Sierra Leone's children of war.
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Adolescent↗
Biomedical subjects
D Parker
Publications and source records attributed to D Parker.
The emotions and coping strategies of caregivers of family members with a terminal cancer.
This study documents the emotional experiences and coping strategies of a group of caregivers as they move from the diagnosis of a close family member with terminal cancer through the stages of caring and post bereavement. Supportive evidence, matching that of previous literature, was gathered regarding the impact of such care, but additional findings counter the notion of "burden" by revealing that strong positive emotions were experienced by these caregivers regarding the opportunity given to them to express their love through care. By contrast and post bereavement, however, intense grief was reported. There appeared to be a complete lack of emotional support throughout from health professionals, particularly in the bereavement phase when need is very apparent.
Adaptation, Psychological↗
Validation of the AmpFlSTR Profiler Plus PCR amplification kit for use in forensic casework.
According to TWGDAM guideline 4.5 (1), prior to implementing a new DNA analysis procedure or an existing DNA analysis procedure developed by another laboratory, the forensic laboratory must first demonstrate reliability of the procedure in-house. Seven phases were designed to validate the use of the AmpFlSTR Profiler Plus PCR Amplification Kit, as well as the PE Applied Biosystems 310 Genetic Analyzer. This report summarizes the results obtained for each of the seven phases of the validation study which included the following evaluations: polymer, reproducibility, sensitivity, stutter, precision, mixtures and nonprobative casework.
DNA Fingerprinting↗
A New Self-Assembling System for Targeted Gene Delivery We thank the BBSRC Chiroptical Service for CD studies, Brian McManus (Optokem Instruments, Nercyws, Flintshire) for assistance with the light-scattering studies, Dr. Clive Roberts (Molecular Profiles Ltd.) for AFM studies, Professor J.-H. Fuhrhop for many discussions, Dr. I. S. Blagbrough for related synthetic work, the EPSRC for support, and the Royal Society for a Leverhulme Trust Senior Research Fellowship (D.P.).
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Journal Article↗
Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial.
BACKGROUND: Some patients with chronic obstructive pulmonary disease (COPD) respond to corticosteroid therapy. Whether these patients have different airway pathology from other COPD patients is unclear. We tested the hypothesis that response to prednisolone is related to the presence of eosinophilic airway inflammation. METHODS: We did a randomised, double-blind, crossover trial. Patients who had COPD treated with bronchodilators only were assigned placebo and 30 mg prednisolone daily for 2 weeks each, in a random order, separated by a 4-week washout period. Before and after each treatment period, we assessed patients with spirometry, symptom scores, the chronic respiratory disease questionnaire (CRQ), incremental shuttle walk test, and induced sputum. Analysis was done by intention to treat. FINDINGS: 83 patients were recruited, of whom 67 were randomised. The geometric mean sputum eosinophil count fell significantly after prednisolone (from 2.4% to 0.4%; mean difference six-fold [95% CI 3.1-11.4]) but not after placebo. Other sputum cell counts did not change. After stratification into tertiles by baseline eosinophil count, postbronchodilator forced expiratory volume in 1 s (FEV1) and total scores on the CRQ improved progressively after prednisolone from the lowest to the highest eosinophilic tertile, compared with placebo. The mean change in postbronchodilator FEV1, total CRQ score, and shuttle walk distance with prednisolone compared with placebo in the highest tertile was 0.19 L (0.06-0.32), 0.62 (0.31-0.93), and 20 m (5-35), respectively. INTERPRETATION: Our findings suggest that eosinophilic airway inflammation contributes to airflow obstruction and symptoms in some patients with COPD and that the short-term effects of prednisolone are due to modification of this feature of the inflammatory response. The possibility that sputum eosinophilia identifies a subgroup of patients who particularly respond to long-term treatment with inhaled corticosteroids should be investigated.
Adult↗
Solution structure of the catalytic domain of human collagenase-3 (MMP-13) complexed to a potent non-peptidic sulfonamide inhibitor: binding comparison with stromelysin-1 and collagenase-1.
