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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 37 records · Page 2Linked to original sources

Measles immunity testing: comparison of two measles IgG ELISAs with plaque reduction neutralisation assay.

Two commercial IgG ELISAs, one based on recombinant nucleocapsid antigen and one based on cell culture grown native virus antigens, were evaluated for measles immunity testing by comparison with plaque reduction neutralisation test (PRNT). Qualitative results of the two ELISAs showed 92% agreement with those of PRNT. The sensitivity of the two ELISAs was 89.6%. False negative ELISA results were obtained in 10% of sera, mainly sera containing low levels of neutralising antibody. The specificity of both ELISAs was 100%. Measles IgG ELISAs perform adequately for immunity testing, correctly identifying seronegative individuals for vaccination.

Antibodies, Viral↗

Small threat and contraband detection with TNA-based systems.

The detection of small threats, such as explosives, drugs, and chemical weapons, concealed or encased in surrounding material, is a major concern in areas from security checkpoints to UneXploded Ordnance (UXO) clearance. Techniques such as X-ray and trace detection are often ineffectual in these applications. Thermal neutron analysis (TNA) provides an effective method for detecting concealed threats. This paper shows the effectiveness of Ancore's SPEDS, based on TNA, in detecting concealed liquid threats and differentiating live from inert mortar shells.

Chemical Warfare↗

Proposal for genetic characterisation of wild-type mumps strains: preliminary standardisation of the nomenclature.

Though mumps virus (MuV) is a monotypic virus, genetic variation between strains has been described. Viruses have been placed into genotypes designated A-L based on the nucleotide sequence of the small hydrophobic (SH) gene, which is the most variable gene in the mumps genome. Molecular characterisation of MuV is an important component of mumps surveillance because it can help identify the transmission pathways of the virus as well as distinguish between wild-type and vaccine strains. Here, we propose a standardized nomenclature and an analysis protocol for the genetic characterisation of mumps strains to facilitate expansion of molecular epidemiological studies. In addition to assigning standard reference strains for the recognized genotypes of MuV, a convention is proposed for naming for strains and criteria to designate a new genotype.

Humans↗

Effect of different immunisation schedules on the excretion and reversion of oral poliovaccine strains.

Excretion of live oral poliovaccine and molecular markers of increased virulence in the viruses isolated were examined in children who were either previously immunised with inactivated or live vaccine or were unimmunised. There appeared to be some effect of previous immunisation with either live or killed vaccine at the second dose of live vaccine. Where an effect was seen it took the form of reduced rates of excretion, shorter time periods of excretion and more rapid and complete reversion of the excreted virus. The data are consistent with the view that poliovirus is able to escape the immune pressure in the gut to some extent by improving its general fitness rather than direct evasion of immunity.

5' Untranslated Regions↗

An airport cargo inspection system based on X-ray and thermal neutron analysis (TNA).

A cargo inspection system incorporating a high-resolution X-ray imaging system with a material-specific detection system based on Ancore Corporation's patented thermal neutron analysis (TNA) technology can detect bulk quantities of explosives and drugs concealed in trucks or cargo containers. The TNA process utilises a 252Cf neutron source surrounded by a moderator. The neutron interactions with the inspected object result in strong and unique gamma-ray signals from nitrogen, which is a key ingredient in modern high explosives, and from chlorinated drugs. The TNA computer analyses the gamma-ray signals and automatically determines the presence of explosives or drugs. The radiation source terms and shielding design of the facility are described. For the X-ray generator, the primary beam, leakage radiation, and scattered primary and leakage radiation were considered. For the TNA, the primary neutrons and tunnel scattered neutrons as well as the neutron-capture gamma rays were considered.

Aircraft↗

Atypical anti-psychotics in the real world--a naturalistic comparative outcome study.

