Biomedical subjects

D Parker

Publications and source records attributed to D Parker.

At least 37 records · Page 2Linked to original sources

PubMed2003

Psychological contribution to the understanding of adverse events in health care.

In the past it has sometimes been assumed in health care that all adverse events involve individual incompetence and therefore blameworthiness, an assumption that is likely to hinder the development of comprehensive and honest incident reporting systems. At the same time, a full understanding of adverse events in healthcare systems requires that distinctions are drawn between a variety of error types, each of which has different origins and demands different strategies for remediation. In this paper a range of cognitive biases identified by psychologists is described. Examples are given of these biases, which are naturally employed in trying to understand our own behaviour and that of others, and therefore affect our understanding of adverse events. It is suggested that awareness of these biases, which form part of our normal thinking, should help to avoid a narrow focus on individual culpability and facilitate a more sophisticated approach to the investigation of adverse events.

Adaptation, Psychological↗

PubMed2002

Evaluation of a commercial line probe assay for identification of mycobacterium species from liquid and solid culture.

The performance of a commercial line probe assay (LiPA) (Inno-LiPA Mycobacteria; Innogenetics, Belgium) for the detection and identification of Mycobacterium species from liquid and solid culture was evaluated at five routine clinical laboratories. The LiPA method is based on the reverse hybridization principle, in which the mycobacterial 16S-23S ribosomal RNA (rRNA) spacer region is amplified by polymerase chain reaction (PCR). Amplicons are subsequently hybridized with oligonucleotide probes arranged on a membrane strip and detected by a colorimetric system. The test detects the presence of Mycobacterium species and specifically identifies Mycobacterium tuberculosis complex, Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium gordonae, Mycobacterium avium complex, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium scrofulaceum, and Mycobacterium chelonae - Mycobacterium abscessus complex. The results of LiPA were compared with the results obtained using traditional biochemical and molecular tests (DNA probe-based techniques, PCR restriction enzyme analysis of the 65 kDa heat-shock protein gene, and sequencing of the 16S rDNA). A total of 669 isolates, 642 of which were identified as Mycobacterium species and 27 as non- Mycobacterium species, were tested by LiPA. After analysis of 14 initially discordant results and exclusion of one isolate, concordant results were obtained for 636 of 641 Mycobacterium isolates (99.2% accuracy). All Mycobacterium species reacted with the MYC ( Mycobacterium species) probe (100% sensitivity), and all non- Mycobacterium species were identified as such (100% specificity).

Bacterial Typing Techniques↗

PubMed2002

Nature of the liquid crystalline phase transitions in the cesium pentadecafluorooctanoate-water system: the nematic-to-smectic-A transition.

Measurements of the diamagnetic susceptibility chi(a), the rotational viscosity coefficient gamma(1), and the micellar orientational order parameter S have been made as a function of temperature across the entire nematic phases of cesium pentadecafluorooctanoate (CsPFO)-D2O samples over the concentration range weight fraction CsPFO w from 0.350 to 0.500. This has been chosen so as to embrace the pseudo-nematic phase-lamellar tricritical point that has been purported to occur at w=0.43 (volume fraction phi=0.26). The values of gamma(1) vary from about 0.1 kg m(-1) s(-1) to 1000 kg m(-1) s(-1) as the temperature decreases across the nematic phase, covering a much larger range than those reported for thermotropic liquid crystals. Measurements of gamma(1) have been made much closer to the critical temperature T(LN) than have previously been reported [(T-T(LN))/T(LN)=2 x 10(-5) for the w=0.350 sample]. The rotational viscosity critical exponents x calculated from the divergence of gamma(1) on approaching the nematic-phase-to-lamellar transition are found to be constant at 2/3 independent of the concentration. These values differ from those of 1/3 and 1/2, respectively, predicted by the He-like three-dimensional XY and mean-field models, in combination with mean-field dynamical relaxation. However, the former would be supported if complete Fisher renormalization (at alpha=1/2) was appropriate over an extended concentration range. Alternatively, this could be an indication of the importance of coupling between the micellar rotational dynamics and critical fluctuations since the latter are seen to be predominant across the entire temperature range of the nematic phase as revealed in the temperature dependence of gamma(1).

