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Biomedical subjects

A Brown

Publications and source records attributed to A Brown.

At least 181 records · Page 10Linked to original sources
PubMed1998

Re-engineering the elective surgical service of a tertiary hospital: a historical controlled trial.

OBJECTIVE: To study the clinical effects of re-engineering the processes associated with elective surgery. DESIGN: A prospective, historical controlled trial. Control patients were enrolled from March 1995 to January 1996, and postintervention patients from February 1996 to October 1996. SETTING: A major teaching, tertiary care hospital (Prince of Wales Hospital, Sydney). PATIENTS: 224 patients (123 before and 101 after the intervention) undergoing elective herniorrhaphy of laparoscopic cholecystectomy who lived in the local area. INTERVENTION: Introduction of a re-engineered surgical service consisting of preadmission assessment and education, admission on day of surgery, and postacute care after discharge. There were no changes to the operative methods or infection control procedures. MAIN OUTCOME MEASURES: Length of stay, operative complications, pain scores and patient satisfaction. RESULTS: The risk of a patient suffering one or more complications was reduced in the postintervention group (postintervention v. control patients: 25.7% v. 38.2%; relative risk [RR], 0.66; 95% confidence interval [CI], 0.44-0.98; P = 0.035) because of a reduced risk of wound infections (5.0% v. 16.3%; RR, 0.30; 95% CI, 0.12-0.78; P = 0.0075). Other complications (perioperative or postoperative) and pain scores were unchanged. Patients treated by the re-engineered service had a significantly shorter length of stay, reported a higher level of satisfaction with the preoperative and postdischarge care, and were more likely to say that they would have the same treatment again (92.9% v 82.6%; P = 0.037). CONCLUSIONS: Re-engineering surgical services, with an associated reduction in length of stay, does not lead to a deterioration in care and may decrease postoperative complications and increase patient satisfaction.

Australia↗
PubMed1998

Protein recovery using gas-liquid dispersions.

Two separation techniques, foam separation and colloidal gas aphrons (CGAs), both of which are based on gas-liquid dispersions, are compared as potential applications for protein recovery in downstream processing. The potential advantages of each method are described and the concentration and selectivity achieved with each method, for a range of proteins is discussed. The physical basis of foam separation is the preferential adsorption of surface active species at a gas-liquid interface, with surface inactive species remaining in bulk solution. When a solution containing surface active species is sparged with gas, a foam is produced at the surface: this foam can be collected, and upon collapse contains surface active species in a concentrated form. CGAs are microbubble dispersions (bubble diameters 10-100 microm) with high gas hold ups (>50%) and relatively high stability, which are formed by stirring a surfactant solution at speeds above a critical value (typically around 5000 rpm). It is expected that when proteins are brought into contact with aphrons, protein adsorbs to the surfactant through electrostatic and/or hydrophobic forces. The aphron phase can be separated easily from the bulk solution due to its buoyancy, thus allowing separation of protein in a concentrated form.

Chemistry Techniques, Analytical↗
PubMed1998

The incidence and prevalence of HIV infection among childbearing women living in Edinburgh city, 1982-1995.

OBJECTIVE: To track the complete course of the HIV epidemic among women from the city of Edinburgh who delivered babies during 1982-1995. METHODS: The performance of the modified Serodia HIV test on dried blood spots from archived neonatal metabolic screening cards stored for up to 11 years was evaluated by testing 221 cards from neonates whose mothers' HIV infection status was already known (100 HIV-positive, 121 HIV-negative). Unlinked anonymous HIV testing of cards from neonates born during 1982-1989 was then performed and the resulting prevalence data were combined with existing data from 1990-1995. Maximum and minimum limits of HIV incidence among women during the 36-month period prior to delivery were calculated using data held on a clinical database of HIV-infected pregnant women that had been generated under strict conditions of confidentiality; these data included the date of the woman's first HIV-positive and, if available, last HIV-negative specimen. RESULTS: The evaluation revealed a sensitivity of 91%, not clearly related to storage time, and a specificity of 100%. HIV infection first entered Edinburgh's childbearing population during the early 1980s with prevalence peaking at 0.4% in 1986 and then decreasing to 0.1% in 1995; a similar incidence profile was seen during this period. Since 1986, the first full year that HIV testing was available, 78% of all infections were known during the pregnancy, 13% were identified retrospectively, and only 10% (10 cases) remain unaccounted for. For infected cases during 1984-1987, 78% were injecting drug users (IDU) and only 22% acquired their infection sexually; this distribution had reversed by 1992-1995. CONCLUSION: HIV testing of neonatal metabolic screening cards stored for up to 11 years can yield results of sufficient accuracy for epidemiological purposes. There has been a substantial decline in the prevalence and incidence of HIV since the mid-1980s. Although new infections are still occurring, the numbers are small. The decline may largely be explained by the impact of preventive measures on the spread of HIV amongst IDU, and thus from IDU to their sexual partners.

