PubMed Health⌕ Search

Biomedical subjects

B Edwards

Publications and source records attributed to B Edwards.

At least 19 recordsLinked to original sources
PubMed2001

Moxifloxacin: clinical efficacy and safety.

The activity, pharmacokinetics, pharmacodynamics, efficacy, safety, drug interactions, and dosage and administration of moxifloxacin are reviewed. Moxifloxacin is an oral 8-methoxyquinolone antimicrobial approved in December 1999 for use in the treatment of acute bacterial sinusitis, acute bacterial exacerbations of chronic bronchitis, and community-acquired pneumonia. This fluoroquinolone is active against common community-acquired respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis), atypical pathogens, and many anaerobes. Moxifloxacin has an absolute bioavailability of 90% after oral administration and a mean elimination half-life of 12 hours. The drug is not a substrate or inhibitor of the hepatic cytochrome P-450 isoenzyme system thereby avoiding many potential drug interactions. Moxifloxacin has limited phototoxic potential. In clinical trials, moxifloxacin had clinical success rates of 88-97% and bacteriologic eradication rates of 90-97%. Reported adverse effects were primarily gastrointestinal (nausea, diarrhea) and were mild to moderate in severity. Moxifloxacin prolongs the QT interval by a mean + S.D. of 6 +/- 26 milliseconds above baseline and should be used with caution in patients with proarrhythmic conditions and avoided in patients receiving antiarrhythmia agents, such as quinidine, procainamide, amiodarone, and sotalol. The standard oral dosage is 400 mg once a day. Dosage adjustment is unnecessary in patients with renal dysfunction or mild to moderate hepatic dysfunction. Moxifloxacin is a safe and effective antimicrobial that will be useful for treating acute sinusitis, acute bacterial exacerbations of chronic bronchitis, and community-acquired pneumonia.

Anti-Infective Agents↗
PubMed2001

Vascular endothelial growth factor effects on nuclear factor-kappaB activation in hematopoietic progenitor cells.

Vascular endothelial growth factor (VEGF) inhibits of the activation of transcription factor nuclear factor-kappaB (NF-kappaB) in hematopoietic progenitor cells (HPCs), and this is associated with alterations in the development of multiple lineages of hematopoietic cells and defective immune induction in tumor-bearing animals. Antibodies to VEGF have been shown to abrogate this effect. The mechanism by which VEGF antagonizes the induction of NF-kappaB was investigated in this study. Using supershift electrophoretic mobility shift analysis, we found that although tumor necrosis factor alpha (TNF-alpha) induced the nuclear translocation and DNA binding of p65-containing complexes, VEGF alone induced nuclear translocation and DNA binding of the complexes containing RelB. These results were confirmed by immunofluorescence confocal microscopy. VEGF effectively blocked TNF-alpha-induced NF-kappaB activation in HPCs from RelB-/- mice, however, similar to the effect observed in HPCs obtained from RelB+/- and RelB+/+ mice. This suggests that RelB is not required for VEGF to inhibit NF-kappaB activation. However, although TNF-alpha induced rapid activation of IkappaB kinase (IKK) as expected, this activity was substantially reduced in the presence of VEGF. This decreased IKK activation correlated with the inhibition of IkappaB alpha phosphorylation and degradation of IkappaB alpha and IkappaB epsilon in HPCs. VEGF alone, however, did not have any effect on phosphorylation of IkappaB alpha or degradation of IkappaB alpha and other inhibitory molecules IkappaB beta, IkappaB epsilon, or Bcl-3. SU5416, a potent inhibitor of the VEGF receptor I (VEGFR1) and VEGFR2 receptor tyrosine kinases, did not abolish the inhibitory effect of VEGF, indicating that the VEGF effect is mediated by a mechanism unrelated to VEGFR1 or VEGFR2 tyrosine kinase activity. Thus, VEGF appears to inhibit TNF-alpha-induced NF-kappaB activation by VEGFR kinase-independent inhibition of IKK. Therapeutic strategies aimed at overcoming VEGF-mediated defects in immune induction in tumor-bearing hosts will need to target this kinase-independent pathway.