Journal Article↗

PubMed2002

Barriers to incident reporting in a healthcare system.

BACKGROUND: Learning from mistakes is key to maintaining and improving the quality of care in the NHS. This study investigates the willingness of healthcare professionals to report the mistakes of others. METHODS: The questionnaire used in this research included nine short scenarios describing either a violation of a protocol, compliance with a protocol, or improvisation (where no protocol exists). By developing different versions of the questionnaire, each scenario was presented with a good, poor, or bad outcome for the patient. The participants (n = 315) were doctors, nurses, and midwives from three English NHS trusts who volunteered to take part in the study and represented 53% of those originally contacted. Participants were asked to indicate how likely they were to report the incident described in each scenario to a senior member of staff. RESULTS: The findings of this study suggest that healthcare professionals, particularly doctors, are reluctant to report adverse events to a superior. The results show that healthcare professionals, as might be expected, are most likely to report an incident to a colleague when things go wrong (F(2,520) = 82.01, p < 0.001). The reporting of incidents to a senior member of staff is also more likely, irrespective of outcome for the patient, when the incident involves the violation of a protocol (F(2,520) = 198.77, p < 0.001. It appears that, although the reporting of an incident to a senior member of staff is generally not very likely, particularly among doctors, it is most likely when the incident represents the violation of a protocol with a bad outcome. CONCLUSIONS: An alternative means of organisational learning that relies on the identification of system (latent) failures before, rather than after, an adverse event is proposed.

Attitude of Health Personnel↗

PubMed2002

Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids.

BACKGROUND: The debate as to whether asthma is a single or heterogeneous disease remains unresolved although pathological studies, mostly using fibreoptic bronchoscopy on small numbers of subjects, have emphasised the similarities between different clinical phenotypes. METHODS: Lower airway inflammation was assessed non-invasively using induced sputum in 34 normal controls and 259 adults with symptomatic asthma receiving treatment at steps 1-3 of the British Thoracic Society (BTS) guidelines. A subgroup of 49 patients treated with as required beta(2) agonists only who met BTS criteria for a step up in treatment were studied before and 2 months after treatment with inhaled budesonide 400 micro g twice daily. RESULTS: There was considerable heterogeneity in induced sputum cell counts, particularly in non-atopic patients. A subgroup of 60 patients had a distinctive sputum cell profile with a neutrophil count higher than our normal range (>65.3%) and a normal sputum eosinophil count (<1.9%). These patients were older, predominantly female, and were more likely to be non-atopic but otherwise had similar clinical and physiological features to the group as a whole. Among the 49 subjects studied before and after inhaled budesonide, 11 patients had an isolated sputum neutrophilia. Following treatment, these patients showed significantly less improvement in visual analogue symptom scores (-5.5 v -19.4 mm; mean difference 13.9; 95% CI 0.7 to 27.0), forced expiratory volume in 1 second (FEV(1)) (-0.08 v 0.13 l; mean difference 0.21; 95% CI 0.03 to 0.39), and concentration of methacholine provoking a fall in FEV(1) of 20% or more (PC(20)) (0.15 v 1.29 doubling doses; mean difference 1.11; 95% CI 0.13 to 2.15) than the remaining 38 patients. CONCLUSIONS: These results suggest the presence of a distinct subgroup of patients with mild to moderate asthma who have predominantly neutrophilic airway inflammation and who respond less well to treatment with inhaled corticosteroids.

Administration, Inhalation↗

PubMed2001

Lanthanide macrocyclic quinolyl conjugates as luminescent molecular-level devices.