BACKGROUND: There are few real life independent comparative studies of atypical antipsychotics. We prospectively examined five commonly used atypical antipychotics in the UK, without support from the pharmaceutical industry. METHOD: Prospective naturalistic systematic clinical evaluation. Patients being newly prescribed atypical anti-psychotics over a one year period were assessed by psychiatrists at initiation and after six months treatment using five outcome measures: clinical global impression; positive and negative psychotic symptoms; drug related side effects; and quality of life. RESULTS: 373 patients participated in total. Olanzapine and risperidone produced statistically significant reductions in all ratings at six months. Amisulpride, clozapine, and quetiapine were also studied. There was limited variance between the different drugs, although some sample sizes were small. CONCLUSION: Atypical anti-psychotics were found to be clinically effective, and produced similar outcomes. Routine monitoring of outcomes in psychiatry is feasible.

Adolescent↗

Investigation of human contacts: a Mycobacterium bovis outbreak among cattle at a California dairy.

BACKGROUND: In May 2002, a Mycobacterium bovis outbreak occurred among cattle at a California dairy. We investigated to determine whether persons were infected after working with the cattle or drinking their raw milk. METHODS: We identified persons with potential contact with infected cattle, including dairy workers, their family members, and slaughterhouse workers. Persons were given a tuberculin skin test (TST), and their occupational and milk-drinking habits were recorded. RESULTS: Of 88 potential contacts, 78 (90%) were given a TST; 33 (43%) had positive TST results, of whom 32 were Mexican-born (RR 15.8, 95%CI 2.3-108.8). No persons had active tuberculosis. Eighteen (72%) dairy workers, 11 (27%) family members, and four (33%) slaughterhouse workers had positive TST results. After adjusting for Mexican-birth and age, dairy workers were no more likely to have positive TST results than others (adjusted RR 1.2, 95%CI 0.6-2.1). Forty-one (62%) dairy staff and their family members drank raw milk from the dairy; 21 (51%) had positive TST results and were Mexican-born. All 13 US-born raw milk drinkers had negative TST results. CONCLUSION: A high prevalence of positive TST results was documented among workers at the affected dairy, although results were not independently associated with contact with infected cattle or milk products. Further assessment of California dairy workers should be considered.

Agricultural Workers' Diseases↗

Measurement of the generalized forward spin polarizabilities of the neutron.

The generalized forward spin polarizabilities gamma(0) and delta(LT) of the neutron have been extracted for the first time in a Q2 range from 0.1 to 0.9 GeV2. Since gamma(0) is sensitive to nucleon resonances and delta(LT) is insensitive to the Delta resonance, it is expected that the pair of forward spin polarizabilities should provide benchmark tests of the current understanding of the chiral dynamics of QCD. The new results on delta(LT) show significant disagreement with chiral perturbation theory calculations, while the data for gamma(0) at low Q2 are in good agreement with a next-to-leading-order relativistic baryon chiral perturbation theory calculation. The data show good agreement with the phenomenological MAID model.

Journal Article↗

Q2 evolution of the neutron spin structure moments using a 3He target.

We have measured the spin structure functions g(1) and g(2) of 3He in a double-spin experiment by inclusively scattering polarized electrons at energies ranging from 0.862 to 5.058 GeV off a polarized 3He target at a 15.5 degrees scattering angle. Excitation energies covered the resonance and the onset of the deep inelastic regions. We have determined for the first time the Q2 evolution of Gamma(1)(Q2)= integral (1)(0)g(1)(x,Q2)dx, Gamma(2)(Q2)= integral (1)(0)g(2)(x,Q2)dx, and d(2)(Q2)= integral (1)(0)x(2)[2g(1)(x,Q2)+3g(2)(x,Q2)]dx for the neutron in the range 0.1< or =Q2< or =0.9 GeV2 with good precision. Gamma(1)(Q2) displays a smooth variation from high to low Q2. The Burkhardt-Cottingham sum rule holds within uncertainties and d(2) is nonzero over the measured range.

Journal Article↗

Multi-layer compression: comparison of four different four-layer bandage systems applied to the leg.

