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Biomedical subjects

L Keating

Publications and source records attributed to L Keating.

11 recordsLinked to original sources

The PRIMA study: presentation ischaemia-modified albumin in the emergency department.

OBJECTIVES: To investigate the diagnostic accuracy of presentation ischaemia-modified albumin (IMA), in addition to cardiac troponin I (TnI), as a strategy to rapidly ascribe low risk to patients with chest pain attending an emergency department, and to determine whether IMA has the potential to reduce transit time in emergency departments. METHODS: A prospective observational study was carried out in two emergency departments (belonging to the John Radcliffe Hospital, Oxford, UK; and the Frenchay Hospital, Bristol, UK) of similar size. Consecutive adult patients presenting with features of possible ischaemic cardiac chest pain and a normal electrocardiogram were eligible. The index test (measurement of IMA and TnI at presentation) and reference standard (delayed TnI measurement, taken at least 8 h after pain onset) were applied to all recruited patients. All clinicians were blinded to the results of the index test. Assays were carried out in a single laboratory using standard techniques. RESULTS: 399 patients were recruited; 277 patients had a result for both the index test and reference standard. The sensitivity was 97.6% (95% confidence interval (CI) 87.4 to 99.9), negative predictive value 97% (95% CI 84.2 to 99.9) and specificity 13.6% (95% CI 9.5 to 18.7). Sensitivity analysis showed similar findings in three alternative scenarios. Receiver operating characteristic analysis indicated that a different "cut-off" value for IMA would not improve the properties of the test. The median potential time saved (n = 268) was 6 h and 10 min. CONCLUSION: The diagnostic accuracy of presentation IMA in this study does not support its use as an effective risk stratification tool for patients with chest pain in the emergency department. The sensitivity is insufficiently high, with a small number of false negatives undermining the safety of the test. Frequent false positives produce a low specificity that limits the practical value of the test.

Adult↗

Effects of storage at -20 degrees C on ischaemia-modified albumin results.

BACKGROUND: Ischaemia-modified albumin (IMA) is being studied as a new marker for reversible ischaemia in patients presenting with possible cardiac chest pain. The conditions under which samples are stored prior to analysis may be critical in influencing the analytical result and hence the cut-off used in any particular study. METHODS: Sixty-eight samples taken during a study assessing the performance of IMA for risk stratification in patients presenting with possible cardiac chest pain were analysed both within 2.5 h of collection and after periods of storage at -20 degrees C. RESULTS: Samples stored at -20 degrees C yielded IMA values on average 3 units higher than those analysed within 2.5 h (mean 90.5 vs. 87.5; P < 0.00001). A Bland-Altman plot showed that the difference was not concentration dependent. CONCLUSIONS: These results indicate that decision cut-offs will be influenced by conditions of sample storage prior to IMA analysis, and that these should be stated in detail for each study.

Freezing↗

Electrocardiographic features of Wolff-Parkinson-White syndrome.

Wolff-Parkinson-White syndrome is not uncommon in the emergency department. Its early recognition and initial treatment allows rapid restoration to sinus rhythm. Prompt referral to cardiology is essential for risk stratification through electrophysiological studies.

Adolescent↗

Protein 4.1 in forebrain postsynaptic density preparations: enrichment of 4.1 gene products and detection of 4.1R binding proteins.

4.1 Proteins are a family of multifunctional cytoskeletal components (4.1R, 4.1G, 4.1N and 4.1B) derived from four related genes, each of which is expressed in the nervous system. Using subcellular fractionation, we have investigated the possibility that 4.1 proteins are components of forebrain postsynaptic densities, cellular compartments enriched in spectrin and actin, whose interaction is regulated by 4.1R. Antibodies to each of 4.1R, 4.1G, 4.1N and 4.1B recognize polypeptides in postsynaptic density preparations. Of these, an 80-kDa 4.1R polypeptide is enriched 11-fold in postsynaptic density preparations relative to brain homogenate. Polypeptides of 150 and 125 kDa represent 4.1B; of these, only the 125 kDa species is enriched (threefold). Antibodies to 4.1N recognize polypeptides of approximately 115, 100, 90 and 65 kDa, each enriched in postsynaptic density preparations relative to brain homogenate. Minor 225 and 200 kDa polypeptides are recognized selectively by specific anti-4.1G antibodies; the 200 kDa species is enriched 2.5-fold. These data indicate that specific isoforms of all four 4.1 proteins are components of postsynaptic densities. Blot overlay analyses indicate that, in addition to spectrin and actin, postsynaptic density polypeptides of 140, 115, 72 and 66 kDa are likely to be 4.1R-interactive. Of these, 72 kDa and 66 kDa polypeptides were identified as neurofilament L and alpha-internexin, respectively. A complex containing 80 kDa 4.1R, alpha-internexin and neurofilament L was immunoprecipitated with anti-4.1R antibodies from brain extract. We conclude that 4.1R interacts with the characteristic intermediate filament proteins of postsynaptic densities, and that the 4.1 proteins have the potential to mediate the interactions of diverse components of postsynaptic densities.

Actins↗

Mid-thoracic tenderness: a comparison of pressure pain threshold between spinal regions, in asymptomatic subjects.

Palpation for tenderness forms an important part of the manual therapy assessment for musculoskeletal dysfunction. In conjunction with other testing procedures it assists in establishing the clinical diagnosis. Tenderness in the thoracic spine has been reported in the literature as a clinical feature in musculoskeletal conditions where pain and dysfunction are located primarily in the upper quadrant. This study aimed to establish whether pressure pain thresholds (PPTs) of the mid-thoracic region of asymptomatic subjects were naturally lower than those of the cervical and lumbar areas. A within-subject study design was used to examine PPT at four spinal levels C6, T4, T6, and L4 in 50 asymptomatic volunteers. Results showed significant (P<0.001) regional differences. PPT values increased in a caudal direction. The cervical region had the lowest PPT scores, that is was the most tender. Values increased in the thoracic region and were highest in the lumbar region. This study contributes to the normative data on spinal PPT values and demonstrates that mid-thoracic tenderness relative to the cervical spine is not a normal finding in asymptomatic subjects.

