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Biomedical subjects

M Hardy

Publications and source records attributed to M Hardy.

At least 19 recordsLinked to original sources

Interpretation of trauma radiographs by radiographers and nurses in the UK: a comparative study.

The purpose of this study was to identify the number of hospitals employing nurses and radiographers formally to undertake radiographic interpretation of trauma images and to compare the education undertaken by these professionals and any limitations imposed. A cross-sectional questionnaire survey of nurse and radiographer managers responsible for Accident and Emergency services within National Health Service hospitals in the UK was undertaken in January 2002. A total of 526 questionnaires were distributed. Response rates of 75.3% (n=198/263) and 69.2% (n=182/263) were received from radiographer and nurse managers, respectively. 96 nurse managers (52.7%, n=96/182) indicated that nurses within their departments were formally interpreting radiographs as part of their extended role whereas only 68 radiography managers (34.3%, n=68/198) indicated that radiographers were undertaking this role. Education to support radiographic interpretation varied markedly with 92.6% (n=63/68) of radiographers having undertaken a postgraduate qualification in image interpretation. In contrast, nurse education at all levels was more generic to the nursing role. The range of examinations which nurses and radiographers were permitted to interpret also varied markedly. Radiographic interpretation is undertaken by both nurses and radiographers. However, there is interprofessional and intraprofessional inconsistency in the range of examinations they are permitted to interpret and the level of education provided to support this role. Consequently, it can be surmised that national variation in service delivery and quality exists and a review of current service delivery strategies is recommended.

Clinical Competence↗

Noninvasive ventilation: application to the cancer patient admitted in the intensive care unit.

The objective of this retrospective study of prospectively registered patients was to determine the usefulness and efficacy of noninvasive ventilation (NIV) in cancer patients admitted to the medical intensive care unit of an European cancer hospital for a medical complication, as reflected in discharges from the intensive care unit (ICU) and from hospital. The subjects were a total of 40 consecutive cancer patients (28 with solid tumours and 12 with haematological malignancies) who required immediate or delayed NIV. Variables relating to demographic parameters, severity scores, cancer characteristics, intensive care data and hospital discharge were recorded. The complications making NIV necessary were hypoxaemic pneumonia in 32.5%, hypercapnic ventilatory failure in 30%, multifactorial respiratory failure in 17.5%, acute haemodynamic oedema in 10%, acute respiratory distress syndrome in 2.5%, alveolar haemorrhage in 2.5%, pulmonary embolism in 2.5% and lysis pneumopathy in 2.5%. Most of the patients, 57.5% and 42.5%, respectively, were discharged from the ICU and from the hospital. Among the 10 patients (25%) who required salvage invasive mechanical ventilation, only 1 was discharged from hospital. Sixty-four per cent of the solid tumour patients and 42% of those with haematological malignancies were discharged from the ICU and 50% and 25%, respectively, from the hospital. NIV thus appears to be an effective form of ventilatory support for cancer patients, including those with solid tumours.

Adult↗

Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years.

BACKGROUND: A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing tacrolimus+MMF. The present report describes results at 2 years. METHODS: Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus+MMF, CsA+MMF, or tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years. RESULTS: The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the tacrolimus+MMF, CsA+MMF, and tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P=0.06). Patients randomized to tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF. CONCLUSIONS: All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the tacrolimus treatment groups compared with the CsA group.

Administration, Oral↗

Structural studies on gastroenteritis viruses.

There are many recent advances in our understanding of the structure-function relationships in rotavirus, a major pathogen of infantile gastroenteritis, and Norwalk virus, a causative agent of epidemic gastroenteritis in humans. Rotavirus is a large (1000 A) and complex icosahedral assembly formed by three concentric capsid layers that enclose the viral genome of 11 dsRNA segments. Because of its medical relevance, intriguing structural complexity, and several unique strategies in the morphogenesis and replication, this virus has been the subject of extensive biochemical, genetic and structural studies. Using a combination of electron cryomicroscopy and computer image processing together with atomic resolution X-ray structural information, we have been able to provide not only a better description of the rotavirus architecture, but also a better understanding of the structural basis of various biological functions such as trypsin-enhanced infectivity, virus assembly and the dynamic process of endogenous transcription. In contrast to rotavirus, Norwalk virus has a simple architecture with an icosahedral capsid made of 180 copies of a single protein. We have determined the structure of the Norwalk virus capsid to a resolution of 3.4 A using X-ray crystallographic techniques. These studies have provided valuable information on domain organization in the capsid protein, and residues that may be critical for dimerization, assembly, strain-specificity and antigenicity.

Capsid↗

Attenuated LTP in hippocampal dentate gyrus neurons of mice deficient in the PAF receptor.