OBJECTIVE: To compare performance of four commercial four-layer bandage systems when applied to the leg. METHODS: Four experienced bandagers applied each system: [Profore Regular (Smith and Nephew); Ultra-Four (Robinson); System 4 (Seton) and K Four (Parema)] to the same leg. Bandages were applied as single layers and as completed systems using standard techniques. For each application, 18 pressure measurements were taken using the Borgnis Medical Stocking Tester (MST) at three measuring points (ankle, gaiter and mid-calf) on medial and lateral aspects in three postures: (horizontal, standing and sitting). RESULTS: In all 2304 observations were made, 576 for each bandager, 576 for each bandaging system, 768 for each measuring point, 1152 for each aspect and 768 for each posture. The increase in pressure produced by each additional layer was 65-75% of the pressure of the same bandage when used as a single layer. There were significant differences in the final pressures achieved by the bandagers (means: 45-54 mmHg, p<0.001) and between bandage systems (means: System 4: 46 mmHg, Profore: 47 mmHg, K Four: 52 mmHg, Ultra-Four: 54 mmHg; p=0.005). The relationships between the final pressures achieved at each of the three measuring points, the three postures and the two aspects were not consistent among the bandage systems (p<0.01). CONCLUSIONS: When a bandage is applied as part of a multi-layered system it exerts approximately 70% of the pressure exerted when applied alone, thus challenging the commonly-held assumption that the final pressure achieved by a multi-layer bandaging system is the sum of the pressures exerted by each individual layer. Each of the four bandaging systems exerted different final pressures and gradients and different changes with posture change. These differences have important implications, which could influence the selection (or avoidance) of a particular bandage system according to a patient's condition and circumstances.

Bandages↗

The public health response to a case of Lassa fever in London in 2000.

OBJECTIVES: Evaluation of the Department of Health 1996 guidance, the Memorandum on the Management and Control of Viral Haemorrhagic Fevers. METHODS: Description of the public health management in 2000 of the fifth UK patient confirmed to have Lassa fever. RESULTS: Delayed risk categorisation of the patient occurred for a variety of reasons. DH Guidance was followed once infection control advice was sought. Active surveillance of 125 contacts was extremely resource intense, involving over 3000 communications. Self-monitoring by healthcare workers should be considered in future. Advice on use of ribavirin prophylaxis is not included in the Memorandum, nor advice or templates for information sheets for contacts. Information sheets are now available from the Health Protection Agency in the event of future cases. International aspects not adequately addressed include the need for reliable risk assessment to be carried out before patients are medically evacuated from the country of origin, and the steps required to repatriate UK nationals. Effective and efficient communication is required between national and international organisations involved in such incidents. CONCLUSIONS: If guidelines are unclear or impracticable they will not be followed. It is important that lessons are learned and documented and that national guidance be regularly reviewed.

Communicable Disease Control↗

Oxytocin neurones are recruited into co-ordinated fluctuations of firing before bursting in the rat.

Hypothalamic oxytocin neurones have dual physiological functions with associated characteristic activity patterns: a homeostatic osmoregulatory role involving continuous low frequency firing at a relatively constant rate, and roles associated with reproduction involving periodic, brief, synchronised, high frequency bursts of spikes. Apparently the same neurones maintain both roles during reproduction, when both activity patterns occur simultaneously, although sometimes factors linked to the homeostatic response predominate and prevent bursting. With the object of understanding how oxytocin neuronal networks manage both roles during lactation, we analysed basal activity between bursts in simultaneously recorded neurones to reveal potentially adaptive changes in network behaviour. Negative autocorrelation on a time scale of 0.5-2 s occurs in basal activity between bursts but also in non-bursting oxytocin neurones, and can therefore be associated with the system's homeostatic role. Although the system responds to the pups suckling by the induction of bursting, there are also increasing fluctuations in firing that are positively correlated in some simultaneously recorded neurones during basal activity between bursts. A few seconds before bursts, cross-correlation strengthens, irregularity of firing increases, and serial correlation (autocorrelation) weakens, all substantially. After pharmacological treatments known to facilitate bursting, cross-correlation and irregularity of firing increase and autocorrelation weakens, and the reverse occurs in conditions that delay bursting (hyperosmotic stress and pharmacological interventions). Our analyses suggest heterogeneity in the population of oxytocin neurones during lactation; the range including 'leader neurones' that readily display co-ordinated fluctuations in firing in response to suckling and escape from negative autocorrelation just before bursts, and 'follower neurones' that fire at a relatively constant rate in no apparent relationship to others, except when recruited late to bursting, probably in response to massive stimulation from already bursting neurones. The steep increases in correlation a few seconds before bursts reflect an accelerating process of recruitment of follower neurones to co-ordinated fluctuations, leading to the phase transition that constitutes the critical stage of burst generation.

