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Biomedical subjects

R Graham

Publications and source records attributed to R Graham.

At least 19 recordsLinked to original sources

The role of inflammatory bowel disease susceptibility loci in multiple sclerosis and systemic lupus erythematosus.

To date, three loci have been validated to confer susceptibility to inflammatory bowel disease (IBD): the CARD15/NOD2 gene, the discs large homolog 5 gene (DLG5), and the IBD5 locus on 5q31 (IBD5). We have explored the possibility that these loci may also be associated with susceptibility to two other chronic inflammatory diseases, multiple sclerosis (MS) and systemic lupus erythematosus (SLE). As the CARD15 risk alleles had previously been assessed in our collection of 496 MS trios, we focused our efforts on the DLG5 risk allele and the IBD5(risk) haplotype (IBD5(risk)) for MS. While there is no evidence of association within our MS sample with either of these polymorphisms, screening of 1027 subjects with SLE suggests that IBD5(risk) may have a modest contribution to disease risk in the subset of SLE subjects without lupus nephritis. In addition, a pooled analysis of existing published and unpublished data in 1305 cases of SLE genotyped for the CARD15 risk alleles suggests that only the CARD15(908R) IBD risk allele may have a strong effect on risk of SLE. Our data, therefore, suggest that both the CARD15 gene and the IBD5 locus may have a role as general susceptibility loci for certain common, genetically complex inflammatory diseases.

Chromosomes, Human, Pair 5↗

Determining "need" for a Removable Partial Denture: a qualitative study of factors that influence dentist provision and patient use.

OBJECTIVE: To identify factors that influence Removable Partial Denture (RPD) provision, and patient use of RPDs in the UK. DESIGN: Exploratory qualitative interview study. SUBJECTS AND METHODS SUBJECTS: There were two sample groups. A purposive sample of 16 male and female dentists was categorised in terms of level of RPD provision, experience, and practice characteristics. A purposive sample of 17 male and female partially dentate patients was categorised in terms of RPD use and demographic characteristics. DATA COLLECTION: Semi-structured in-depth interviews. RESULTS: For dentists, RPD provision was indicated by patient demand and physical function of the remaining teeth, but was mediated by NHS fee structures and professional satisfaction. For patients, RPD use was influenced by the trade-off between improved appearance and the unpalatable presence of an RPD in their mouth. The location of the gap(s) was important, but other issues were relevant such as ability to "manage" without the RPD. CONCLUSION: When defining "need" for an RPD, dentists focused on physical function of the teeth whereas patients focused on social meanings of the mouth. These differing priorities may improve understandings of patient non-compliance in RPD use. Further research on the relationship between denture use and social identity could be beneficial.

Attitude of Health Personnel↗

Exact results for one-dimensional disordered bosons with strong repulsion.

We study one-dimensional disordered bosons with strong repulsive interactions. A Bose-Fermi mapping expresses this problem in terms of noninteracting Anderson-localized fermions, whereby known results for the distribution function of the local density of states, the spectral statistics, and density-density correlations can be transferred to this new domain of applicability. We show that disorder destroys bosonic quasi-long-range order by calculating the momentum distribution, and comment on the experimental observability of these predictions in ultracold atomic gases.

Journal Article↗

[Paediatric musculoskeletal ultrasound].

Ultrasound examination is often the most effective and sometimes the only practical means of examining children with soft tissue, tendon and joint diseases. This review will cover the important application of diagnostic ultrasound in children musculoskeletal disorders. We will consider topics where ultrasound is the only sensible means of examination such as developmental dysplasia of the hip, where it is the best choice of several possible methods such as painful hip and when it provides an alternative or adjunct to other imaging such as the examination of soft tissue masses.

Child↗

One year results of the Middlesbrough early revascularisation to limit infarction (MERLIN) trial.

