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Biomedical subjects

A Day

Publications and source records attributed to A Day.

At least 19 recordsLinked to original sources

Function and health status outcomes in a randomized trial comparing preoperative and postoperative radiotherapy in extremity soft tissue sarcoma.

PURPOSE: Morbidity associated with wound complications may translate into disability and quality-of-life disadvantages for patients treated with radiotherapy (RT) for soft tissue sarcoma (STS) of the extremities. Functional outcome and health status of extremity STS patients randomized in a phase III trial comparing preoperative versus postoperative RT is described. PATIENTS AND METHODS: One hundred ninety patients with extremity STS were randomized after stratification by tumor size dichotomized at 10 cm. Function and quality of life were measured by the Musculoskeletal Tumor Society Rating Scale (MSTS), the Toronto Extremity Salvage Score (TESS), and the Short Form-36 (SF-36) at randomization, 6 weeks, and 3, 6, 12, and 24 months after surgery. RESULTS: One hundred eighty-five patients had function data. Patients treated with postoperative RT had better function with higher MSTS (25.8 v 21.3, P <.01), TESS (69.8 v 60.6, P =.01), and SF-36 bodily pain (67.7 v 58.5, P =.03) scores at 6 weeks after surgery. There were no differences at later time points. Scores on the physical function, role-physical, and general health subscales of the SF-36 were significantly lower than Canadian normative data at all time points. After treatment arm was controlled for, MSTS change scores were predicted by a lower-extremity tumor, a large resection specimen, and motor nerve sacrifice; TESS change scores were predicted by lower-extremity tumor and prior incomplete excision. When wound complication was included in the model, patients with complications had lower MSTS and TESS scores in the first 2 years after treatment. CONCLUSION: The timing of RT has minimal impact on the function of STS patients in the first year after surgery. Tumor characteristics and wound complications have a detrimental effect on patient function.

Adult↗

Is your patient taking the medicine? A simple assay to measure compliance with 5-aminosalicylic acid-containing compounds.

BACKGROUND: Poor compliance with 5-aminosalicylic acid therapy has been reported amongst patients with inflammatory bowel disease. Currently, there is no easy method to monitor 5-aminosalicylic acid; however, the chemical similarity between 5-aminosalicylic acid and salicylate might provide a solution. AIM: To determine the feasibility of using salicylate levels to monitor compliance with 5-aminosalicylic acid medication. METHODS: Thirty-six patients with inflammatory bowel disease, taking maintenance 5-aminosalicylic acid, provided either a paired serum and urine sample or an intestinal biopsy. Samples were split into two: half were sent to the hospital biochemistry department for salicylate measurement, and half were analysed for 5-aminosalicylic acid and its metabolite, N-acetyl-5-aminosalicylic acid, using high performance liquid chromatography. Correlation between the results was calculated. RESULTS: Serum and urine were available for 25 patients. Serum salicylate was undetectable, but urinary salicylate ranged from 31 to 3254 microg/mL. The correlations between urinary salicylate and 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid were 0.96 (95% confidence interval, 0.91-0.98) and 0.9 (95% confidence interval, 0.77-0.96), respectively. Sixteen biopsies were available from 13 patients. The 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid concentrations were 0.2-657 ng/mg and 1.6-1598 ng/mg, respectively; there was no correlation with bowel salicylate. CONCLUSIONS: The close correlation between 5-aminosalicylic acid and salicylate levels offers a simple method to assess compliance with 5-aminosalicylic acid therapy.

Anti-Inflammatory Agents, Non-Steroidal↗

Is fast mapping good mapping? A review of the benefits of high-speed orientation mapping using electron backscatter diffraction.

Orientation mapping using automated electron backscatter diffraction (EBSD) is now a common technique for characterizing microstructures. Improvements in software and hardware have resulted in high-speed mapping capabilities above 80,000 points h(-1). For 'routine' microstructural analyses of materials such as steel and aluminium (e.g. texture and grain size measurements and high angle boundary characterization), high-speed orientation mapping is an ideal approach with minimal penalty on the final statistics. However, for the accurate analysis of very low angle boundaries and for routine analyses of more difficult materials (e.g. most rock samples), we advocate a more patient approach to orientation mapping with an emphasis on data accuracy and reliability. It is important that the objectives of any EBSD analysis are carefully considered before starting--in this way the maximum potential of an EBSD system can be achieved.

Journal Article↗

Controlling factors in the synthesis of cucurbituril and its homologues.

The acid-catalyzed synthesis of cucurbit[n]urils from formaldehyde and glycoluril is poorly understood. In this paper, we examine a wide range of reaction conditions that include the effects of acid type, acid concentration, reactant concentrations, and temperature to both probe the mechanism and optimize the yields of isolated cucurbit[n]urils, where n = 5-10. A mechanism for the formation of these cucurbit[n]urils is presented. Individual cucurbit[n]urils were unambiguously identified in reaction mixtures using ESMS and (13)C NMR.