Acetylcholine↗

Psychostimulants and delirium in patients receiving palliative care.

The use of psychostimulants to relieve opioid-induced drowsiness and symptoms of depression in medically ill patients has become increasingly established in North America. The role of psychostimulants in the care of patients receiving palliative care is beginning to be debated in the United Kingdom both in the hospice and hospital setting. Delirium has been well defined and reported as a significant problem in populations of patients receiving palliative care. Two case histories are presented to illustrate the potential benefit of psychostimulants in hypoactive delirium.

Aged↗

The LILR family: modulators of innate and adaptive immune pathways in health and disease.

Leukocyte immunoglobulin (Ig)-like receptors [LILRs, also known as Ig-like transcripts (ILTs)] are a family of inhibitory and stimulatory receptors encoded within the leukocyte receptor complex and are expressed by immune cell types of both myeloid and lymphoid lineage. Several members of the LILR family recognize major histocompatibility complex class I. The immunomodulatory role of LILR receptors indicates that they may exert an influence on signaling pathways of both innate and adaptive immune systems. LILR activity can also influence the antigen-presenting properties of macrophages and dendritic cells and may thus play a role in T-cell tolerance. The wide-ranging effects of LILR signaling on immune cell activity imply that these receptors are likely to play an important role in a range of clinical situations including pregnancy, transplantation, and arthritis (including the human leukocyte antigen B27-associated spondyloarthropathies). In this review, we summarize current knowledge on the nature and function of LILRs, focusing on their regulation of immune cell activity and their potential role in disease.

Animals↗

Modelling the pituitary response to luteinizing hormone-releasing hormone.

The pituitary response to luteinizing hormone-releasing hormone (LHRH) is steroid-dependent and varies throughout the reproductive cycle, but the rapid rise in pituitary sensitivity on the day of the ovulation-inducing LH surge is due to a 'self-priming' effect of exposure to LHRH that results in a potentiation of pituitary responsiveness 35-40 min later. The expression of this effect is itself steroid-dependent, and is most marked on pro-oestrus. Here, a model of LHRH-induced LH release was developed to incorporate the changes in pituitary sensitivity observed throughout the reproductive cycle. LH release is based on the Law of Mass Action, and a component related to self-priming is included in the model, incorporating the delay between initial exposure and potentiation of responsiveness and an upper maximum to the achievable level of priming. Where possible, model parameters were obtained from biological values, otherwise they were optimized to fit an experiment performed in vivo. These parameters were then used to test the model against other experimental data obtained both in vivo and in vitro. The model provided a good fit to the in vivo data but the in vitro experimental data required a change in one parameter, the upper limit of priming. We conclude that this model of the pituitary release mechanism can simulate the changes in pituitary responsiveness throughout the reproductive cycle. We suggest that substitution of this model in a previous model of the LHRH pulse generator could allow more appropriate tests of the LHRH pulse generator model.

Animals↗

Increased breakthrough bleeding during prophylaxis with B-domain deleted factor VIII--a robust meta-analytic finding.

