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Biomedical subjects

D Ross

Publications and source records attributed to D Ross.

At least 19 recordsLinked to original sources
PubMed2006

Validity of self-report measures of pain and disability for persons who have undergone arthroplasty for osteoarthritis of the carpometacarpal joint of the hand.

OBJECTIVE: To establish the validity of three self-report scales used to measure function following arthroplasty for osteoarthritis (OA) of the carpometacarpal joint. METHOD: Persons with OA of the carpometacarpal joint (n=122) were assessed on one occasion 9-117 months following tendon interposition arthroplasty. They completed three self-report measures of hand/upper limb disability: the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Patient-Rated Wrist Hand Evaluation (PRWHE), and the Disabilities of Arm, Shoulder and Hand (DASH). They also completed the Short Form 36 (SF-36) and performed tests of strength, range of motion (ROM), and dexterity. Factor analysis and correlations were used to determine the association among the scales and subscales considered to measure similar constructs (e.g., pain and physical disability). Correlations between the scales and measures of impairment were also conducted to examine construct validity of the disability measures. t-Tests evaluated the hypotheses that subjects with isolated hand OA would have lower scores than those with additional joint involvement. RESULTS: All three scales or their subscales loaded on one factor. Convergent validity of the disability measures was demonstrated by high correlations between similar subscales (r>0.75), and divergent validity by a lack of correlation between the measures and self-report hand appearance. As expected, correlations between disability and strength, dexterity, or a global measure of ROM were higher than with ROM of individual joints. The AUSCAN and the DASH were better able to discriminate those with localized hand OA from those with involvement of other joints. CONCLUSIONS: The AUSCAN, PRWHE, and DASH are valid assessments of pain and/or disability of hand OA, and provide information distinct from impairment measures.

Activities of Daily Living↗
PubMed2006

Overexpression of NQO1 protects human SK-N-MC neuroblastoma cells against dopamine-induced cell death.

NAD(P)H quinone oxidoreductase 1 (NQO1) can metabolize dopamine-derived quinones (DAQ) and absence of NQO1 due to the NQO1*2 polymorphism has been suggested to be a risk factor for Parkinson's disease. In order to define whether NQO1 plays a protective role in dopamine toxicity, we have examined the potential role of NQO1 in the SK-N-MC human neuroblastoma cell line. SK-N-MC cells were stably transfected with NQO1 to generate stable clones with NQO1 enzymatic activity of 245 nmol/mgmin while vector control and parental cells had NQO1 activities of less than 12 nmol/mgmin. Incubation of dopamine for 24 h in both parental and vector control SK-N-MC cells resulted in 85% and 72% cell death as assessed by annexin-V/propidium iodide analysis. In agreement, 88% and 84% of parental and vector control cells, respectively underwent loss of mitochondrial membrane potential (MMP) assessed by tetramethylrhodamine ethyl ester. In contrast, NQO1-transfected cells were resistant to dopamine toxicity and both cell death and loss of MMP were markedly abrogated in NQO1-transfected SK-N-MC cells. When dopamine was added to medium, oxygen uptake could be detected indicating autoxidation with concomitant formation of oxygen radicals and quinones. However, dopamine-induced cell death was not affected by the inclusion of either superoxide dismutase or catalase suggesting that superoxide and hydrogen peroxide were not involved in toxicity. Quinones formed in medium may exert toxicity extracellularly or intracellularly but the protective role of NQO1 argues for an intracellular mechanism. In summary, transfection of SK-N-MC cells with NQO1 protects against dopamine-induced toxicity.

Annexin A5↗
PubMed2005

Sources of priority substances entering an urban wastewater catchment--trace organic chemicals.

The implementation of new legislation such as the Water Framework Directive (WFD) requires Member States to gain a better understanding of priority substances entering surface waters. This will include inputs from wastewater treatment works as well as from other urban, industrial and agricultural sources. There is currently a lack of available data regarding the magnitude and sources of organic priority substances entering treatment works. As a consequence the concentrations of organic priority substances including PAHs, surfactants, polybrominated diphenylethers (PBDEs), diethylhexyl phthalate (DEHP), pesticides and solvents were determined in the wastewater from an urban catchment located in the UK, as part of a project undertaken for UK Water Industry Research (UKWIR). Most organic priority substances were detected in the microg/l range. Significant variations in the concentration of linear alkylbenzene sulphonate (LAS), DEHP, PBDEs and nonylphenol ethoxylates (NPEOs), in particular, were observed for the different sources. The greatest differences were evident between new and older domestic discharges. Solvent levels varied considerably reflecting use and production within the catchment. Chloroform levels were highest in domestic effluent, while trichloroethene and tetrachloroethene were detected only in commercial samples.