Animals↗
PubMed2001

Simulation of thermal diffuse scattering including a detailed phonon dispersion curve.

Thermal vibration of the atoms in a crystal give rise to a diffuse background in the diffraction pattern (in between the normal allowed Bragg reflections). The Einstein model for phonon vibrations in a crystal leads to Gaussian statistics for the phonons. However, the Einstein model ignores the possibility of correlation between the atoms. An accurate model of the phonon dispersion curves for silicon is used to generate a set of more accurate random atomic displacements. These displacements are used in a multislice-style simulation to gauge the validity of the Einstein approximation. The phonon dispersion curve yields a small additional oscillatory structure in the thermal diffuse scattering (TDS) pattern. This does not produce significant changes in the annular dark field scanning transmission electron microscope (ADF-STEM) image signal, but could have a large impact on convergent beam measurements of bond charges.

Journal Article↗
PubMed2001

Are there hangover-effects on physical performance when melatonin is ingested by athletes before nocturnal sleep?

Athletes ingest melatonin in an attempt to improve sleep quality or alleviate symptoms of jet lag after transmeridian travel. It is not known whether there are residual effects of this hormone on physical performance in fit subjects. After a sample size estimation involving a meaningful effect on performance of 5%, five milligrams of melatonin or placebo were ingested by twelve physically-active subjects before sleep in a double-blind experiment. The following morning, subjective sleep quality (latency and maintenance) were measured together with intra-aural temperature, grip strength of the left and right hands, and time to complete a 4 km time trial on a cycle ergometer. The subjects also rated perceived exertion during the latter test. The null hypothesis of no effect of melatonin on either subjective sleep quality or physical performance measured the morning after administration could not be rejected on the basis of our observations (P > 0.30). The mean differences between treatments were less than 1% for the strength tests and time trial performance. The confidence intervals for these differences for left and right grip strength and the cycling test were - 2.1 to 2.8 kg, - 3.1 to 2.7 kg and -3.0 to 4.5 s, respectively. In conclusion, it is unlikely that 5 mg of melatonin would have any meaningful effects on physical performance in the morning after fit subjects ingest the hormone. There was also little evidence that it improves sleep quality in this population. Further research is needed concerning the effects of daytime and nighttime admistration of melatonin on performance, in both situations of normal and disturbed sleep.

Adult↗
PubMed2001

How to show that unicorn milk is a chronobiotic: the regression-to-the-mean statistical artifact.

Few chronobiologists may be aware of the regression-to-the-mean (RTM) statistical artifact, even though it may have far-reaching influences on chronobiological data. With the aid of simulated measurements of the circadian rhythm phase of body temperature and a completely bogus stimulus (unicorn milk), we explain what RTM is and provide examples relevant to chronobiology. We show how RTM may lead to erroneous conclusions regarding individual differences in phase responses to rhythm disturbances and how it may appear as though unicorn milk has phase-shifting effects and can successfully treat some circadian rhythm disorders. Guidelines are provided to ensure RTM effects are minimized in chronobiological investigations.

Biometry↗
PubMed2000

Development of a sensitive chemiluminescent neuraminidase assay for the determination of influenza virus susceptibility to zanamivir.

Determination of the sensitivity of influenza viruses to neuraminidase (NA) inhibitors is presently based on assays of NA function because, unlike available cell culture methods, the results of such assays are predictive of susceptibility in vivo. At present the most widely used substrate in assays of NA function is the fluorogenic reagent 2'-O-(4-methylumbelliferyl)-N-acetylneuraminic acid (MUN). A rapid assay with improved sensitivity is required because a proportion of clinical isolates has insufficient NA to be detectable in the current fluorogenic assay, and because some mutations associated with resistance to NA inhibitors reduce the activity of the enzyme. A chemiluminescence-based assay of NA activity has been developed that uses a 1,2-dioxetane derivative of sialic acid (NA-STAR) as the substrate. When compared with the fluorogenic assay, use of the NA-STAR substrate results in a 67-fold reduction in the limit of detection of the NA assay, from 200 pM (11 fmol) NA to 3 pM (0.16 fmol) NA. A panel of isolates from phase 2 clinical studies of zanamivir, which were undetectable in the fluorogenic assay, was tested for activity using the NA-STAR substrate. Of these 12 isolates with undetectable NA activity, 10 (83%) were found to have detectable NA activity using the NA-STAR substrate. A comparison of sensitivity to zanamivir of a panel of influenza A and B viruses using the two NA assay methods has been performed. IC(50) values for zanamivir using the NA-STAR were in the range 1.0-7.5 nM and those for the fluorogenic assay in the range 1. 0-5.7 nM (n = 6). The NA-STAR assay is a highly sensitive, rapid assay of influenza virus NA activity that is applicable to monitoring the susceptibility of influenza virus clinical isolates to NA inhibitors.