Meta-analyses of observational studies have become increasingly common to support evidence-based clinical decisions. We analyzed currently available clinical studies of full-length factor VIII (FL-FVIII) vs. B-domain deleted recombinant factor VIII (BDD-rFVIII) using a random effects model to investigate possible differences in clinical efficacy in patients treated during prophylaxis. Some studies reported breakthrough bleeding incidence as mean annual total bleeds, whereas others reported median bleeds. In accord with the consensus recommendations by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group, all available studies where included. For analysis, data were combined by converting median to mean annual total bleeds using a conversion factor of 2.6, based on clinical data previously compiled by the Universal Data Collection Program of the U.S. Centers for Disease Control and Prevention. To evaluate the sensitivity of our model upon the choice of conversion factor, we re-estimated incidence rate ratios for breakthrough bleeding over a wide range of conversion factors from 1.4-2.6. Even at the lowest extreme conversion factor of 1.4, bleeding incidence was statistically higher in patients treated with BDD-rFVIII compared with FL-FVIII. We also examined the impact of reported patient age on our multivariate model. Exposure to BDD-rFVIII remained an independent predictor of bleeding, regardless of patient age at start or mean age during prophylaxis. These analyses further support the robustness of our meta-analysis and its conclusions.

Age Factors↗

Meta-analytic evidence of increased breakthrough bleeding during prophylaxis with B-domain deleted factor VIII.

A recent meta-analysis of 13 observational studies suggested reduced haemostatic efficacy during prophylaxis and shortened half-life of B-domain deleted factor VIII (BDD-rFVIII) as compared with full-length factor VIII (FL-FVIII). The meta-analysis included a multivariate model that took both dose and age into account. In addition, several assumptions and interpretations were required in order to conduct the meta-analysis. It is important to test the impact of such assumptions and interpretations through sensitivity analysis. In the published meta-analysis, results of several sensitivity analyses were described involving the effect of study design; heterogeneity of subjects in some studies; type of assay used for half-life determinations; and year of publication. In two subsequent brief reports, additional sensitivity analyses addressed choice of median-to-mean conversion factor over a wide range of scenarios and use of age at start of prophylaxis vs mean age during prophylaxis in the multivariate model. A recognized inherent difficulty in the meta-analysis of multiple published reports from similar studies is the possibility of some subject or data overlap. Therefore, the present communication details further sensitivity analyses encompassing assumptions regarding the possibility of subject duplication in a subgroup of subjects from one study and possible duplication of pharmacokinetic data from two smaller studies within the reports of two larger studies. All the sensitivity analyses support the main conclusions of the meta-analysis, namely, that BDD-rFVIII substantially increases the risk of breakthrough bleeding during prophylaxis, possibly at least partly because of shorter half-life than that of FL-FVIII.

Data Interpretation, Statistical↗

An assessment of dose-uniformity of samples delivered from paediatric oral droppers.

BACKGROUND AND OBJECTIVES: To assess the accuracy and precision of delivery from containers containing oral drops, both under optimal laboratory conditions and during use by volunteers using a variety of real pharmaceutical products and specially prepared fluids. METHODS: The effects of the physical properties (viscosity, surface tension, fluid density) of fluids and the angle of a dropper upon the accuracy and precision of dispensing were investigated under standard laboratory conditions. Dose delivery was then assessed using a number of volunteers who were either given no instructions on the use of containers or were instructed to hold the droppers vertically. RESULTS: Viscosity, surface tension, fluid density and residual volume had little or no effect upon the volume of liquid delivered by a dropper clamped in the vertical position. However, when the angle of the dropper was moved towards 45 degrees from the vertical, the volume dispensed declined and became more variable to a point where the requirements of the European Pharmacopoeia were no longer fulfilled. This finding applied to a variety of products. When volunteers used the same droppers manually, the mean volumes dispensed were lower than when the droppers were vertically clamped and the variability was greater. It appeared that these problems were associated with volunteers failing to hold the dropper vertically and the precision and accuracy were indeed increased if the volunteers were instructed as to how the dropper should be held. The results from volunteers were more precise and accurate with the most viscous of the fluids tested and it was speculated that this may have been because the volunteers could more easily use the droppers vertically as there was less fear of dispensing too many drops. CONCLUSIONS: The key factor in achieving satisfactory dispensing from droppers is to ensure that the dropper is held vertically and this should form the basis of instructions to patients. Formulators should consider increasing the viscosity of prepared dropper solutions to reduce further errors in dose.

Administration, Oral↗