Biomedical subjects
A Taylor
Publications and source records attributed to A Taylor.
Chronic pain in a family of 6 in the context of litigation.
We describe a family of 6 (2 parents and 4 children), evaluated 6 and 8 years after a minor car accident for chronic pain. A near identical complex of multiple physical, constitutional, and psychological symptoms were shared by all family members, all of whom bore the diagnosis of fibromyalgia. The case was brought to court after nearly a decade of symptomatology and extensive use of the health care system. The minor compensation awarded was consumed ultimately by legal fees. Psychosocial/personality issues and iatrogenic and medico-legal contributions in the evolution and resolution of the legal claim are discussed.
Good test--retest reliability for standard and advanced false-belief tasks across a wide range of abilities.
Although tests of young children's understanding of mind have had a remarkable impact upon developmental and clinical psychological research over the past 20 years, very little is known about their reliability. Indeed, the only existing study of test-retest reliability suggests unacceptably poor results for first-order false-belief tasks (Mayes, Klin, Tercyak, Cicchetti, & Cohen, 1996), although this may in part reflect the nonstandard (video-based) procedures adopted by these authors. The present study had four major aims. The first was to re-examine the reliability of false-belief tasks, using more standard (puppet and storybook) procedures. The second was to assess whether the test-retest reliability of false-belief task performance is equivalent for children of contrasting ability levels. The third aim was to explore whether adopting an aggregate approach improves the reliability with which children's early mental-state awareness can be measured. The fourth aim was to examine for the first time the test-retest reliability of children's performances on more advanced theory-of-mind tasks. Our results suggest that most standard and advanced false-belief tasks do in fact show good test-retest reliability and internal consistency, with very strong test-retest correlations between aggregate scores for children of all levels of ability.
Preventing transmission of bloodborne virus infections in prisons.
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Treatment of head injuries in the public sector in South Africa.
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Functional testing: ACEI renography.
Angiotensin-converting enzyme inhibition (ACEI) renography is the only imaging examination that tests directly for the presence of renovascular hypertension (RVH); other imaging examinations test only for the presence of renal artery stenosis (RAS). Consensus panels have recommended that ACEI renograms be interpreted as low, intermediate, or high probability for RVH. ACEI renography is highly accurate in patients with normal renal function and suspected RVH. In this patient population, the sensitivity and specificity of ACEI renography for RAS are approximately 90%; as an initial approach, angiography is not cost effective. Data from 10 studies evaluating cure or improvement in blood pressure in 291 patients undergoing revascularization showed the mean positive predictive value of ACEI renography to be 92%. When azotemic patients present with suspected RVH, as many as 50% of patients may have an intermediate probability ACEI renogram and the sensitivity of detecting RVH falls to approximately 80% even when intermediate and high probability tests are combined.
Trace elements and inflammation.
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Effect of protein binding on renal extraction of 131I-OIH and 99mTc-labeled tubular agents.
UNLABELLED: The clearance of 99mTc-mercaptoacetyltriglycine (MAG3) is less than the clearances of o-131I-iodohippurate (OIH) and 99mTc-labeled DD- and LL-ethylenedicysteine (EC). This difference could be associated with the lower affinity of MAG3 for the tubular transport receptor, but MAG3 is more highly protein bound than OIH and the EC isomers; protein binding could also be an important factor governing tubular extraction. To separate the effects of protein binding from tubular receptor affinity, the extraction fractions (EFs) of MAG3, OIH, and the DD, LL, and DL isomers of 99mTc-EC were measured in an isolated perfused rat kidney model using a protein-free perfusate and perfusates containing bovine serum albumin. METHODS: The right kidney was removed from the rat and perfused with modified Krebs-Henseleit buffers containing 7.5 or 2.5 g/dL bovine serum albumin or a protein-free perfusate. OIH was coinjected into the renal artery with each of the 99mTc-tracers. Protein binding was measured in each of the perfusates, and the venous outflow was collected to determine the EF. RESULTS: The protein binding of MAG3 in the albumin perfusates ranged from 87% to 95%, significantly higher than the 20%-34% range of protein binding observed with the three EC complexes (P < 0.05). In the 2.5 g/dL albumin perfusate, the EF of MAG3 was 44%, significantly less than the 57%-77% EF of the three EC complexes; in the 7.5 g/dL perfusate, the MAG3 EF fell to 18% versus 39%-45% for the EC complexes (P < 0.05). However, in the protein-free perfusate, the EF of MAG3 was 64%, equal to or higher than the 46%-62% EF of the three EC complexes. CONCLUSION: Protein binding modulates the tubular extraction of renal tracers. Protein binding and receptor affinity must be considered in the design of future renal radiopharmaceuticals as well as radiopharmaceuticals targeting other receptors.