Adamantane↗
PubMed2000

Do subjective symptoms predict our perception of jet-lag?

A total of 39 subjects were studied after a flight from the UK to either Sydney or Brisbane (10 time-zones to the east). Subjects varied widely in their age, their athletic ability, whether or not they were taking melatonin, and in their objectives when in Australia. For the first 6 days after arrival, subjects scored their jet-lag five times per day and other subjective variables up to five times per day, using visual analogue scales. For jet-lag, the scale was labelled 0 = no jet-lag to 10 = very bad jet-lag; the extremes of the other scales were labelled - 5 and + 5, indicating marked changes compared with normal, and the centrepoint was labelled 0 indicating 'normal'. Mean daily values for jet-lag and fatigue were initially high (+ 3.65 +/- 0.35 and + 1.55 +/- 0.22 on day 1, respectively) and fell progressively on subsequent days, but were still raised significantly (p < 0.05) on day 5 (fatigue) or day 6 (jet-lag). In addition, times of waking were earlier on all days. By contrast, falls in concentration and motivation, and rises in irritability and nocturnal wakings, had recovered by day 4 or earlier, and bowel activity was less frequent, with harder stools, on days 1 and 2 only. Also, on day 1, there was a decrease in the ease of getting to sleep (- 1.33 +/- 0.55), but this changed to an increase from day 2 onwards (for example, + 0.75 +/- 0.25 on day 6). Stepwise regression analysis was used to investigate predictors of jet-lag. The severity of jet-lag at all the times that were measured was strongly predicted by fatigue ratings made at the same time. Its severity at 08:00 h was predicted by an earlier time of waking, by feeling less alert 30 min after waking and, marginally, by the number of waking episodes. Jet-lag at 12:00 and 16:00 h was strongly predicted by a fall of concentration at these times; jet-lag at mealtimes (12:00, 16:00 and 20:00 h) was predicted by the amount of feeling bloated. Such results complicate an exact interpretation that can be placed on an assessment of a global term such as jet-lag, particularly if the assessment is made only once per day.

Adult↗
PubMed2000

A comparison of the immediate effects of moderate exercise in the late morning and late afternoon on core temperature and cutaneous thermoregulatory mechanisms.

Twelve healthy male subjects each undertook two bouts of moderate exercise (70% VO2max for 30 minutes) in the morning (08:00) and late afternoon (18:00) at least 4 days apart. Measurements were made of heart rate, core (rectal) temperature, sternum skin temperature, and forearm skin blood flow during baseline conditions, during the bout of exercise, and throughout a 30-minute recovery period. Comparisons were made of the changes of heart rate, temperature, and skin blood flow produced by the exercise at the two times of day. Student t tests indicated that baseline values for core temperature (37.15 degrees C +/- 0.06 degrees C vs. 36.77 degrees C +/- 0.06 degrees C) and sternum temperature (33.60 degrees C +/- 0.29 degrees C vs. 32.70 degrees C + 0.38 degrees C) were significantly (p < .05) higher in the late afternoon than the early morning. Two-way analysis of variance (ANOVA) indicated that the increases in core and sternum temperatures during exercise were significantly less (p = .0039 and .0421, respectively) during the afternoon bout of exercise compared with the morning, even though the work loads, as determined by changes in heart rate, were not significantly different (p = .798) at the two times of testing. There were also tendencies for resting forearm skin blood flow to be higher in the afternoon than in the morning and for exercise to produce a more rapid rise in this variable in the afternoon. The possible mechanisms producing these responses to exercise are discussed in terms of those that are responsible for the normal circadian rhythm of core temperature. It is concluded that the body's ability to remove a heat load is less in the early morning, when the circadian system is in a "heat gain" mode, than in the late afternoon, when heat gain and "heat loss" modes are balanced more evenly.

