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Biomedical subjects

S J Brown

Publications and source records attributed to S J Brown.

At least 37 records · Page 2Linked to original sources
PubMed2000

Impact of motion artefact on the measurement of coronary calcium score.

Reports have shown that total coronary calcium (CC) measured by electron beam CT (EBCT) correlates well with atheroma extent, and this in turn is a reliable indicator of risk for future ischaemic events. Although total CC may be measured using a conventional CT scanner, image quality is degraded by cardiac motion artefact. Errors in CC measurement owing to slice misregistration between adjacent breath-holds affect both conventional CT and EBCT. The latest generation conventional CT scanners have acquisition times of 500 ms or shorter, and, when combined with ECG triggering, quantitative CC measurement without reliance upon EBCT becomes a real possibility. We investigated the effect of motion on the measured calcium score using a moving phantom. Our results show that use of ECG triggering with conventional CT improves reproducibility of Agatston calcium score measurement. Increasing motion time during image acquisition results in an apparent increase in the Agatston CC score. Alternative measures of the amount of CC may be less susceptible to motion-induced bias, but have a similar reproducibility.

Algorithms↗
PubMed1999

Molecular and genetic analysis of the Tribolium Ultrabithorax ortholog, Ultrathorax.

Ultrabithorax (Ubx) is essential for the proper patterning of the posterior thorax and anterior abdomen in Drosophila. The Coleoptera and Diptera differ in the organization and structure of their thorax and anterior abdomen. Changes in the regulation of Ubx and/or its downstream target genes are predicted to underlie these altered morphologies. We exploited the feasibility of genetic analysis in the red flour beetle, Tribolium castaneum, to examine the role of its Ubx ortholog in development. We analyzed genomic and cDNA clones that predict a polypeptide with nearly 100% identity with the Drosophila Ubx gene in the homeodomain and flanking sequences. Southern blot analysis indicates that these clones represent DNA sequences within the Homeotic complex (HOM-C) of Tribolium. Phenotypic analysis of mutant variants of the Ultrathorax (Utx) gene, and its location within the beetle HOM-C, strongly supports Utx being the Tribolium ortholog of Ubx. The embryonic expression pattern of Ubx-homologous transcripts coincides with the phenotypes associated with Utx mutations, providing support that the Ubx-homologous cloned DNA represents the Utx locus. By mid-germband extension Utx transcripts are expressed in a pattern similar to Ubx in Drosophila. However, during early germband formation Utx transcripts differ in both spatial and temporal progression. Utx expression is initially detected in parasegments 4 and 5 (T1p-T3a) as they are established during early germband formation. This is the first report of the wild-type parasegmental expression of an insect Ubx ortholog extending through parasegment 4. The earlier and more anterior expression in the thorax may underlie the modification of the Coleopteran thorax.

Amino Acid Sequence↗
PubMed1999

Feeding outcome in breast-fed term babies supplemented by cup or bottle.

OBJECTIVE: To describe the feeding method at discharge from midwifery care of term babies supplemented either by cup or bottle while in hospital. DESIGN: A retrospective review of the obstetric and midwifery records of 531 consecutively born babies. SETTING: A large maternity unit, with an integral General Practitioner Unit, in an inner city in the south of England. PARTICIPANTS: 63 term breast-feeding babies; 30 supplemented by cup and 33 supplemented by bottle. MAIN OUTCOME MEASURE: Breast feeding on discharge from midwifery care. FINDINGS: There were no significant differences between the bottle and cup supplementation groups in relation to feeding outcome (OR 1 94 95% CI 0.61, 6.31), or in the length of time from the beginning of supplementation to leaving hospital (median difference 1 95% CI 0, 1) or discharge from midwifery care (median difference 0 95% CI, -1, 1). Babies who received supplements of expressed breast milk, as opposed to artificial milk, were more likely to be supplemented by cup (OR 4 29, 95% CI 0.9, 26.91; p = 0.05), but were not more likely to be discharged from midwifery care breast feeding (OR 3.79, 95% CI 0.69, 38.36). CONCLUSION: Owing to the small scale and retrospective nature of this survey, its results must be viewed with caution. However, given the apparent lack of evidence in this area, prospective work should be undertaken to examine the most appropriate method of supplementation for term babies. Generalisation from work related to babies in special care baby units is no longer acceptable.

Bottle Feeding↗
PubMed1999

RAPD-based genetic linkage maps of Tribolium castaneum.

A genetic map of the red flour beetle (Tribolium castaneum) integrating molecular with morphological markers was constructed using a backcross population of 147 siblings. The map defines 10 linkage groups (LGs), presumably corresponding to the 10 chromosomes, and consists of 122 randomly amplified polymorphic DNA (RAPD) markers, six molecular markers representing identified genes, and five morphological markers. The total map length is 570 cM, giving an average marker resolution of 4.3 cM. The average physical distance per genetic distance was estimated at 350 kb/cM. A cluster of loci showing distorted segregation was detected on LG9. The process of converting RAPD markers to sequence-tagged site markers was initiated: 18 RAPD markers were cloned and sequenced, and single-strand conformational polymorphisms were identified for 4 of the 18. The map positions of all 4 coincided with those of the parent RAPD markers.