OBJECTIVE: To report one year results of the MERLIN (Middlesbrough early revascularisation to limit infarction) trial, a prospective randomised trial comparing the strategy of coronary angiography and urgent revascularisation with conservative treatment in patients with failed fibrinolysis complicating ST segment elevation myocardial infarction (STEMI). The 30 day results have recently been published. At the planning stage of the trial, it was determined that follow up of trial patients would continue annually to three years to determine whether late benefit occurred. SUBJECTS: 307 patients who received a fibrinolytic for STEMI but failed to reperfuse early according to previously described ECG criteria and did not develop cardiogenic shock. METHODS: Patients were randomly assigned to receive either emergency coronary angiography with a view to proceeding to urgent revascularisation (rescue percutaneous coronary intervention (rPCI) arm) or continued medical treatment (conservative arm). The primary end point was all cause mortality at 30 days. The secondary end points included the composite end point of death, reinfarction, stroke, unplanned revascularisation, or heart failure at 30 days. The same end points were evaluated at one year and these results are presented. RESULTS: All cause mortality at one year was similar in the conservative arm and the rPCI arm (13.0% v 14.4%, p = 0.7, risk difference (RD) -1.4%, 95% confidence interval (CI) -9.3 to 6.4). The incidence of the composite secondary end point of death, reinfarction, stroke, unplanned revascularisation, or heart failure was significantly higher in the conservative arm (57.8% v 43.1%, p = 0.01, RD 14.7%, 95% CI 3.5% to 25.5%). This was driven almost exclusively by a significantly higher incidence of subsequent unplanned revascularisation in the conservative arm (29.9% v 12.4%, p < 0.001, RD 17.5%, 95% CI 8.5% to 26.4%). Reinfarction and clinical heart failure were numerically, but not statistically, more common in the conservative arm (14.3% v 10.5%, p = 0.3, RD 3.8%, 95% CI -3.7 to 11.4, and 31.2% v 26.1%, p = 0.3, RD 5.0%, 95% CI -5.1 to 15.1). There was a strong trend towards fewer strokes in the conservative arm (1.3% v 5.2%, p = 0.06, RD -3.9%, 95% CI -8.9 to 0.06). CONCLUSION: At one year of follow up, there was no survival advantage in the rPCI arm compared with the conservative arm. The incidence of the composite secondary end point was significantly lower in the rPCI arm, but this was driven almost entirely by a highly significant reduction in the incidence of further revascularisation.

Adult↗

Bioprocess development for the production of a recombinant MUC1 fusion protein expressed by CHO-K1 cells in protein-free medium.

The mucin MUC1 is a candidate for use in specific immunotherapy against breast cancer, but this requires the large-scale production of a MUC1 antigen. In this study, a bioprocess for the expression of a recombinant MUC1 fusion protein with a cancer associated glycosylation in CHO-K1 cells has been developed. Cells permanently expressing parts of the extracellular portion of MUC1 fused to IgG Fc were directly transferred from adherent growth in serum-containing medium to suspension culture in the protein-free ProCHO4-CDM culture medium. Using the Cellferm-pro system, optimal culture parameter as pH and pO(2) were determined in parallel spinner flask batch cultures. A pH of 6.8-7.0 and a pO(2) of 40% of air saturation was found to give best cell growth and productivity of secreted recombinant protein. Specific productivity strongly depended the pO(2) and correlated with the online monitored oxygen uptake rate (OUR) of the cells, which indicates a positive influence of the rate of oxidative phosphorylation on productivity. The optimised conditions were applied to continuous perfusion culture which gave very high cell densities and space time yields of the recombinant MUC1 fusion protein, allowing production at gram scale. The product degradation was much lower in supernatants from continuous perfusion culture compared to batch mode. Antibodies reacting with cancer associated MUC1 glycoforms strongly bound to the fusion protein, indicating that the desired glycoforms were obtained and suggesting that the recombinant MUC1 protein could be tested for use in immunotherapy.

Animals↗

Interference of atomic levels and superfluid-Mott insulator phase transitions in a two-component Bose-Einstein condensate.

The superfluid-Mott insulator phase transition in a Bose-Einstein condensate of neutral atoms with doubly degenerate internal ground states in an optical lattice is theoretically investigated. The optical lattice is created by two counterpropagating linearly polarized laser beams with the angle theta between the polarization vectors (lin-angle-lin configuration). The phase diagram of the system and the critical values of the parameters are worked out. It is shown that the sign of the detuning plays an important role and that there is a strong suppression of the Mott transition in the case of blue detuning. Varying the laser intensity and/or the angle theta one can manipulate the Mott insulator to superfluid quantum phase transition as well as prepare the condensate in physically distinguishable "ferromagnetic" and "antiferromagnetic" superfluid states.