Adult↗
PubMed2000

Field-by-field evaluation of intraoperative transoesophageal echocardiography interpretative skills.

A quality assurance system is essential for the credibility and structured growth of anaesthesiology-based transoesophageal echocardiography (TEE) programmes. We have developed software (Q/A Kappa), involving a 400-line source code, capable of directly reporting kappa correlation coefficient values, using external reviewer interpretations as the 'gold standard', and thereby allowing systematic assessment of the validity of intraoperative echocardiographic interpretation. This paper presents assessment of the validity of 240 intraoperative anaesthesiologists' echocardiographic interpretations, and, in addition, the results of field testing of this prototypical software. Data, derived from consecutive cardiac surgery patients, consisted of standardized two-dimensional transoesophageal echocardiographic, colour flow and Doppler imaging sequences. Intraoperative and off-line 'gold standard' TEE interpretations were compared for 19 fields or variables using the Q/A Kappa program. The kappa correlation coefficients were highly variable and dependent on the examination field, ranging from 0.08 for apical regional wall motion scores to 1.00 for tricuspid regurgitation grade, left atrial measurement, aortic valve anatomy and left ventricular long axis and short axis global function. The correlation coefficients were also operator dependent. These data (480 interpretations) were also manually integrated into the equation required for calculation of values of the variable kappa correlation coefficient. The relationship between Q/A Kappa-derived values and manually calculated values was highly significant (p < 0.001; r = 1.0). The implications and possible explanations of the results for particular examination fields are discussed. This study also demonstrates successful seamless functioning of this software program from data entry, segmentation into tables and valid statistical analysis. These findings suggest that it is practical to provide sophisticated continuous quality improvement TEE data on a routine basis.

Adult↗
PubMed1999

Th1 cells that adoptively transfer experimental hypersensitivity pneumonitis are activated memory cells.

Cultured murine CD4+ T cell lines from Saccharopolyspora rectivirgula-sensitized donors with cytokine secretion characteristics of Th1 cells can adoptively transfer murine experimental hypersensitivity pneumonitis (EHP), whereas Th2 CD4+ cell lines cannot (Cell Immunol 177:169-175, 1997). To assess the differences between these cell lines that may be related to the ability to transfer EHP, we determined cell surface markers that distinguish naive from activated/memory cells that indicate activation and that mediate endothelial adhesion. Both Th1 and Th2 T cell lines are CD4+, CD11a+, ICAM-1+, and L-selectin negative. Th1 cells are CD49d (alpha 4) and LPAM (alpha 4 beta 7) positive, with 32% and 42% of the apparent membrane site density quantitated as the mean molecules of equivalent soluble fluorochromes (MESF) values of unstimulated spleen cells, respectively. Th2 cells are weakly alpha 4 and alpha 4 beta 7 positive, with 15% and 11% of the MESF of unstimulated spleen cells. Th1 cell lines are CD45Rb negative and CD44+, whereas Th2 cell lines are CD45Rb intermediate and CD44-/low. Th1 cells are CD25 (IL-2 receptor) low and Th2 cells CD25 high. We conclude that Th1 cells capable of transfer are activated/memory T cells, and Th2 cells incapable of transfer lack some characteristics of memory/activated T cells (i.e., increase of CD44 and decrease of CD45Rb). Both Th1 and Th2 cell lines express alpha 4 beta 7 and alpha 4 (Th1 > Th2), suggesting that alpha(4) integrin may be important in conferring ability to cells to adoptively transfer EHP.

Adoptive Transfer↗
PubMed1999

Evaluation of bovine lactoferrin as a topical therapy for chemotherapy-induced mucositis in the golden Syrian hamster.

