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J Ward

Publications and source records attributed to J Ward.

At least 55 records · Page 3Linked to original sources
PubMed2001

Peptide bis-intercalator binds DNA via threading mode with sequence specific contacts in the major groove.

BACKGROUND: We previously described a general class of DNA polyintercalators in which 1,4,5,8-naphthalenetetracarboxylic diimide (NDI) intercalating units are connected via peptide linkers, resulting in the first known tetrakis- and octakis-intercalators. We showed further that changes in the composition of the peptide tether result in novel DNA binding site specificities. We now examine in detail the DNA binding mode and sequence specific recognition of Compound 1, an NDI bis-intercalator containing the peptide linker gly-gly-gly-lys. RESULTS: 1H-NMR structural studies of Compound 1 bound to d(CGGTACCG)(2) confirmed a threading mode of intercalation, with four base pairs between the diimide units. The NMR data, combined with DNAse I footprinting of several analogs, suggest that specificity depends on a combination of steric and electrostatic contacts by the peptide linker in the floor of the major groove. CONCLUSIONS: In view of the modular nature and facile synthesis of our NDI-based polyintercalators, such structural knowledge can be used to improve or alter the specificity of the compounds and design longer polyintercalators that recognize correspondingly longer DNA sequences with alternating access to both DNA grooves.

Base Sequence↗
PubMed2001

Implementing guidelines about colorectal cancer: a national survey of target groups.

BACKGROUND: An Australia-wide postal survey was undertaken to determine surgeons' attitudes towards guidelines and their preferred strategies for dissemination and implementation of guidelines for the management of colorectal cancer, developed by the Australian Cancer Network (ACN) and the Clinical Oncological Society of Australia (COSA). This survey was conducted as a baseline before the release of the definitive guidelines. METHODS: All members of the Royal Australasian College of Surgeons (RACS) with a self-nominated special interest in colorectal surgery and members of the Colorectal Surgical Society of Australia (CSSA) were surveyed. RESULTS: A total of 195 of the 219 surgeons eligible for the study returned questionnaires (89% response rate). Most (86%) were aware that these guidelines were being developed. More than one-half had read at least one draft version. Almost half (44.6%; 95%CI: 37.6-51.9%) agreed that guidelines represented 'cookbook medicine' and one-third (33.3%; 95%CI: 26.9-40.5%) agreed that guidelines might increase the number of malpractice suits. Local adaptation of guidelines and 'academic detailing' were most favourably ranked to assure implementation. Further, 54.9% (95%CI: 47.6-61.9%) of respondents believed that a successful legal defence of a surgeon whose practice had been within the guidelines would encourage uptake. Surgeons operating outside teaching hospitals were more likely to endorse this view than others. CONCLUSIONS: These results demonstrate that an important target group for colorectal cancer guidelines, namely surgeons, appears receptive to clinical practice guidelines. These results could also permit interventions that target attitudinal barriers to implementing guidelines and subgroups of surgeons who have particular concerns. Expensive strategies for implementation ought to be subject to rigorous evaluation for their impact in modifying clinical practice.

Attitude of Health Personnel↗
PubMed2001

Dual phase helical CT versus portal venous phase CT for the detection of colorectal liver metastases: correlation with intra-operative sonography, surgical and pathological findings.