Organic Chemicals↗
PubMed2005

Diffuse sources of heavy metals entering an urban wastewater catchment.

New legislation such as the Water Framework Directive (WFD) will require Member States to better understand the concentrations and loads of contaminants entering surface waters. This will include inputs from wastewater treatment plants (WWTP) as well as from other urban, industrial and agricultural sources. A review of available literature revealed a shortage of data on the levels and sources of heavy metals entering WWTP from urban sources. As a consequence, the concentrations of heavy metals (cadmium, chromium, copper, mercury, nickel, lead and zinc) were determined in the wastewater from an urban catchment located in the UK, as part of a project undertaken for UK Water Industry Research (UKWIR). Both foul and surface water samples were taken. Metal concentrations varied considerably in the foul water samples, both between sources and over the course of the week. Concentrations of most metals were higher in the Monday town centre samples, attributed to leaching from stagnant water remaining in the pipework of office buildings over the weekend. Runoff concentrations were higher in the light industrial estate samples than in the domestic samples for all the metals, and exhibited highest levels in the 'first flush' samples, coincident with the initial flow of runoff containing the highest concentrations of suspended solids.

Agriculture↗
PubMed2005

The Rap-B-Raf signalling pathway is activated by glucose and glucagon-like peptide-1 in human islet cells.

AIMS/HYPOTHESIS: Glucose and glucagon-like peptide-1 have been shown to activate extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase in beta cells. We examined the contributions of the small GTPases Rap and Ras and the serine-threonine kinases B-Raf and Raf-1 to the activation of these kinases in human islet cells. METHODS: The expression of Rap, Ras, B-Raf and Raf-1 in human islets was examined by immunohistochemistry and immunoblotting. Human islets were incubated in glucose at concentrations of 2.5 and 15 mmol/l and were stimulated with 10 nmol/l glucagon-like peptide-1. The activation of ERK and Raf kinases was examined by phosphorylation-specific antibodies and immuno-complexed kinase assays. The activation of Rap and Ras was determined by pull-down assays. Stimulation of phosphoinositide 3-kinase was detected by immuno-complexed lipid kinase assays. RESULTS: Extracellular-regulated kinase and protein kinase B (a downstream target of phosphoinositide 3-kinase) were activated in islets stimulated with glucose and glucagon-like peptide-1. In these islets, the Rap-B-Raf signalling pathway was activated preferentially compared with Ras and Raf-1, and activated Rap and B-Raf mediated ERK stimulation in kinase assays in vitro. In addition, Rap rather than Ras mediated activation of phosphoinositide 3-kinase in islets stimulated with glucose and glucagon-like peptide-1. CONCLUSIONS/INTERPRETATION: In human islet cells, glucose and glucagon-like peptide-1 activate the Rap and B-Raf signalling module, which mediates ERK activation in assays in vitro. Rap also activates phosphoinositide 3-kinase, delineating central roles for Rap and B-Raf as therapeutic targets for beta cell growth in diabetes mellitus.

Cells, Cultured↗
PubMed2004

There is no difference in the disease severity of gastro-oesophageal reflux disease between patients infected and not infected with Helicobacter pylori.

BACKGROUND: The role of Helicobacter pylori in gastro-oesophageal reflux disease (GERD) is controversial. AIM: To compare the severity of GERD in infected vs. non-infected patients, as part of an ongoing randomized controlled trial that examines the impact of H. pylori eradication on GERD-related outcomes. METHODS: Consecutive GERD patients underwent urea breath testing and completed validated GERD symptom severity, and quality of life questionnaires as well as, 24-h pH-metry. These parameters, as well as demographics and endoscopic findings were assessed in double-blinded fashion and compared between H. pylori-infected and non-infected subjects. RESULTS: Helicobacter pylori-infected GERD patients (n=50) were significantly older and less educated than non-infected patients (n=51). They also used proton pump inhibitors less often but had no difference in symptoms (as measured with both the Spechler's Activity Index and the Gastrointestinal Symptom Rating Scale), quality of life, endoscopic findings or 24-h pH-metry findings. CONCLUSION: This prospective, double-blind study demonstrates, using excellent GERD quantifying measures including validated symptom severity scores, endoscopy, and 24-h pH-metry, that there exist no clinically significant differences in clinical or laboratory-related GERD manifestations between H. pylori-infected and non-infected GERD patients.

