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Biomedical subjects

D Livingstone

Publications and source records attributed to D Livingstone.

At least 19 recordsLinked to original sources

A novel point-of-care information system reduces anaesthesiologists' errors while managing case scenarios.

BACKGROUND AND OBJECTIVES: The On-Line Electronic Help (OLEH) is a point-of-care information system for anaesthesia providers prepared by the European Society of Anaesthesiologists. In this preliminary study the effect of the OLEH availability on the incidence of knowledge-based errors during the management of case scenarios and participants' subjective evaluation of the OLEH were evaluated. METHODS: After a short training session, 48 anaesthesiologists (24 junior residents, 12 senior residents and 12 board-certified) were presented randomly with six computer screen-based case scenarios with, and six without, the option of using the OLEH. Two reviewers evaluated the answers independently according to preconfigured guidelines. RESULTS: The availability of the OLEH was associated with higher scores in 11 of the 12 scenarios, and with a decrease in the incidence of critical errors in 10 scenarios. Time to task completion was increased in one scenario only when the OLEH was used. The degree of professional experience was associated with better scores in five of the scenarios and with a reduced occurrence of critical errors in three scenarios. Forty-two out of 48 participants stated that finding information in the OLEH software was easy and that the system was helpful in managing the scenarios. CONCLUSIONS: This preliminary study demonstrates the potential value of the OLEH in decreasing the number of knowledge-based errors made by anaesthesiologists. According to the encouraging results, the OLEH system is currently under evaluation using full-scale simulation scenarios in an operating room environment.

Anesthesia↗

Pulse pressure and stroke volume variations during severe haemorrhage in ventilated dogs.

BACKGROUND: Similarly to systolic pressure variation (SPV), pulse pressure variation (PPV) and stroke volume variation (SVV) derived from arterial pulse contour analysis have been shown to reflect fluid responsiveness in ventilated patients. However, unlike the SPV, both PPV and SVV have not been validated during extreme hypovolaemia. The aim of the present study was to examine whether these newly introduced variables respond to gradual hypovolaemia like the SPV by increasing gradually with each step of the haemorrhage even during extreme hypovolaemia. METHODS: SPV, SVV and PPV were measured in 8 dogs following initial volume loading (10% of the estimated blood volume administered as colloid solution), 5 steps of graded haemorrhage, each consisting of 10% of the estimated blood volume, followed by retransfusion of the shed blood. RESULTS: The correlations of the SVV, SPV and PPV to the stroke volume (SV) throughout the study were -0.89, -0.91 and -0.91, respectively. Correlations of the CVP and the global end-diastolic volume (GEDV) of the heart chambers to the SV were 0.79 and 0.95, respectively. The SPV correlated significantly with both the PPV and the SVV (r=0.97 and 0.93 respectively). However, the PPV increased by more than 400% at 50% haemorrhage compared with increases of 200% and 120% for the SVV and %SPV, respectively. CONCLUSION: This study demonstrates that the present algorithm used for the calculation of the SVV and the formula used to calculate the PPV, perform well over a wide range of preload states including severe hypovolaemia. However, the PPV changes more than the SPV and SVV. This may be due to the changing relation of the SV to the pulse pressure when the filling of the aorta is greatly decreased.

Algorithms↗

Separase is required for chromosome segregation during meiosis I in Caenorhabditis elegans.

BACKGROUND: Chromosome segregation during mitosis and meiosis is triggered by dissolution of sister chromatid cohesion, which is mediated by the cohesin complex. Mitotic sister chromatid disjunction requires that cohesion be lost along the entire length of chromosomes, whereas homolog segregation at meiosis I only requires loss of cohesion along chromosome arms. During animal cell mitosis, cohesin is lost in two steps. A nonproteolytic mechanism removes cohesin along chromosome arms during prophase, while the proteolytic cleavage of cohesin's Scc1 subunit by separase removes centromeric cohesin at anaphase. In Saccharomyces cerevisiae and Caenorhabditis elegans, meiotic sister chromatid cohesion is mediated by Rec8, a meiosis-specific variant of cohesin's Scc1 subunit. Homolog segregation in S. cerevisiae is triggered by separase-mediated cleavage of Rec8 along chromosome arms. In principle, chiasmata could be resolved proteolytically by separase or nonproteolytically using a mechanism similar to the mitotic "prophase pathway." RESULTS: Inactivation of separase in C. elegans has little or no effect on homolog alignment on the meiosis I spindle but prevents their timely disjunction. It also interferes with chromatid separation during subsequent embryonic mitotic divisions but does not directly affect cytokinesis. Surprisingly, separase inactivation also causes osmosensitive embryos, possibly due to a defect in the extraembryonic structures, referred to as the "eggshell." CONCLUSIONS: Separase is essential for homologous chromosome disjunction during meiosis I. Proteolytic cleavage, presumably of Rec8, might be a common trigger for the first meiotic division in eukaryotic cells. Cleavage of proteins other than REC-8 might be necessary to render the eggshell impermeable to solutes.