Journal Article↗

Multilocation trial of ceftiofur for treatment of postpartum cows with fever.

OBJECTIVE: To evaluate the effect of ceftiofur for treatment of postpartum cows with fever. DESIGN: Multilocation randomized complete block design trial. ANIMALS: 330 cows. PROCEDURE: Cows with rectal temperature > or = 39.5 C (103.1 F) during the first 10 postpartum days were randomly assigned to a treatment (ceftiofur; 1 mg/kg [0.45 mg/lb] of body weight daily for 3 days) or untreated control group. Cure (no additional or alternative antimicrobial treatment used, rectal temperature < 39.5 C, and no other concurrent clinical signs of disease when evaluated at 9 or 10 days after enrollment), milk production, and rectal temperature were evaluated. RESULTS: Ceftiofur-treated cows were significantly more likely to be cured than control cows (56.0 vs 28.9%, respectively), with an odds ratio of 3.14 when vaginal discharge (a factor with moderate interaction with treatment) was present at enrollment. Among cows that had an abnormal calving (a significant interaction factor), treated cows had first milking yield 2.27 kg (5 lb) greater than control cows. Treated cows had a significantly greater reduction in rectal temperature (1.19 C [2.14 Fl), compared with control cows (1.04 C [1.87 F]). CONCLUSIONS AND CLINICAL RELEVANCE: Parenteral administration of ceftiofur significantly improved cure rate, milk yield, and rectal temperature in postpartum cows with fever and vaginal discharge or dystocia. These findings provide information to determine appropriate treatment for postpartum cows, which for years has been debated in the dairy industry.

Animals↗

Event-related potentials of recognizing happy and neutral faces.

In event-related potentials (ERPs) studies, recognition memory is associated with two positivities: one over parietal regions, and one over frontal regions. With nameable neutral stimuli, such as words or common objects, the parietal effect is usually left lateralized, and the frontal effect is usually right lateralized. We investigated the lateralization of these effects for nonnameable emotional stimuli: unfamiliar faces with happy and neutral expressions. The parietal effect was bilateral, suggesting that the left lateralization of this effect in studies using nameable stimuli reflected verbal processing. The frontal effect was left lateralized for happy faces, but right lateralized for neutral faces. This finding is consistent with the valence hypothesis, which posits that processing of pleasant emotions is lateralized to the left hemisphere.

Analysis of Variance↗

MDC-9 (ADAM-9/Meltrin gamma) functions as an adhesion molecule by binding the alpha(v)beta(5) integrin.

MDC-9 is a widely expressed member of the metalloproteinase/disintegrin/cysteine-rich protein family. The disintegrin domain of MDC-9 lacks an RGD motif but has recently been reported to bind the alpha(6)beta(1) integrin; however, it is unclear whether MDC-9 can bind other integrins. In the present study myeloma cells, but not lymphoblastoid cells, were shown to bind to immobilised, recombinantly expressed MDC-9 disintegrin domain (A9dis). Binding was divalent cation-dependent, being supported by Mn(2+) and Ca(2+). Adhesion of myeloma cells to A9dis was completely inhibited by an antibody to the alpha(v)beta(5) integrin but not by antibodies to other subunits. RGD-containing peptides had no effect on binding, suggesting that MDC-9 interacts with alpha(v)beta(5) in an RGD-independent manner. Flow cytometric analyses demonstrated that myeloma cells, but not lymphoblastoid cells, expressed alpha(v)beta(5) on the cell membrane. These data indicated that the disintegrin domain of MDC-9 can function as an adhesion molecule by interacting with an alpha(v)beta(5) integrin.

ADAM Proteins↗

Haematologic determinants of left atrial spontaneous echo contrast in mitral stenosis.

