced incidence of wheeze.

Adolescent↗
PubMed2003

Assessment of white blood cell phagocytosis as an immunological indicator of methylmercury exposure in birds.

White blood cell (WBC) phagocytosis was investigated as a potential immunological indicator of methylmercury (MeHg) exposure in birds. The assay was first assessed using chicken WBCs dosed with MeHg in vitro either in whole blood or as isolated cells and later using blood of wild common loons exposed in vivo to a range of dietary MeHg and having a range of blood-Hg concentrations. Whole blood and isolated WBCs from captive chickens were exposed to a range of MeHg concentrations for 3 h. After MeHg exposure, cells were incubated with fluorescent latex microbeads (diameter = 1.75 microm), fixed, and analyzed for size, complexity, and fluorescent intensity by flow cytometry. MeHg significantly depressed phagocytic activity when added to isolated WBCs at concentrations > 0.01 microg/ml, but not when added to whole blood up to 50 microg/ml. Similarly, no significant relationship between the concentration of Hg in whole blood and phagocytic capacity of WBCs in free-living loons was observed. Our results suggest that the phagocytosis assay, although rapid and convenient for use in field studies with wildlife species, is not a responsive immunological indicator of MeHg exposure at environmentally realistic concentrations of blood-Hg in wild loons. Assays that measure other immunologic endpoints (e.g., bacterial killing assay, PHA skin test, and mitogen-induced lymphocyte proliferation) should be assessed with respect to their ability to detect MeHg immunotoxicity in wild birds.

Animals↗
PubMed2003

Comparison of clevidipine with sodium nitroprusside in the control of blood pressure after coronary artery surgery.

BACKGROUND AND OBJECTIVE: We set out to compare the efficacy of clevidipine and sodium nitroprusside infusions in the control of blood pressure and the haemodynamic changes they produce in hypertensive patients after operation for elective coronary bypass grafting. METHODS: Thirty patients were randomly allocated to receive either clevidipine or sodium nitroprusside after their mean arterial pressure (MAP) had reached > 90 mmHg for at least 10 min in the postoperative period. The MAP was continuously measured and related to time. Thus, the efficacy of the drugs in controlling arterial pressure could be inversely related to the total area under the MAP-time curve outside a target MAP range of 70-80 mmHg normalized per hour (AUC(MAP) mmHg min h(-1)). Haemodynamic variables and the number of dose-rate adjustments required to maintain MAP were also studied. RESULTS: There was no statistically significant difference in the efficacy (AUC(MAP) mmHg min h(-1)) of clevidipine (106 +/- 25 mmHg min h(-1)) compared with sodium nitroprusside (101 +/- 28 mmHg min h(-1)). Nor was any significant difference found in the total number of dose adjustments required to control MAP within the target range. The heart rate in patients receiving clevidipine increased less than in those given sodium nitroprusside. Stroke volume, central venous pressure and pulmonary artery pressure were significantly reduced upon administration of sodium nitroprusside but not of clevidipine. CONCLUSIONS: There was no significant difference between clevidipine and sodium nitroprusside in their efficacy in controlling MAP. The haemodynamic changes, including tachycardia, were less pronounced with clevidipine than with sodium nitroprusside.

Adult↗
PubMed2003

Potentiation of a propargite and fenpyroximate mixture against two-spotted spider mite, Tetranychus urticae (Acari: Tetranychidae).

Using susceptible and resistant reference strains and standard bioassay methods a new miticide product was screened for efficacy and cross-resistance against two-spotted spider mite, Tetranychus urticae Koch. Experimental product NN1 850.0 EW (fenpyroximate and propargite 3:10 ratio) was significantly (P<0.05) more toxic than either compound tested alone (co-toxicity index 1029). Non-overlapping 95% CIs at the LC50 and LC99 level suggest that there is no cross-resistance to NN1 850.0 EW from existing organophosphate and pyrethroid resistance. NN1 850.0 EW is worthy of further development for T. urticae control.

Animals↗
PubMed2001

A randomized controlled trial of the effects of multi-sensory stimulation (MSS) for people with dementia.