AIM: To assess whether dual phase helical computed tomography (DPCT) of the liver improves the detection of colorectal liver metastases compared with portal venous phase (PVP) imaging alone. MATERIALS AND METHODS: DPCT was performed in 33 consecutive patients before laparotomy for resection of colorectal liver metastases. CT comprised 8-mm slice collimation with a pitch of 1 to 1.25; imaging was commenced 20-25 and 65-70 s after the start of injection of 150 ml of contrast medium at 5 ml/s to coincide with hepatic arterial phase (HAP) and PVP contrast enhancement, respectively. Four blinded observers independently reviewed the HAP, PVP and DPCT images recording the site and size of all lesions. Alternative-free response receiver operating characteristic (AFROC) methodology was used to analyse the results, which were correlated with surgery, intra-operative ultrasound and histology. RESULTS: The mean observer sensitivities for malignant lesion detection were 75.3% for DPCT, 69.7% for PVP imaging and 66.7% for HAP imaging alone. There was a statistically significant improvement in malignant lesion detection using DPCT when compared with PVP imaging alone (P < 0.05). The mean areas under the AFROC curves were 0.84 for DPCT and 0.82 for PVP (P < 0.03) imaging alone. CONCLUSION: The detection of colorectal liver metastases was marginally better with DPCT than with PVP imaging alone, but the discovery of additional lesions did not affect the management of any of the patients in this study.

Aged↗
PubMed2001

Preliminary report: skeletal muscle cell lipid and oxygen supply.

In a group of 12 normal-weight, normotensive, nondiabetic adult females, the intramyocellular lipid (IMCL) to creatine ratio of the soleus muscle was determined using localized (1)H-magnetic resonance spectroscopy ((1)H-MRS) and related to skeletal muscle blood (and oxygen) supply (as assessed by near infrared spectroscopy [NIRS] of the forearm). A significant positive association was found between IMCL content and reoxygenation rate of forearm muscle hemoglobin (Hb) after 1 minute of ischemic exercise (r = .70, P = .01). The relative efficiency of skeletal muscle oxygen supply may be a determining factor of IMCL content in skeletal muscle.

Adult↗
PubMed2001

The therapeutic ratio of R-albuterol is comparable with that of RS-albuterol in asthmatic patients.

BACKGROUND: It has been suggested that R-albuterol produces bronchodilation that is comparable with that of racemic albuterol (RS-albuterol) on a 4:1 dose-for-dose basis but systemic side effects on a 2:1 basis, implying better therapeutic ratio for R-albuterol. OBJECTIVE: We sought to carefully compare the bronchodilating and systemic effects of R- and RS-albuterol by using a crossover study design. METHODS: Twenty asthmatic patients (15.1%-28.7% FEV(1) reversibility) were given R-albuterol (6.25-1600 microg), S-albuterol (6.25-1600 microg), RS-albuterol (12.5-3200 microg), or placebo in a crossover, double-blind, placebo-controlled fashion. Cumulative doses were given with a Mefar dosimeter, and FEV(1), heart rate, and plasma K(+) levels were measured 20 minutes after each dose. RESULTS: Both R- and RS-albuterol produced dose-related improvement in FEV(1) and, at higher doses, increased heart rate and decreased plasma K(+) levels. Neither placebo nor S-albuterol had any significant effect. Individual estimates of the potency ratio for R-albuterol/RS-albuterol were calculated and summarized across all subjects. The geometric mean potency ratio for effects on FEV(1) was 1.9 (95% CI, 1.3-2.8), on HR of 1.9 (95% CI, 1.3-2.9), and on K(+) level of 1.7 (95% CI, 1.3-2.1). CONCLUSION: All pharmacologic effects of RS-albuterol reside with the R-enantiomer, and S-albuterol is clinically inactive. The R-albuterol/RS-albuterol potency ratios for local (FEV(1)) and systemic effects (heart rate and K(+)) are similar, suggesting a comparable therapeutic ratio for R-albuterol and RS-albuterol in asthmatic subjects.

Adult↗
PubMed2001

Pharmacokinetics and absolute bioavailability of sitafloxacin, a new fluoroquinolone antibiotic, in healthy male and female Caucasian subjects.