The full three-dimensional structure of the catalytic domain of human collagenase-3 (MMP-13) complexed to a potent, sulfonamide hydroxamic acid inhibitor (CGS 27023) has been determined by NMR spectroscopy. The results reveal a core domain for the protein consisting of three alpha-helices and five beta-sheet strands with an overall tertiary fold similar to the catalytic domains of other matrix metalloproteinase family members. The S1' pocket, which is the major site of hydrophobic binding interaction, was found to be a wide cleft spanning the length of the protein and presenting facile opportunity for inhibitor extension deep into the pocket. Comparison with the reported X-ray structure of collagenase-3 showed evidence of flexibility for the loop region flanking the S1' pocket in both NMR and X-ray data. This flexibility was corroborated by NMR dynamics studies. Inhibitor binding placed the methoxy phenyl ring in the S1' pocket with the remainder of the molecule primarily solvent-exposed. The binding mode for this inhibitor was found to be similar with respect to stromelysin-1 and collagenase-1; however, subtle comparative differences in the interactions between inhibitor and enzyme were observed for the three MMPs that were consistent with their respective binding potencies.
Amino Acid Sequence↗
Activity and calcium-dependent mechanisms maintain reliable interneuron synaptic transmission in a rhythmic neural network.
Inputs from glutamatergic excitatory interneurons (EIN) to motor neurons in the lamprey spinal cord locomotor network exhibit activity-dependent depression during spike trains. The mechanism underlying this depression has been examined here, and its relevance to transmitter release during rhythmic activity has been investigated. The depression of EIN inputs was greater after larger initial EPSPs and reduced in low-calcium Ringer's solution, effects that are consistent with depression caused by depletion of releasable transmitter stores. However, the depression was greater at lower stimulation frequencies and could be reversed by increasing the stimulation frequency. In addition, high-calcium Ringer's solution and the slow intracellular calcium chelator EGTA-AM, which both failed to affect the amplitude of low frequency-evoked EPSPs, reduced and increased the depression, respectively. These results are inconsistent with a simple depletion mechanism but suggest that ongoing activity and calcium-dependent mechanisms oppose depletion. The network relevance of this mechanism was examined using physiologically relevant bursts to simulate EIN spiking during rhythmic activity. Although considerably more EPSPs were evoked than during spike trains, burst-evoked EPSPs did not depress. However, single EPSPs evoked at the interburst interval depressed, and burst transmission was disrupted by EGTA-AM, again suggesting the involvement of activity and calcium-dependent mechanisms. By responding to the calcium changes evoked by increased interneuron activity, this mechanism can monitor transmitter requirements caused by EIN spiking, allowing reliable transmission across different patterns of network activity. However, not all types of spinal interneurons exhibit reliable burst transmission, suggesting specificity of this mechanism to a subset of neurons.
Action Potentials↗
Nature, incidence, and cause of work-related amputations in Minnesota.
BACKGROUND: The Minnesota Sentinel Event Notification System for Occupational Risks (SENSOR) has collected data on the nature, incidence, and cause of work-related amputation injuries that have taken place since 1992. METHODS: SENSOR defined an amputation as any finger amputation or the loss of any other body part; 832 workers were identified as having amputation injuries between 1994 and 1995 and 72% of these workers completed telephone interviews. RESULTS: The amputation injury rate for Minnesota workers was 39 per 100,000 workers, with agriculture and manufacturing having the highest rates. Sixty-six percent of the injuries involved one finger; 14% involved two or more fingers. Persons working with machinery reported 73% of the injuries. CONCLUSIONS: A closer examination of the incidence and causes for amputation injuries shows that these were not random events. Reliance on human reactions to prevent injury is inadequate; therefore, additional research needs to be conducted.
Accidents, Occupational↗
Medical, personal, and occupational outcomes for work-related amputations in Minnesota.
BACKGROUND: The Minnesota Sentinel Event Notification System for Occupational Risks (SENSOR) surveillance system has collected data on the medical, personal, and occupational outcomes associated with work-related amputations since 1992. METHODS: SENSOR defined amputations as any finger amputation or the loss of any other body part; 832 workers were identified as having amputation injuries between 1994 and 1995 and 72% of these workers completed a telephone interview. RESULTS: Twenty percent of those injured required overnight hospitalization. Ninety-one percent of the cases reported having missed work, with 56% reporting missing ten or more days. Individuals working on their usual jobs at the time of injury were more likely to report less serious medical and occupational outcomes. CONCLUSIONS: Severe injuries were significantly associated with worse medical, personal, and occupational outcomes. Two groups of machines, material handling, and powered handtools were associated with a higher proportion of severe injuries.