Bovine lactoferrin was applied topically to the oral mucosa of Syrian hamsters and assessed for its ability to decrease the severity of chemotherapy-induced oral mucositis. Results indicated that the chemotherapy agent 5-fluorouracil (5-FU) administered to hamsters on days 0 and 2 produced severe leukopenia between days 4 and 7 of the trial, and that severity of oral mucositis coincided with the suppressed immune state in these animals. Bovine lactoferrin applied continuously to oral wounds in hamsters induced by a combination of chemotherapy treatment and mild abrasion of the cheek pouch, failed to decrease the severity of mouth ulcers relative to a group receiving BSA as a control protein source. Hamster cheek pouches treated twice daily with lactoferrin had a significantly worse condition score between days 6 and 8, and days 12 and 13 (p < 0.05 to p < 0.001), a higher ulcer score between days 6 and 15 (p < 0.05 to p < 0.001) and larger ulcer area between days 7 and 14 (p < 0.05 to p < 0.001) compared to animals administered the control protein. Body weight changes between treatment and control groups showed no significant difference over the trial period. In contrast to the pre-study hypothesis, we report a detrimental effect from topical administration of bovine lactoferrin to the wounded oral mucosa of immunocompromised hamsters.

Animals↗
PubMed1999

Purification of masked temperature data from humans: some preliminary observations on a comparison of the use of an activity diary, wrist actimetry, and heart rate monitoring.

Fourteen ambulatory subjects, varying in their amount of habitual physical activity, were studied for 24 h during a total of 25 "typical" days. Rectal temperature was recorded every 6 minutes, an activity diary was filled in every half hour, and wrist activity and heart rate were monitored every minute. Actimetry and heart rate data generally showed close parallelism with each other and with the masking effects on body temperature. Psychological stressors such as public speaking produced a greater effect on heart rate and body temperature than on wrist movement, while typing produced high values for wrist movement, but affected heart rate and temperature much less. When data for the circadian rhythm of body temperature were purified, the diary, actimetry, and measurement of heart rate were all useful in reducing masking effects, but the present evidence indicates that heart rate can be more successful than actimetry--as judged by the closeness of the purified data to a sinusoid. This superiority of heart rate monitoring over wrist activity as a method of purification might be because core temperature can be increased by stressor-induced thermogenesis, as well as by physical activity, and because wrist movement can, with some activities, give an inaccurate estimate of the factors that contribute to whole-body thermogenesis.

Adult↗
PubMed1999

Spotlight. Interview by Sarah Powell.

Professor Brain Edwards, Professor of Health Care Development at the University of Sheffield, UK talks to Sarah Powell about changes in emphasis in health-care service management, inequalities of access to health care, the concept of mutuality, and the challenges of the future.

Delivery of Health Care↗
PubMed1999

Lead stimulates lymphocyte proliferation through enhanced T cell-B cell interaction.

We have studied the in vitro effects of lead (Pb) as Pb-acetate (0. 1-1000 ppm) on the activation of rat spleen (SP) cells. At a concentration of 0.5 to 200 ppm, Pb augmented the uptake of [3H]thymidine, progression of SP cells through the cell cycle, and allogeneic and syngeneic mixed lymphocyte reactions. However, at concentrations above 200 ppm, Pb inhibited the proliferation of these cells. To understand the cellular and molecular basis of these responses, we examined the effects of Pb on the proliferation of isolated T and/or B cell populations. Pb failed to stimulate the proliferation of isolated T and B cells; however, the addition of gamma-irradiated B cells to T cell cultures or irradiated T cells to B cell cultures resulted in Pb-induced incorporation of [3H]thymidine. On the other hand, macrophages were unable to reconstitute this response. Pb also induced a significant rise in the intracellular concentration of inositol 1,4,5-trisphosphate in SP cells; however, unlike the activation of lymphocytes through the antigen receptors, Pb did not significantly stimulate protein tyrosine kinase activity. These observations suggest that Pb facilitates the T cell-B cell interaction-dependent proliferation of lymphocytes through a signaling pathway(s) independent of the antigen receptor.

Animals↗
PubMed1998

Preclinical evaluation of the novel hypoxic marker 99mTc-HL91 (Prognox) in murine and xenograft systems in vivo.

