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D R Jones

Publications and source records attributed to D R Jones.

At least 37 records · Page 2Linked to original sources
PubMed2003

Reporting of prognostic markers: current problems and development of guidelines for evidence-based practice in the future.

Prognostic markers help to stratify patients for treatment by identifying patients with different risks of outcome (e.g. recurrence of disease), and are important tools in the management of cancer and many other diseases. Systematic review and meta-analytical approaches to identifying the most valuable prognostic markers are needed because (sometimes conflicting) evidence relating to markers is often published across a number of studies. To investigate the practicality of this approach, an empirical investigation of a systematic review of tumour markers for neuroblastoma was performed; 260 studies of prognostic markers were identified, which considered 130 different markers. The reporting of these studies was often inadequate, in terms of both statistical analysis and presentation, and there was considerable heterogeneity for many important clinical/statistical factors. These problems restricted both the extraction of data and the meta-analysis of results from the primary studies, limiting feasibility of the evidence-based approach.Guidelines for reporting the results of primary prognostic marker studies in cancer, and other diseases, are given in order to facilitate both the interpretation of individual studies and the undertaking of systematic reviews, meta-analysis and, ultimately, evidence-based practice. General availability of full individual patient data is a necessary step forward and would overcome the majority of problems encountered, including poorly reported summary statistics and variability in cutoff level, outcome assessed and adjustment factors used. It would also limit the problem of reporting bias, although publication bias will remain a concern until studies are prospectively registered. Such changes in practice would help important evidence-based reviews to be conducted in order to establish the most appropriate prognostic markers for clinical use, which should ultimately improve patient care.

Biomarkers, Tumor↗
PubMed2003

A systematic review of molecular and biological markers in tumours of the Ewing's sarcoma family.

The aims of this study were to perform the first systematic review of molecular and biological tumour markers in tumours of the Ewing's sarcoma family (ESFT), and evaluate the current evidence for their clinical use. A well-defined, reproducible search strategy was used to identify the relevant literature from 1966 to February 2000. Papers were independently assessed for tumour markers used in the screening, diagnosis, prognosis or monitoring of patients with ESFT. Eighty-four papers studying the use of 70 different tumour markers in ESFT's were identified. Low-quality, inconsistent reporting limited meta-analysis to that of prognostic data for 28 markers. Patients with tumours lacking S-100 protein expression have a better overall survival (OS) (hazard ratio (HR)=0.41, 95% confidence interval (CI) 0.19, 0.89) than those with expression; patients with high levels of serum LDH had a worse OS and disease-free survival (DFS) (OS: HR=2.92, CI 2.16, 3.94, DFS: HR=3.38, 95% CI 2.28, 4.99); patients with localised disease and tumours expressing type 1 EWS-FLI1 fusion transcripts had an improved DFS compared with those with other fusion transcript types (HR=0.17, 95% CI 0.079, 0.37). The knowledge base formed should facilitate more informative future research. Improved statistical reporting and large, multicentre prospective studies are advocated.

Biomarkers, Tumor↗
PubMed2003

Survey of shell egg processing plant sanitation programs: effects on egg contact surfaces.

Sanitation standard operating procedures (SSOPs) are an integral component of process control and are often the first step in the implementation of food safety regulations. The objective of this study was to assess and compare the efficacies of sanitation programs used in a variety of shell egg processing facilities. In-line, off-line, and mixed operations were evaluated. Sixteen direct or indirect egg contact surfaces were sampled in various shell egg processing facilities in the southeast United States. Samples were collected at the end of a processing day (POST) and again the next morning before operations began (PRE). Total aerobic plate counts (APCs) were obtained and Enterobacteriacae were enumerated. No significant differences (P > 0.05) between POST and PRE bacterial counts were found for the 16 sampling sites. In general, high APCs were found on the wall of the recirculating water tank both POST and PRE. The APCs for the rewash belt were considerably high for all plants sampled. APCs were also high for the vacuum loaders. APCs for washers and washer brushes were relatively low for most plants sampled. PRE and POST levels of plant sanitation, as determined by direct microbial plating, did not differ significantly. At this point, it is difficult to draw definitive conclusions about how rigid SSOPs should be for the shell egg processing industry.

Animals↗
PubMed2003

Glomerular filtration rate in children with solid tumors: normative values and a new method for estimation.

