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Biomedical subjects

J Lawson

Publications and source records attributed to J Lawson.

At least 19 recordsLinked to original sources
PubMed2005

Benign paroxysmal positional vertigo: clinical characteristics of dizzy patients referred to a Falls and Syncope Unit.

BACKGROUND: Dizziness is a common symptom in older people that affects quality of life and increases the risk of falls. Benign paroxysmal positional vertigo (BPPV) is a common cause of dizziness that increases in prevalence with age, and is potentially curable. AIM: To compare patients with BPPV referred initially to a Falls and Syncope Unit (FSS group) with those initially referred to a Regional ENT/Balance Service (ENT group). DESIGN: Retrospective case-note review. METHODS: Medical notes, investigations and outcomes were reviewed for all patients. RESULTS: Of 59 patients with BPPV confirmed by Dix-Hallpike test, 31 (53%) were initially referred to the FSS (2.6 patients per month, 71% females) and 28 (47%) were initially referred to ENT (4.7 patients per month, 86% females). Compared to those referred initially to ENT, FSS patients were significantly older (mean +/- SD 69 +/- 13 vs. 55.4 +/- 13 years, p = 0.0003) and had dizzy symptoms for longer before diagnosis (median (range) 12 (4-120) vs. 6 (1-36) months, p = 0.0273). FSS patients were more likely to have more than one type of dizziness (16% vs. 0%, p = 0.001), more likely to have cerebrovascular or cardiovascular co-morbidity (13% vs. 4%, p = 0.0152) and were taking significantly more medications (3.2 vs. 1.7; p = 0.0271). Cure rates on intervention were similar (83% FSS, 86% ENT). DISCUSSION: BPPV is a potentially curable cause for dizziness in older people. Older people are frequently referred directly to Falls units, who will be seeing increasing numbers of patients with dizziness. A high index of suspicion allows early identification and treatment of this condition.

Accidental Falls↗
PubMed2005

Work stress and physical assault of nursing aides in rural nursing homes with and without dementia special care units.

PURPOSE: This study compared nursing aides (NAs) employed in rural nursing homes with and without dementia special care units (SCUs) on (1) exposure to and distress from disruptive behaviours exhibited by residents, (2) job strain and (3) physical assault. DESIGN AND METHODS: The data were drawn from a larger study conducted in Saskatchewan, Canada, in which all rural nursing homes of < or = 100 beds that had an SCU were matched to same-sized rural facilities with no SCU. Nursing aides (n = 355) completed a mailed survey questionnaire. RESULTS: Nursing aides employed in nursing homes with an SCU reported significantly less frequent exposure to disruptive behaviours (including aggressive and aversive behaviours) than NAs in non-SCU facilities, less distress when these behaviours were directed toward them, less exposure to aggressive behaviour during caregiving, lower job demands and lower job strain. There was a trend toward increased risk of being assaulted in the last year associated with being in a non-SCU facility. Having a permanent position, increased job strain, and feeling inadequately prepared for dementia care were significantly associated with higher risk of being assaulted. In the SCU facilities, NAs who worked more time on the SCU reported more assaults but less distress from disruptive behaviour, lower psychological job demands, lower job strain and greater work autonomy. IMPLICATIONS: Providing more dementia care training and reducing job demands and job strain may help to reduce work-related stress and physical assault of nursing aides employed in nursing homes.

Adult↗
PubMed2004

Validation of the Alder Hey Triage Pain Score.

AIMS: To describe the validation and reliability of a new pain tool (the Alder Hey Triage Pain Score, AHTPS) for children at triage in the accident and emergency (A&E) setting. METHODS: A new behavioural observational pain tool was developed because of dissatisfaction with available tools and a lack of confidence in self-assessment scores at triage. The study was conducted in a large paediatric A&E department; 575 children (aged 0-16 years) were included. Inter-rater reliability and various aspects of validity were assessed. In addition this tool was compared to the Wong-Baker self-assessment tool. The children were concurrently scored by a research nurse and triage nurses to assess inter-rater reliability. Construct validity was assessed by comparing the research nurse's triage score with the research nurse reassessment score after intervention and/or analgesia. Known group construct validity was assessed by comparing the research nurse's score at triage with the level of pain of the condition as judged by the discharge diagnosis. Predictive validity was assessed by comparing the research nurse's AHTPS with the level of analgesia needed by each patient. The AHTPS was also compared to a self-assessment score. RESULTS: A high level of inter-rater reliability, kappa statistic 0.84 (95% CI 0.80 to 0.88), was shown. Construct validity was well demonstrated; known group construct validity and predictive validity were also demonstrated to a varying degree. CONCLUSIONS: Results support the use of this observational pain scoring tool in the triage of children in A&E.