OBJECTIVES: To investigate short-term effects of Multi-Sensory Stimulation (MSS) on behaviour, mood and cognition of older adults with dementia, the generalization of effects to day hospital and home environments and the endurance of any effects over time. DESIGN: A randomized controlled trial comparing MSS with a credible control of one-to-one activities. METHODS: Fifty patients with diagnoses of moderate to severe dementia were randomized to either MSS or Activity groups. Patients participated in eight 30-minute sessions over a 4-week period. Ratings of behaviour and mood were taken before, during and after sessions to investigate immediate effects. Pre, mid, post-trial, and follow-up assessments were taken to investigate any generalization of effects on cognition, behaviour at the day hospital and behaviour and mood at home and endurance of effects once sessions had ceased. RESULTS: Immediately after MSS and Activity sessions patients talked more spontaneously, related better to others, did more from their own initiative, were less bored/inactive, and were more happy, active or alert. Both groups were more attentive to their environment than before, with a significantly greater improvement from the MSS group. At the day hospital, patients in the Activity group improved on their 'speech skills' (amount of speech; initiation of speech), whereas the MSS group remained unchanged during the trial. The MSS group showed a significant improvement in mood and behaviour at home compared to the Activity group whose behaviour deteriorated. No longer-term benefits were shown; indeed, behaviour declined sharply during the month follow-up period. CONCLUSIONS: Both MSS and Activity sessions appear to be effective and appropriate therapies for people with dementia.

Acoustic Stimulation↗
PubMed2000

Paraesthesiae and nerve damage following combined spinal epidural and spinal anaesthesia: a pilot survey.

Concern has been expressed that recent changes in techniques of spinal blockade may have resulted in an increase in frequency of neurological sequelae. In order to make preliminary enquiries about anaesthetists' recent experiences of neurological sequelae following spinal and combined spinal-epidural anaesthesia, a questionnaire, covering numbers of procedures, needles used and any neurological problems that had been encountered, was sent to the anaesthetist in charge of each obstetric centre on the Royal College of Obstetricians and Gynaecologists' United Kingdom list. Replies were received from 222 of the 259 units, of whom 40 reported a total of 56 cases involving prolonged neurological sequelae, of which nine were probable obstetric palsies, 18 could be attributed to the regional procedure (one instance of conus damage and the rest largely sensory disturbances) and 29 were of uncertain origin, including a second conus damage. There was no obvious difference in incidence of problems associated with combined spinal-epidural vs. the single-shot spinal technique (odds ratio 1.14, confidence interval 0.53 to 2.46), or Sprotte vs. Whitacre atraumatic needle (odds ratio 1.40, confidence interval 0.64 to 3.08). A prospective survey, or better still, randomisation would be needed to verify these findings.

Journal Article↗
PubMed2000

Human ERRgamma, a third member of the estrogen receptor-related receptor (ERR) subfamily of orphan nuclear receptors: tissue-specific isoforms are expressed during development and in the adult.

The nuclear receptor protein superfamily is a large group of transcription factors involved in many aspects of animal development, tissue differentiation, and homeostasis in the higher eukaryotes. A subfamily of receptors, ERRalpha and beta (estrogen receptor-related receptor alpha and beta), closely related to the ER, were among the first orphan nuclear receptors identified. These receptors can bind DNA as monomers and are thought to activate transcription constitutively, unaffected by beta-estradiol. Studies of the expression patterns of ERRalpha and gene disruption experiments of ERRbeta indicate that they play an important role in the development and differentiation of specific tissues in the mouse. In this work we demonstrate the existence in humans of a third member of this subfamily of receptors, termed ERRgamma, which is highly expressed in a number of diverse fetal and adult tissues including brain, kidney, pancreas, and placenta. The ERRgamma mRNA is highly alternatively spliced at the 5'-end, giving rise to a number of tissue-specific RNA species, some of which code for protein isoforms differing in the N-terminal region. Like ERRalpha and beta, ERRgamma binds as a monomer to an ERRE. A GAL4-ERRgamma fusion protein activates transcription in a ligand-independent manner in transfected HEK293 cells to a greater degree than either the GAL4-ERRalpha or -beta fusion proteins.

Adult↗
PubMed2000

Positive urine nitrite test: an accurate predictor of absence of pure enterococcal bacteriuria.

BACKGROUND: The aim of this study was to determine the potential ability of the urine nitrite test (NT) to predict the class of organism causing urinary tract infection. METHODS: We retrospectively reviewed the records of all adult patients with a positive urine culture over a 6-month period. The infecting microorganisms and the urine NT results were recorded. RESULTS: A total of 729 positive cultures met inclusion criteria. Twenty-one (11%) of the 190 gram-positive organisms and 199 (46%) of the 429 gram-negative organisms yielded a positive NT. Only 5.3% of samples with pure growth of enterococcus yielded a positive NT. The predictive value that a sample yielding a positive NT would show pure growth of enterococcus was low at 2.3%. CONCLUSION: A positive NT is highly predictive of the absence of pure enterococcal bacteriuria.