Many chemotherapy regimens used in children are nephrotoxic. Accurate dosing of these medications requires that some estimation of glomerular filtration rate (GFR) be performed prior to initiating chemotherapy. However, few studies evaluating normal GFR in children exist. The authors report normal values for GFR for children with nonhematogenous malignancies using a highly accurate method of directly measuring GFR and an equation for estimating absolute GFR in these children. Children with nonhematogenous malignancies with no evidence of renal involvement or prior use of nephrotoxic agents had their GFR measured using an iothalamate infusion methodology. A total of 111 children (males and females) with a mean age = 7.95 years (range 2.8 months-19.5 years) were included in the study. GFR adjusted for body surface area (mL/min/1.73 m(2)) increases in the first 2 years of life and then plateaus at a level comparable to adult values. GFR adjusted for body surface area for males >2 years = 131.3 +/- 22.5, females = 126.8 +/- 24.4 mL/min/1.73 m(2) (p value not significant). Absolute GFR in mL/min can be easily estimated by a simple formula (r(2) =.97) based on the child's weight and serum creatinine: GFR (mL/min) = k sqrt[ ( (agemos+ 6)* wt) / Cr serum ] where agemos is age in months, wt is weight in kg, and k = 1.05 for males and 0.95 for females. The accurate measurement of GFR remains vitally important in the safe and effective treatment of pediatric solid tumors. This study provides a set of normal GFR values for these children and an equation for easy estimate of absolute GFR.

Adolescent↗
PubMed2002

Femtosecond laser time-of-flight mass spectrometry of labile molecular analytes: laser-desorbed nitro-aromatic molecules.

Femtosecond laser time-of-flight mass spectra of solid samples of trinitrobenzene (TNB), trinitrotoluene (TNT) and trinitrophenol (TNP) have been recorded. Desorption of the solid samples was enacted by the fourth harmonic output (266 nm) of a 5 ns Nd:YAG laser. Subsequent femtosecond post-ionisation of the plume of neutral molecules was achieved using 800 nm laser pulses of 80 fs duration. Mass spectra have been recorded for desorption laser intensities from 2-6 x 10(9) W cm(-2) with ionisation laser intensities between 2 x 10(14) and 6 x 10(15) W cm(-2). Femtosecond laser ionisation has been shown to be capable of generating precursor and characteristic high-mass fragment ions for labile nitro-aromatic molecules commonly used in high-explosive materials. This feature is critical in the future development of femtosecond laser-based analytical instruments that can be used for complex molecular identification and quantitative analysis of environmentally important labile molecules. Furthermore, a comparison of femtosecond post-ionisation mass spectra with standard 70 eV electron impact data has revealed similarities in the spectra and hence the fragmentation processes.

Journal Article↗
PubMed2002

A comparison of summary patient-level covariates in meta-regression with individual patient data meta-analysis.

OBJECTIVES: To compare meta-analysis of summary study level data with the equivalent individual patient data (IPD) analysis when interest lies in identification of binary patient characteristics related to treatment efficacy. DESIGN: A simulation study comparing meta-regression with IPD analyses of randomized controlled trials. METHODS: Twenty-seven different meta-analysis situations were simulated with 1000 repetitions in each case. The following parameters were varied: (1) the treatment effect magnitude for different patient risk groups; (2) sample sizes of individual studies; and (3) number of studies. The meta-regression and IPD results were then compared for each situation. RESULTS: The statistical power of meta-regression was dramatically and consistently lower than that of IPD analysis, with little agreement between the parameter estimates obtained from the two methods. Only in meta-analyses of large numbers of large trials, did meta-regression detect differential treatment effects between risk groups with any consistency. CONCLUSIONS: Meta-analysis of summary data may be adequate when estimating a single pooled treatment effect or investigating study level characteristics. However, when interest lies in investigating whether patient characteristics are related to treatment, IPD analysis will generally be necessary to discover any such relationships. In these situations practitioners should try to obtain individual-level data.

Humans↗
PubMed2002

Role of surgery in Rhodococcus equi pulmonary infections.

Rhodococcus equi (R. equi) is a soil-dwelling bacterium that is increasingly associated with pulmonary infections in immunocompromised patients. While antibiotic therapy remains the cornerstone of treatment, surgery combined with antibiotics has an important role in select cases. We report two cases of pulmonary R. equi in immunocompromised patients who were treated with antibiotics, followed by surgical resection of the infected tissues, and then long-term antibiotics. Both patients had excellent outcomes. We advocate surgical resection of grossly infected pulmonary tissue as an adjunct to antimicrobial therapy for treatment of this uncommon, but potentially lethal pathogen.

Abscess↗
PubMed2002

Reversible and irreversible inhibition of CYP3A enzymes by tamoxifen and metabolites.