1. The aim was to compare the pharmacokinetics of sitafloxacin from a capsule formulation (dose of 500 mg sitafloxacin) and an intravenous (i.v.) formulation infused over 1 h (dose of 400 mg sitafloxacin) in healthy male and female subjects and to estimate the absolute bioavailability of sitafloxacin from the capsule formulation. 2. Following oral administration, sitafloxacin was rapidly absorbed, with a mean maximum concentration in plasma of 4.65 microgml(-1) occuring at median tmax = 1.25 h giving a mean AUC(0-infinity) = 28.1 microg h ml(-1). For the i.v. administration, a mean Cmax = 5.53 microm(-1) occurred at the end of the 1-h infusion with a mean AUC(0-infinity) = 25.4 microg h ml(-1). The mean terminal elimination half-life was 7.0 h (oral) and 6.6 h (i.v.). For the oral and i.v. formulations, the mean total plasma clearance was 296 and 263 mlmin(-1), respectively and the mean volume of distribution was 180 and 150 litres, respectively. 3. Within 48 h post-dose, approximately 61% (range 22-86%) of the administered dose was excreted unchanged in urine following capsule administration, compared with approximately 75% (range 42-101%) following the i.v. formulation. For both formulations, the renal clearance of sitafloxacin (means of 181 and 198 ml min(-1) for the capsule and i.v. doses, respectively) implies active tubular secretion of the drug. 4. The absolute bioavailability of sitafloxacin from the capsule formulation was high at 89%, with a 95% CI of 84-94%. The intersubject variability (CV%) in the sitafloxacin AUC(0-infinity) for the capsule was low at 18.6%. 5. Gender differences in the pharmacokinetics of sitafloxacin were small and would not warrant dose adjustment. 6. The findings show that the capsule formulation offers good oral bioavailability and merits further clinical evaluation of sitafloxacin as an orally effective fluoroquinolone antibacterial.

Administration, Oral↗
PubMed2001

Australian dentists' educational needs for smoking cessation counseling.

BACKGROUND: Australian dentists' continuing educational needs and their attitudes towards and self-reported practices related to smoking cessation counseling were examined. METHOD: Self-administered questionnaires were received from 149 dentists (83% response rate). RESULTS: Many dentists were aware that smoking is a risk factor for the development of oral cancer (n = 128, 86%). Most considered smoking cessation counseling to be part of their professional role (n = 105, 70%). However, few "always" asked about the smoking status of their patients (n = 21, 14%). The dentists' use of specific behavioral techniques known to assist patients to quit also was low. Furthermore, the dentists were as likely to use ineffective (advice to "cut down") as effective (advice to "quit") (p > 0.05) strategies. The respondents were significantly more interested in self-help pamphlets for their patients than in either evidence-based guidelines (McNemar's chi2 = 9.76, df = 1, p < 0.01) or a self-study module about smoking cessation (McNemar's chi2 = 42.0, df = 1, p < 0.001). CONCLUSIONS: Continuing education for dentists that combines skills training, patient materials, and epidemiology is likely to be acceptable and effective.

Adult↗
PubMed2001

Identification of the exported proteins of the oral opportunistic pathogen Actinobacillus actinomycetemcomitans by using alkaline phosphatase fusions.

A phoA fusion library of Actinobacillus actinomycetemcomitans genomic DNA has been screened to identify genes encoding exported and secreted proteins. A total of 8,000 colonies were screened, and 80 positive colonies were detected. From these, 48 genes were identified with (i) more than half having homology to known or hypothetical Haemophilus influenzae genes, (ii) 14 having no ascribed function, and (iii) 4 having very limited or no homology to known genes. The proteins encoded by these genes may, by virtue of their presence on the cell surface, be novel virulence determinants.

Aggregatibacter actinomycetemcomitans↗
PubMed2001

Continuous measurement of breathlessness during exercise: validity, reliability, and responsiveness.

