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Biomedical subjects

A Thompson

Publications and source records attributed to A Thompson.

At least 37 records · Page 2Linked to original sources
PubMed2004

Patient, carer and health service outcomes of nurse-led early discharge after breast cancer surgery: a randomised controlled trial.

Patients with breast cancer who require axillary clearance traditionally remain in hospital until their wound drains are removed. Early discharge has been shown to improve clinical outcomes, but there has been little assessment of the psychosocial and financial impact of early discharge on patients, carers and the health service. This study aimed to evaluate the effectiveness of a nurse-led model of early discharge from hospital. Main outcome measures were quality of life and carer burden. Secondary outcomes included patient satisfaction, arm morbidity, impact on community nurses, health service costs, surgical cancellations and in-patient nursing dependency. A total of 108 patients undergoing axillary clearance with mastectomy or wide local excision for breast cancer were randomised to nurse-led early discharge or conventional stay. Nurse-led early discharge had no adverse effects on quality of life or patient satisfaction, had little effect on carer burden, improved communication between primary and secondary care, reduced cancellations and was safely implemented in a mixed rural/urban setting. In total, 40% of eligible patients agreed to take part. Nonparticipants were significantly older, more likely to live alone and had lower emotional well being before surgery. This study provides further evidence of the benefits of early discharge from hospital following axillary clearance for breast cancer. However, if given the choice, most patients prefer to stay in hospital until their wound drains are removed.

Aged↗
PubMed2004

Phototransposition reactions of arylboronate esters in acetonitrile and 2,2,2-trifluoroethanol.

The phototransposition (para, meta, ortho) reactions of the arylboronate esters 4-, 3-, and 2-(4',4',5',5'-tetramethyl-1',3',2'-dioxaborolanyl)toluenes (1, 2, and 3, respectively) in both acetonitrile and 2,2,2-trifluoroethanol (TFE) using 254 nm irradiation have been examined. The irradiations resulted in steady-state compositions of para (5%), meta (19%), and ortho (76%) isomers in acetonitrile starting from the ortho isomer and para (12%), meta (54%), and ortho (35%) isomers in TFE starting from the para isomer. Analysis of the (13)C NMR spectrum of the product mixture obtained from the photochemistry of the para isomer selectively deuterated at C3 and C5 (1d(2)()) revealed that the boron-substituted carbon is the active one in the phototransposition reactions in both acetonitrile and TFE. Similar results were observed for irradiations of 1 in cyclohexane. Fluorescence spectra, singlet-state lifetimes, and Stern-Volmer quenching of fluorescence with 2,3-dimethyl-1,3-butadiene indicated that the excited singlet states of these three isomers were spectroscopic minima and that the excited singlet state was the reactive one for 3 in acetonitrile.

Journal Article↗
PubMed2004

Structure determination of the extracellular xylanase from Geobacillus stearothermophilus by selenomethionyl MAD phasing.

Xylanases are hemicellulases that hydrolyze the internal beta-1,4-glycoside bonds of xylan. The extracellular thermostable endo-1,4-beta-xylanase (EC 3.2.1.8; XT6) produced by the thermophilic bacterium Geobacillus stearothermophilus T-6 was shown to bleach pulp optimally at pH 9 and 338 K and was successfully used in a large-scale biobleaching mill trial. The xylanase gene was cloned and sequenced. The mature enzyme consists of 379 amino acids, with a calculated molecular weight of 43 808 Da and a pI of 9.0. Crystallographic studies of XT6 were performed in order to study the mechanism of catalysis and to provide a structural basis for the rational introduction of enhanced thermostability by site-specific mutagenesis. XT6 was crystallized in the primitive trigonal space group P3(2)21, with unit-cell parameters a = b = 112.9, c = 122.7 A. A full diffraction data set for wild-type XT6 has been measured to 2.4 A resolution on flash-frozen crystals using synchrotron radiation. A fully exchanged selenomethionyl XT6 derivative (containing eight Se atoms per XT6 molecule) was also prepared and crystallized in an isomorphous crystal form, providing full selenium MAD data at three wavelengths and enabling phase solution and structure determination. The structure of wild-type XT6 was refined at 2.4 A resolution to a final R factor of 15.6% and an R(free) of 18.6%. The structure demonstrates that XT6 is made up of an eightfold TIM-barrel containing a deep active-site groove, consistent with its 'endo' mode of action. The two essential catalytic carboxylic residues (Glu159 and Glu265) are located at the active site within 5.5 A of each other, as expected for 'retaining' glycoside hydrolases. A unique subdomain was identified in the carboxy-terminal part of the enzyme and was suggested to have a role in xylan binding. The three-dimensional structure of XT6 is of great interest since it provides a favourable starting point for the rational improvement of its already high thermal and pH stabilities, which are required for a number of biotechnological and industrial applications.