1. Preliminary studies have identified cytochrome P450 (CYP) 3A4 and CYP1B1 as the human CYPs inhibited by tamoxifen. To quantify the inhibitory potency of tamoxifen and its major metabolites, the metabolism of three substrates of CYP3A, midazolam, diltiazem and testosterone, and 7-ethoxyresorufin as a substrate of CYP1B1 were examined in catalytic assays carried out using human liver microsomes and cDNA-expression systems. 2. Tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and 3-hydroxytamoxifen reversibly inhibited midazolam 1'-hydroxylation, diltiazem N-demethylation and testosterone 6beta-hydroxylation with K(i) ranging from 3 to 37 micro M in human liver microsomes. Tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and 3-hydroxytamoxifen also reversibly inhibited the activity of cDNA-expressed CYP3A4, CYP3A5 and CYP1B1. 3. Tamoxifen and N-desmethyltamoxifen exhibited time-dependent inactivation of testosterone 6beta-hydroxylation by cDNA-expressed CYP3A4 (+ cytochrome b5) yielding k(inact) and K(i) of 0.04 min(-1) and 0.2 micro M for tamoxifen and 0.08 min(-1) and 2.6 micro M for N-desmethyltamoxifen. A metabolic intermediate complex (MIC) was also formed by tamoxifen and N-desmethyltamoxifen with CYP3A4 (+ cytochrome b5) and CYP3A4 but not with CYP3A5 or CYP3A7. Pre-incubation with 4-hydroxytamoxifen and 3-hydroxytamoxifen did not result in any CYP3A inactivation or detectable MIC formation. There was no detectable time-dependent inactivation or MIC formation with tamoxifen or metabolites with CYP1B1. 4. These data indicate that tamoxifen and its three major metabolites are effective inhibitors of CYP3A in vitro and that tamoxifen and N-desmethyltamoxifen are effective mechanism-based inhibitors. Thus, caution should be exercised when tamoxifen is coadministered with other CYP3A substrates.

Antineoplastic Agents, Hormonal↗
PubMed2002

Variations in levels of acid phosphatase present in chicken whole leg meat.

Acid phosphatase (ACP) has been identified as a potential biomarker for endpoint temperature determination in further-processed poultry. Multiple analyses of the same sample for ACP have produced consistent results. The degree of variation in ACP levels present in different production lots has not been identified. This study was conducted utilizing a single flock of broilers. Birds were slaughtered on four separate days (replications), and whole leg, without skin, was homogenized. Proximate composition was analyzed for each replication. Water-soluble proteins were extracted from raw meat and assessed for initial ACP levels. Samples of meat were cooked to an internal temperature of 71.1 C. There were differences (P < 0.05) between replications for both moisture and fat content. When dry fat content was analyzed, no significant differences occurred between replicates. Initial ACP levels were different (P < 0.0001) between replicates (500.33 to 348.97 units of activity/kg). Levels of ACP activity after cooking were also different (P < 0.0001) between replicates (17.61 to 10.82 units of activity/kg). Percentage degradation of activity during cooking was similar (96.98 to 95.89%) between replicates. ACP levels were consistently measured within a replicate. Differences between replicates for both initial and cooked levels indicate a threshold level for determination of thermal endpoint would be difficult to establish. ACP may not be a sensitive measure to estimate the degree of doneness of meat samples in which initial ACP concentration is unknown. Identical raw sample required for such a comparison would be difficult for the processing industry to maintain.

Acid Phosphatase↗
PubMed2002

Microbial contamination in inoculated shell eggs: I. Effects of layer strain and hen age.

Three Ottawa control strains and a current commercial laying stock were reared and housed under identical environmental and management conditions. Eggs were collected from each strain when hens were 32, 45, 58, 71, and 84 wk of age. The eggs were inoculated with Salmonella enteritidis (SE), Pseudomonasfluorescens (PF), or a combination of the two. After storage at 26 C, bacterial counts were obtained from the exterior shell surfaces (rinse), air cell, egg contents, and shell structure. SE and PF survived at different rates on the shell surface with as much as a 1 log difference during a given collection period. Egg content counts tended to be higher than eggshell counts in PF, whereas the opposite was true for SE. These data suggest that PF is a primary invader of eggs that is more capable of contaminating egg contents through the shell membranes than SE. The PF and SE data suggest that bacterial contamination of air cells, shells, and egg contents is more easily achieved in eggs from older hens than from younger hens. There were also differences between the strains. Control Strain 10 consistently maintained a lower level of contamination for both organisms in each sampling location. The overall results of this study suggest that genetic selection has altered the ability of eggs to resist microbial contamination and that screening for microbial integrity should be considered in the selection process among the laying egg breeders.

Age Factors↗
PubMed2002

Effects of cryogenic cooling of shell eggs on egg quality.