The Eu(III) tetraazamacrocyclic complexes [Eu.1] and [Eu.2], and the Tb(III) and Yb(III) complexes [Tb.1] and [Yb.2], have been synthesized as luminescent molecular-level devices. The Eu complexes exhibit unique dual pH switching behavior in water under ambient conditions. The delayed Eu emission is reversibly switched on in acid, with an enhancement factor of several hundred for [Eu.1]. These observations are consistent with the protonation of the quinoline aryl nitrogen moiety (pK(a) approximately equal to 5.9 for [Eu.1]). The fluorescence emission spectra of these complexes are unaffected by acid, but pronounced changes occur in alkaline solution due to the deprotonation of the aryl amide nitrogen (pK(a) approximately 9.4 for [Eu.1]). [Tb.1] shows a more intriguing pH dependence; Tb emission is switched "on" only in the presence of H+ and in the absence of molecular oxygen, whereas the fluorescence emission properties are similar to those observed with [Eu.1]. This behavior can be conveniently described as a molecular-level logic gate, corresponding to a two-input INHIBIT function, A wedge B'. The analogous [Yb.2] complex shows no such pH or O(2) dependence.

Journal Article↗

PubMed2001

Towards rational design of fast water-exchanging Gd(dota-like) contrast agents? Importance of the M/m ratio.

1H NMR line-shape analysis and magnetisation-transfer experiments at variable temperature and pressure have been used to elucidate the solution dynamics of both M and m isomers of three [Eu(dota-tetraamide)(H2O)]3+ complexes. The direct 1H NMR observation of the bound water signal allows the water-exchange rates on each isomer to be measured individually. They are definitely independent of the ligand for both M and m isomers (M: k298(ex)=9.4+/-0.2 x 10(3) s(-1) for [Eu(dotam)(H2O)]3+, 8.2+/-0.2 x 10(3) s(-1) for [Eu(dtma)(H2O)]3+ and 11.2+/-1.4 x 10(3) s(-1) for [Eu(dotmam)-(H2O)]3+; m: k298(ex)=474+/-130 x 10(3) s(-1) for [Eu(dotam)(H2O)3+, 357+/-92 x 10(3) s(-1) for [Eu(dtma)(H2O)3+), and proceed through a dissociative mechanism (M isomers: deltaV++ = +4.9 cm3 mol(-1) for [Eu(dotam)(H2O)]3+ and + 6.9 cm3 mol(-1) for [Eu(dtma)(H2O)]3+). The overall water exchange only depends on the M/m isomeric ratio. The m isomer, which exchanges more quickly, is favoured by a-substitution of the ring nitrogen. Therefore the synthesis of DOTA-like ligands, which predominantly form complexes in the m form, should be a sufficient condition to ensure faster water exchange on potential Gd(III)-based contrast agents. Furthermore the activation parameters for the water-exchange and isomerisation processes are both compatible with a nonhydrated complex as intermediate.

Contrast Media↗

PubMed2001

Experimental assessment of lanthanide ion donor preference: spectroscopic and theoretical dissection of static charge and dynamic polarisation contributions to axial ligation in a C4-symmetric chiral europium complex.

Measurements of the equilibrium constants for ligand exchange (MeCN, 295 K) involving the axial donor in a C4-symmetric, mono-capped, square antiprismatic cationic Eu complex, supported by calculations based on an electrostatic perturbation model, have been interpreted in terms of a predominant ligand polarisation interaction defined by observation of the hypersensitive delta J = 2 normalised emission intensity, in association with measurements correlating delta J = 1 band splitting and 1H NMR dipolar shifts that vindicate Bleaney's theory of magnetic anisotropy.

Journal Article↗

PubMed2001

Narrow-range optical pH sensors based on luminescent europium and terbium complexes immobilized in a sol gel glass.

The metal-based emission of a series of luminescent europium and terbium complexes incorporating an aromatic chromophore is rendered pH-dependent either through perturbation of the aryl singlet or triplet energy or by modulating the degree of quenching of the lanthanide excited state. Systems exhibiting each of these pathways have been incorporated in thin-film sol gel matrixes and evaluated as pH sensors in static and flow analyses at constant ionic strength. pH-dependent intensity or ratiometric methods, for emission or excitation spectra, have been defined for lanthanide complexes incorporating substituted phenanthridine (pK(a) from ca. 6.8 to 7.2) or 6-cyanophenanthridine-2-sulfonyl chromophores (pK(a) approximately 7.14 in human serum solution) (lambda(exc) 365 nm, phi H(2)O = 7.2%).

Journal Article↗

PubMed2001

Gating and braking of short- and long-term modulatory effects by interactions between colocalized neuromodulators.