A continuous method for recording changes in breathlessness (dyspnea) during exercise is introduced and compared with the traditional discrete method. In study 1, a category-rating scale was presented on a computer screen, and 14 healthy, young female subjects exercised on a cycle ergometer until exhaustion. Two approaches were used to obtain ratings of breathlessness: a discrete method, in which subjects gave single judgments every minute, and a continuous method, in which subjects throughout exercise moved the mouse so that a bar on the screen extended to the desired location along the scale. Psychophysical results relating measures of breathlessness and the variables of work, oxygen consumption, and minute ventilation were statistically indistinguishable with the two methods, and both methods were highly reliable across test sessions. In study 2, both measurement methods were employed, and the subjects were 14 healthy, young males. In each of two sessions (discrete or continuous method), subjects first rated their breathlessness during an incremental test in which the workload was increased over time and levels of work, and minute ventilation were recorded. Subjects then exercised for 10 min at 60% of the maximal oxygen consumption achieved during the incremental test. At two points during steady-state exercise, a respiratory load was introduced that lasted for 1 min. It was possible to determine the responsiveness of subjects to onset and offset of the respiratory load for the continuous method but not for the discrete method. In study 3, patients with chronic obstructive pulmonary disease employed both methods, and it was found that the continuous method was better at determining whether subjects showed a significant positive slope of the regression line between breathlessness ratings and physiological variables.

Adult↗
PubMed2001

Intravenous safety and pharmacokinetics of a novel dimerizer drug, AP1903, in healthy volunteers.

AP1903 is a novel gene-targeted drug that is being developed for use in drug-regulated cell therapies. An intravenous, single-blind, placebo- and saline-controlled, ascending-dose study was performed to evaluate the safety, tolerability, and pharmacokinetics of AP1903. Twenty-eight normal healthy male volunteers were randomized into five dosage groups of AP1903 (0.01, 0.05, 0.1, 0.5, and 1 mg/kg). Within each group, 4 volunteers received a single dose of AP1903, 1 volunteer received an equal volume of placebo, and 1 received an equal volume of normal saline. The only exception was in the 0.5 mg/kg group, in which 4 volunteers were dosed: 3 received AP1903 and 1 received normal saline. All dosages were administered as intravenous infusions over 2 hours. Clinical safety parameters were monitored, and serial blood and urine samples were collected for analysis of AP1903. No drug-related adverse events were observed at any of the dose levels with the possible exception of facial flushing in 1 volunteer at the 1.0 mg/kg dose level. AP1903 plasma levels were directly proportional to the administered dose, with mean Cmax values ranging from approximately 10 to 1,275 ng/mL over the 0.01 to 1.0 mg/kg dose range. Following the infusion period, blood concentrations revealed a rapid distribution phase, with plasma levels being reduced to approximately 18%, 7%, and 1% of the maximal concentration at 0.5, 2, and 10 hours postdose, respectively. AP1903 was shown to be safe and well tolerated at all dose levels and demonstrated a favorable pharmacokinetic profile at doses well above the anticipated therapeutic dose.

Adult↗
PubMed2001

Effectiveness of salmeterol versus ipratropium bromide on exertional dyspnoea in COPD.

The hypothesis of the study was that salmeterol and ipratropium would have similar dyspnoea ratings during steady-state cycle ergometry at 1 h, but that salmeterol would reduce dyspnoea at 6 h after administration in patients with chronic obstructive pulmonary disease (COPD). The study design was a randomized, double-blind trial in 16 patients (aged 63 +/- 11 yrs) with symptomatic COPD. Two days after familiarization with testing procedures, patients were randomly assigned to receive either two puffs (42 microg) of salmeterol and two puffs of placebo inhaler, or two puffs (36 microg) of ipratropium from each of two inhalers (total, 72 microg). Two days later, patients received the alternative medication. During exercise at 60% of peak oxygen consumption patients rated dyspnoea and performed inspiratory capacity manoeuvres each minute. Forced expiratory volume in one second was 1.13+/-0.48 L (37+/-13% predicted). Dyspnoea ratings were similar for salmeterol and ipratropium at 1 and 6 h. Inspiratory capacity was similar for salmeterol and ipratropium at 1 h, but significantly higher for salmeterol at 6 h (delta = 120 mL; p = 0.03). It is concluded that with the doses used, salmeterol and ipratropium provided similar dyspnoea ratings during exercise at 1 and 6 h after administration.