Alleles↗
PubMed1999

Validity of the Dementia Rating Scale in assessing cognitive function in Parkinson's disease.

Two studies examined the validity of the Dementia Rating Scale (DRS) as a measure of cognitive functioning among patients with Parkinson's disease (PD). The DRS accounted for more variation in the level of cognitive functioning of PD patients than either the Mini-Mental Status Examination or a battery of tests selected to assess specific cognitive deficits associated with PD. Further, DRS subtests displayed strong convergent and discriminant validity with a comprehensive Criterion Neuropsychology Battery. The DRS subtests appear to be valid measures of attention, perseveration, conceptualization, and memory among PD patients. However, the DRS-Construction subtest should be supplemented with additional visuoconstructional items to provide a thorough screen of cognitive functioning in PD. Although about three-quarters of nondemented PD patients did not appear to have any specific cognitive deficits on the DRS, the remaining patients were impaired on the Construction or Initiation/Perseveration subtests of the DRS. In summary, the DRS is a valid mental status screening test of cognitive functioning for individuals with PD.

Aged↗
PubMed1999

Patient-centered communication.

The term patient-centered communication (PCC) has been used to describe a group of communication strategies and behaviors that promote mutuality, shared understandings, and shared decision making in health care encounters. There is evidence to suggest that advanced practice nurse and patients use these strategies to co-produce highly individualized clinical discourse. Although the communication behaviors associated with PCC have been studied separately, their impact as an integrated communications strategy has not been studied. Suggestions for developing PCC as a mid-range theory of health care communication encompassing other more specific communication concepts are offered.

Communication↗
PubMed1998

Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment.

BACKGROUND: Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala-peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms. OBJECTIVE: To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment. PATIENTS AND METHODS: This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4+ cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP score derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4+ count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared. RESULTS: There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4+ cell count between treatment arms, analyses were also adjusted for this variable. These CD4+-adjusted analyses suggested (P = .07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4 cell count was above 0.200 x 10(9)/L (200 cells/microL) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P = .02; Mantel-Haenszel chi(2) test). CONCLUSIONS: Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment (ie, NP global deficit score > or = 0.5) or with relatively preserved immunological status (ie, CD4+ cell count > 0.200 x 10(9)/L).

AIDS Dementia Complex↗
PubMed1998

Electromyogram activity and mean power frequency in exercise-damaged human muscle.

Eight volunteers performed two bouts of 50 voluntary maximal eccentric contractions of the knee extensors of one leg 3 weeks apart. During maximal voluntary isometric contractions performed at intervals after each bout, electromyogram (EMG) mean power frequency declined after bout one (P < 0.01 Duncan's test), whereas integrated EMG did not change after either bout. These results suggest that unaccustomed eccentric contractions produce a temporary reduction in mean muscle activation frequency during subsequent maximal isometric contractions.

Adult↗
PubMed1998

Expression and ligand binding assays of soluble cytokine receptor-immunoglobulin fusion proteins.

We have developed a cloning vector for the expression of type I cytokine receptor, NO, extracellular domain (ECD)-mouse IgG1 Fc fusion proteins. The vector has a versatile polylinker that allows in-frame cloning of the receptor ECD with the mouse IgG1 sequence to encode a receptor ECD-IgG1 fusion construct. The receptor-IgG1 fusion proteins are transiently expressed in useful amounts following transfection of the expression vector into COS7 cells and G418 selection. The mouse IgG1 portion of the fusion protein provides a universal handle for purification on an affinity matrix and detection by anti-mouse IgG antibodies in ELISA or Western blot formats. The expressed receptor ECD-IgG1 fusion proteins bind their cognate ligands. In order to demonstrate that the fusion proteins have similar ligand binding affinities as the native receptors, the affinity constants (Kd) for EPOR, TNFR, IL-4R, and IL-6R-IgG1 fusion proteins were measured by surface plasmon resonance and shown to be in good agreement with published values. The TNFR-IgG1 fusion protein was employed in a demonstration of a novel ELISA format for detecting cytokine receptor binding to cytokine.

Amino Acid Sequence↗
PubMed1998

Molecular characterization of the Tribolium abdominal-A ortholog and implications for the products of the Drosophila gene.

The Drosophila homeotic selector gene abdominal-A is important for determinative decisions in the anterior abdomen. Insects vary considerably with respect to abdominal morphology, and changes in the function of homeotic selector genes and/or downstream genes under their control presumably have been important to the evolution of these differences. Mutations in Abdominal, the Tribolium ortholog of abdominal-A, have been described, and have more posterior homeotic transformations than do Drosophila variants. Here we present the organization of the Abdominal gene and the sequences of its predicted proteins, the first such report for a non-Drosophilid insect. Two predicted proteins share N-terminal sequences with those proposed to be synthesized by the Drosophila ortholog. In addition, we describe the distribution of Abdominal transcripts during embryogenesis. The Tribolium expression pattern closely resembles that of Drosophila, and does not account for the differences in mutant phenotypes.