Animals↗

Prediction of aqueous solubility for a diverse set of organic compounds based on atom-type electrotopological state indices.

We describe robust methods for estimating the aqueous solubility of a set of 734 organic compounds from different structural classes based on multiple linear regression (MLR) and artificial neural networks (ANN) model. The structures were represented by atom-type electrotopological state (E-state) indices. The squared correlation coefficient and standard deviation for the MLR with 34 structural parameters were r(2) = 0.94 and s = 0.58 for the training set of 675 compounds. For the test set of 21 compounds, the equivalent statistics were r(2)(pred) = 0.80 and s = 0.87, respectively. Neural networks gave a significant improvement using the same set of parameters, and the standard deviations were s = 0.52 for the training set and s = 0.75 for the test set when an artificial neural network with five neurons in the hidden layer was used. The results clearly show that accurate models can be rapidly calculated for the estimation of aqueous solubility for a large and diverse set of organic compounds using easily calculated structural parameters.

Linear Models↗

A soybean G2 glycinin allergen. 1. Identification and characterization.

BACKGROUND: Multiple allergens have been documented in soybean extracts. IgE from individuals allergic to soybeans, but not to peanut, was shown by immunoblot analysis to bind to proteins with a molecular weight of approximately 21 kD. These findings suggested that unique proteins in soybeans might be responsible for soybean allergic reactivity. The objective of the present study was to identify unique proteins in soybean extracts that bind to specific IgE from soybean-sensitive individuals, and to characterize the allergen using physicochemical methods and IgE binding. METHODS: Two-dimensional and preparative SDS-PAGE/IgE immunoblot analysis was used to identify a 22-kD soybean-specific allergen from crude soybean extracts. N-terminal sequence analysis was used to determine the identification of the protein binding IgE from soybean-sensitive individuals. RESULTS: IgE immunoblot and amino acid sequence analysis identified the 22-kD protein as a member of the G2 glycinin soybean protein family. Further investigation revealed that the IgEs reacted with basic chains from each member of the glycinin family of soybean storage proteins. CONCLUSIONS: Each of the subunits from glycinin, the storage protein that is the most prevalent component of soybean, are major allergens.

Allergens↗

Cellular and axonal migrations are misguided along both body axes in the maternal-effect mau-2 mutants of Caenorhabditis elegans.

We have characterized the mau-2 mutants of Caenorhabditis elegans and found that migrating cells and axons are mispositioned along both the antero-posterior and dorsoventral body axes. This is in contrast to previously characterized guidance mutations in Caenorhabditis and in Drosophila, which have been found to be axis-specific. Two observations suggest that mau-2 acts very early during development: most behavioral phenotypes of mau-2 can be rescued by a maternal effect, and variations in expressivity involve an entire body side at a time. The possibility that mau-2 is involved in the spatial organization of guidance cues encoded by other genes is discussed.

Animals↗

An intron-containing tRNAArg gene within a large cluster of human tRNA genes.

The insert within lambda Ht363, a recombinant selected from a bank of human genomic DNA cloned in lambda Ch4A, is described. Southern blot hybridization with a mixed tRNA[32P]pCp probe revealed the presence of four tRNA genes, which were shown to represent further copies of genes previously identified as a solitary tRNAGly gene and as a three gene cluster on two different recombinants. In vitro transcription of a fragment containing the three gene cluster revealed the presence of a further pol III gene, which was shown to be that for a tRNAArgTCT. This gene contains a 15 bp intron, the presence of which presumably prevented its detection on Southern blots by tRNA hybridisation. The gene is present in the previously reported cluster and occurs in higher copy number (> 7) in other arrangements in the genome. Most of the copies of the gene have related intron sequences.

Base Sequence↗

Borderline nuclear abnormality in cervical smears: a cytological review of 200 cases with histological correlation.

The cervical cytology and histology specimens from 200 patients referred to colposcopy with borderline nuclear abnormality were reviewed. Human papillomavirus (HPV)-associated changes were identified in 103 of 200 (53%) referral smears and in 139 of 150 (91%) biopsy specimens. Cervical intraepithelial neoplasia (CIN) was less frequently diagnosed on review compared with the original histopathology reports (30.7% vs 45.4%); the discrepancy was largely attributable to a lower incidence of CINI. There was agreement in the grading of borderline nuclear abnormality in 161 of 200 referral smears following review. Twenty-three smears were upgraded to mild dyskaryosis, whereas 16 were reclassified as negative.