Amino Acid Sequence↗
PubMed2004

Differential expression of 11beta-hydroxysteroid dehydrogenase types 1 and 2 mRNA and glucocorticoid receptor protein during mouse embryonic development.

Accumulating evidence suggests that the actions of glucocorticoids in target tissues are critically determined by the expression of not only the glucocorticoid receptor (GR) but also the glucocorticoid-metabolizing enzymes, known as 11beta-hydroxysteroid dehydrogenase types 1 and 2 (11beta-HSD1 and 11beta-HSD2). To gain insight into the role of glucocorticoids in fetal development, the expression patterns of the two distinct 11beta-HSD isozymes and GR were studied in the mouse embryo from embryonic day 12.5 (E12.5, term = E19) to postnatal day 0.5 (P0.5) by in situ hybridization and immunohistochemistry, respectively. 11beta-HSD1 mRNA was detected in the heart as early as E12.5 and maintained thereafter. In the lung and liver, 11beta-HSD1 mRNA was first detected between E14.5 and E16.5, increased to high levels towards term and maintained after birth. Relatively low levels of 11beta-HSD1 mRNA were also detected in the kidney, adrenal glands and gastrointestinal tract at E18.5. However, the mRNA for 11beta-HSD1 was undetectable in all other embryonic tissues including the brain. In contrast, kidney was the only organ that expressed appreciable levels of 11beta-HSD2 mRNA during embryonic life. The level of 11beta-HSD2 mRNA in the kidney increased dramatically in the newborn, which coincided with expression of 11beta-HSD2 mRNA in the whisker follicle, tooth and salivary gland. Distinct from the profiles of 11beta-HSD1 and 11beta-HSD2 mRNA, GR protein was detectable in all tissues at all ages studied except for the thymus, salivary gland, and bone. Taken together, the present study demonstrates that tissue- and developmentally-stage specific expression of 11beta-HSD1 and 11beta-HSD2 as well as GR occurs in the developing mouse embryo, thus highlighting the importance of these two enzymes and GR in regulating glucocorticoid-mediated maturational events in specific tissues during murine embryonic development.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2004

Rounded atelectasis in an asbestos exposed worker.

The case history is presented of a 51-year-old electrical power worker with a history of asbestos exposure presenting with rounded atelectasis. No other radiological markers of asbestos exposure were present. A documented history of asbestos exposure and exclusion of other causes of rounded atelectasis led to the diagnosis of asbestos related rounded atelectasis. It is important to understand that rounded atelectasis can be an isolated finding due to asbestos exposure. This facilitates investigation of lung masses of unknown etiology and initiation of appropriate follow up of patients at risk for future development of more debilitating asbestos related pathology.

Asbestos↗
PubMed2004

Thrombopoietin, flt3-ligand and c-kit-ligand modulate HOX gene expression in expanding cord blood CD133 cells.

Haemopoietic stem/progenitor cell (HSPC) development is regulated by extrinsic and intrinsic stimuli. Extrinsic modulators include growth factors and cell adhesion molecules, whereas intrinsic regulation is achieved with many transcription factor families, of which the HOX gene products are known to be important in haemopoiesis. Umbilical cord blood CD133+ HSPC proliferation potential was tested in liquid culture with 'TPOFLK' (thrombopoietin, flt-3 ligand and c-kit ligand, promoting HSPC survival and self-renewal), in comparison to 'K36EG' (c-kit-ligand, interleukins-3 and -6, erythropoietin and granulocyte colony-stimulating factor, inducing haemopoietic differentiation). TPOFLK induced a higher CD133+ HSPC proliferation (up to 60-fold more, at week 8) and maintained a higher frequency of the primitive colony-forming cells than K36EG. Quantitative polymerase chain reaction analysis revealed opposite expression patterns for specific HOX genes in expanding cord blood CD133+ HSPC. After 8 weeks in liquid culture, TPOFLK increased the expression of HOX B3, B4 and A9 (associated with uncommitted HSPC) and reduced the expression of HOX B8 and A10 (expressed in committed myeloid cells) when compared to K36EG. These results suggest that TPOFLK induces CD133+ HSPC proliferation, self-renewal and maintenance, up-regulation of HOX B3, B4 and A9 and down-regulation of HOX B8 and A10 gene expression.

AC133 Antigen↗
PubMed2004

Outcome measures for multiple sclerosis clinical trials: relative measurement precision of the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite.