Adolescent↗
PubMed1999

Health status of juvenile offenders. A survey of young offenders appearing before the juvenile courts.

This paper reports on the health needs of a sample of juvenile offenders appearing before a Manchester Court during the month of August 1992. Of the 192 subjects interviewed (74% of those listed), 19% had significant medical problems, 42% a history of substance abuse and 7% psychiatric problems requiring further treatment. Substantial numbers (26%) engaged in a variety of dangerous behaviours. Custodial remands were common (21%), particularly in those with multiple psychosocial difficulties.

Adolescent↗
PubMed1999

Markers of inappropriate placement in acute psychiatric inpatient care: a five hospital study.

BACKGROUND: Previous researchers in the UK have measured the prevalence of the 'inappropriateness' of acute adult psychiatric inpatient placements by eliciting the judgements of health professionals. We extended the methodology by identifying inpatient sub-groups with stable characteristics that were associated with elevated risk of inappropriate placement, and by calculating the level of that risk. METHODS: A 1-day census was taken in five hospitals. Using a structured instrument, consultant psychiatrists recorded judgements on current placements, recommended alternative placements and stated why alternatives had not been used. Judgements were obtained for 100% of the 261 inpatients. Risk ratios and adjusted odds ratios were calculated to identify sub-groups that were at high risk. RESULTS: Eighty-eight inpatients were inappropriately placed, a point prevalence of 34% (95% CI 28-40%). Consultants recorded that services outside hospital, if available, could have supported most of these inpatients as an alternative to at least part of their hospital stay. Diagnostic rather than socio-demographic or administrative characteristics, in particular primary diagnoses of substance-related disorder, personality disorder, anxiety/stress, and schizophrenia with co-morbid substance misuse, were the strongest markers of elevated risk. CONCLUSIONS: The point prevalence of inappropriate placement within the British mental health-care system is considerable. Diagnostic categories are reasonable pragmatic markers. Further research should aim to identify a strong marker of risk within the numerically large sub-group of schizophrenia without substance misuse.

Adolescent↗
PubMed1999

Analysis of two IL-4 promoter polymorphisms in a cohort of atopic and asthmatic subjects.

The Th2 cytokine interleukin 4 (IL-4) has been identified as having a central role in driving the inflammatory immune responses which are present in atopic airway disease. This study examined the distribution of two putative IL-4 promoter polymorphisms (-285 C-T and -81 A-G) in groups of patients with severe and moderate asthma, non-asthmatic atopy and control subjects. Neither polymorphism was identified in any of the samples tested. The data suggest that either the polymorphisms are present at very low frequencies or are artefacts of the B cell lines from which they were identified.

Adult↗
PubMed1999

Interleukin-5 production by human airway epithelial cells.

Interleukin (IL)-5 is a pleiotropic cytokine that exhibits biologic activity on cells of diverse hemopoieitic lineages. IL-5 enhances mediator release from human basophils and plays a pivotal role in the chemoattraction, proliferation, differentiation, survival, and activation of eosinophils. Th2- and Tc2-like T cells, mast cells, basophils, and eosinophils are the known cellular sources of this cytokine. Using a sensitive and novel reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay system, we found that IL-5 messenger RNA (mRNA) was constitutively expressed in bronchial biopsies obtained from healthy individuals, and that the levels of IL-5 mRNA expression decreased 1. 5 h after exposure to 0.12 ppm ozone for 2 h. Because the oxidative effects of ozone are confined to the epithelial cell surface and it is known that ozone induces epithelial damage and shedding, we hypothesized that epithelial cells might be a source of IL-5 mRNA. We demonstrate here that both transformed human bronchial epithelial cell lines (A549 and 16HBE14o-) and primary human bronchial and nasal epithelial cells grown in culture constitutively express IL-5 mRNA, which is upregulated on stimulation with tumor necrosis factor (TNF)-alpha. Culture supernatants derived from A549 cells exposed to TNF-alpha and interferon-gamma demonstrated detectable levels of IL-5 protein, and immunostaining of bronchial biopsies obtained from healthy human airways revealed the presence of IL-5 protein localized to the bronchial epithelium. To our knowledge, this is the first report demonstrating IL-5 production by human airway epithelial cells. This observation provides further evidence for the role of airway epithelium in regulating airway immune responses, in particular enhancing chemotaxis, activation, and survival of eosinophils, which could play an important role in the pathogenesis of bronchial asthma.