Adolescent↗
PubMed2003

Fear information and the development of fears during childhood: effects on implicit fear responses and behavioural avoidance.

Field, Argyris and Knowles (Behav Res Ther 39 (2001) 1259), and Field, Hamilton, Knowles and Plews (Behav Res Thera 41 (2003) 113) have developed a prospective paradigm for testing Rachman's (Behav Res Ther 15 (1977) 375) proposition that fear information is important in the development of fears and phobias in children. Despite this paradigm being an advance on retrospective reports, the research so far has been restricted to self-reported fear beliefs measured after the information is given. This gives rise to two possible shortcomings: (1) the effects could simply reflect demand characteristics resulting from children conforming to the experimental demands, and (2) although fear information changes beliefs, this might not translate into the behavioural change that would be expected if this information has a powerful effect relevant to the development of pathological fear. This paper describes an experiment that attempts to address these concerns by improving Field et al.'s (2001, 2003) basic paradigm but with the addition of two measures: (1) a behavioural measure of avoidance, and (2) an implicit attitude task that should not be susceptible to deliberate attempts to conform to experimental demands. The result showed that negative and positive information have dramatic, and opposite, effects on self-reported fear beliefs, behavioural avoidance and implicit attitudes. There were no effects of gender on any of these results. This study fully supports Rachman's model and suggests that past work does not merely reflect demand characteristics and that fear information increases behavioural avoidance as well as fear beliefs.

Animals↗
PubMed2001

A human CD46 transgenic pig model system for the study of discordant xenotransplantation.

BACKGROUND: The chronic shortage in the supply of human organs available for allotransplantation has turned attention toward the use of animals as potential donors, with pigs as the most likely species under consideration. Hyperacute rejection, the initial and immediate barrier to a pig-to-primate xenograft, has been addressed by generation of transgenic pigs that express the human membrane-bound complement-regulatory proteins CD59 and/or CD55. Difficulty has been encountered in generation of transgenic animals that express a third membrane-bound complement-regulatory protein, CD46. METHODS: We have generated transgenic animals by using a large genomic construct that encompasses the entire human CD46 gene. RESULTS: We report the first description of transgenic mice and pigs that express high levels of human CD46 in a cell and tissue type-specific manner, resembling patterns of endogenous CD46 expression observed in human tissues. Furthermore, when human CD46 transgenic porcine hearts were transplanted into baboons, the grafts did not succumb to hyperacute rejection, and survival extended for up to 23 days. Under the same conditions, nontransgenic grafts underwent hyperacute rejection within 90 min. CONCLUSIONS: This is the first report to describe generation of transgenic pigs that express human CD46, and the first in vivo demonstration of the ability of human CD46 expressed on pig organs to regulate complement activation and overcome hyperacute rejection upon transplantation of a vascularized organ into nonhuman primates.

Animals↗
PubMed2001

Generation of species cross-reactive aptamers using "toggle" SELEX.

Species cross-reactivity facilitates the preclinical evaluation of potentially therapeutic molecules in animal models. Here we describe an in vitro selection strategy in which RNA ligands (aptamers) that bind both human and porcine thrombin were selected by "toggling" the protein target between human and porcine thrombin during alternating rounds of selection. The "toggle" selection process yielded a family of aptamers, all of which bound both human and porcine thrombin with high affinity. Toggle-25, a characteristic member, inhibited two of thrombin's most important functions: plasma clot formation and platelet activation. If appropriate targets are available, the toggle strategy is a simple measure that promotes cross-reactivity and may be generalizable to related proteins of the same species as well as to other combinatorial library screening strategies. This strategy should facilitate the isolation of ligands with needed properties for gene therapy and other therapeutic and diagnostic applications.

Animals↗
PubMed2001

Bone phenotype of the aromatase deficient mouse.