Spinal locomotor networks in the lamprey are modulated by tachykinin neuropeptides. A single 10 min application of the tachykinin substance P evokes a short-term ( approximately 1 hr) presynaptic facilitation of glutamate release and the postsynaptic potentiation of NMDA responses. The latter effect induces a long-term (>24 hr) protein synthesis-dependent increase in the frequency of network activity. Tachykinins are contained in a ventromedial spinal plexus into which the medial dendrites of network neurons project. Neurons in this plexus also contain colocalized dopamine and 5-HT. Here, dynamic plasticity evoked by modulator interactions has been examined by investigating the effects of 5-HT and dopamine on specific cellular, synaptic, and network effects of substance P. Preapplied 5-HT blocked the substance P-mediated increase in the network burst frequency and the potentiation of NMDA-evoked cellular responses that underlies its induction. 5-HT also blocked the presynaptic facilitation of glutamatergic synaptic transmission by substance P. The presynaptic, but not postsynaptic, effect of 5-HT was reduced by the protein phosphatase 2B inhibitor cypermethrin. Dopamine did not directly modulate the effects of substance P. However, it reduced the presynaptic interactive effect of 5-HT and thus gated the presynaptic potentiation of glutamatergic inputs by substance P. However, the substance P-mediated potentiation of NMDA responses was not gated by dopamine, and thus the long-term network modulation was not induced. Neuromodulator effects and their interactions can thus be modulated. By selecting components from the modulatory repertoire of substance P, these interactions evoke dynamic changes in short- and long-term synaptic and network plasticity.

Animals↗

PubMed2001

pH-dependent modulation of relaxivity and luminescence in macrocyclic gadolinium and europium complexes based on reversible intramolecular sulfonamide ligation.

A series of macrocyclic Eu, Gd, and Tb complexes has been prepared in which the intramolecular ligation of a beta-arylsulfonamide nitrogen is rendered pH-dependent, giving rise to changes in the hydration state, q, at the lanthanide center. In complexes based on DO3A, variation of the p-substituent in the arylsulfonamide moiety determines the apparent protonation constant log K(MLH) with values of 5.7, 6.4, and 6.7 for the -CF(3), -Me, and -OMe substituents, respectively. Introduction of three beta-carboxyalkyl substituents, alpha to three ring nitrogens, inhibits displacement of the bound water by added protein and also suppresses intermolecular binding by endogenous anions (lactate, HCO(3)(-)). Measurements of the pH dependence of the form and intensity of the Eu complexes revealed that intramolecular carboxylate coordination occurred competitively. This was reduced either by enhancing the electron density at the sulfonamide nitrogen or by enlarging the chelate ring from 7--8. Amplification of the relaxivity changes in the pH range 8--5 occurred on protein binding, and over the pH range 7.4--6.8 a 48% change in relaxivity was defined for [Gd.3a] (298 K, 65.6 MHz) in 50% human serum solution.

Journal Article↗

PubMed2001

Zinc co-localizes with GABA and glycine in synapses in the lamprey spinal cord.

The presence of zinc in synaptic terminals in the lamprey spinal cord was examined utilizing a modification of the Timm's sulfide silver method and with the fluorescent marker 6-methoxy-8-quinolyl-p-toluenesulfonamide (TSQ). Axons labeled with a Timm's staining method were predominantly located in the lateral region of the dorsal column. This correlated with a maximum of TSQ fluorescence in this region of the spinal cord. Single labeled terminals accumulating Timm reaction product were also found throughout the gray matter and fiber tracts. At the ultrastructural level, zinc was located in a population of synaptic terminals that co-localized gamma-aminobutyric acid (GABA) and glycine. Possible effects of Zn2+ on neuronal activity were examined. In spinobulbar interneurons, which receive GABAergic input in the dorsal column, zinc potentiated responses to GABA application, but it did not affect responses to GABA in motoneurons. Responses in motoneurons to pressure application of glycine were also not affected by Zn2+. Zinc, however, potentiated monosynaptic glycinergic inhibitory postsynaptic potentials (IPSPs) evoked in motoneurons by inhibitory locomotor network interneurons and increased frequency, but not amplitude of spontaneous miniature IPSPs recorded in the presence of tetrodotoxin (TTX), suggesting presynaptic effects. Glutamate responses and the amplitude of monosynaptic excitatory postsynaptic potentials (EPSPs) in motoneurons were reduced by zinc. These effects appeared to be mediated largely postsynaptically through an effect on the N-methyl-D-aspartate (NMDA) component of the glutamatergic input. Our results thus show that free zinc is present in inhibitory synaptic terminals in the lamprey spinal cord, and that it may function as a modulator of inhibitory synaptic transmission.