Managing pressure ulcers: the need for pain assessment.
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Can children recall their experiences of admission to an intensive care unit?
OBJECTIVE: To perform a pilot study to prospectively determine children's ability to recall events experienced during admission to a paediatric intensive care unit. METHODS: Children's recall of the intensive care experience was evaluated, using telephone interview, at four to eight weeks and six to twelve months following discharge. Separate scores were assigned to reflect children's recall of general events and painful events. Recall was classified as either limited or extensive. Statistical analysis was performed to detect change in recall status over time and the association between the ability to recall and relevant admission variables (previous admission status, type of admission, frequency/intensity of painful procedures, length of stay and administration of analgesia/sedation). RESULTS: In a sample of 50 children, recall of general events was extensive 4-8 weeks after discharge in 29 (58%) children and extensive in 26 (52%) children 6-12 months after discharge. Recall of painful events was extensive 4-8 weeks after discharge in 15 (30%) children and 14 (28%) children at 6-12 months after discharge. Thirteen (33.3%) of the 39 children who received analgesia/sedation had extensive recall of painful events at 4-8 weeks after discharge; 12 (30.8%) children had extensive recall at 6-12 months after discharge. CONCLUSIONS: Children have the ability to recall many of their experiences related to admission to a paediatric intensive care unit and can continue to recall many of these experiences twelve months after discharge. Despite current methods for guiding titration of opiate infusions and intermittent administration of benzodiazepines, many children can recall painful experiences and general events encountered within the intensive care unit.
Audio-computer interviewing to measure HIV-risk behaviour.
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Fragile X syndrome and an isodicentric X chromosome in a woman with multiple anomalies, developmental delay, and normal pubertal development.
We report on an individual with developmental delays, short stature, skeletal abnormalities, normal pubertal development, expansion of the fragile X triplet repeat, as well as an isodicentric X chromosome. S is a 19-year-old woman who presented for evaluation of developmental delay. Pregnancy was complicated by a threatened miscarriage. She was a healthy child with intellectual impairment noted in infancy. Although she had global delays, speech was noted to be disproportionately delayed with few words until age 3.5 years. Facial appearance was consistent with fragile X syndrome. Age of onset of menses was 11 years with normal breast development. A maternal male second cousin had been identified with fragile X syndrome based on DNA studies. The mother of this child (S's maternal first cousin) and the grandfather (S's maternal uncle) were both intellectually normal but were identified as carrying triplet expansions in the premutation range. S's mother had some school difficulties but was not identified as having global delays. Molecular analysis of S's fragile X alleles noted an expansion of more than 400 CGG repeats in one allele. Routine cytogenetic studies of peripheral blood noted the presence of an isodicentric X in 81of 86 cells scored. Five of 86 cells were noted to be 45,X. Cytogenetic fra(X) studies from peripheral blood showed that the structurally normal chromosome had the fragile site in approximately 16% of the cells. Analysis of maternal fragile X alleles identified an allele with an expansion to approximately 110 repeats. FMRP studies detected the expression of the protein in 24% of cells studied. To our knowledge, this is the first patient reported with an isodicentric X and fragile X syndrome. Whereas her clinical phenotype is suggestive of fragile X syndrome, her skeletal abnormalities may represent the presence of the isodicentric X. Treatment of S with 20 mg/day of Prozac improved her behavior. In the climate of cost con trol, this individual reinforces the recommendation of obtaining chromosomes on individuals with developmental delay even with a family history of fragile X syndrome.
Neurite outgrowth in PC12 cells. Distinguishing the roles of ubiquitylation and ubiquitin-dependent proteolysis.
Nerve growth factor (NGF)-induced neurite outgrowth from rat PC12 cells was coincident with elevated (>/=2-fold) levels of endogenous ubiquitin (Ub) protein conjugates, elevated rates of formation of 125I-labeled Ub approximately E1 (Ub-activating enzyme) thiol esters and 125I-labeled Ub approximately E2 (Ub carrier protein) thiol esters in vitro, and enhanced capacity to synthesize 125I-labeled Ub-protein conjugates de novo. Activities of at least four E2s were increased in NGF-treated cells, including E2(14K), a component of the N-end rule pathway. Ubiquitylation of 125 I-labeled beta-lactoglobulin was up to 4-fold greater in supernatants from NGF-treated cells versus untreated cells and was selectively inhibited by the dipeptide Leu-Ala, an inhibitor of Ub isopeptide ligase (E3). However, Ub-dependent proteolysis of 125I-labeled beta-lactoglobulin was not increased in supernatants from NGF-treated cells, suggesting that neurite outgrowth is promoted by enhanced rates of synthesis (rather than degradation) of Ub-protein conjugates. Consistent with this observation, neurite outgrowth was induced by proteasome inhibitors (lactacystin and clasto-lactacystin beta-lactone) and was associated with elevated levels of ubiquitylated protein and stabilization of the Ub-dependent substrate, p53. Lactacystin-induced neurite outgrowth was blocked by the dipeptide Leu-Ala (2 mM) but not by His-Ala. These data 1) demonstrate that the enhanced pool of ubiquitylated protein observed during neuritogenesis in PC12 cells reflects coordinated up-regulation of Ub-conjugating activity, 2) suggest that Ub-dependent proteolysis is a negative regulator of neurite outgrowth in vitro, and 3) support a role for E2(14K)/E3-mediated protein ubiquitylation in PC12 cell neurite outgrowth.