Cervix Uteri↗

Smaller local brain volumes and cerebral atrophy in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) have enlarged cerebral ventricles from 8 weeks of age onward and smaller brains than age-matched, normotensive Wistar-Kyoto (WKY) rats (controls). At 6-7 months of age local cerebral glucose utilization is apparently lower in many brain areas of SHR relative to WKY rats. These observations led to the hypothesis that there are morphological differences between these two strains of rats in many, if not all, brain areas. This hypothesis was tested in 6-7-month-old SHR and WKY rats by quantitating 1) the volumes of the ventricular system, whole brain, six gray matter structures, and two white matter areas; 2) the thickness of two regions of the cerebral cortex; and 3) the frequency of neuronal nuclei (neuronal frequency) in nine brain areas. Ventricular volume was twofold greater in SHR than in control rats. The volumes of the entire brain and all six gray matter structures plus the thickness of the two cortical regions were 11-25% less in SHR. Neuronal frequency was, however, similar in the two rat strains. The latter finding coupled with the smaller regional tissue volumes indicates appreciably fewer neurons per brain structure in young adult SHR than in controls. These results indicate significant cerebral structural differences between young adult SHR and WKY rats and suggest that structure as well as metabolism are abnormal in the SHR brain.

Animals↗

Protein-losing enteropathy in an infant with a lymphangiomyoma.

A 3-month-old girl with intractable diarrhoea had protein-losing enteropathy secondary to a lymphangiomyoma. This is the first reported case of lymphangiomyoma in an infant. As enteral feeds were not tolerated, she was maintained on parenteral nutrition for 2 months. Pancreatic enzyme supplementation produced a rapid clinical improvement and normalization of serum albumin level. Weaning was subsequently tolerated and the vitamin, mineral, and trace element deficiencies improved. Subsequent recurrence was associated with normal pancreatic function and has proved refractory to treatment.

Adult↗

Physicochemical characteristics of non-electrolytes and their uptake by Brugia pahangi and Dipetalonema viteae.

The uptake of a diverse set of 14C-labelled non-electrolytes by Brugia pahangi and Dipetalonema viteae was measured relative to the free diffusion of tritiated water. Inulin was used as a non-absorbable surface marker to account for non-electrolyte adherent to the surface of the parasite which had not crossed the cuticle. B. pahangi and D. viteae took up the non-electrolytes to a similar degree; a comparison of tissue uptake indices gave a correlation coefficient of 0.99. Worm uptake could not be described by non-electrolyte octanol/aqueous partition coefficients alone. However, greater success was achieved using further descriptors and pattern recognition techniques for data analysis. The whole molecule descriptors log P, molar refraction, melting point, dipole moment and CNDO total energy were obtained from computer chemistry and the literature. Using a linear learning machine to relate uptake to these 5 physicochemical descriptors it was possible to successfully classify non-electrolytes as high or low uptake. Multivariate regression analysis of uptake versus these 5 parameters gave a correlation coefficient of 0.77. However, this was not statistically significant and therefore could not be used for quantitative predictions of substance uptake by worms. This illustrates the value of 'pattern recognition' techniques such as the linear learning machine. Using such 'pattern recognition' methods on a chemically related set of compounds it is anticipated that predictions of uptake can be achieved and improved upon. Such predictions could then be used in drug design.

Animals↗

Heat shock protein synthesis and cytoskeletal rearrangements occur independently of intracellular free calcium increases in Drosophila cells and tissues.

Heat shock causes significant changes in intracellular free calcium ([Ca2+]i) which occur rapidly following temperature elevation. The resting level of free calcium in single Drosophila melanogaster larval salivary gland cells measured with the fluorescent indicator fura-2 is 198 +/- 31 nM (n = 4). It increases approximately 10-fold to 1870 +/- 770 nM (n = 4), during a heat shock. When salivary glands are incubated in calcium-free, EGTA-buffered medium the resting free calcium is reduced to 80 +/- 7 nM (n = 3) and heat shock results in a 4-fold increase in free calcium to 353 +/- 90 nM (n = 3). Drosophila Kc cells show a heat shock-induced increase in [Ca2+]i from 118.4 +/- 2 nM (n = 11) to 323 +/- 18 nM. Procedures were devised to block the effects of heat shock on the increase in intracellular calcium and assess its role in the induction of heat shock proteins and in the stress-induced rearrangement of the vimentin cytoskeleton. We report here the changes in [Ca2+]i are not required for a complete induction of the heat shock response or for the collapse of the vimentin cytoskeleton.

Animals↗