PURPOSE: The 99mTc-labelled amine oxime 99mTc-HL91 (Prognox) is under investigation as a potential noninvasive clinical marker of tumour hypoxia whose uptake can be monitored by gamma camera imaging. The aim was to assess its retention in 3 tumours under control and enhanced oxygenation conditions. MATERIALS AND METHODS: The SaF murine sarcoma, grown subcutaneously in CBA mice, and human colon carcinoma HT29 and lung adenocarcinoma A549, grown as xenografts in SCID mice, were used at 6-8 mm diameter. Oxygenation status was enhanced by giving 500 mg/kg nicotinamide i.p. and breathing carbogen until the point of assay. Oxygenation/hypoxia was measured using the Eppendorf pO2 histograph (KIMOC 6650) with at least 5 tracks and at least 70 values, and expressing pO2 values as % < 2.5 mmHg. 99mTc-HL91 (0.8 or 8 MBq per mouse) was injected i.v. immediately before nicotinamide or saline, and animals were killed 2 h after injection. Tumour, skin, muscle, and blood samples were counted and isotope retention was expressed as % injected dose per gram. 14C-labelled uncomplexed HL91 was used similarly (0.2-0.4 MBq per mouse) and samples were solubilised and decolourised before counting. RESULTS: Nicotinamide and carbogen treatment reduced 99mTc-HL91 retention in all tumours to 54%-64% of control; it also reduced the proportion of pO2 values < 2.5 mmHg in all tumours. The mean proportion of pO2 values < 2.5 mmHg correlated very well with the mean ratio of tumour to blood retention at 2 h for all tumours, both unperturbed and oxygen-enhanced (r = 0.996, p < 0.001). Retention of 14C-HL91 in SaF tumour was unchanged by nicotinamide and carbogen, confirming that 99mTc complexation of the ligand is required for hypoxia specificity. CONCLUSION: There is excellent correlation between 99mTc-HL91 retention and hypoxia, as measured by the Eppendorf histograph, over the range of 50%-90% of values < 2.5 mmHg in 3 different tumour models, including 2 human xenografts. 99mTc complexation of the ligand is required for hypoxia specificity. 99mTc-HL91 (Prognox) shows good potential as a clinical marker for hypoxia and warrants further development.

Adenocarcinoma↗
PubMed1998

99mTc-HL91: "hot spot" detection of ischemic myocardium in vivo by gamma camera imaging.

BACKGROUND: 99mTc-HL91 is a new hypoxia imaging agent that demonstrates increased uptake and retention in globally hypoxic myocardium in vitro. The purpose of this study was to determine whether 99mTc-HL91 could detect regional ischemia in vivo by gamma camera imaging. METHODS AND RESULTS: Eight open-chest dogs with left circumflex (LCx) stenoses were studied. Injection of 5 mCi of 99mTc-HL91 and microspheres was followed by imaging over 4 hours. Heart slices were imaged, then stained with triphenyltetrazolium chloride (TTC), and tissues were well-counted. TTC staining demonstrated no injury. Mean LCx blood flow was 0.32+/-0.04 mL x min(-1) x g(-1), and mean left anterior descending coronary artery (LAD) flow was 0.96+/-0.02 mL x min(-1) x g(-1) (ratio, 0.33). "Hot spots" were detected in 8 of 8 experiments in vivo within 60 minutes and improved over 4 hours. Region of interest analysis of LCx/LAD activity ratios demonstrated significant increases within 30 minutes (final ratio, 3.0; P<0.05). LCx and LAD washout curves demonstrated significant differences within 15 minutes. Washout curves were biexponential over 1 hour, followed by linear retention from 1 to 4 hours. Four-hour fractional retention was 0.12 for LAD and 0.44 for LCx (P<0.01). Myocardial flow versus tracer uptake demonstrated 2 phases: phase 1 (flow, 0.05 to 0.7 mL x min(-1) x g(-1)) had an inverse linear correlation (r= -0.80); phase 2, (flow, >0.7 mL x min(-1) x g(-1)) had no correlation. Ischemic heart/liver ratios remained near 1.0 for 4 hours. CONCLUSIONS: 99mTc-HL91 positively identifies regional myocardial ischemia in a canine model using 99mTc imaging. Quantitative techniques allowed identification of ischemic myocardium within 15 minutes of tracer administration.

Animals↗