Cohort Studies↗
PubMed1998

Transmembrane-truncated alphavbeta3 integrin retains high affinity for ligand binding: evidence for an 'inside-out' suppressor?

The molecular mechanisms of alphavbeta3 integrin affinity regulation have important biological implications in tumour development, wound repair and angiogenesis. We expressed, purified and characterized recombinant forms of human alphavbeta3 (r-alphavbeta3) and compared the activation state of these with alphavbeta3 in its cellular environment. The ligand specificity and selectivity of recombinant full-length and double transmembrane truncations of r-alphavbeta3 cloned in BacPAK6 vectors and expressed in Sf9 and High Five insect cells were compared with those of native placental alphavbeta3 and the receptor in situ on the cell surface. r-alphavbeta3 integrins were purified by affinity chromatography from detergent extracts of cells (full-length), and from the culture medium of cells expressing double-truncated r-alphavbeta3. r-alphavbeta3 had the same epitopes, ligand-binding specificities, bivalent cation requirements and susceptibility to RGD-containing peptides as native alphavbeta3. On M21-L4 melanoma cells, alphavbeta3 mediated binding to vitronectin, but not to fibrinogen unless activated with Mn2+. Non-activated alphaIIbbeta3 integrin as control in M21-L-IIb cells had the opposite profile, mediating binding to fibrinogen, but not to vitronectin unless activated with Mn2+. Thus these receptors had moderate to low ligand affinity. In marked contrast, purified alphavbeta3 receptors, with or without transmembrane and cytoplasmic domains, were constitutively of high affinity and able to bind strongly to vitronectin, fibronectin and fibrinogen under physiological conditions. Our data suggest that, in contrast with the positive regulation of alphaIIbbeta3 in situ, intracellular controls lower the affinity of alphavbeta3, and the cytoplasmic domains may act as a target for negative regulators of alphavbeta3 activity.

Amino Acid Sequence↗
PubMed1998

Systematic study of the six cysteines of the E1 subunit of the pyruvate dehydrogenase multienzyme complex from Escherichia coli: none is essential for activity.

Variants of the Escherichia coli 1-lip pyruvate dehydrogenase multienzyme complex (1-lip PDHc) with the C259N and C259S substitutions in the putative thiamin diphosphate-(ThDP-) binding motif of the pyruvate dehydrogenase component (E1, EC 1.2.4.1) were characterized. Single substitutions were made at the five remaining cysteines of the E1 component, creating the C120A, C575A, C610A, C654A, and C770S variants to test the hypothesis that the activity loss that accompanies exposure of the enzyme to fluoropyruvate, bromopyruvate, and 2-oxo-3-butynoic acid is the result of the modification of approximately one cysteine residue per E1 monomer. Surprisingly, all single cysteine E1 variants could be reconstituted with E2-E3 subcomplex and showed PDHc activity ranging from 74% to 96% that of the parental enzyme. The specific activities of C259N and C259S variants of 1-lip PDHc were 58% and 27% relative to that of the parental 1-lip PDHc. All five single cysteine E1 variants, along with the C259N and C259S variants of 1-lip PDHc, could also (1) be inactivated with fluoropyruvate and 2-oxo-3-butynoic acid, (2) were subject to inactivation by the monoclonal antibody 18A9 reported from one of our laboratories, and (3) were subject to regulation by pyruvate and acetyl-CoA. It was therefore concluded that none of the six cysteine residues is essential for the activity of the E1 component or of the complex. When tested with the putative transition-state analogue, thiamin 2-thiothiazolone diphosphate, all but the C259S and C259N variants were very potently inhibited, the stoichiometry for parental E1 being about 1.6 mol of inhibitor/mol of E1 subunit. The C259S and C259N E1 variants required at least 25-fold greater inhibitor concentration to achieve the same level of inhibition. C259 is located in the putative thiamin diphosphate-binding motif of the enzyme [more exactly, it is adjacent to a ligand to the Mg(II) ion]. It is therefore concluded that thiamin 2-thiothiazolone diphosphate is not a transition-state analogue; rather, it is a potent inhibitor of the complex because of a specific interaction with the C259 residue.