OBJECTIVES: To determine if a relationship exists in mitral stenosis, in patients with either sinus rhythm or atrial fibrillation, between left atrial spontaneous echo contrast and the haematologic indices haematocrit, red cell concentration, mean corpuscular volume, platelet count and volume. METHODS: Left atrial spontaneous echo contrast severity was graded on a scale of 0-4 in 163 patients with symptomatic mitral stenosis (84 patients in sinus rhythm, 79 patients in atrial fibrillation) undergoing transesophageal echocardiography, cardiac catheterization and full blood examination as part of assessment prior to balloon mitral valvuloplasty. RESULTS: In sinus rhythm, spontaneous echo contrast grade was negatively correlated with cardiac index (r=-0.33), mitral valve area (r=-0.25) and mitral regurgitation grade (r=-0.22) and positively correlated with haematocrit (r=0.24) and red cell concentration (r=0.25). Spontaneous echo contrast grade was not correlated with left atrial diameter or mean corpuscular volume. In atrial fibrillation, spontaneous echo contrast grade was also negatively correlated with mitral valve area (r=-0.25) and mitral regurgitation (r=-0.36) but was positively correlated with left atrial diameter (r=0.34) and was not correlated with cardiac index, haematocrit or red cell concentration. There was no correlation between spontaneous echo contrast grade and platelet variables in either group. CONCLUSIONS: Natural variation in red cell concentration in patients with symptomatic mitral stenosis was an independent predictor of the severity of left atrial spontaneous echo contrast in sinus rhythm, but no relationship between red cell concentration and spontaneous echo contrast grade was evident in atrial fibrillation.

Adult↗

Dissociating the neural correlates of item and context memory: an ERP study of face recognition.

We investigated the neural correlates of item and context retrieval using event-related potentials (ERPs). Participants studied unfamiliar faces with happy or neutral expressions, and at test, they decided whether test faces were studied in the same or in a different expression, or were new. The parietal ERP effect, which is hypothesized to indirectly reflect medial-temporal lobe (MTL) function, was sensitive to item retrieval, whereas the frontal ERP effect, which is thought to reflect prefrontal cortex (PFC) function, was sensitive to context retrieval. Converging with lesion, functional neuroimaging (PET and fMRI), and ERP evidence, these results support the notion that item retrieval is primarily associated with MTL function whereas context retrieval is primarily associated by PFC function.

Adult↗

Echocardiographic aspects of percutaneous atrial septal defect closure in adults.

Echocardiography plays an integral role in the diagnosis and management of atrial septal defects. With percutaneous closure of secundum defects becoming widespread, transoesophageal echocardiography in particular has assumed an important role in patient selection, as well as being central to the device deployment procedure, and an important tool in patient follow up.

Journal Article↗

Impact of nosocomial infection on length of stay and functional improvement among patients admitted to an acute rehabilitation unit.

OBJECTIVE: To identify factors predictive of length of stay (LOS) and the level of functional improvement achieved among patients admitted to an acute rehabilitation unit for the first time, with special reference to the role of nosocomial infection. SETTING: A 40-bed acute rehabilitation unit within a 300-bed, tertiary-care, public, university-affiliated hospital. STUDY POPULATION: All patients admitted to the unit between January 1997 and July 1998. DESIGN: Prospective cohort study in which demographic and clinical data, including occurrence of nosocomial infection, were collected during the entire unit admission of each patient. Multivariate linear regression analysis was used to identify factors predictive of unit LOS or improvement in functional status as measured by the change in the Functional Independence Measure (FIM) score between admission and discharge (deltaFIM). RESULTS: There were 423 admissions to the rehabilitation unit during the study period, of which 91 (21.5%) had spinal cord injury (SCI) as a principal diagnosis. One hundred seven nosocomial infections occurred during 84 (19.9%) of the 423 admissions. The most common infections were urinary tract (31.8% of all infections), surgical-site (18.5%), and Clostridium difficile diarrhea (15%). Only one patient died of infection. After controlling for severity of illness on admission, functional status on admission, age, and other clinical factors, the significant positive predictors of unit LOS were as follows: SCI (P<.001), pressure ulcer (.002), and nosocomial infection (<.001). Significant negative predictors of deltaFIM were age (P<.001), FIM score on admission (<.001), prior hospital LOS (.002), and nosocomial infection (.007). CONCLUSIONS: Several variables were identified as contributing to a longer LOS or to a smaller improvement in functional status among patients admitted for the first time to an acute rehabilitation unit. Of these variables, only nosocomial infection has the potential for modification. Studies of new approaches to prevent infections among patients undergoing acute rehabilitation should be pursued.