Adolescent↗
PubMed2004

Contraceptive efficacy and safety of DMPA-SC.

DMPA-SC 104 mg/0.65 mL is a new, low-dose subcutaneous (SC) formulation of Depo-Provera contraceptive injection (150 mg/mL medroxyprogesterone acetate injectable suspension) that provides efficacy, safety and immediacy of onset equivalent to Depo-Provera intramuscular (IM) injection. Two large, open-label, Phase 3 studies assessed the 1-year contraceptive efficacy, safety and patient satisfaction with DMPA-SC administered every 3 months (12-13 weeks). Zero pregnancies were reported in both studies, which included a total of 16,023 woman-cycles of exposure to DMPA-SC and substantial numbers of overweight or obese women. DMPA-SC was well-tolerated and adverse events were similar to those reported previously with Depo-Provera IM. Thus, DMPA-SC offers women a new, highly effective and convenient long-acting contraceptive option.

Adult↗
PubMed2004

Expression of NAD(P)H:quinone oxidoreductase in the normal and Parkinsonian substantia nigra.

Dopamine (DA) autooxidation, and consequent formation of neurotoxic DA-derived quinones and reactive oxygen species, has been implicated in dopaminergic cell death and, hence, in the pathogenesis of Parkinson's disease (PD). Stimulation of pathways involved in the detoxication of DA-quinones in the brain is hypothesized to be an effective means to limit oxidative stress and to confer neuroprotection in PD. In this respect, the inducible flavoprotein NAD(P)H:quinone oxidoreductase (NQO1) is of particular interest as it is directly implicated in the detoxication of DA-quinones and, in addition, has broad spectrum anti-oxidant properties. To study the potential pathophysiological role of NQO1 in PD, the cellular expression of NQO1 was examined in the mesencephalon of PD patients and age-matched controls. In the substantia nigra pars compacta (SNpc), NQO1 was found to be expressed in astroglial and endothelial cells and, albeit less frequently, also in dopaminergic neurons. Moreover, while overt NQO1 immunoreactivity was absent in the surrounding nervous tissue, in the Parkinsonian SNpc a marked increase in the astroglial and neuronal expression of NQO1 was consistently observed.

Adult↗
PubMed2004

Cholesterol-lowering effects of plant sterol esters differ in milk, yoghurt, bread and cereal.

OBJECTIVE: To measure the relative effects of each of four phytosterol ester-enriched low-fat foods (bread, breakfast cereal, milk and yoghurt) on serum lipids, plasma phytosterols and carotenoids. DESIGN: : Three research centres undertook a randomised, incomplete crossover, single-blind study consisting of four treatment periods of 3 weeks each, one of which was a control period. Each sterol-enriched test food provided 1.6 g/day of phytosterols as sterol esters. SETTING: General Community. SUBJECTS: In all 58, free-living men and women with mean age (s.d.) 54 (8) y, moderately elevated plasma total cholesterol 6.2 (0.7) mmol/l and body mass index 26.2 (3.0) kg/m(2). MAIN OUTCOME MEASURES: Serum lipids, plasma phytosterols and carotenoids. RESULTS: Serum total and LDL cholesterol levels were significantly lowered by consumption of phytosterol-enriched foods: milk (8.7 and 15.9%) and yoghurt (5.6 and 8.6%). Serum LDL cholesterol levels fell significantly by 6.5% with bread and 5.4% with cereal. They were both significantly less efficacious than sterol-enriched milk (P<0.001). Plasma sitosterol increased by 17-23% and campesterol by 48-52% with phytosterol-enriched milk and bread. Lipid-adjusted beta-carotene was lowered by 5-10% by sterols in bread and milk, respectively. CONCLUSIONS: This is the first study to demonstrate that cholesterol-lowering effects of plant sterol esters may differ according to the food matrix. Plant sterols in low-fat milk was almost three times more effective than in bread and cereal. Despite phytosterol-enriched cereal products resulting in lower serum cholesterol reductions compared to sterol-enriched milk, the detection of similar changes in plasma phytosterols demonstrated that such products still delivered and released phytosterols to the gut.