Acetyl Coenzyme A↗
PubMed1998

The Human PAX6 Mutation Database.

The Human PAX6 Mutation Database contains details of 94 mutations of the PAX6 gene. A Microsoft Access program is used by the Curator to store, update and search the database entries. Mutations can be entered directly by the Curator, or imported from submissions made via the World Wide Web. The PAX6 Mutation Database web page at URL http://www.hgu.mrc.ac.uk/Softdata/PAX6/ provides information about PAX6, as well as a fill-in form through which new mutations can be submitted to the Curator. A search facility allows remote users to query the database. A plain text format file of the data can be downloaded via the World Wide Web. The Curation program contains prior knowledge of the genetic code and of the PAX6 gene including cDNA sequence, location of intron/exon boundaries, and protein domains, so that the minimum of information need be provided by the submitter or Curator.

Computer Communication Networks↗
PubMed1998

Correlation analysis of somatosensory evoked potential waveforms: clinical applications.

OBJECTIVE: To assess the validity of the correlation coefficient (CC) as a diagnostic tool in evaluating somatosensory evoked potential (SEP) waveforms. DESIGN: SEP waveforms were recorded over the spine and scalp in response to tibial nerve stimulation at the ankle for 30 patients. SETTING: A general community, ambulatory, private referral center. PATIENTS: Patients were all ambulatory and were selected randomly from among existing patient records at the medical center. MAIN OUTCOME MEASURE: The test for validity uses the CC to verify reproducibility. The test for side-to-side symmetry uses the CC to obtain a measure of similarity between left and right tibial scalp responses. For both tests, a table is presented with CCs for normal subjects. If the CC for each patient falls below the appropriate critical value from the table, then the CC is taken to be abnormal; p values are provided at specific levels in this table. RESULTS: A new data base for the means and critical values of CCs with corresponding p values is established for normal subjects. Most of the patient data reveal significant CC nonreproducibility and lack of symmetry in tibial scalp SEP waveforms. CONCLUSION: The CC provides objective and quantitative waveform information that complements latency and amplitude measurements in the clinical interpretation of tibial scalp SEP waveforms.

Algorithms↗
PubMed1998

Rate of accumulation of Luxol Fast Blue staining material and mitochondrial ATP synthase subunit 9 in motor neuron degeneration mice.

The rate of accumulation of Luxol Fast Blue staining material in the hippocampus of motor neuron degeneration (mnd/mnd) mice, a model of Batten Disease, was quantitated. Stained material increased linearly up to 8 months of age. A quantitative immunoassay was used to measure levels of mitochondrial ATP synthase subunit 9 in brain and liver of mnd/mnd mice. Levels of subunit 9 increased progressively throughout the lifespan of mnd/mnd mice reaching levels approximately 5-fold higher than in control animals. The rate of accumulation of subunit 9 is not consistent with any simple complete or partial degradation defect that is constant throughout the animal's life. Two more complicated models are discussed which are consistent with the observed accumulation rate of subunit 9.

Animals↗
PubMed1998

Spread of the multiresistant Iberian clone of methicillin-resistant Staphylococcus aureus (MRSA) to Italy and Scotland.

The multidrug-resistant "Iberian" clone of methicillin-resistant Staphylococcus aureus (MRSA) was first identified on the basis of its unique DNA fingerprints as the strain responsible for the massive 1989 outbreak of MRSA disease in the hospital Princeps d'Espanya, Barcelona, Spain. Most Iberian MRSA carry a constitutive beta-lactamase. They are resistant to most beta-lactam antibiotics, macrolides, aminoglycosides, tetracycline, rifampin and ciprofloxacin and are susceptible to fosfomycin, fusidic acid, mupirocin, sulfamethoxazole/trimethoprim and vancomycin. The characteristic DNA fingerprints of the clone include the mecA polymorph I, Tn554 pattern E (or its variants), a chromosomal macrorestriction pattern (pulsed-field gel electrophoretic type) A (or its subtype variants), the lack of the mecI regulatory gene and a homogeneous, high level of expression of methicillin resistance. Molecular surveillance studies have documented the extensive spread of this clone to many Portuguese hospitals during the 1990s. In this article, we describe the spread of the Iberian MRSA to hospitals in Rome, Italy, and Scotland.