The role of DnaK/DnaJ and GroEL/GroES systems in the removal of endogenous proteins aggregated by heat-shock from Escherichia coli cells.
The submission of Escherichia coli cells to heat-shock (45 degrees C, 15 min) caused the intracellular aggregation of endogenous proteins. In the wt cells the aggregates (the S fraction) disappeared 10 min after transfer to 37 degrees C. In contrast, the S fraction in the dnaK and dnaJ mutant strains was stable during approximately one generation time (45 min). This demonstrated that neither the renaturation nor the degradation of the denatured proteins was possible in the absence of DnaK and DnaJ. The groEL44 and groES619 mutations stabilised the aggregates to a lesser extent. It was shown by the use of cloned genes, dnaK/dnaJ or groEL/groES, producing the corresponding proteins in about 4-fold excess, that the appearance of the S fraction in the wt strain resulted from a transiently insufficient supply of the heat-shock proteins. Overproduction of the GroEL/GroES proteins in dnaK756 or dnaJ259 background prevented the aggregation, however, overproduction of the DnaK/DnaJ proteins did not prevent the aggregation in the groEL44 or groES619 mutant cells although it accelerated the disappearance of the aggregates. The properties of the aggregated proteins are discussed from the point of view of their competence to renaturation/degradation by the heat-shock system.
A review of the volatile metabolites of fungi found on wood substrates.
The holdings of eight collections of fungi have been examined for organisms isolated from wood and/or trees. Further selection of these fungi has been made according to their reported ability to produce volatile, biologically active metabolites. It is emphasized that the isolates in the collections do not necessarily produce such metabolites. The list of fungi fulfilling these conditions is slightly augmented by reports we have found in the literature, where the fungi concerned have not yet been deposited. The biochemistry of these compounds is considered with particular emphasis on their biosynthesis including that by Homo sapiens. The physiological and toxicological activity of these metabolites is reviewed especially with reference to their potential role in the complex symbioses existent in, for example, a tree. The review concludes with a discussion of areas of botany deserving increased attention in the hope that this will stimulate further work. The statements in the review are based on 173 references.
Physiological response to a short period of exercise training in patients with chronic heart failure.
BACKGROUND AND PURPOSE: Whilst cardiac rehabilitation is regularly offered to patients recovering from a myocardial infarction, people with chronic heart failure are often excluded from exercise training programmes. This study was designed to investigate the effects of eight weeks' exercise training in patients with moderate chronic heart failure. METHOD: Eight male patients entered a 16-week randomized, controlled, crossover study of two months' exercise training versus a control period. They performed supervised training three times a week and measures of indices of aerobic function and exercise tolerance were performed monthly throughout the study period. RESULTS: After training, the time walked on a treadmill during an exercise tolerance test increased from 14.8 min (95% CI; range 10.4-18.1 min) to 15.9 min (range 12.1-15.9 min). Significant changes at peak exercise levels (p < 0.05) were seen in oxygen uptake increasing from 3.4 metabolic equivalents (METs) (95% CI; range 2.6-4.2 METs) to 4.0 METs (range 3.2-4.9 METs), and in cardiac index, improving from 5.0 l/min-1/m-2 (95% CI; range 2.9-8.1 l/min-1/m-2) to 5.5 l/min-1/m-2 (range 3.0-9.4 l/min-1/m-2). Resting heart rate decreased significantly (p < 0.05), from 84 beats/min-1 (95% CI; range 73-105 beats/min-1) to 76 beats/min-1 (range 64-90 beats/min-1). Blood flow measurements by venous occlusion plethysmography showed a 21.5% decrease (range 58.5-238.9%) in resting blood flow to the lower leg and a 31.6% increase (range -7.2% to 52.5%) after submaximal exercise, but these changes were not significant (p > 0.05). All benefits were lost within two months of ceasing regular exercise. CONCLUSION: This study demonstrated that patients with moderate chronic heart failure derived beneficial physiological responses from eight weeks' exercise training, but these were soon lost after cessation of regular exercise.