Platelet-activating factor (PAF), a bioactive lipid (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) derived from phospholipase A(2) and other pathways, has been implicated in neural plasticity and memory formation. Long-term potentiation (LTP) can be induced by the application of PAF and blocked by a PAF receptor (PAF-R) inhibitor in the hippocampal CA1 and dentate gyrus. To further investigate the role of PAF in synaptic plasticity, we compared LTP in dentate granule cells from hippocampal slices of adult mice deficient in the PAF-R and their age-matched wild-type littermates. Whole cell patch-clamp recordings were made in the current-clamp mode. LTP in the perforant path was induced by a high-frequency stimulation (HFS) and defined as >20% increase above baseline of the amplitude of excitatory postsynaptic potentials (EPSPs) from 26 to 30 min after HFS. HFS-induced enhancement of the EPSP amplitude was attenuated in cells from the PAF-R-deficient mice (163 +/- 14%, mean +/- SE; n = 32) when compared with that in wild-type mice (219 +/- 17%, n = 32). The incidence of LTP induction was also lower in the cells from the deficient mice (72%, 23 of 32 cells) than in the wild-type mice (91%, 29 of 32 cells). Using paired-pulse facilitation as a synaptic pathway discrimination, it appeared that there were differences in LTP magnitudes in the lateral perforant path but not in the medial perforant path between the two groups. BN52021 (5 microM), a PAF synaptosomal receptor antagonist, reduced LTP in the lateral path in the wild-type mice. However, neither BN52021, nor BN50730 (5 microM), a microsomal PAF-R antagonist, reduced LTP in the lateral perforant path in the receptor-deficient mice. These data provide evidence that PAF-R-deficient mice are a useful model to study LTP in the dentate gyrus and support the notion that PAF actively participates in hippocampal synaptic plasticity.

Animals↗

Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation.

BACKGROUND: Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation. METHODS: A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year. RESULTS: There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the tacrolimus + MMF groups. CONCLUSIONS: All regimens yielded similar acute rejection rates and graft survival, but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.

Adult↗

Multiple roles and well-being among midlife women: testing role strain and role enhancement theories.

OBJECTIVE: Research on women's multiple roles frequently adopts one of two perspectives: role strain, which argues that assuming multiple roles is detrimental to mental well-being, or role enhancement, which argues that engaging in multiple roles enhances mental well-being. We argue that the relationship between role occupancy and well-being is manifested through multiple dimensions of role experiences. We investigate the association between depressive symptomatology and various dimensions of the roles of wife, mother, paid worker, and informal caregiver to aging parents. METHODS: Data are from the 1992 wave of the Health and Retirement Study. Depressive symptomatology, measured by a subset of the CES-D scale, is the dependent variable. To assess the robustness of findings relative to different functional forms of the dependent variable, we estimate multiple regression, log-linear regression, and multinomial logit models. Independent variables include demographic characteristics, measures of role occupancy, role demands, and role satisfaction. RESULTS: Although the number of roles women assume affects their reports of depressive symptoms, once the demand and satisfaction associated with these roles is controlled, number has no effect; that is, the effect of the number of roles is indirect. DISCUSSION: Our results highlight the importance of women's perceptions of the quality of their roles in relation to their overall well-being. Future investigations of women's multiple roles should examine how roles may provide rewards, impose constraints, or generate conflict, as well as the extent to which the willingness to assume multiple roles and the reported levels of role satisfaction and mental well-being may be jointly endogenous.

Caregivers↗

Spatial reproducibility of the ring and tandem high-dose rate cervix applicator.

PURPOSE: High-dose rate (HDR) applicators for uterine cervix brachytherapy are used with increasing frequency. Because multiple HDR fractions are required for treatment, the applicator position reproducibility is of most importance. To study this effect, the clinical data from patients with uterine cervix cancer were examined retrospectively to evaluate the interfraction geometric variation of the HDR applicator and its potential treatment impact. METHODS AND MATERIALS: Eighteen patients with invasive cervical cancer who were treated with definitive radiotherapy at William Beaumont Hospital were included in the study. Patients were treated with 45-50.4 Gy megavoltage external beam to the pelvis, and 35 Gy to the prescription point A from 7 fractions of HDR brachytherapy. The 3-dimensional (3D) interfraction geometrical variation of the ring and tandem (R & T) applicator was measured using predefined reference points in the 7 sets of orthogonal simulation films obtained prior to each HDR application. Spatial reproducibility of the R & T insertion and time-trend of the R & T position variation related to patient's anatomy during the treatment course were analyzed with respect to different groups of patients who had either early or advanced disease. RESULTS: The translational variation of the applicator position for all patients was 6.5, 5.9, and 7.7 mm (one standard deviation), respectively, in the patient's superior-to-inferior (SI), right-to-left lateral (RL), and anterior-to-posterior (AP) direction. The rotational variation was 3.4, 4.6, and 6.0 degrees (one standard deviation) in the patient's coronal, transverse, and sagittal planes. When the patients were grouped based on early disease or advanced disease, the latter demonstrated substantially larger variation (factor of 2) in the applicator position than the former. Furthermore, the time-trend of position variation was observable for both groups of patients. The variations occurred primarily during the first 3 fractions. CONCLUSIONS: Based on the good spatial reproducibility observed in our study, the current clinical procedure for the HDR R & T applicator placement is reliable. Positional reproducibility of the R & T applicator is highly dependent upon the size of tumor volume, which, in turn, deviates the applicator during the early course of HDR brachytherapy. Attention to the construction of the midline block is of paramount importance.