Aminoquinolines↗

PubMed2001

Are aggressive people aggressive drivers? A study of the relationship between self-reported general aggressiveness, driver anger and aggressive driving.

In this study the relationships among self-reported general aggressiveness, impulsiveness, driver anger, and aggressive responses to anger-provoking situations on the road were studied. The British version of a driver anger scale (UK DAS), aggression questionnaire (AQ), and an impulsiveness questionnaire (I7) together with background questions (gender, age, annual mileage) were administered to a sample of 270 British drivers. Variation in strength of correlations between anger and aggressive reactions in the 21 UK DAS items showed that the relationship between driver anger and aggression depends in part on the characteristics of the situation. In addition, three path models for describing the relationships among the measures were constructed separately for women and men. The models suggested that the effects of verbal aggressiveness on self-reported driver aggression were mediated by driver anger whereas physical aggressiveness was directly related to aggressive behaviour. Age was negatively related to both driver anger and aggression among men whereas annual mileage was negatively related to aggression among women. The models constructed indicate that aggressive driver behaviour is a complex phenomenon with a range of psychological causes.

Adult↗

PubMed2001

High-performance liquid chromatographic analysis and stability of anti-tumor agent temozolomide in human plasma.

Temozolomide (SCH 52365; TEMODAL) is an antineoplastic agent with activity against a broad spectrum of murine tumors. This compound is currently marketed in the European Union for the treatment of patients with glioblastoma multiforme and anaplastic astrocytoma, which are serious and aggressive types of brain cancers. It has been postulated that temozolomide exerts its in vivo activity via the decomposition product MTIC, which is believed to alkylate nucleophiles, and in the process is converted to AIC. A high-performance liquid chromatographic (HPLC) method was developed and validated for the analysis of temozolomide in human plasma. The determination of temozolomide involved extraction with ethyl acetate followed by separation on a reversed phase C-18 column and quantification by UV absorbance at 316 nm. The calibration curve was linear over a concentration range of 0.1-20 microg/ml. The limit of quantitation was 0.1 microg/ml, where the coefficient of variation (CV) was 0% and the bias was 10.0%. The method was precise with a coefficient of variation ranging from 2.5 to 6.9% and accurate with a bias ranging from 5.0 to 10.0%. Temozolomide was unstable at 37 degrees C in human plasma with a degradation t1/2 of 15 min; however, it was stable at 4 degrees C for at least 30 min. Temozolomide was stable in acidified human plasma (pH < 4) for at least 24 h at 25 degrees C, and for at least 30 days at -20 degrees C. Moreover, temozolomide was stable in acidified human plasma after being subjected to three freeze thaw cycles. The assay was shown to be specific, accurate, precise, and reliable for use in pharmacokinetic studies.

Antineoplastic Agents↗

PubMed2001

Management of lymphoma patients in a cancer unit: an audit of 15 years' experience in a district general hospital.

The objectives were to analyse data obtained in a district general hospital medical oncology unit over a 15-year period, and to provide a comparator for standards of care for lymphoma patients in new cancer units. Prospectively collected data were analysed on 208 consecutive patients presenting with lymphoma, on an 'all-comers' basis, between 1981 and 1996. Treatment was with radiotherapy and/or chemotherapy, according to local protocols. The outcome measure was survival from the date of diagnosis. The 5-year actuarial survival was 72.7% for Hodgkin's disease and 55.7% for non-Hodgkin's lymphoma. Age and stage of disease were the only predictors of survival in a multivariate analysis. Histological classification was not a useful predictor of survival in this analysis. Survival figures comparable with those obtained nationally and across Europe are attainable in a cancer unit. Multiple pathways of referral of lymphoma patients operate in our region.

