Biomedical subjects

S E Campbell

Publications and source records attributed to S E Campbell.

At least 19 recordsLinked to original sources

PubMed2006

A novel method to determine lean body water using localized skin biopsies: correlation between lean skin water and lean body water in an overhydration model.

To determine the relationship between total body water (TBW) fraction and local water content measured in the skin (SW) this study assessed eight anesthetized piglets in an overhydration model. TBW was assessed by deuterium oxide dilution and body mass measurements taken throughout the experiments, and by whole body carcass analysis at the end of each experiment. Additionally, extracellular water and plasma volume were assessed using bromide dilution and Evan's blue dilution, respectively. SW was assessed by tissue biopsies taken at 60-min intervals throughout the experiment. Lean body water (LBW) fraction and lean skin water (LSW) fraction were assessed by extracting the fat from the carcass and biopsy samples. A correlation does exist between TBW fraction and SW fraction with r2=0.58 (P<0.05); however, the strongest correlation occurred between the LBW fraction and LSW fraction with r2=0.87 (P<0.05) and an SE of prediction of 0.77%. These data demonstrate that LSW gives an accurate and precise estimate of LBW and could therefore be used to determine the hydration index in appropriate research settings.

Animals↗

PubMed2005

Disease- and cell-type-specific transcriptional targeting of vectors for osteoarthritis gene therapy: further development of a clinical canine model.

OBJECTIVES: The potential for undesirable systemic effects related to constitutive expression of certain therapeutic transgenes may be limited through the development of transcriptionally targeted disease- and cell-type-specific vectors. The objective of this study was to analyse the canine matrix metalloproteinase-9 (MMP-9) promoter and deletion constructs for its ability to drive expression in response to pro-inflammatory cytokines (interleukin-1beta and tumour necrosis factor-alpha). METHODS: Initial analysis of MMP-9 deletion constructs was made using a luciferase reporter system. The promoter was subsequently engineered to incorporate multiple NF-kappaB sites. In parallel experiments we used the mouse collagen type XI promoter to study cell-type-specific promoter activity in chondrocyte-specific cells (SW1353) and undifferentiated chondroprogenitor cells (ATDC5). RESULTS: Incorporation of multiple NF-kappaB sites into the MMP-9 promoter enhanced activity while maintaining disease specificity. Further, manipulation of the mouse collagen type XI (mColXI) promoter by the incorporation of SOX9 enhancer sites downstream of a reporter gene, increased gene activity while maintaining cell type specificity. CONCLUSIONS: Manipulation of promoter and enhancer regions can improve transcriptionally targeted genes. A combination of these systems, in the context of the canine model, has the potential to improve the safety of osteoarthritis gene therapy vectors.

Animals↗

PubMed2004

Assessment of individual quality of life using the SEIQoL-DW in older medical patients.

BACKGROUND: Many hospital admissions aim to optimize quality of life (QoL). However, the standard medical clerking does not systematically record QoL items. AIM: To examine whether the current disease-based clerking could be supplemented in older people with QoL information. DESIGN: Survey of non-elective admissions aged > or = 65 years. METHODS: Participants (n = 60) were interviewed on day 3-5 of their admission. QoL was measured using the SEIQoL-DW and the SF36 (version 2). Cognitive and physical function were also assessed. Aspects of feasibility and acceptability were explored, and the potential clinical benefits of the information investigated. RESULTS: Mean patient age was 81 years; 36 (60%) were female. Forty-five completed the SEIQoL-DW, (mean time 37.7 min), of whom 17 experienced practical difficulties drawing the cue levels, and 25 had difficulty manipulating the direct weighting device of the SEIQoL-DW. However, the assessment process was judged as acceptable, and elicited more subjective information than was recorded in medical and nursing notes. Doctors considered the individual QoL information potentially useful for planning discharge and follow-up. DISCUSSION: The SEIQoL-DW is probably too time-consuming for standard medical clerking. However, as it was judged acceptable by patients, and according to medical staff, gives potentially valuable information, there may be circumstances in which its use is worthwhile.