Journal Article↗

The distributed annotation system.

BACKGROUND: Currently, most genome annotation is curated by centralized groups with limited resources. Efforts to share annotations transparently among multiple groups have not yet been satisfactory. RESULTS: Here we introduce a concept called the Distributed Annotation System (DAS). DAS allows sequence annotations to be decentralized among multiple third-party annotators and integrated on an as-needed basis by client-side software. The communication between client and servers in DAS is defined by the DAS XML specification. Annotations are displayed in layers, one per server. Any client or server adhering to the DAS XML specification can participate in the system; we describe a simple prototype client and server example. CONCLUSIONS: The DAS specification is being used experimentally by Ensembl, WormBase, and the Berkeley Drosophila Genome Project. Continued success will depend on the readiness of the research community to adopt DAS and provide annotations. All components are freely available from the project website http://www.biodas.org/.

Base Sequence↗

Differential cytokine mRNA expression in swine whole blood and peripheral blood mononuclear cell cultures.

The kinetics of interleukin-2 (IL-2), IL-6, IL-8 and IL-10 gene expression in concanavalin A (Con A)-activated whole blood (WB) and peripheral blood mononuclear cell (PBMC) cultures were examined using reverse transcriptase-polymerase chain reaction (RT-PCR). Unstimulated PBMC or WB cultures failed to show increases in basal cytokine PCR amplicon levels for any cytokine examined. PBMC cultures demonstrated peak expression of IL-2, IL-6, IL-8 and IL-10 mRNA levels at 12, 24, 24 and 6h, respectively. WB cultures exhibited peak IL-2, IL-6, IL-8 and IL-10 mRNA levels at 24, 12, 6 and 24h, respectively. PBMC cultures consistently exhibited higher levels of IL-2 mRNA at all times examined than did WB cultures. WB cultures consistently had higher levels of IL-6 mRNA than PBMC cultures. IL-8 and IL-10 protein levels in PBMC cultures were first detected 12h after stimulation and continued to increase in concentration through 48h. In WB cultures, IL-8 and IL-10 protein levels were first noted at 12 and 6h, respectively. WB culture IL-8 and IL-10 levels quickly reached equilibrium after being detected and remained at levels lower than those noted in PBMC cultures. These results show WB cultures represent an approach with reduced cost and time when compared to traditional cell culture and isolation methods. It may also produce an in vitro test system that more closely resembles in vivo conditions.

Animals↗

The systemic effects of intermittent claudication are reversed by angioplasty.

INTRODUCTION: exercise in patients with intermittent claudication causes systemic effects, the consequences of which are unknown. This study investigates whether successful PTA reverses the systemic effects. PATIENTS AND METHODS: ten patients with IC were recruited prior to PTA. Having emptied their bladders and rested for 1 h, pre-exercise blood and urine samples were collected. Patients underwent treadmill exercise to maximum walking time and blood samples were collected at 10, 20 and 30 min. A second urine sample was collected at 60 min. Total antioxidant capacity (TAC) and von Willebrands Factor (vWF) were measured in blood and albumin/creatinine ratio (ACR) and retinol binding protein/creatinine ratio (RBP/Cr) in urine. Patients were recalled 2 weeks after successful angioplasty and the protocol repeated. Following PTA patients walked for a maximum of 5 min. RESULTS: there was no significant change in vWF. Exercise in claudicants induced a significant increase in median ACR (pre/post exercise=0.85 p =0.03) and in median RBP/Cr (pre/post exercise=1.8 p =0.04). These changes were no longer evident after successful PTA. TAC was significantly different before and after angioplasty at all time intervals. CONCLUSION: successful PTA reverses glomerular effects of exercise in claudicants. Future work should investigate the use of PTA in conjunction with exercise in the treatment of peripheral vascular disease.

Adult↗

Randomised controlled trial of problem solving treatment, antidepressant medication, and combined treatment for major depression in primary care.