Adolescent↗

PubMed2001

Induced sputum and other outcome measures in chronic obstructive pulmonary disease: safety and repeatability.

The forced expiratory volume in 1 sec (FEV1) is the most established outcome measure in chronic obstructive pulmonary disease (COPD). However, changes in FEV1 in response to treatment are small in relation to the repeatability of the measurement and there is increasing interest in other measures including markers of lower airway inflammation in induced sputum, assessment of symptoms and health status using visual analogue scores, and questionnaires. Little is known about the repeatability of these measures or the safety of sputum induction in COPD. We have assessed the safety of sputum induction in 61 subjects with moderate and severe COPD who participated in a placebo-controlled cross-over study The within-subject repeatability of sputum markers of airway inflammation, health status using the chronic respiratory disease questionnaire (CRQ) and symptom visual analogue scores (VAS) were estimated from the data obtained from before and after 2 weeks of treatment with placebo. Sputum induction was performed on 122 occasions and was successful resulting in a cytospin adequate to assess a differential cell count in 95% of inductions. The group mean (SEM) FEV1 was 1.09 (0.05)[41.6 (2.9)% predicted] and the mean (SEM) fall in FEV1 after sputum induction was 120 ml (6) and % fall 10.9% (0.55%). Seven inductions were stopped due to a fall in FEV1 >20% and at a further 13 visits the full sputum induction protocol was not completed due to development of symptoms. The reproducibility of measurements, calculated by the intra-class correlation coefficient, was relatively high for all indices measured (0.4-0.95) with the exception ofthe proportion of lymphocytes (0.15) and epithelial cells (0.3). The ICC for symptom scores and the CRQ domains ranged between 0.87 and 0.96. In conclusion, sputum induction is safe and the cell and fluid phase mediators repeatable in the investigation of airway inflammation in patients with COPD. VAS symptom scores and the CRQ are reproducible outcome measures in COPD.

Aged↗

PubMed2001

Relationship of disability prevention to patient health status and satisfaction with primary care provider.

A sample of 625 patients aged 18 to 65 with primary care visits was used to explore the relationship of disability prevention to patient health status and satisfaction with health care provider. Disability prevention and the patient-provider relationship, the latter a potential mediating factor, were measured using reliable and valid scales. The joint effects of disability prevention and a strong patient-provider relationship were associated with decreased risks for poor physical health, as measured by the Medical Outcomes Study 12-item short-form health survey, decreased restricted activity days, and overall satisfaction with their primary care provider. Patient-provider relationship was independently associated with increased patient satisfaction with the provider overall and endorsement of the provider to family or friends. The evidence questions the conventional wisdom among some primary care providers that incorporating disability prevention principles into their daily practice jeopardizes patient satisfaction. These results suggest that primary care providers with strong patient-provider relationships can successfully add disability prevention to their practice.

Adult↗

PubMed2001

Life-cycle effects of sediment-associated 2,4,5-trichlorophenol on two groups of the midge Chironomus riparius with different exposure histories.

Effects of 2,4,5-trichlorophenol (TCP) on life-cycle traits of the midge Chironomus riparius and the ability of the midge to evolve tolerance to TCP were assessed using a reference group and a group preexposed to TCP during three generations, both originating from the same laboratory culture. F1 larvae of these groups were then exposed to nominal TCP concentrations of 51, 177, 355, and 532 micromol TCP/kg dry sediment and a control sediment in a life-cycle experiment. Most studied life-cycle traits (mortality, egg production, life span, male dry wt) were fairly insensitive to TCP, and significant effects were observed only at high (> or = 355 micromol/kg) concentrations. Larval development rate was variable, and in some cases it responded more readily to low TCP concentrations than other life-cycle parameters. Some of the observed responses were attributed to changes in food availability. No clear evidence of tolerance to 2,4,5-trichlorophenol was found, but the preexposed midges produced more eggs than the reference group. They also emerged earlier and at a smaller size than the reference midges. These differences between the midge groups suggest that some changes toward tolerance induction had occurred during the preexposure.

Animals↗