Aged↗

PubMed2003

Plasmalemmal fatty acid transport is regulated in heart and skeletal muscle by contraction, insulin and leptin, and in obesity and diabetes.

It has been assumed that the uptake of long chain fatty acids (LCFAs) into skeletal muscle and the heart muscle, as well as other tissues, occurred via passive diffusion. In recent years our work has shown that the LCFA uptake into skeletal muscle is a highly regulated process. The use of giant sarcolemmal vesicles obtained from skeletal muscle and heart has been used to demonstrate that LCFA uptake into these tissues occurs via a protein-mediated mechanism involving the 40 kDa plasma membrane associated fatty acid binding protein (FABPpm) and the 88 kDa fatty acid translocase, the homologue of human CD36 (FAT/CD36). Both are ubiquitously expressed proteins and correlate with LCFA uptake into heart and muscle, consistent with the known differences in LCFA metabolism in these tissues. It has recently been found that FAT/CD36 is present in an intracellular (endosomal) compartment from which it can be translocated to the plasma membrane within minutes by muscle contraction and by insulin, to stimulate LCFA uptake. In rodent models of obesity and type 1 diabetes LCFA uptake into heart and muscle is also increased, either by permanently relocating FAT/CD36 to the plasma membrane without altering its expression (obesity) or by increasing the expression of both FAT/CD36 and FABPpm (type 1 diabetes). Chronic leptin treatment decreases LCFA transporters and transport in muscle. Clearly, recent evidence has established that LCFA uptake into heart and muscle is regulated acutely and chronically.

Animals↗

PubMed2003

17beta-estradiol upregulates the expression of peroxisome proliferator-activated receptor alpha and lipid oxidative genes in skeletal muscle.

This study examined the actions of 17beta-estradiol (E(2)) and progesterone on the regulation of the peroxisome proliferator-activated receptors (PPARalpha and PPARgamma) family of nuclear transcription factors and the mRNA abundance of key enzymes involved in fat oxidation, in skeletal muscle. Specifically, carnitine palmitoyltransferase I (CPT I), beta-3-hydroxyacyl CoA dehydrogenase (beta-HAD), and pyruvate dehydrogenase kinase 4 (PDK4) were examined. Sprague-Dawley rats were ovariectomized and treated with placebo (Ovx), E(2), progesterone, or both hormones in combination (E+P). Additionally, sham-operated rats were treated with placebo (Sham) to serve as controls. Hormone (or vehicle only) delivery was via time release pellets inserted at the time of surgery, 15 days prior to analysis. E(2) treatment increased PPARalpha mRNA expression and protein content (P<0.05), compared with Ovx treatment. E(2) also resulted in upregulated mRNA of CPT I and PDK4 (P<0.05). PPARgamma mRNA expression was also increased (P<0.05) by E(2) treatment, although protein content remained unaltered. These data demonstrate the novel regulation of E(2) on PPARalpha and genes encoding key proteins that are pivotal in regulating skeletal muscle lipid oxidative flux.

Animals↗

PubMed2002

Assessment of nutritional status in hospital in-patients.

BACKGROUND: The King's Fund and British Association of Parenteral and Enteral Nutrition recommend that all hospital patients should have height and weight recorded, to detect the need for nutritional support. Systematic review evidence also suggests that protein and energy supplementation of adults in hospital with a wide range of conditions improves outcome. AIM: To assess the recording of weight and height in hospitals. DESIGN: Survey (random sample). METHODS: As part of a survey on the provision of deep venous thrombosis prophylaxis, we collected information on height and weight recording from medical and nursing notes. We randomly selected five medical, five surgical, five orthopaedic, and five obstetrics and gynaecology directorates from across Scotland. Six hundred case notes were requested, and 88% were available for data extraction. Some 67% of hospital episodes provided information about weight, and 41% on both height and weight. General medicine directorates had the lowest recording of weight, and in medical and surgical directorates, both weight and height were rarely recorded in comparison with the other two directorates (p<0.001). DISCUSSION: Our survey suggests that recommendations to assess nutritional risk are not being followed, and that many patients at risk of malnutrition are not being detected or treated.