Anti-Bacterial Agents↗
PubMed1998

Risk of admission within 4 weeks of discharge of elderly patients from the emergency department--the DEED study. Discharge of elderly from emergency department.

OBJECTIVE: to identify risk factors for admission for patients aged 75 years and older after discharge from the emergency department (DEED: discharge of elderly from emergency department). DESIGN: Prospective evaluation of discharged elderly patients from the emergency department who were followed up after 4 weeks. SETTING: emergency department of a teaching hospital for 1 year. SUBJECTS: patients aged 75 and over discharged to their home or hostel. MAIN OUTCOME MEASURES: demographic data, indices of function and cognitive status and admission to hospital within 4 weeks. RESULTS: 468 patients aged 75 and over (mean age 81.7 years; range 75-98) were enrolled; 80 patients (17.1%) were admitted to hospital during the subsequent 4 weeks. Risk factors for admission included dependence in the following activities of daily living (relative risk; 95% confidence interval): bathing (2.41; 1.32-4.41); dressing (2.38; 1.22-4.63); stairs (1.60; 1.09-2.33); finance (1.66; 1.23-2.25); shopping (1.39; 1.12-1.73) and transport (1.61; 1.25-2.06), as well as use of a community nurse (1.88; 1.12-3.17). Logistic regression analysis found two variables to be significant in predicting admission or not: dependence in transport and use of a community nurse. CONCLUSIONS: older patients are at increased risk of readmission within 4 weeks of being sent home from the emergency department. It is possible to identify high-risk patients by a questionnaire. This allows targeting of these patients for more intensive follow-up in an attempt to ameliorate further deteriorations in their health.

Activities of Daily Living↗
PubMed1998

Genistein modulates neuroblastoma cell proliferation and differentiation through induction of apoptosis and regulation of tyrosine kinase activity and N-myc expression.

Genistein is a specific inhibitor of protein tyrosine kinase (PTK) and is considered as a therapeutic candidate for various cancers. In this paper we investigate the effects of genistein on cell proliferation and differentiation in neuroblastoma (NB) cell lines and its possible mechanism of action. Genistein substantially inhibited the growth of five (N2A, JC, SKNSH, MSN and Lan5) of the six tumor cell lines examined in a dose-dependent manner with an IC50 value of approximately 5 microg/ml. The exception was GC cells. N2A cells were treated with genistein for 6 days and exhibited morphological features of differentiation, as evidenced by the development of dendritic extensions. Terminal deoxynucleotidyl transferase (TDT) histochemical staining showed a significant elevation in darkly stained nuclei in genistein-treated N2A cells compared with controls, indicating the occurrence of apoptosis. Fluorescent quantitation of DNA fragments confirmed apoptosis in genistein-treated N2A cells. To further elucidate the possible mechanisms by which genistein modulates NB cell growth and differentiation we investigated the effect of genistein on the activities of PTK and mitogen-activated protein (MAP) kinase and N-myc proto-oncogene expression in N2A cells. The results showed that genistein down-regulated intrinsic PTK activity by approximately 33% and inhibited insulin-like growth factor (IGF)-stimulated PTK activity by 75%. The effect of genistein on the intrinsic activity of MAP kinase was insignificant. In addition, genistein significantly reduced N-myc expression in a dose-dependent fashion. Our study suggests that genistein arrests cell growth and induces NB cell differentiation by mediating apoptosis and modulating PTK activity and N-myc proto-oncogene expression.

Apoptosis↗
PubMed1998

Educating health educators: a survey of hospital staff completing a certificate in health education course.

Health care professionals (nurses, a midwife, a physiotherapist and an occupational therapist) working in a large NHS Trust hospital who had completed the Certificate in Health Education with the support of their employer, were interviewed. The study objectives were to seek their views on the quality of the course, to determine the extent to which participants were able to apply their new found knowledge and skills in the care they provided to patients and the level of support received to allow them to do this. Barriers that prevented staff from routinely applying health education in their work were identified. The findings indicated that the majority found the course content to be good and relevant to their clinical work but they identified lack of time due to the pressure of routine clinical work as the main barrier to the promotion of health education in their clinical area.

Allied Health Personnel↗