Estrogens are important for normal bone growth and metabolism. The mechanisms are incompletely understood. Thus, we have undertaken characterization of the skeletal phenotype of aromatase (ArKO) deficient mice. No abnormalities have been noted in skeletal patterning in newborns. Adult ArKO mice show decreased femur length and decreased peak Bone Mineral Density (BMD) with accelerated bone loss by 7 months of age in females. Magnetic resonance microscopy (MR) and microCT (microCT) imaging disclosed decreased cancellous connectivity and reduced cancellous bone volume in ArKO females. Bone formation rate (BFR) is increased in ArKO females and decreased in ArKO males. Estradiol therapy reverses these changes. This anabolic effect of estradiol in the male skeleton is supported by 18-F- Positron Emission Tomography (PET) imaging, which clearly demonstrates decreased spinal uptake, but marked increase after estradiol therapy. Serum IGF-1 levels are high in young female ArKO mice but low in young ArKO males. The reduced BMD in ArKO females, despite the presence of elevated serum IGF 1, suggests that other mechanism(s) are operative. There is increased B-cell lymphopoiesis in adult female ArKO bone marrow cells. These results show that ArKO mice show the effects of estrogen deficiency on bone growth, mass, metabolism, microarchitecture and the hematopoietic microenvironment.

Animals↗
PubMed2000

Spatial convergence and divergence between cutaneous afferent axons and dorsal horn cells are not constant.

We have proposed a quantitative model of the development of dorsal horn cell receptive fields (RFs) and somatotopic organization (Brown et al. [1997] Somatosens. Motor Res. 14:93-106). One component of that model is a hypothesis that convergence and divergence of connections between low-threshold primary afferent mechanoreceptive axons and dorsal horn cells are invariant over skin location and dorsal horn location. The more limited, and more easily tested, hypothesis that spatial convergence and divergence between cutaneous mechanoreceptors and dorsal horn cell are constant was examined. Spatial divergence is the number of dorsal horn cells whose RFs overlap the RF center of a primary afferent, and spatial convergence is the number of afferent RF centers that lie within the RF of a dorsal horn cell. Innervation density was determined as a function of location on the hindlimb by using peripheral nerve recording and axon counting. A descriptive model of dorsal horn cell receptive fields (Brown et al. [1998] J. Neurophysiol. 31:833-848) was used to simulate RFs of the entire dorsal horn cell population in order to estimate RF area and map scale as a function of location on the hindlimb. Previously reported correlations among innervation density, map scale, and RF size were confirmed. However, these correlations were not linear. The hypothesis that spatial convergence and divergence are constant was rejected. The previously proposed model of development of dorsal horn cell somatotopy and RF geometries must be revised to take variable spatial convergence and divergence into account.

Afferent Pathways↗
PubMed2000

Assessment of growth factor effects on post-thaw development of cryopreserved mouse morulae to the blastocyst stage.

The objective of this study was to assess the influence of specific factors on post-thaw development of mouse cryopreserved morulae. Thawed morulae (n = 206) were randomly distributed between 10 treatment groups: medium alone control (CT), Vero (VR) cells, leukaemia inhibitory factor (1 ng/ml), interleukin-6 (1 ng/ml), transforming growth factor (TGF) alpha (2 ng/ml), epidermal growth factor (EGF) (4 ng/ml), platelet-derived growth factor (1 ng/ml), insulin-like growth factor (IGF)-I (30 ng/ml), IGF-II (1 ng/ml) and TGFbeta (2 ng/ml). At 4, 8, 20, 30 and 48 h, a digitized image of each thawed embryo was captured and stored for later analysis. The following parameters were examined: blastocoel formation, blastocyst expansion, zona thickness and hatching. At termination of the experiment, cell number per embryo was determined by bisbenzimide staining. When contrasted to the medium alone control, co-culture consistently accelerated the development of frozen-thawed morulae to the hatched blastocyst stage, allowing embryos to recover rapidly from any damage sustained during the cryopreservation process. While no single growth factor/cytokine was able to completely mimic the results achieved with co-culture, all of the growth factors impacted positively on at least one of the morphological parameters studied. Cell proliferation was significantly stimulated by just 48 h exposure to growth factors, either through co-culture or by direct media supplementation. Co-culture again yielded the best results with a mean cell count of 217 +/- 76 cells per blastocyst as compared with 131 +/- 36 in control medium alone. Amongst the factors tested, IGF-I, IGF-II and EGF had the greatest impact, with mean cell counts of 172 +/- 50, 168 +/- 50 and 179 +/- 55 respectively. Whereas only 5% of CT embryos developed to blastocysts with > 200 cells, 51% of thawed embryos placed on co-culture monolayers and 25-32% of embryos cultured with IGF-I, IGF-II or EGF had > 200 cells. This study for the first time systematically describes the effect of culture regimen and growth factor additives on the post-thaw development of cryopreserved embryos.