Brachytherapy↗

Evidence that the factor used by the tapeworm, Hymenolepis diminuta, to direct the foraging of its intermediate host, Tribolium confusum, is a volatile attractant.

We have previously demonstrated that flour beetles, Tribolium confusum, are more attracted to the feces from rats with patent Hymenolepis diminuta infections than to feces from uninfected rats. The objective of this study was to determine if this effect is due to a volatile attractant. Volatile substances emitted by feces from H. diminuta-infected rats or from uninfected controls were collected by aspirating fresh rat feces, while trapping the volatiles on Porapak Q (a solid adsorbant). The volatiles were eluted from the Porapak Q with diethyl ether, and the relative attractancy of the volatiles to prestarved beetles was assessed by bioassay. More beetles were attracted to volatiles of feces from infected rats than to volatiles of feces from uninfected controls (P< or =0.0001). The magnitude of the response varied with the time in the bioassay test arena and also the concentration of the volatiles (P< or =0.0232). When the volatiles we re concentrated by aspirating more boli over a longer period of time, the beetles responded more quickly and in greater numbers to the volatiles of feces from infected rats. The experiments presented here provide the first indication that a tapeworm (H. diminuta) can enhance its chances of transmission by directing the foraging of its intermediate host (T. confusum) through the use of attractive, volatile material released from the feces of its definitive host.

Animals↗

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors mediate excitotoxicity in the oligodendroglial lineage.

We demonstrate by reverse transcriptase-polymerase chain reaction and Southern blotting that an immortalized rat oligodendroglial cell line (CG-4) expresses the non-N-methyl-D-aspartate (non-NMDA) glutamate receptor (GluR) genes GluR2-7, KA-1, and KA-2 and that nonimmortalized cells of the rat oligodendroglial lineage express the GluR1-3, GluR5-7, KA-1, and KA-2 genes. Lactic dehydrogenase release assays show that both immortalized and nonimmortalized cells of the oligodendroglial lineage are damaged by a 24-h exposure to 500 microM kainate or 5 mM L-glutamate, but not by a 24-h exposure to up to 10 mM alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). Damage is prevented by the non-NMDA GluR channel inhibitor 6-cyano-7-nitroquinoxaline-2,3-dione and is also averted if Ca2+ is removed from the culture medium. Cyclothiazide, which blocks desensitization of AMPA-preferring GluRs, increases cytotoxicity of kainate as well as inducing toxicity of AMPA. We conclude that cells of the oligodendroglial lineage express a population of AMPA-preferring and possibly also kainate-preferring GluR channels that are capable of mediating Ca(2+)-dependent excitotoxicity and that AMPA-induced cytotoxicity is blocked by desensitization of AMPA-preferring GluRs.

Animals↗

The CCK-B antagonist CI-988 increases dopamine levels in microdialysate from the rat nucleus accumbens via a tetrodotoxin- and calcium-independent mechanism.

CI-988, a water-soluble, selective cholecystokinin-B antagonist, was perfused through a microdialysis probe into the anterior nucleus accumbens, posterior nucleus accumbens, or caudate nucleus of anesthetized rats. High concentrations of CI-988 produced three- to fivefold increases in dopamine overflow, at all three sites, that were temporally correlated with the CI-988 perfusion and returned to baseline levels upon cessation of CI-988 perfusion. However, the cholecystokinin-A antagonist CAM-1481, and the relatively inactive enantiomer of CI-988, CAM-1241, also increased dopamine overflow in the nucleus accumbens. Furthermore, the ability of CI-988 to increase dopamine overflow persisted in the absence of calcium in the perfusate and was not sensitive to tetrodotoxin treatment. The mechanism by which locally administered CI-988 increases dopamine overflow appears not to be anatomically specific, not selective for one cholecystokinin receptor subtype, and may be nonvesicular.

Animals↗