OBJECTIVES: To determine whether problem solving treatment combined with antidepressant medication is more effective than either treatment alone in the management of major depression in primary care. To assess the effectiveness of problem solving treatment when given by practice nurses compared with general practitioners when both have been trained in the technique. DESIGN: Randomised controlled trial with four treatment groups. SETTING: Primary care in Oxfordshire. PARTICIPANTS: Patients aged 18-65 years with major depression on the research diagnostic criteria-a score of 13 or more on the 17 item Hamilton rating scale for depression and a minimum duration of illness of four weeks. INTERVENTIONS: Problem solving treatment by research general practitioner or research practice nurse or antidepressant medication or a combination of problem solving treatment and antidepressant medication. MAIN OUTCOME MEASURES: Hamilton rating scale for depression, Beck depression inventory, clinical interview schedule (revised), and the modified social adjustment schedule assessed at 6, 12, and 52 weeks. RESULTS: Patients in all groups showed a clear improvement over 12 weeks. The combination of problem solving treatment and antidepressant medication was no more effective than either treatment alone. There was no difference in outcome irrespective of who delivered the problem solving treatment. CONCLUSIONS: Problem solving treatment is an effective treatment for depressive disorders in primary care. The treatment can be delivered by suitably trained practice nurses or general practitioners. The combination of this treatment with antidepressant medication is no more effective than either treatment alone.

Adolescent↗

Removal of antibiotic resistance genes from transgenic tobacco plastids.

Removal of antibiotic resistance genes from genetically modified (GM) crops removes the risk of their transfer to the environment or gut microbes. Integration of foreign genes into plastid DNA enhances containment in crops that inherit their plastids maternally. Efficient plastid transformation requires the aadA marker gene, which confers resistance to the antibiotics spectinomycin and streptomycin. We have exploited plastid DNA recombination and cytoplasmic sorting to remove aadA from transplastomic tobacco plants. A 4.9 kbp insert, composed of aadA flanked by bar and uidA genes, was integrated into plastid DNA and selected to remove wild-type plastid genomes. The bar gene confers tolerance to the herbicide glufosinate despite being GC-rich. Excision of aadA and uidA mediated by two 174 bp direct repeats generated aadA-free T(0) transplastomic plants containing the bar gene. Removal of aadA and bar by three 418 bp direct repeats allowed the isolation of marker-free T(2) plants containing a plastid-located uidA reporter gene.

Aminobutyrates↗

Marking cell layers with spectinomycin provides a new tool for monitoring cell fate during leaf development.

Spectinomycin, an inhibitor of plastid protein synthesis, can be used to mark specific cell layers in the shoot meristem of Brassica napus. Pale yellow-green (YG) plants resulting from spectinomycin-treatment can be propagated indefinitely in vitro. Microscopic examination showed that YG-plants result from inactivation of plastids in the L2 and L3 layers and are composed of a pale green epidermis covering a white mesophyll layer. Epidermal cells of YG and normal green plants are similar and contain 10-20 small pale green plastids. YG plants are equivalent to periclinal chimeras with the important distinction that there is no genotypic difference between the white and green cell layers. Periclinal divisions of epidermal cells take place at all stages of leaf development to produce invaginations of green mesophyll located in sectors of widely varying sizes. A periclinal division rate of 1 in 3000-4000 anticlinal divisions for the adaxial epidermis, was 2-3-fold higher than that estimated for the abaxial epidermis. Analysis of white and green mesophyll showed that chloroplasts are essential for palisade cell differentiation and this requirement is cell-autonomous. Stable marking of cell lineages with spectinomycin is simple, rapid and reveals the requirement for functional plastids in cellular differentiation.

Brassica↗

Palliative effect of chemotherapy: objective tumor response is associated with symptom improvement in patients with metastatic breast cancer.

PURPOSE: Because one of the goals of chemotherapy for metastatic breast cancer is to provide symptom palliation, we were interested in identifying the relationship between tumor shrinkage and improvement in disease-related symptoms. PATIENTS AND METHODS: Three hundred patients enrolled onto a randomized trial of metastatic breast cancer formed the basis of our study. The nine most common baseline symptoms were identified and followed. Changes from baseline (improvement, stable, worsening) were defined using patient responses to a quality-of-life (QoL) questionnaire (the European Organization for Research and Treatment of Cancer EORTC QLQ-C30) as well as using graded toxicity data collected on case report forms (CRFs). The association between symptom improvement and tumor response was assessed using a linear trend test via a logistic regression model. RESULTS: The most commonly reported baseline symptoms were cancer pain in 38% (CRF data) and 81% of patients (QoL data) and tiredness in 26% (CRF data) and 89% (QoL data) of patients. Three symptoms-cancer pain, shortness of breath, and abnormal mood-showed a significant relationship between improvement and objective response, using both CRF and QoL assessments. Constipation, anorexia, and nausea showed a similar trend when QoL data were used but not when CRF information was used. The converse was seen for lethargy. There was no correlation between symptom change and response for cough and insomnia. CONCLUSION: For some symptoms, we found a significant association between symptom improvement and objective tumor regression. In these cases, symptom improvement was greatest in those patients who had complete or partial responses, followed by those with stable disease and then those with progressive disease. Further work in this area will be useful in determining the surrogate value of objective tumor response in identifying the efficacy of palliative chemotherapy.