Adult↗

PubMed2002

Effect of the ovarian hormones on GLUT4 expression and contraction-stimulated glucose uptake.

This study examined the roles of the female sex steroids, 17beta-estradiol (E(2)) and progesterone (Prog), on glucose uptake and GLUT4 protein expression. Female Sprague-Dawley rats were either sham operated (C) or ovariectomized and treated with placebo (O), E(2) (E), Prog (P), or both hormones at physiological doses (P + E) or the same dose of Prog with a high dose of E(2) (P + HiE) via timed-release pellets inserted at the time of surgery, 15 days before metabolic testing. On the morning of day 15, animals received a 300-microCi injection (ip) of 2-deoxy-[(14)C]glucose and then either exercised on a motorized treadmill for 30 min at 0.35 m/s or remained sedentary in their cages for the same period. Basal glucose uptake was not different between the treatment groups in either the red or white quadriceps. However, glucose uptake was decreased (P < 0.05) in O, P, and P + E rats during exercise in the red quadriceps compared with C rats, whereas E and P + HiE treatment restored glucose uptake. Glycogen content in skeletal muscle followed similar trends, with no differences seen in resting animals. Postexercise red quadriceps glycogen levels were higher (P < 0.05) in the E and P + HiE rats compared with O and P. Treatment of ovariectomized rats with progesterone (P rats) decreased (P < 0.05) GLUT4 content in the red quadriceps by 21% compared with C rats. These data demonstrate that estrogen-deficient animals have a decreased ability for contraction-stimulated glucose uptake and increased glycogen use during aerobic exercise. However, changes in contraction-stimulated glucose uptake could not be explained by altered transporter protein content, since the absence of E(2) had no effect on GLUT4 protein.

Animals↗

PubMed2001

Molecular cloning and characterization of canine metalloproteinase-9 gene promoter.

This paper describes the cloning and characterization of the canine matrix metalloproteinase-9 (MMP-9) gene promoter. The 5' untranslated region was obtained by genome walking upstream of the canine MMP-9 translation start site using canine genomic DNA as template. A DNA fragment of 1894 bp was isolated and on analysis demonstrated regions of sequence homology with the MMP-9 promoter sequences already determined for other species. In general, conserved regions correlated with DNA binding motifs such as a TATA-like box, AP-1 sites, GC boxes and a nuclear factor-kappaB binding domain. The DNA promoter fragment was sufficient to drive basal expression of a luciferase reporter gene in Madin Darby canine kidney (MDCK) cells and to a lesser extent in feline embryonic fibroblast (FEA) cells. Activity of the promoter was enhanced by the treatment of transfected MDCK cells with phorbol 12-myristate 13-acetate but no effect was observed in the FEA cells. Promoter deletion studies revealed that regions of promoter were necessary for induction of reporter gene expression.

Amino Acid Sequence↗

PubMed2001

Cloning of canine IL-1ra, TNFR and TIMP-2.

This paper describes the cloning and sequence analysis of the cDNA's encoding the canine homologues of interleukin-1 receptor antagonist (IL-1ra), tumour necrosis factor receptor extra-cellular domain (TNFR/ECD) and tissue inhibitor of metalloproteinase-2 (TIMP-2). The coding sequences for canine IL-1ra and TNFR/ECD were obtained using reverse transcription polymerase chain reaction (RT-PCR) using RNA harvested from canine peripheral blood mononuclear cells (PBMC) and TIMP-2 was isolated in a similar fashion from the canine D17 osteosarcoma cell line. Sequence analysis of the canine genes demonstrated open reading frames of 531, 633 and 663 base pairs (bp), respectively. All three canine proteins IL-1ra, TNFR/ECD and TIMP-2 (177, 211 and 221 amino acids, respectively) showed considerable sequence similarity with the homologous sequences published for other species.

Amino Acid Sequence↗

PubMed2001

Autogenous osteochondral "plug" transfer for the treatment of focal chondral defects: postoperative MR appearance with clinical correlation.