Absenteeism↗
Ternary Gd(III)L-HSA adducts: evidence for the replacement of inner-sphere water molecules by coordinating groups of the protein. Implications for the design of contrast agents for MRI.
Two novel gadolinium(III) chelates based on the structure of the heptadentate macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) ligand have been synthesized and their relaxometric and luminescent properties thoroughly investigated. They contain two water molecules in the inner coordination sphere in fast exchange with the bulk solvent and bear either a p-bromobenzyl or a p-phosphonatomethylbenzanilido substituent for promoting further interaction with macromolecular substrates. Upon interaction with human serum albumin the expected relaxation enhancement is not observed owing to displacement of the two inner-sphere water molecules of the complexes by a donor atom (likely from a carboxylate group) on the protein and possibly the phosphate anion of the buffered solution, respectively. We modeled the observed behavior by measuring the decrease of the relaxation rate of the water protons upon addition of malonate anion to aqueous solutions of the complexes. Conversely, no change in the hydratation state of the Gd(III) center for both complexes has been observed when the substrate for the formation of the macromolecular adduct is represented by poly-beta-cyclodextrin.
Contrast Media↗
Elderly drivers and their accidents: the Aging Driver Questionnaire.
The Manchester Driver Behavior Questionnaire (DBQ) was included as part of a questionnaire survey of 1989 drivers aged 50 or over. Previous research has differentiated three main types of aberrant driver behavior: errors, lapses and violations. Each of these has different psychological origins, and different implications for road safety interventions [Reason et al., 1990. Ergonomics 33, 1315-1312]. It has also been shown that, using a full age-range sample of drivers, reported violations were statistically associated with accident involvement, whereas errors and lapses were not [Parker et al., 1995a. Ergonomics 38, 1036-1048; Parker et al., 1995b. Accident Analysis and Prevention 27, 571-581]. Although factor analysis of the DBQ responses of this sample produced five factors, the original three-way distinction was preserved. However the pattern of relationships between factor scores and accident involvement was different. Relatively high scores on the error factor and the lapse factor were predictive of involvement in an active accident, while passive accident involvement was associated with high scores on the lapse factor.
Accidents, Traffic↗
Identification of bacterial class I accessible proteins by disseminated insertion of class I epitopes.
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Amino Acid Sequence↗
Neuronal mechanisms of synaptic and network plasticity in the lamprey spinal cord.
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Animals↗
Judging the use of clinical protocols by fellow professionals.
The objective of this study was to investigate the judgements of British doctors, nurses and midwives about behaviour which complies with a protocol, violates a protocol, or constitutes an improvisation where no protocol exists. Primary data were collected on the judgments of hospital healthcare professionals (N = 310) from three specialties in each of three hospitals. Respondents were required to judge the appropriateness of the behaviour of a fellow professional in each of nine hypothetical scenarios generated on the basis of previous focus group discussions. They were also asked how likely they would be to report this professional to a senior member of staff. Within the scenarios, both behaviour with respect to the relevant clinical protocol and outcome for the patient were experimentally manipulated. Data were collected using a survey questionnaire. The three professional groups studied (doctors, nurses and midwives) were found to make significantly different judgements. Crucially, doctors judged the violation of a protocol as less inappropriate than did nurses or midwives. Midwives were disapproving of violations, even when the patient outcome was good. These differences were reflected in the ratings of reporting likelihood. The proliferation of clinical protocols likely to occur in Britain in the coming years will need to be managed with great care if the regulation of clinical behaviour is the goal. Particular care will be needed to avoid the exacerbation of professional tensions.
Anesthesiology↗
Luminescence imaging microscopy and lifetime mapping using kinetically stable lanthanide(III) complexes.
The sensitised luminescence from stable lanthanide complexes (1 and 2) bearing a phenanthridine antenna has been used to generate time-resolved images of silica particles. The millisecond order luminescent lifetime of these complexes is utilised to demonstrate time-gated imaging of the sample from a fluorescent background and to facilitate lifetime mapping over the area of the sample.
Europium↗
A genotypic analysis of patients receiving Zidovudine with either Lamivudine, Didanosine or Zalcitabine dual therapy using the LiPA point mutation assay to detect genotypic variation at codons 41, 69, 70, 74, 184 and 215.