Adult↗

The Belt mutation in pigs is an allele at the Dominant white (I/KIT) locus.

A white belt is a common coat color phenotype in pigs and is determined by a dominant allele (Be). Here we present the result of a genome scan performed using a Hampshire (Belt)/Pietrain (non-Belt) backcross segregating for the white belt trait. We demonstrate that Belt maps to the centromeric region of pig Chromosome (Chr) 8 harboring the Dominant white (I/KIT) locus. Complete cosegregation between Belt and a single nucleotide polymorphism in the KIT gene was observed. Another potential candidate gene, the endothelin receptor type A gene (EDNRA), was excluded as it was assigned to a different region (SSC8q21) by FISH analysis. We argue that Belt is a regulatory KIT mutation on the basis of comparative data on mouse KIT mutants and our previous sequence analysis of the KIT coding sequence from a Hampshire pig. Quantitative PCR analysis revealed that Belt is not associated with a KIT duplication, as is the case for the Patch and Dominant white alleles. Thus, Belt is a fourth allele at the Dominant white locus, and we suggest that it is denoted I(Be).

Alleles↗

Vascular surgical society of great britain and ireland: systemic effects of exercise in claudicants are associated with neutrophil activation

BACKGROUND: Claudication induces potentially harmful systemic effects which may be mediated through free radicals and neutrophil activation. This study examined the impact of these mechanisms on renal tubular function. METHODS: Flow cytometry was used to determine CD11b expression by neutrophils and monocytes, and expression of P selectin (CD62P) by platelets, in 16 patients with intermittent claudication and eight matched controls before and at intervals after exercise. Total antioxidant capacity (TAC) and von Willebrand factor (vWF) were measured at similar intervals. Renal tubular function was assessed before and 60 min after exercise by assay of retinol binding protein : creatinine ratio (RBP : Cr) in urine. All patients and none of the controls had a significant exercise-induced fall in ankle pressure. Fluorescein isothiocyanate-labelled monoclonal antibodies against CD11b and CD62P were added to blood and analysis was performed on the flow cytometer within 72 h. RESULTS: There were no significant differences in monocytes, platelets or vWF between patients and controls over time. There was a significant change in RBP : Cr following exercise in patients (median 4.2 (95 per cent confidence interval 2.4-85.2); P </= 0.01, Wilcoxon test) but not controls (2.7 (-1 to 7.5); P not significant). See Table above. CONCLUSION: Renal tubular function was adversely affected by acute exercise in claudicants. TAC was higher in claudicants at rest and was increased after exercise suggesting an increased free radical challenge. Neutrophil activation is significantly different between claudicants and controls before and after exercise, and may provide a link between free radical generation and renal tubular injury.

Journal Article↗

Vascular surgical society of great britain and ireland: patients with a failed infrainguinal bypass graft have abnormal lipid metabolism

BACKGROUND: Dyslipidaemias adversely affect vascular tone, endothelial function and platelet activation. Abnormal lipid metabolism has not been established as a risk factor for infrainguinal bypass graft failure. Lipid metabolism was evaluated prospectively in patients with patent and occluded grafts. METHODS: Twenty-eight patients with failed infrainguinal grafts (group 1) were identified from a prospective computerized database. Twenty matched controls with functioning grafts (group 2) were recruited from a graft surveillance programme. Fasting blood samples were analysed for triglyceride (TG), high-density lipoprotein (HDL) and cholesterol. A newly devised rapid TG tolerance test was conducted with analysis of TG at 1, 2 and 2.5 h. Endothelial lipoprotein lipase (LPL) was measured 30 min after intravenous administration of heparin 50 units kg-1. RESULTS: The cholesterol : HDL ratio was significantly higher in group 1 than group 2 (median 6.0 (range 3. 1-10.0) versus 4.7 (2.3-9.4); P = 0.0008, Mann-Whitney test) as was fasting TG (2.6 (1.0-6.3) versus 1.7 (0.6-4.7) mmol l-1; P = 0.03). The area under the curve of the TG tolerance test was not significantly different (P = 0.08); however, the 2.5-h levels of TG were significantly different between the groups (group 1, 2.0 (0.5-6. 6) mmol l-1; group 2, 1.2 (0.3-6.8) mmol l-1; P = 0.01). LPL was significantly lower in group 1 (52.4 (2.2-235.9) versus 86.8 (28. 6-281.5) mmol/l; P = 0.04). CONCLUSION: These data suggest that abnormal lipid metabolism is a significant risk factor for infrainguinal graft occlusion. This study provides a rationale for randomized trials of lipid-modifying therapies in patients undergoing arterial reconstruction for peripheral vascular disease.

Journal Article↗