OBJECTIVE: To describe the MR appearance following autogenous osteochondral "plug" transfer for the treatment of focal chondral defects of the knee. DESIGN AND PATIENTS: Twenty-nine 1.5-T MR knee studies including dynamic gadolinium enhancement were performed on 21 patients following autogenous osteochondral "plug" transfer. Three musculoskeletal radiologists retrospectively reviewed images to evaluate graft and donor site appearance and MR findings were correlated with clinical outcomes. RESULTS: MR images demonstrated graft protuberance (n=12/21; range 1-2 mm), depression (n=2/21; range 1 mm), and surface incongruity: mild (n=17/21), moderate (n=2/21), marked (n=1/21). The T2 signal of graft cartilage was similar to that of adjacent cartilage in 25 of 29 examinations, and increased in four. Graft cartilage thickness relative to adjacent cartilage was <50% in six patients, 50-100% in 15. Graft enhancement in bone was absent at 2 weeks, but present at between 4 and 6 weeks following surgery. All patients had clinical follow-up examinations and knee outcome survey scores were obtained in 15 patients with follow-up greater than 3 months after surgery. All patients demonstrated the expected short-term progressive clinical improvement. CONCLUSION: MR images reveal a wide range of appearances following osteochondral "plug" transfer. Minor variations in graft orientation and surface congruity do not result in adverse clinical outcome in the short term.

Adult↗

PubMed2001

The prevalence of prophylaxis for deep vein thrombosis in acute hospital trusts.

OBJECTIVE: The effectiveness of activities to promote routine prophylaxis to prevent thromboembolism is difficult to assess because information about the prevalence of prophylaxis is sparse. The aim of this study was to assess the prevalence of deep vein thrombosis (DVT) prophylaxis for patients at risk in general medicine, general surgery, orthopaedics and gynaecology in Scotland and the North of England. DESIGN: Retrospective case note review of a random sample of episodes of care in a stratified random sample of directorates in Scotland and a convenience sample in England. SETTING: Twenty acute hospital directorates in Scotland and eight in the North of England. PARTICIPANTS: Case notes of patients at risk of thrombosis and discharged from the selected directorates in a 12-month period (n = 742). MAIN OUTCOME MEASURES: The proportion of patients receiving prophylaxis in each directorate. RESULTS: Overall, 469/526 (89%) of patients in Scotland and 199/216 (92%) in England received prophylaxis. The proportion varied from 71% in general medicine to 100% in orthopaedics. The frequency of use of different forms of prophylaxis varied between directorates. Approximately 60% of the patients who received prophylaxis received more than one form. CONCLUSIONS: Prophylaxis for DVT is well established for procedures and conditions that are known to increase the risk of thrombosis and for which there are no contraindications. Additional efforts to promote prophylaxis for these conditions are unlikely to be cost effective. Further research is needed to establish whether rates are equally high in other conditions, and whether the high prophylaxis rates are due to clinical effectiveness initiatives.

Anticoagulants↗

PubMed2001

A systematic review of discharge coding accuracy.

BACKGROUND: The aim of the study was to review systematically the literature measuring the accuracy of routine UK hospital statistics that classify patients on discharge. METHODS: A systematic review was carried out of studies comparing routine discharge statistics about an episode of hospital care with the original medical record. Dual quality assessment and extraction was completed for included studies. Qualitative and descriptive analyses were undertaken. Additional comparisons of factors that could potentially introduce systematic variation in coding accuracy were also undertaken. RESULTS: Thirty studies were identified, of which 21 were included in the review. Twelve of these were conducted in England and Wales, and nine in Scotland. The majority assessed the accuracy of a single diagnosis, or selection of diagnoses in a limited range of hospital settings. The median coding accuracy rates were 91 per cent for diagnostic codes and 69.5 per cent for operation or procedure codes in studies in England or Wales; 82 per cent for diagnostic codes and 98 per cent for operation or procedure codes in Scottish studies. There were no significant differences in coding accuracy over time or in the type or rarity of the codes being assessed. Accuracy rates were higher for ICD7 codes (median 96.5 per cent) than for ICD8 (median 87 per cent) or ICD9 (median 77 per cent). CONCLUSIONS: Coding accuracy on average is high in the United Kingdom, especially for operations and procedures. However, policy-makers, planners and researchers need to recognize and account for the degree of inaccuracy in routine hospital information statistics. Further research is needed into methods of improving and maintaining coding accuracy.