Animals↗
PubMed1999

A continuous fluorometric assay for leukotriene D4 hydrolase.

A fluorogenic substrate for assay of leukotriene D4 hydrolase (LTDase; EC 3.4.13.19) has been prepared and evaluated, using enzyme purified from porcine kidney. The compound is based on internal quenching of the synthetic, fluorescent amino acid d, l-2-amino-3-(7-methoxy-4-coumaryl)propanoic acid (d,l-Amp) by a 2, 4-dinitrophenyl (DNP) group. The compound is epsilon-DNP-l-Lys-d-Amp which incorporates the D-isomer of Amp to exploit the unique ability among mammalian peptidases for LTDase to hydrolyze peptides containing a d-amino acid in the C-terminal position. epsilon-DNP-l-Lys-d-Amp was found to be an excellent substrate for LTDase, with Km value of 370 microoffUnder the conditions of assay, the substrate was without noticeable quenching effect on the fluorescence of the product (d-Amp) liberated by the action of LTDase. Using porcine kidney microvillar membranes, which contain a battery of peptidases, the specific inhibitor of LTDase, cilastatin, completely inhibited the breakdown of epsilon-DNP-l-Lys-d-Amp, indicating that the substrate is selective for LTDase.

Animals↗
PubMed1999

Digital enlargement in tuberous sclerosis.

A 23-year-old woman with a medical history significant for tuberous sclerosis presented with symptoms of postpartum endometritis. Focal gigantism of the third digit of her right hand was incidentally noted and is reported to be a rare manifestation of tuberous sclerosis.

Adult↗
PubMed1999

Testing a rating scale of video-taped consultations to assess performance of trainee nurse practitioners in general practice.

BACKGROUND: Nurse practitioners (NPs) in the United Kingdom are taking on some of the consultation work previously done by general practitioners (GPs) without there being any established professional standards that they must achieve before doing so. There is a need to develop and test methods of assessing their consultation performance for reasons of professional accreditation and patient safety. AIMS: 1. To make independent summative assessments of trainee nurse practitioners' (TNPs) consultation performance. 2. To assess the validity and reliability of an existing video-taped assessment tool. METHOD: Four TNPs taking part in the EROS (extended roles of staff) study video recorded seven or eight consecutive consultations with typical patients during one surgery. Each consultation was rated nine times by members of a panel comprising eight independent GP trainers, four NPs and the GPs and TNPs in the EROS practices. A rating scale developed by Cox & Mulholland was used for the purpose. RESULTS: Eight of the 37 items and four consultations had more than 10% missing data, mean = 7.7 items per rater. Factor analysis yielded a single factor solution explaining 32.6% of the variance and indicated that items could be summed to provide a single score. Internal consistency was high, alpha coefficient = 0.92. Individual differences between raters in scoring consultations were taken into account in providing a score for each consultation. Scores obtained were found to cluster at the positive end of the distribution indicating a high level of performance. Greater differences were found between scorers than between consultations. CONCLUSIONS: This instrument is appropriate for scoring NP consultations and this small sample was rated as showing a uniformly high standard of performance. Some items could be deleted since they do not feature in the range of consultations currently performed. If this or a similar tool was to be adopted more widely for summative rating purposes then it should be tested rigorously for validity and reliability, training should be given to raters and criteria provided by which to make judgements.

Employee Performance Appraisal↗
PubMed1999

Evaluation of the effect of interleukin-6 and human extracellullar matrix on embryonic development.