Adult↗

The postsynaptic spectrin/4.1 membrane protein "accumulation machine".

An important aspect of the function of the membrane-associated cytoskeleton has been suggested to be to trap and retain selected transmembrane proteins at points on the cell surface specified by cell adhesion molecules. In the process, cell adhesion molecules are cross-linked to each other, and so junctional complexes are strengthened. In this short review, we will discuss recent advances in understanding the role of this "accumulation machine" in postsynaptic structures. Function in the brain depends on correct ordering of synaptic intercellular junctions, and in particular the recruitment of receptors and other apparatus of the signalling system to postsynaptic membranes. Spectrin has long been known to be a component of postsynaptic densities, and recent advances in molecular cloning indicate that beta spectrins at PSDs are all "long" C-terminal isoforms characterised by pleckstrin homology domains. Isoforms of protein 4.1 are also present at synapses. All four 4.1 proteins are represented in PSD preparations, but it is 4.1R that is most enriched in PSDs. 4.1R binds to several proteins enriched in PSDs, including the characteristic PSD intermediate filament, alpha-internexin. Both 4.1 and spectrin interact with ionotropic glutamate receptors (AMPA and NMDA receptors, respectively): 4.1 stabilises AMPA receptors on the cell surface. By linking these receptors to the cytoskeletal and cell adhesion molecules that specify glutamatergic synapses, the membrane protein accumulation machine is suggested to direct the formation of postsynaptic signalling complexes.

Animals↗

Rule compliance and peer sociability: a study of family process, school-focused parent-child interactions, and children's classroom behavior.

This study examined the associations among family processes (cohesion, control, and conflict), school-focused parent-child interactions (support and pressure about achievement), and the child's own characteristics (assertiveness, frustration tolerance, intellectual effectiveness, and self-esteem) as correlates of rule compliance and peer sociability in the classroom. The sample consisted of 161 Grade 4 and 151 Grade 7 children. Family processes and parent-child interactions about school issues were associated with children's personal characteristics, which, in turn, predicted children's rule compliance and peer sociability. Some differences were found between the 4th- and 7th-grade samples; however, many variables consistently predicted the same outcomes across grades.

Adolescent↗

Mechanism of action and the substrate-dependent pH maximum shift of the alpha-amylase of Bacillus coagulans.

The alpha-amylase of Bacillus coagulans is a saccharifying alpha-amylase which hydrolyses the disaccharide maltose [L. Keating, C. Kelly, and W. Fogarty, Biochem. Soc. Trans., 24 (1996) 44S]. The pH maximum for maltose hydrolysis is pH 5.0, differing from the pH maximum for starch hydrolysis which is pH 6.0. Studies using reducing end 14C-labeled maltooligosaccharides revealed a substrate-dependent pH maximum shift; hydrolysis of radiolabeled maltotriose (G3*) was maximal at pH 5.0 while the pH maximum for hydrolysis of radiolabeled maltopentaose (G5*) and maltohexaose (G6*) was pH 6.0. With maltotetraose (G4*) however, the pH maximum was pH 5.0-6.0. In addition, the bond cleavage pattern of G4* was dependent on pH. At pH 5.0, the pH maximum for maltose hydrolysis, the frequency of hydrolysis of the reducing end terminal bond of G4* was maximal. Determination of the pH maximum of the productive binding modes of the cleavage patterns of G3* to G6* illustrated the possible role of the occupation of subsite r + 2 in the pH control mechanism of B. coagulans alpha-amylase.

Bacillus↗

Improved harness crutch to reduce upper limb effort in swing-through gait.

A novel crutch, the harness crutch, is described which reduces loading on the arms during the swing phase of swing-through gait. The device was fabricated by attaching a modified mountaineering harness by two side straps, to modified axillary crutches. The harness crutch was compared with the saddle crutch, described by Taylor in 1883. The saddle crutch produced pressures in excess of 500 mmHg in the perineal area; no pressures were produced in this area with the harness crutch. Ischial pressures produced by both systems were similar. In six out of eight non-impaired subjects, significantly more force was transmitted to the harness crutch (an average 47% of body weight) than to the saddle crutch (an average 40% of body weight). A comparison of the oxygen cost of swing-through gait was made between the harness crutch and unmodified axillary crutches; with the harness crutch oxygen cost was significantly lower (p < 0.01) and there were no significant differences in speed and stride length.

Arm↗

Second fingerstick: a simple method to increase the blood supply.

Before blood donors are deferred because of a low hemoglobin determination by the copper sulfate procedure, they are routinely retested with a microhematocrit. The copper sulfate test and the microhematocrit usually are performed on blood samples taken from the same finger (or earlobe) puncture. We studied 201 male and female volunteer blood donors who failed the copper sulfate test to determine if more donors would be accepted for donation if blood from a second fingerpuncture, instead of the original fingerstick, was used for the microhematocrit determination. Venous blood samples were obtained to evaluate complete blood count and measures of iron status. The results indicated that the deferral rate was reduced by 46% using a fresh fingerpuncture for the microhematocrit determination. The iron status of the additional donors accepted on the basis of the second puncture was not significantly different from that of the donors accepted by the original fingerstick. We conclude that using a second fresh fingerpuncture for the microhematocrit determination after failing the copper sulfate test decreases the number of hematocrit deferrals and does not compromise the iron status of the additional donors.

Blood Donors↗