We compared the relative measurement precision (RMP) of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) for discriminating between groups of patients known to differ in their extent of multiple sclerosis (MS). A total of 133 patients were rated with the EDSS and MSFC and had magnetic resonance imaging (MRI) scans. Patients were grouped on the basis of MRI appearances (T1- and T2-weighted lesion loads, parenchymal and ventricular fractions--T1LL, T2LL, PF, VF, respectively) and RMP was determined using the method of group differences. For each MRI parameter, the total sample was arranged in ascending order of magnitude and divided into two, three, four and five similar sized groups. For each division (two, three, four or five groups), EDSS and MSFC scores for the groups were compared using parametric (paired samples t-tests, one-way ANOVA) and nonparametric (Wilcoxon's rank-sum test, Kruskal-Wallis analysis of variance) statistical methods and RMP was estimated. The EDSS and MSFC were correlated substantially (r = -0.64). Relative to the MSFC, the EDSS had inferior measurement precision regardless of the number of groups into which the total sample was divided, or the statistical method. However, the RMP of the EDSS compared with the MSFC varied from 2% to 86%. Results suggest the MSCF is better than the EDSS for detecting differences between groups of patients, defined by these MRI markers of MS. However, the finding that both scales correlated weakly with MRI markers, indicated that they are limited as predictors of MS pathology as defined by MRI. An explanation for this well-established clinical-MRI paradox is that rating scales and MRI measure fundamentally different manifestations of MS.

Adolescent↗
PubMed2004

Non spiral and spiral (helical) flow patterns in stenoses. In vitro observations using spin and gradient echo magnetic resonance imaging (MRI) and computational fluid dynamic modeling.

AIM: Physiological blood flow patterns are themselves poorly understood despite their impact on arterial disease. Stable spiral (helical) laminar flow (SLF) has been observed in normal subjects. The purpose of the present study is to develop a method of magnetic resonance (MR) flow pattern visualization and to analyze spiral and non-spiral flow patterns with and without luminal narrowing in vitro. The flow conditions were then modeled using computational fluid dynamics (Star-CD). METHODS: Laminar integrity was examined in a flow-rig using spin and gradient echo magnetic resonance imaging (MRI) in non-stenosed and stenosed conduits in the presence of non-spiral and spiral flow. RESULTS: No difference was observed in a non-stenosed conduit between non-spiral and spiral flow. In the presence of a stenosis spiral flow preserves flow velocity coherence whereas non-spiral flow increasingly lost coherence beginning proximal to the stenosis. Computational fluid dynamic modeling of the in vitro experiment showed marked differences between the 2 flow patterns. Non-spiral flow produced greater inwardly directed forces just beyond the stenosis and greater outward pressures at more distal sites. The near wall turbulent energy was up to 700% less with spiral flow over non-spiral flow beyond the stenosis. CONCLUSIONS: Spiral flow appears to offer clear flow profile stabilizing advantages over non-spiral flow, by significantly reducing the turbulence caused by a stenosis. Spiral flow also produces lower forces acting on the vessel wall.

Blood Flow Velocity↗
PubMed2003

Adjuvant and neoadjuvant therapy for gastric cancer using epirubicin/cisplatin/5-fluorouracil (ECF) and alternative regimens before and after chemoradiation.

Chemoradiation is now used more commonly for gastric cancer following publication of the US Intergroup trial results that demonstrate an advantage to adjuvant postoperative chemoradiotherapy. However, there remain concerns regarding the toxicity of this treatment, the optimal chemotherapy regimen and the optimal method of radiotherapy delivery. In this prospective study, we evaluated the toxicity and feasibility of an alternative chemoradiation regimen to that used in the Intergroup trial. A total of 26 patients with adenocarcinoma of the stomach were treated with 3D-conformal radiation therapy to a dose of 45 Gy in 25 fractions with concurrent continuous infusional 5-fluorouracil (5-FU). The majority of patients received epirubicin, cisplatin and 5-FU (ECF) as the systemic component given before and after concurrent chemoradiation. The overall rates of observed grade 3 and 4 toxicities were 38 and 15%, respectively. GIT grade 3 toxicity was observed in 19% of patients, while haematologic grade 3 and 4 toxicities were observed in 23%. Our results suggest that this adjuvant regimen can be delivered safely and with acceptable toxicity. This regimen forms the basis of several new studies being developed for postoperative adjuvant therapy of gastric cancer.

Adenocarcinoma↗
PubMed2003

Neutralizing antibodies during treatment of secondary progressive MS with interferon beta-1b.

OBJECTIVE: To investigate the relationship between neutralizing antibodies (NAB) and disease progression, relapses, and MR measures of MS. METHODS: Sequential serum samples from all 718 patients of the European Study Group in Interferon beta-1b in Secondary Progressive MS were analyzed to investigate relations between NAB and disease progression, relapses, and MR measures. RESULTS: This study showed no attenuating effect of NAB development on progression in disability. The effects of NAB on relapse rate showed substantial variation, depending on the statistical approach and definition of positivity, though analyses comparing low- and high-NAB+ periods with NAB- periods suggested a titer-related effect. MR T2 lesion volume changes from baseline were significantly higher for NAB+ patients but remained lower than for placebo patients. A substantial proportion of NAB+ patients became NAB-. No untoward effect of NAB development on safety was observed. CONCLUSION: These results support the conclusion that even though high NAB titers appear to have impact on treatment efficacy with respect to relapses, treatment decisions should be based primarily on clinical grounds.