Ubiquitin-dependent pathway is up-regulated in differentiating lens cells.
The mammalian eye lens is composed of two distinct types of cells, epithelial cells and fiber cells. The fiber cells are generated throughout life via continuous differentiation of epithelial cells. Differentiation of lens cells involves dramatic changes in cellular components including altered activity of the ubiquitin dependent pathway. The concentration of high mass ubiquitin conjugates in the mitotically active-, differentiating-equatorial epithelial cells was 5-10 fold higher than that observed in mitotically quiescent, non-differentiated, central epithelial cells, even though there was a significant dilution of non-crystallin proteins due to an increase in level of crystallins in the differentiating cells. Similar observations were made when differentiation was modeled by exposure of lens epithelial explants to bFGF in culture. Activities of ubiquitin-activating enzyme (E1) and ubiquitin-conjugating enzymes (E2s) in the differentiating equatorial epithelial cells were also up to 100% higher than those noted in non-differentiated central epithelial cells and E1 appears to be rate controlling for ubiquitinylation. Consistent with the higher concentrations of high mass ubiquitin conjugates, there was a trend of enhanced ability to execute ATP-dependent protein degradation in the differentiating equatorial epithelial cells as compared with degradation in the non-differentiated central epithelial cells. These data indicate that the ubiquitin dependent pathway is up-regulated during differentiation of lens cells. In the differentiated fibers, the concentration of high mass ubiquitin conjugates and relative activities of E1 and E2s were 50% lower than in the non-differentiated central epithelial cells. In comparison, the concentration of the 110 kDa E1 was unchanged in differentiated fibers. However, if the factor of dilution by the significant increase in the level of crystallins was taken into account, the level or activities of the components of ubiquitin pathway in the differentiated cells was higher than the level noted in non-differentiated cells. These data indicate that, as compared with other non-crystallin proteins, there is differential stabilization and/or synthesis of the 110 kDa E1 and some other components of the ubiquitin dependent pathway in differentiated fibers.
Severe brain injury in children: long-term outcome and its prediction using somatosensory evoked potentials (SEPs).
OBJECTIVE: To evaluate the outcome of children 1 and 5 years after severe brain injury (Glasgow Coma Score < 8) using a functional measure [Glasgow Outcome Scale (GOS)] and a health status measure (the Torrance Health State (HUI:1)) and to determine the ability of somatosensory evoked potentials (SEPs) to predict these long-term outcomes. DESIGN: Prospective study. SETTING: A 16-bed paediatric intensive care unit in a tertiary children's hospital. PATIENTS AND PARTICIPANTS: 105 children with severe brain injury. INTERVENTIONS: SEPs were recorded once in the first week after admission. Outcome was assessed 1 and 5 years after injury using the GOS and at 5 years after injury using HUI:1. MEASUREMENTS AND RESULTS: At 5 years, using the GOS, 46 (43.8%) children had a good outcome, 10 (9.5%) were moderately disabled, 2 (1.9%) severely disabled, 3 (2.9%) vegetative and 44 (41.9%) had died. At 5 years, 17 of 40 (42.5%) survivors from 1 year had changed outcomes: 12 had improved, 3 had worsened and 2 had died. For a normal SEP, positive predictive power was 85.4%, sensitivity 62.5%, specificity 87.8%, negative predictive power 67.2% and the positive likelihood ratio was 5.1. For bilaterally absent responses, positive predictive power was 90.9%, sensitivity 61.2%, specificity 94.6%; negative predictive power 73.6% and the positive likelihood ratio was 11.4. Outcomes using HUI:1 were: 30 (28.6%) had a good quality of life, 21 (20.0%) had a moderate quality of life, 7 (6.7%) a poor quality, 44 died (41.9%) and 3 (2.9%) survived in a state deemed worse than death. For a normal SEP, positive predictive power was 85.4%, sensitivity 68.6%, specificity 88.9%, negative predictive power 75.0% and the positive likelihood ratio was 6.2. For bilaterally absent responses, positive predictive power was 93.9%, sensitivity 57.4%, specificity 96.1%, negative predictive power 68.1% and the positive likelihood ratio was 14.6. CONCLUSION: The outcome for children with severe brain injury should be assessed 5 years after injury because important changes occur between 1 year and 5 years. Differences exist between outcomes assessed using the GOS and HUI:1 as they measure slightly different aspects of function. Consideration should therefore be given to using both measures. SEPs are excellent predictors of long-term outcome measured by either the GOS or the HUI:1.