Adult↗
PubMed1998

Immunoregulatory networks in asthma.

It is now well established that a subset of T-cell-derived cytokines (termed Th2 cytokines) programme the timing and characteristics of atopic airway disease including mast-cell sensitization, eosinophil and lymphocyte infiltration and recently mucus secretion. To date, attempts to devise ways to selectively limit the activities of Th2 cytokine-producing cells have been frustrated. However, the recent identification of the molecules which direct the activation and maturation of T cells has led to some successful attempts to block the activities of Th2 cells in models of atopic airway inflammation. Some of the agents with the most potential include antagonists of the T-cell costimulatory molecule CD28, local stimulators of the Thl subset of cytokines such as the BCG vaccine and potentially, antagonists of the eotaxin chemokine receptor and agonists of the T-cell costimulatory molecule CTLA-4. Not only do such agonists and antagonists represent potential new therapies, they could represent a rich hunting ground for those who aim to determine the ways in which atopic airway disease can be diagnosed and understood.

Abatacept↗
PubMed1998

Experiences and career intentions of general practice registrars from The Netherlands.

For some years prospective general practitioners (GPs) from the Netherlands have come to Britain to complete their training. Not all report enjoying their time here, and many leave this country after training. The aim of this study was to examine reasons for coming to Britain, experiences, perceptions and career intentions. The sample consisted of 14 general practice registrars working in their practice year in Southern England. Data were collected through in-depth semistructured interviews and analysed by thematic qualitative analysis. The main reasons for training in this country were easier access, a quicker route to specialization and the quality of training provided. Most had positive professional and personal experiences and saw the British system of training GPs as up to date and supportive of their educational and professional needs. They highlighted some of the positive aspects of the British system, such as the emphasis on teamwork and collaboration with other primary care professionals. They did, however, point out problems and conflicts; for instance, they saw the health care system in Britain as more bureaucratic and as providing unequal access for different groups of the population. Despite their fear of litigation, which they saw as one of the drawbacks for British general practitioners, most looked favourably on the option of staying in or returning to this country if possible. All registrars valued their stay in Britain; however, personal circumstances often dictated a return to Holland. Our findings have implications for manpower planning and recruitment for general practice in both Britain and Holland.

Attitude of Health Personnel↗
PubMed1998

Churg-Strauss syndrome associated with zafirlukast.

In recent years, the leukotriene modifiers, a new class of drugs, have become commercially available as a promising medication for asthma. According to the 1997 National Institutes of Health guidelines, the leukotriene modifiers are indicated in mild persistent asthma as an alternative to inhaled steroids. Nonetheless, they have been used in patients with moderate and severe asthma and, in some cases, they have made it possible for patients to taper or discontinue their use of oral steroids, thereby controlling their asthma while avoiding the side effects of oral corticosteroids. Since the introduction of zafirlukast, there have been reported at least eight cases of Churg-Strauss syndrome, a granulomatous, necrotizing vasculitis with eosinophilia, associated with the use of zafirlukast. No other leukotriene modifier has yet to be associated with the syndrome. All the patients in whom Churg-Strauss syndrome developed were patients with asthma who were taking zafirlukast and were being weaned from oral corticosteroids. Reported here is a case of Churg-Strauss syndrome in a patient referred to the authors. Included is a review of the literature of the association of Churg-Strauss syndrome and zafirlukast therapy.

Adult↗
PubMed1996

The psychosocial characteristics of juvenile sexual offenders referred to an adolescent forensic service in the UK.

Criminal statistics indicate that a high percentage of sexual offences are committed by perpetrators under the age of 18 years. Descriptive data based on a retrospective case note study of 121 juvenile sexual offender referrals to an adolescent forensic unit are presented. The results suggest that adolescents commit an array of offences and present with generalized adjustment difficulties. Conduct disorder was the most common diagnosis, while rates of mental illness were lower than in earlier studies. Abused as opposed to non-abused offenders experienced more dysfunctional upbringings and demonstrated higher rates of personal disturbance. Theoretical and treatment implications are discussed in relation to the available literature on adolescent sexual offending.

Adolescent↗