Amino Acid Sequence↗
PubMed1998

Angiographic progression in patients with angina pectoris and normal or near normal coronary angiograms who are restudied due to unstable symptoms.

BACKGROUND: Syndrome X patients commonly remain symptomatic during follow-up and may be readmitted with unstable anginal symptoms. Angiographic disease progression must be considered as a possible mechanism for instability, particularly where multiple coronary risk factors are present and an interval of several years has elapsed since previous angiography. METHODS AND RESULTS: We reviewed data from 139 consecutive patients with chest pain and normal or near normal coronary angiograms (101 patients with completely normal angiograms and 38 patients with minimal lumenal irregularities). During a 5-year period, 24 patients (19 women, median age 56 years) underwent repeat angiography due to primary unstable angina (median interval between angiograms 58 months (range 8-130 months)). This group included three patients with minimal lumenal irregularities and four patients with left bundle branch block. Only two patients had progression to significant angiographic stenosis (> 30% diameter reduction); both were male patients with minimal irregularities at baseline angiography, left bundle branch block and multiple coronary risk factors. However, overall only two of 18 (11%) patients with one or more conventional coronary risk factors had angiographic progression. CONCLUSIONS: Unstable symptoms in patients with chest pain and previously normal or near normal coronary arteriograms are rarely due to angiographic disease progression. However, the presence of minimal lumenal irregularities at baseline angiography and LBBB may identify a sub-group at increased risk.

Adult↗
PubMed1998

Manipulation of knee extensor force using percutaneous electrical myostimulation during eccentric actions: effects on indices of muscle damage in humans.

Percutaneous electrical myostimulation (PES) was used to manipulate the force produced by the knee extensor muscles during eccentric exercise, thereby providing a model to investigate the role of force in muscle damage. Two eccentric exercise bouts of equal work were performed by nine subjects, using fixed voltage PES at 20 Hz (to produce moderate muscle forces) and 100 Hz (to produce high muscle forces). Muscle contractility, serum creatine kinase activity (CK) and muscle soreness (MS) were evaluated before, and up to 14 days after exercise. Data are presented as means+/-SEM, and were analysed using repeated measures analysis of variance (ANOVA), t-tests and Wilcoxon tests. Peak forces were higher during the 100 Hz bout than the 20 Hz bout for repetitions 1 (472+/-60 vs 237+/-23 Newtons), 10 (381+/-26 vs 233+/-26 Newtons), 20 (310+/-24 vs 218+/-24 Newtons), all p < 0.01, t-test and 30 (297+/-27 vs 204+/-21 Newtons), p < 0.05, t-test. Following the 100 Hz bout, maximum voluntary contractile force (MVC) was lower (p<0.01, ANOVA), and CK was higher (p<0.0001, ANOVA) than after the 20 Hz bout. Subjects also reported greater MS on days 2 to 6 (p<0.05, Wilcoxon test) following the 100 Hz bout. Despite a decline in the stimulated 20:100 Hz tetanic force ratio after each bout (p<0.01, ANOVA) there was no difference between bouts (p>0.05, ANOVA). The higher rise in CK and MS after the 100 Hz bout, together with the greater deficit in MVC, suggest that in humans, muscle force is a contributing factor to muscle injury during eccentric actions.

Adolescent↗
PubMed1998

Isolation of erythropoietin receptor agonist peptides using evolved phage libraries.

Cyclic peptides capable of activating the erythropoietin receptor (EPOR) were isolated from phage display libraries by screening with a novel EPOR-IgG fusion protein reagent. A parental clone ERB1 (EPO Receptor Binder 1) was first isolated from a phage display library displaying 38 random amino acids as an N-terminal fusion with the M13 minor capsid protein, pill. An evolved library was then produced from the parental sequence using an oligonucleotide saturation mutagenesis strategy which yielded EPOR binding sequences with 20 times the relative affinity of ERB1. Two synthetic peptides were constructed from these sequences both of which bind the EPO receptor in specific ELISA, and act as full agonists in EPO dependent cell proliferation assays. These peptides are 18 amino acids in length, disulfide-bonded, and have a minimum consensus sequence of CXXGWVGXCXXW, where X represents positions tolerant of several amino acids.

Amino Acid Sequence↗
PubMed1997

Serum endothelin levels and pain perception in patients with cardiac syndrome X and in healthy controls.

The possible algogenic effects of elevated serum endothelin levels in cardiac syndrome X were investigated in a case-control study that examined somatic pain perception in the forearm during submaximal effort tourniquet and cold immersion tests. Pain threshold to both ischemic and cold stimulation of the forearm was demonstrated to be significantly lower in patients with syndrome X than in matched healthy controls, and a negative correlation between ischemic pain threshold and endothelin levels was demonstrated.

Aged↗