Administration, Inhalation↗
PubMed2001

Feto-placental hypoxemia regulates the release of fetal activin A and prostaglandin E(2).

The evaluation of the role of critical hypoxia in unexplained fetal death in utero has been hampered by the lack of a physiological marker. Here we report the novel observation that feto-placental hypoxemia is an acute trigger for increased activin secretion from the feto-placental unit in late pregnancy. Hypoxemia was induced in chronically cannulated late pregnant fetal sheep by restricting blood flow through the maternal uterine arteries. Using maternal and fetal blood samples and amniotic fluid obtained via chronically implanted catheters, fetal blood gas parameters, plasma and amniotic fluid concentrations of activin A, prostaglandin (PG) E(2) and PGFM, the circulating metabolite of PGF(2alpha), were determined before, during and after a ten hour period of fetal hypoxemia. Hypoxemia acutely increased activin A and PGE(2) levels in both amniotic fluid and the fetal circulation with values rapidly returning to baseline with normoxemia. PGFM also increased in both compartments with a relatively delayed time frame compared to that of activin A and PGE(2). The increase in activin A and PGE(2) induced by hypoxemia may be a mechanism to regulate feto-placental blood flow during fetal compromise and also offers the possibility that activin A represents a useful marker of feto-placental hypoxemia.

Activins↗
PubMed2001

Data-driven recognition memory: a new technique and some data on age differences.

In this study, we investigate the effect on recognition memory of having target and distractor stimuli consisting of different combinations of low-level elements (letters), relative to when targets and distractors consist of combinations of the same elements (nonoverlap and overlap conditions, respectively). It was found that recognition memory was enhanced in the nonoverlap condition, even though subjects reported being unaware of this experimental manipulation. This confirms the importance of perceptually driven processing in the implicit memory component of recognition memory. The extent to which this effect occurs is found to be age dependent, with elderly subjects benefiting more from having targets and distractors consisting of nonoverlapping elements. This is consistent with the notion that elderly subjects show less reliance on item-specific/contextual detail to support recognition memory.

Adult↗
PubMed2001

Combined use of MR contrast agents for evaluating liver disease.

The sequential administration of superparamagnetic iron oxide (SPIO) and extracellular gadolinium chelates combines the sensitivity of SPIO for lesion detection with the specificity of dynamic gadolinium-enhanced imaging for lesion characterization. This approach also may improve the detection of hypervascular lesion, because the different magnetic properties of SPIO and gadolinium produce a synergistic increase in contrast between the reduced signal intensity of background liver and the increased signal intensity of enhancing lesions. Despite the benefits, the additional cost and increased examination time of a combined contrast procedure requires the careful selection of patients. This article presents a brief overview of the different properties and the current status of SPIO and gadolinium for the diagnosis of focal liver lesions.

Contrast Media↗
PubMed2001

Patient and health care system delays in Queensland tuberculosis patients, 1985-1998.

SETTING: Queensland tuberculosis (TB) control centre QTCC). OBJECTIVE: To investigate patient and health care system delays in the diagnosis of active TB in Queensland. DESIGN: Analysis of data extracted from the QTCC database and review of charts. Symptomatic patients with bacteriologically or histologically proven TB were considered as a total group and a pulmonary smear-positive (PSP) group. RESULTS: The median patient delays were 29 days (total group) and 30 days (PSP group). The median health care system delays were 22 days (total group) and 11 days (PSP group). There were significant trends towards increasing health care system delays with increasing age and longer residency of migrants in Australia. Health care system delays were significantly longer for females and those aged over 45. Migrants from countries of high TB incidence and indigenous Australians had shorter health care system delays compared to non-indigenous Australians. Common reasons for diagnostic delays of more than 90 days were failure to perform appropriate investigations and misdiagnosis of chest X-rays. CONCLUSION: Physicians need to consider including TB in the differential diagnosis in older age groups and migrants with longer residency in Australia. There should be a low threshold for obtaining chest X-rays and sputum samples in patients with persistent cough.

Adolescent↗