Adult↗
PubMed2003

Amylase-binding proteins A (AbpA) and B (AbpB) differentially affect colonization of rats' teeth by Streptococcus gordonii.

Streptococcus gordonii produces two alpha-amylase-binding proteins, AbpA and AbpB, that have been extensively studied in vitro. Little is known, however, about their significance in oral colonization and cariogenicity (virulence). To clarify these issues, weanling specific pathogen-free Osborne-Mendel rats, TAN : SPFOM(OM)BR, were inoculated either with wild-type strains FAS4-S or Challis-S or with strains having isogenic mutations of abpA, abpB, or both, to compare their colonization abilities and persistence on the teeth. Experiments were done with rats fed a sucrose-rich diet containing low amounts of starch or containing only starch. The mutants and wild-types were quantified in vivo and carious lesions were scored. In 11 experiments, S. gordonii was a prolific colonizer of the teeth when rats were fed the sucrose (with low starch)-supplemented diet, often dominating the flora. Sucrose-fed rats had several-fold higher recoveries of inoculants than those eating the sucrose-free, starch-supplemented diet, regardless of inoculant type. The strain defective in AbpB could not colonize teeth of starch-only-eating rats, but could colonize rats if sucrose was added to the diet. Strains defective in AbpA surprisingly colonized better than their wild-types. A double mutant deficient in both AbpA and AbpB (abpA/abpB) colonized like its wild-type. Wild-types FAS4-S and Challis-S had no more than marginal cariogenicity. Notably, in the absence of AbpA, cariogenicity was slightly augmented. Both the rescue of colonization by the AbpB- mutant and the augmentation of colonization by AbpA- mutant in the presence of dietary sucrose suggested additional amylase-binding protein interactions relevant to colonization. Glucosyltransferase activity was greater in mutants defective in abpA and modestly increased in the abpB mutant. It was concluded that AbpB is required for colonization of teeth of starch-eating rats and its deletion is partially masked if rats eat a sucrose-starch diet. AbpA appears to inhibit colonization of the plaque biofilm in vivo. This unexpected effect in vivo may be associated with interaction of AbpA with glucosyltransferase or with other colonization factors of these cells. These data illustrate that the complex nature of the oral environment may not be adequately modelled by in vitro systems.

Animals↗
PubMed2003

Expression of beta2 adrenoreceptors on peripheral blood mononuclear cells in patients with primary and secondary progressive multiple sclerosis: a longitudinal six month study.

BACKGROUND: Beta(2) adrenoreceptor expression on peripheral blood mononuclear cells is increased in progressive multiple sclerosis. This increase has been correlated with disease activity in relapsing-remitting multiple sclerosis. OBJECTIVE: To determine the beta(2) adrenoreceptor expression in primary and secondary progressive multiple sclerosis in relation to findings on magnetic resonance imaging (MRI) and clinical disease activity. METHODS: 10 patients with multiple sclerosis were studied (five with primary progressive and five with secondary progressive forms of the disease) over a period of six months. Monthly clinical and MRI assessments of the brain and spinal cord were carried out. Beta(2) adrenoreceptor expression was assessed monthly using a ligand binding assay with [(125)I]iodocyanopindolol. Expression of beta(2) adrenoceptors on peripheral blood mononuclear cells was also assessed in five normal controls over a similar period. RESULTS: The mean (SEM) value of beta(2) adrenoreceptor density for the five normal controls was 1346 (183) sites/cell, with affinity Kd of 120 (40) pM. MRI disease activity in primary progressive multiple sclerosis was reported on two occasions and on those occasions the expression of beta(2) adrenoreceptors was increased in excess of 1900 sites/cell; in the remaining 28 observations beta(2) adrenoreceptor expression was within the normal range (800 to 1900 sites/cell). In patients with secondary progressive disease, MRI disease activity was observed on 16 occasions. In these patients expression of beta(2) adrenoreceptors was increased in excess of 2000 sites/cell in all measurements except in one subject who did not show MRI activity throughout the six months period of study. The affinity of the receptors was within the normal range in all cases. CONCLUSIONS: Increased expression of beta(2) adrenoreceptors was correlated with MRI disease activity in two patients with primary progressive multiple sclerosis. In secondary progressive multiple sclerosis, increased expression of beta(2) adrenoreceptors tended not to correlate with MRI disease activity. This may reflect a persistent Th1 immune reaction in the secondary progressive form of the disease.

Adult↗