Extracellular matrices and their associated growth factors can modulate the in-vitro growth of cells. In this study, the effects of culture substrata and the cytokine interleukin-6 (IL-6) on embryonic development were investigated. In-vitro fertilized mouse oocytes were pooled and randomly distributed amongst treatment groups. The test treatments were: (i) IL-6, at either 500 or 1000 pg/ml; (ii) human extracellular matrix (HECM) applied to organ culture dishes at either 5.0 or 10.0 microg/ml; and (iii) HECM and IL-6 combined. A total of 1285 embryos was evaluated. The effect of IL-6 on embryos was dose dependent. Treated embryos exhibited higher blastulation and hatching rates than untreated control embryos. Culture of embryos on human matrix proteins versus standard culture surfaces significantly improved in-vitro hatching. The combination of both of these treatments was superior to the medium alone control, and the mean cell count per blastocyst was higher (131.7 +/- 29.7 versus 82. 5 +/- 14.3 in control embryos; P < 0.0001). In a pilot study with human triploid embryos, the HECM/IL-6 culture system appeared to support embryonic compaction, blastulation and hatching. This work suggests that extracellular matrix components in combination with growth factors/cytokines may be another avenue for formulating more physiological culture systems.

Animals↗
PubMed1999

Diagnosis of geriatric patients with severe dizziness.

OBJECTIVE: To identify the causes of dizziness in older patients presenting to the general practitioner and the clinical characteristics at presentation that might guide the general practitioner to the likely cause of dizziness and the most appropriate specialty for subsequent referral if referral is required. DESIGN: A prospective case control study of older patients presenting with dizziness. SETTING: The initial assessment was made in four general practices, three urban practices and one inner city practice (Newcastle). Subsequent investigations were conducted randomly in the Neurocardiovascular Investigation Unit and the Otolaryngology (ENT) Unit at local University hospitals (Newcastle). PARTICIPANTS: Fifty consecutive patients more than 60 years of age presented with dizziness. Twenty-two age- and sex-matched case controls were recruited from the same general practices. MEASUREMENTS: Measurements were of diagnoses attributable to symptoms. RESULTS: Symptoms were of long duration (median 1 year). Forty-six percent of patients had syncope and/or falls in addition to dizziness. Twenty-eight percent had a cardiovascular diagnosis, 18% had a peripheral vestibular disorder, 14% had a central neurological disorder, 18% had more than one diagnosis, and 22% had no attributable cause of symptoms identified. A cardiovascular diagnosis was predicted by the presence of syncope (P < .001), dizziness described as lightheadedness (P < .001), the need to sit or lie down during symptoms (P < .001), pallor with symptoms (P < .001), symptom precipitation by prolonged standing (P < .05), and whether patients had coexisting cardiovascular disease (P < .05). The description of dizziness as "vertigo" predicted a peripheral vestibular disorder (P < .001). The predictive strength of these prognostic indicators was then validated on a separate sample of 50 additional older patients. CONCLUSIONS: Clinical characteristics can predict an attributable cause of dizziness in most older patients and thus guide general practitioners in treatment and appropriate specialist referral. The presence of syncope, falls, or cardiovascular comorbidity increases the likelihood of a cardiovascular diagnosis. Otolaryngological investigations are rarely diagnostic, but vertiginous symptoms do predict peripheral vestibular disorders.

Accidental Falls↗
PubMed1999

The behaviour of aryl pyrrolines with monoamine oxidase.

We have examined the effects of monoamine oxidase (MAO) on two pyrrolines, 1-methyl-3-phenyl-delta 3-pyrroline and its 4-chlorophenyl analogue. They act as substrates but also inhibit the enzyme in a time-dependent manner. This behaviour is similar to that shown by the neural pro-toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP) which is metabolised by MAO to produce the toxin 4-phenyl pyridinium (MPP+). The end product of the oxidation of the pyrrolines appears to be the corresponding pyrrole. The latter were found to inhibit MAO reversibly. The aryl pyrrolines bear close structural resemblance to MPTP and probably generate a pyrrolium ion, analogous to MPDP or MPP+, during the oxidation by MAO. Whether pyrrolines or their metabolites might mimic the effects of MPTP on mitochondrial respiration remains an unanswered question.

Animals↗
PubMed1998

Mechanism-based inhibition of monoamine oxidase by 3-aryl-Delta3-pyrrolines.

The compound 1-methyl-3-phenyl-Delta3-pyrroline and its 4-chlorophenyl analogue appear to act as irreversible inhibitors of monoamine oxidase B (MAO B) in mitochondria of rat liver. The compounds are metabolized by MAO B and concomitantly inhibit the enzyme in what seems to be a two-step process. The metabolic end product of this process is the corresponding pyrrole. This inhibition process is considered in the light of possible intermediates formed during the enzymic oxidation, and comparisons are made with the structurally analogous neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Animals↗