Abstracting and Indexing↗

PubMed2001

Effects of ovarian hormones on exercise metabolism.

Growing evidence suggests that the ovarian hormones have major effects on lipid and carbohydrate metabolism, and may also play a major role in up-stream molecular signaling mechanisms for regulating substrate metabolism. It appears that the absence of estrogen can impair glucose uptake during exercise. In contrast, progesterone not only impairs contraction-mediated glucose uptake when solely administered, but impairs glucose uptake when physiological concentrations of both estrogen and progesterone are administered. Likewise, progesterone administered to rodents for 14 days decreases glucose transporter (GLUT) 4 protein content in skeletal muscle and adipose tissue. Furthermore removing the ovaries decreases the activity of key oxidative enzymes while estrogen treatment restores the activity of these enzymes. It appears, therefore, that estrogen increases the metabolic capacity for both carbohydrate and lipid metabolism, perhaps increasing the overall metabolic flexibility of skeletal muscle. Conversely, progesterone negates both these effects, and could therefore result in a state of relative metabolic inflexibility, similar to that observed in the metabolic syndrome.

Animals↗

PubMed2001

Effect of ovarian hormones on mitochondrial enzyme activity in the fat oxidation pathway of skeletal muscle.

To examine the roles of 17beta-estradiol (E(2)) and progesterone (Prog) in lipid metabolism, skeletal muscle enzyme activities were studied in female Sprague-Dawley rats. Groups included sham-operated rats (C) and ovariectomized rats treated with placebo (O), E(2) (E), Prog (P), both hormones at physiological doses (P + E), or both hormones with a high dose of E(2) (P + HiE). Hormone (or vehicle only) delivery was via time-release pellets inserted at the time of surgery, 15 days before metabolic testing. Results demonstrated that carnitine palmitoyltransferase maximal activity was 19, 21, and 19% lower (P < 0.01) in O, P, and P + E rats, respectively, compared with C rats. Conversely, activity in E and P + HiE rats was 14 and 19% higher (P < 0.01) than in C. beta-Hydroxyacyl-CoA dehydrogenase (beta-HAD) maximal activity was 20% lower (P < 0.01) in O than in C rats; similarly, P and P + E rats were 18 and 19% lower, respectively (P < 0.01); however, treatment with E(2) returned beta-HAD activity to C levels. These results suggest that E(2) plays a role in lipid metabolism by increasing the maximal activity of key enzymes in the fat oxidative pathway of skeletal muscle.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed2001

Glucose kinetics and exercise performance during phases of the menstrual cycle: effect of glucose ingestion.

To study the effect of menstrual cycle phase and carbohydrate ingestion on glucose kinetics and exercise performance, eight healthy, moderately trained, eumenorrheic women cycled at 70% of peak O(2) consumption for 2 h and then performed a 4 kJ/kg body wt time trial. A control (C) and a glucose ingestion (G) trial were completed during the follicular (F) and luteal (L) phases of the menstrual cycle. Plasma substrate concentrations were similar before the commencement of exercise. Glucose rates of appearance and disappearance were higher (P < 0.05) during the 2nd h of exercise in FC than in LC. The percent contribution of carbohydrate to total energy expenditure was greater in FC than in LC, and subjects performed better (13%, P < 0.05) in FC. Performance improved (19% and 26% in FG and LG compared with FC and LC, respectively, P < 0.05) with the ingestion of glucose throughout exercise. These data demonstrate that substrate metabolism and exercise performance are influenced by the menstrual cycle phase, but ingestion of glucose minimizes these effects.