BACKGROUND: The Murex-Innogenetics LiPA HIV-1 RT assay can be used to identify the presence of mutations of the reverse transcriptase gene at codons 41, 69, 70, 74, 184 and 215 of HIV-1, which have been shown to confer resistance to the nucleoside analogs Zidovudine (ZDV), Lamivudine (3TC), Didanosine (ddI) and Zalcitabine (ddC). The M184V mutation of the reverse transcriptase gene of HIV-1 has been associated with resistance to 3TC, ddC and ddI. This mutation has also been observed in patients receiving ZDV+ddC and ZDV+ddI. We used LiPA HIV-1 RT assay to identify the presence of either consensus methionine 184 or the mutant valine 184 with three groups of patients who were treated with ZDV/3TC, ZDV/ddI or ZDV/ddC combination therapy. OBJECTIVES: The aim of our study was to determine the viral genotype of patients who were considered to be failing therapy, by two ways: using sequencing and LiPA assays. In particular we were interested in establishing a possible correlation between these methods. STUDY DESIGN: The study group consisted of a consecutive series of 33 patients with a treatment failure, 18 of whom received ZDV+3TC therapy, seven received ZDV+ddI and eight received ZDV+ddC therapy. We also examined a small cohort of seven seroconverters. RESULTS: The M184V mutation was observed in 47.0% of patients receiving ZDV+3TC combination therapy but was not observed in either patient group receiving either ddI or ddC as co-therapy with ZDV. There was no evidence of the L74V mutation in our study group in either the ZDV/ddI or ZDV/ddC combination therapy group. We found the frequency of the K70R mutation to be higher in patients treated with ZDV/ddI (P=0.033) or ZDV/ddC (P=0.3) when compared with patients treated with ZDV/3TC. CONCLUSION: The LiPA assay allowed for the rapid detection of wild type and amino acid variations at key positions conferring resistance to the most used antiviral RT inhibitors. This represented a rapid, quite sensitive, and simple genotyping test. For these reasons the LiPA assay proved to be useful in studying genetic resistance in large screenings, when key RT mutations could be useful in guiding an effective HIV-1 suppressing regimen.
Anti-HIV Agents↗
Assessment and documentation of bowel care management in palliative care: incorporating patient preferences into the care regimen.
Nurses in a palliative care unit (PCU) recognized that there were several inconsistencies relating to assessment and documentation of patient preferences in bowel care management. Although bowel care is recognized as of key importance to the wellbeing of palliative care patients, there is little evidence in current literature about accommodation of patient preferences in bowel care management. A questionnaire was developed to assess whether patient preferences were elicited on admission to the PCU, were documented, and were included in the bowel care regimen. Data were collected from 100 patients in two PCUs in Australia. The findings suggested that little was assessed or documented about bowel care management on admission except functional or pharmacological information. According to patients in the study, their preferences were seldom incorporated into the bowel care regimen. Lack of documentation of bowel care preferences was also found following an audit of patient notes. Techniques for eliciting information, awareness of alternative or complementary methods of bowel care and better documentation procedures are all recommended for inclusion in nursing practice in the palliative care setting.
Adult↗
The effect of raloxifene on coronary arteries in aged ovariectomized ewes.
BACKGROUND: Ovariectomized sheep are a useful model of postmenopausal osteoporosis and other postmenopausal conditions. Estrogen may have a protective effect on the coronary arteries in postmenopausal women. The effects of raloxifene, a selective estrogen receptor modulator, on coronary arteries in aged ovariectomized ewes was investigated. METHODS AND RESULTS: Forty eight aged ewes were randomly assigned to undergo sham surgery (Sham, n = 7), ovariectomy (OVX, n = 10), ovariectomy with estradiol supplementation (OVXE, n = 8), ovariectomy with raloxifene supplementation, 0.02 mg/kg per day (RAL1, n = 10), or ovariectomy with raloxifene supplementation, 0.10 mg/kg per day (RAL2, n = 13). Contrast coronary angiography was performed 6 months after intervention. Diameters of the right main and left anterior descending coronary arteries in the RAL1, RAL2 and Sham groups were not different from each other, but were significantly greater than the OVX and OVXE groups. Intracoronary nitroglycerin did not affect the relationships of the diameters in any group. There were no differences in vascular remodeling between the groups. CONCLUSIONS: The results indicate that raloxifene in this sheep model allows greater dilation of coronary arteries than estrogen. Raloxifene may provide a significant protective functional effect on coronary arteries in postmenopausal heart disease.
Animals↗