Adult↗
PubMed2004

Identifying and reducing errors with surgical simulation.

The major determinant of a patient's safety and outcome is the skill and judgment of the surgeon. While knowledge base and decision processing are evaluated during residency, technical skills-which are at the core of the profession-are not evaluated. Innovative state of the art simulation devices that train both surgical tasks and skills, without risk to patients, should allow for the detection and analysis of errors and "near misses". Studies have validated the use of a sophisticated endoscopic sinus surgery simulator (ES3) for training residents on a procedural basis. Assessments are proceeding as to whether the integration of a comprehensive ES3 training programme into the residency curriculum will have long term effects on surgical performance and patient outcomes. Using various otolaryngology residencies, subjects are exposed to mentored training on the ES3 as well as to minimally invasive trainers such as the MIST-VR. Technical errors are identified and quantified on the simulator and intraoperatively. Through a web based database, individual performance can be compared against a national standard. An upgraded version of the ES3 will be developed which will support patient specific anatomical models. This advance will allow study of the effects of simulated rehearsal of patient specific procedures (mission rehearsal) on patient outcomes and surgical errors during the actual procedure. The information gained from these studies will help usher in the next generation of surgical simulators that are anticipated to have significant impact on patient safety.

Computer-Assisted Instruction↗
PubMed2003

Strong spatiotemporal localization in a silica nonlinear waveguide array.

We investigate the propagation of short, intense laser pulses in arrays of coupled silica waveguides, in the anomalous dispersion regime. The nonlinearity induces trapping of the pulse in a single waveguide, over a wide range of input parameters. A sharp transition is observed for single waveguide excitation, from strong diffraction at low powers to strong localization at high powers.

Journal Article↗
PubMed2003

Limits on diffuse fluxes of high energy extraterrestrial neutrinos with the AMANDA-B10 detector.

Data from the AMANDA-B10 detector taken during the austral winter of 1997 have been searched for a diffuse flux of high energy extraterrestrial muon neutrinos. This search yielded no excess events above those expected from background atmospheric neutrinos, leading to upper limits on the extraterrestrial neutrino flux measured at the earth. For an assumed E-2 spectrum, a 90% classical confidence level upper limit has been placed at a level E2Phi(E)=8.4 x 10(-7) cm(-2) s(-1) sr(-1) GeV (for a predominant neutrino energy range 6-1000 TeV), which is the most restrictive bound placed by any neutrino detector. Some specific predicted model spectra are excluded. Interpreting these limits in terms of the flux from a cosmological distributions of sources requires the incorporation of neutrino oscillations, typically weakening the limits by a factor of 2.

Journal Article↗
PubMed2003

Lamotrigine for HIV-associated painful sensory neuropathies: a placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and tolerability of lamotrigine (LTG) for the treatment of pain in HIV-associated sensory neuropathies. METHODS: In a randomized, double-blind study, patients with HIV-associated distal sensory polyneuropathy (DSP) received LTG or placebo during a 7-week dose escalation phase followed by a 4-week maintenance phase. Randomization was stratified according to whether or not patients were currently using neurotoxic antiretroviral therapy (ART). RESULTS: The number of patients randomized was 92 (62 LTG, 30 placebo) in the stratum receiving neurotoxic ART and 135 (88 LTG, 47 placebo) in the stratum not receiving neurotoxic ART. Mean change from baseline in Gracely Pain Scale score for average pain was not different between LTG and placebo at the end of the maintenance phase in either stratum, but the slope of the change in Gracely Pain Scale score for average pain reflected greater improvement with LTG than with placebo in the stratum receiving neurotoxic ART (p = 0.004), as did the mean change from baseline scores on the Visual Analogue Scale for Pain Intensity and the McGill Pain Assessment Scale and patient and clinician ratings of global impression of change in pain (p </= 0.02). The incidence of adverse events, including rash, was similar between LTG and placebo. CONCLUSIONS: Lamotrigine was well-tolerated and effective for HIV-associated neuropathic pain in patients receiving neurotoxic antiretroviral therapy. Additional research is warranted to understand the differing response among patients receiving neurotoxic antiretroviral therapy compared with those not receiving neurotoxic antiretroviral therapy.