Adult↗

PubMed2001

MR imaging of meniscal cysts: incidence, location, and clinical significance.

OBJECTIVE: The purpose of this study was to determine the incidence of medial versus lateral meniscal cysts as seen on MR imaging. MATERIALS AND METHODS: A total of 2572 knee MR imaging reports were retrospectively reviewed for the presence of meniscal tears and cysts. Two musculoskeletal radiologists reviewed all images with reported cysts. The type and location of meniscal tear and the presence and location of meniscal cysts were recorded. RESULTS: A total of 1402 meniscal tears were reported in 2572 MR examinations (922 [66%] of 1402 in the medial compartment; 480 [34%] of 1402 in the lateral compartment). Meniscal cysts were present in 109 (4%) of 2572 knees. Of the 109 cysts, 72 (66%) were in the medial compartment, and 37 (34%) were in the lateral compartment. Meniscal cysts were found in association with 72 (7.8%) of the 922 medial meniscal tears and 37 (7.7%) of the 480 lateral meniscal tears. Meniscal cysts showed direct contact with an adjacent meniscal tear in 107 (98%) of 109 cases, with the tear showing a horizontal component in 96 (90%) of 107 cases. CONCLUSION: Meniscal cysts occur almost twice as often in the medial compartment as in the lateral compartment. Medial and lateral tears occur with the same frequency. These findings, when viewed in the context of the historical literature on meniscal cysts, suggest that MR imaging detects a greater number of medial meniscal cysts than physical examination or arthroscopy, and that MR imaging can have an important impact on surgical treatment of patients.

Adult↗

PubMed2000

Tumor induction by the c-Myc target genes rcl and lactate dehydrogenase A.

The characterization of c-Myc target genes, such as rcl and lactate dehydrogenase A (LDH-A), is critical for understanding the mechanisms of c-Myc-induced cell transformation and tumorigenesis. We have previously demonstrated that Rcl induces anchorage-independent growth in Ratla fibroblasts and that LDH-A is required for cell transformation by c-Myc. In this study, we report that Rcl and LDH-A act synergistically to induce anchorage-independent growth. Cells expressing both Rcl and LDH-A form tumors after s.c. injection into nude mice, although neither Rcl or LDH-A overexpression alone induces tumorigenesis. The inability of Rcl and LDH-A to fully recapitulate c-Myc activity, however, indicates that other c-Myc target genes participate in tumorigenesis. In addition, cells that coexpress Rcl and vascular endothelial growth factor are more comparable with c-Myc overexpressing cells in their ability to form tumors in nude mice. These findings confirm Rcl and LDH-A as critical components of the cell transformation program induced by c-Myc and suggest that Rcl is tumorigenic in cells that are provided with a permissive metabolic milieu.

Animals↗

PubMed2000

c-Myc suppresses the tumorigenicity of lung cancer cells and down-regulates vascular endothelial growth factor expression.

The c-myc oncogene is frequently amplified in cells grown from lung tumors and has been linked to the malignancy of these cancers. In support of this, c-myc transfection enhances the in vitro proliferation and soft agar cloning of human small cell lung cancer (SCLC) cells. In this study, we surprisingly found that c-myc expression suppressed the formation of tumors by SCLC cells in athymic nude mice. c-myc expression down-regulated the protein and transcript for vascular endothelial growth factor (VEGF) in these SCLC cells, as well as VEGF transcript in rat fibroblasts manipulated for c-myc expression and in liver cells of c-myc-transgenic mice. Finally, bivariate and multivariate analyses demonstrated that the probability of tumor formation from lung cancer cell lines was negatively correlated with the relative expression of c-Myc, positively correlated with the relative expression of VEGF, and that the latent time to tumor formation was increased by the expression of c-Myc and decreased by the expression of VEGF. We hypothesize that, for lung cancer cells, c-Myc suppresses the formation of tumors in vivo by down-regulating VEGF, and that the amplification of c-myc seen in cells grown from lung tumors with a poor prognosis is an artifact of selection for growth in vitro.

Analysis of Variance↗