Activities of Daily Living↗

A new approach to extraperitoneal rectal injuries: laparoscopy and diverting loop sigmoid colostomy.

BACKGROUND: Current management of extraperitoneal rectal injuries involves a laparotomy and diversion of the fecal stream. In this study, we review our experience with laparoscopy and diverting loop sigmoid colostomy without laparotomy in the management of these injuries. METHODS: All patients admitted to the trauma unit at Groote Schuur Hospital between January 1995 and May 2000 with a rectal injury were evaluated. The presence of a rectal injury was confirmed by rectal examination and proctosigmoidoscopy. Intraperitoneal injuries were excluded by laparoscopy. Only patients who did not have intraperitoneal injuries were included in the study. The patients were then managed with a diverting loop sigmoid colostomy created through an abdominal wall trephine without laparotomy. RESULTS: Ten patients were included in the study. In eight patients, laparoscopy excluded intraperitoneal injuries. All 10 patients had a diverting loop sigmoid colostomy fashioned. There were no complications related to either the rectal injury or colostomy. Nine stomas have since been closed. CONCLUSION: In patients with isolated extraperitoneal rectal injuries, laparoscopic exclusion of intraperitoneal injuries, followed by a diverting loop sigmoid colostomy, is a feasible option.

Adolescent↗

Implications of proposed changes in bulk tank somatic cell count regulations.

Several changes in bulk tank SCC (BTSCC) regulations were proposed at the 1998 annual meeting of the National Conference of Interstate Milk Shippers (NCIMS) by the National Mastitis Council and other proponents. Proposals included 1) using a geometric mean BTSCC in place of the arithmetic mean, reducing the current limit for BTSCC from 750,000 to 400,000, and modifying current regulatory protocols. The purpose of this research was to evaluate possible impacts of proposed changes upon producers in warm climates. Data were monthly BTSCC values, provided by state regulatory agencies in West Texas, Louisiana, and Mississippi. Fifty producers from each state were selected by lot, and all 1998 monthly records were included (n = 1602). Computer simulation was used to compare regulatory actions that would have resulted under current and proposed regulations. Possible regulatory actions were 1) notification of noncompliance and 2) suspension of permits to sell milk. At the 750,000 BTSCC limit, both programs resulted in 41 regulatory actions, but the proposed program had a higher rate of suspensions to notices. A twofold increase in regulatory actions per 100,000 incremental decrease in BTSCC limit below 750,000 resulted under both programs. Actual results could be lower due to the assumption that no management adjustments were made by producers in response to changes in regulations. However, the magnitude of increased actions against producers indicated that lowering limits quickly could be disruptive if producers failed to adjust management quickly and effectively to comply with lower limits.

Animals↗

Do selective serotonin re-uptake inhibitors enhance the efficacy of very brief cognitive behavioral therapy for panic disorder? A pilot study.

Selective serotonin re-uptake inhibitors (SSRIs) and cognitive behavioral therapies (CBTs) are both considered as first-line treatments for panic disorder, but the advantages of a combined therapy have yet to be definitively demonstrated. We evaluated in this pilot study the effects of combining SSRIs (vs. a placebo) with a very brief form of cognitive-behavioral therapy provided to all participants. Thirty-three subjects with DSM-IV panic disorder, with or without agoraphobia, were randomized to receive either paroxetine or a placebo with flexible dosing (10-50 mg/day). Medication visits were brief (15 min), infrequent (6 in total) and non-directive. An expert cognitive-behavior therapist administered one initial 45-min session and one subsequent 30-min session of very brief CBT (vbCBT) at weeks 5 and 7, respectively. Sessions were supplemented with educational and directive reading materials. Patients in both groups (i.e. vbCBT+paroxetine; vbCBT+placebo) improved similarly and substantially on most measures during the 10 weeks of acute treatment. At week 10, the proportion of panic-free patients was significantly higher in the paroxetine-treated group than in the placebo group (80 vs. 25%; P<0.007), as was the proportion of subjects who rated themselves as 'very much improved' at week 10 (60 vs. 13%; P<0.017). These findings point to the need for additional studies to confirm the effectiveness of very brief forms of CBT, and to document the circumstances in which combined treatment with an SSRI would be warranted.

Adolescent↗