Adult↗
PubMed2003

Late salvage of a free TRAM flap.

We present the case of a patient with arterial thrombosis of a free TRAM flap 11 days after surgery. Initial salvage involved thrombectomy through an arteriotomy using a Fogarty catheter. Subsequent return to the operating theatre was necessary because of further vascular compromise. Thrombectomy was combined with flap thrombolysis and anticoagulation, and the flap remained viable at 6 months. Although rates of successful salvage vary, the literature indicates that flaps are rarely saved if signs of compromise present later than 2 days postoperatively. This case demonstrates that aggressive salvage may be successful even in cases of 'late' vascular compromise.

Adult↗
PubMed2003

Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells.

Styryl-lactones such as goniothalamin represent a new class of compounds with potential anti-cancer properties. In this study, we investigated the mechanisms of goniothalamin (GTN), a plant styryl-lactone induced apoptosis in human promyelocytic leukemia HL-60 cells. This plant extract resulted in apoptosis in HL-60 cells as assessed by the externalisation of phosphatidylserine. Using the mitochondrial membrane dye (DIOC(6)) in conjunction with flow cytometry, we found that GTN treated HL-60 cells demonstrated a loss of mitochondrial transmembrane potential (Deltapsi(m)). Further immunoblotting on these cells showed activation of initiator caspase-9 and the executioner caspases-3 and -7. Pretreatment with the pharmacological caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) abrogated apoptosis as assessed by all of the apoptotic features in this study. In summary, our results demonstrate that goniothalamin-induced apoptosis occurs via the mitochondrial pathway in a caspase dependent manner.

Apoptosis↗
PubMed2003

RANTES, eotaxin and eotaxin-2 expression and production in patients with aspirin triad.

BACKGROUND: Polyposis, asthma, aspirin-intolerance and aspirin-triad are mostly accompanied with eosinophilia of mucosal airways. Chemotactic cytokines, the CC-chemokines regulated on activation, normal T-cell expressed (RANTES), eotaxin, and eotaxin-2 activate and attract eosinophilic leukocytes to the site of inflammation. This points to the implication of CC-chemokines in eosinophilia of nasal tissue of these diseases. METHODS: Therefore, nasal polypous tissue specimens of patients suffering from chronic nasal polypous sinusitis (NP), intrinsic asthma (ATA), aspirin-intolerance (AINA), and aspirin-triad (TRIAD) were investigated. The amount of mRNA and protein of CC-chemokines was analyzed using semi-quantitative reverse transcriptase polymerase chain reaction and chemokine-specific enzyme-immuno-assays. The patterns of CC-chemokines were compared. RESULTS: The mRNA-expression as well as protein synthesis of CC-chemokines was quantified in all tissues investigated. The expression of RANTES-mRNA in NP, ATA, AINA, and TRIAD (averaging 148-324% D-glyceraldehyde-3-phosphate dehydrogenase) and protein synthesis (0.13-0.15 ng/mg tissue weight) did not differ significantly. But the protein synthesis of eotaxin- and eotaxin-2-mRNA was significantly (P < 0.05) higher in TRIAD (3.3 pg/mg and 3.4 ng/mg tissue weight) (4 ng/mg tissue weight), than in NP, ATA, or AINA (1.8 pg/mg and 2.1 ng/mg, 2.1 pg/mg and 1.6 ng/mg, or 1.7 pg/mg and 2.2 ng/mg tissue weight, respectively). CONCLUSION: Patients suffering from TRIAD in association with tissue eosinophilia were characterized by elevated eotaxin and eotaxin-2 mRNA-expression as well as protein-synthesis. This pointed to the implication of eotaxins and RANTES in eosinophilia-associated diseases. Further studies will have to prove, whether the analysis of these chemokines might improve the diagnosis of eosinophilia associated polyposis and initiate the development of new therapeutic strategies.

Adult↗