This study was conducted to investigate the effects of cryogenic cooling on shell egg quality. Gaseous nitrogen (GN), liquid nitrogen (LN), and gaseous carbon dioxide (GC) were utilized to rapidly cool eggs in a commercial egg processing facility and were compared to traditional cooling (TC). A modified food freezer was attached to existing egg processing equipment in order to expose eggs to the selected cryogen. In Experiment 1, eggs were treated with GN, LN, and TC then stored and tested over 10 wk. Experiment 2 eggs were treated (GC and TC) and evaluated for 12 wk. Quality factors that were measured included Haugh units, vitelline membrane strength and deformation at rupture, and USDA shell egg grades for quality defects. Haugh unit values were greater for cryogenically treated eggs as compared to traditionally cooled eggs (Experiment 1: 73.27, GN; 72.03, LN; and 71.4, TC and Experiment 2: 74.42, GC and 70.18, TC). The percentage of loss eggs in the GN treatment was significantly (P < 0.01) greater than those of the LN and TC treatments. Vitelline membrane strength was greater for the cryogenically cooled eggs versus traditional processing. Vitelline membrane breaking strength decreased over storage time. Vitelline membrane deformation at rupture was significantly (P < 0.05) greater for the cryogenically cooled eggs compared to the traditional eggs in each experiment. Use of the technology could allow for egg quality to be maintained for a longer time, which could increase international markets and potentially lead to extended shelf lives.

Air↗
PubMed2001

Analysis of ambulatory blood pressure monitor data using a hierarchical model incorporating restricted cubic splines and heterogeneous within-subject variances.

Hypertensive disorders of pregnancy are associated with significant maternal and foetal morbidity. Measurement of blood pressure remains the standard way of identifying individuals at risk. There is growing interest in the use of ambulatory blood pressure monitors (ABPM), which can record an individual's blood pressure many times over a 24-hour period. From a clinical perspective interest lies in the shape of the blood pressure profile over a 24-hour period and any differences in the profile between groups. We propose a two-level hierarchical linear model incorporating all ABPM data into a single model. We contrast a classical approach with a Bayesian approach using the results of a study of 206 pregnant women who were asked to wear an ABPM for 24 hours after referral to an obstetric day unit with high blood pressure. As the main interest lies in the shape of the profile, we use restricted cubic splines to model the mean profiles. The use of restricted cubic splines provides a flexible way to model the mean profiles and to make comparisons between groups. From examining the data and the fit of the model it is apparent that there were heterogeneous within-subject variances in that some women tend to have more variable blood pressure than others. Within the Bayesian framework it is relatively easy to incorporate a random effect to model the between-subject variation in the within-subject variances. Although there is substantial heterogeneity in the within-subject variances, allowing for this in the model has surprisingly little impact on the estimates of the mean profiles or their confidence/credible intervals. We thus demonstrate a powerful method for analysis of ABPM data and also demonstrate how heterogeneous within-subject variances can be modelled from a Bayesian perspective.

Bayes Theorem↗
PubMed2001

Chemokine receptor homo- or heterodimerization activates distinct signaling pathways.

Chemokine receptors of both the CC and CXC families have been demonstrated to undergo a ligand-mediated homodimerization process required for Ca2+ flux and chemotaxis. We show that, in the chemokine response, heterodimerization is also permitted between given receptor pairs, specifically between CCR2 and CCR5. This has functional consequences, as the CCR2 and CCR5 ligands monocyte chemotactic protein-1 (MCP-1) and RANTES (regulated upon activation, normal T cell-expressed and secreted) cooperate to trigger calcium responses at concentrations 10- to 100-fold lower than the threshold for either chemokine alone. Heterodimerization results in recruitment of each receptor-associated signaling complex, but also recruits dissimilar signaling path ways such as G(q/11) association, and delays activation of phosphatidyl inositol 3-kinase. The consequences are a pertussis toxin-resistant Ca2+ flux and trig gering of cell adhesion rather than chemotaxis. These results show the effect of heterodimer formation on increasing the sensitivity and dynamic range of the chemokine response, and may aid in understanding the dynamics of leukocytes at limiting chemokine concentrations in vivo.

Calcium Signaling↗
PubMed2001

The identification and characterization of hydrazinyl urea-based antibacterial agents through combinatorial chemistry.

An effort to identify novel inhibitors of peptidoglycan synthesis with antibacterial activity resulted in the discovery of a series of biaryl urea-based antibacterial agents through isolation of a by-product from a mixture-based combinatorial library of semi-carbazones and subsequent parallel synthesis efforts. The compounds were shown to possess broad spectrum antibacterial activity against gram-positive drug resistant pathogens, and showed apparent specificity for disruption of the bacterial cell wall biosynthesis pathway.

Anti-Bacterial Agents↗
PubMed2001

Role of diacylglycerol kinase alpha in the attenuation of receptor signaling.

Diacylglycerol kinase (DGK) is suggested to attenuate diacylglycerol-induced cell responses through the phosphorylation of this second messenger to phosphatidic acid. Here, we show that DGKalpha, an isoform highly expressed in T lymphocytes, translocates from cytosol to the plasma membrane in response to two different receptors known to elicit T cell activation responses: an ectopically expressed muscarinic type I receptor and the endogenous T cell receptor. Translocation in response to receptor stimulation is rapid, transient, and requires calcium and tyrosine kinase activation. DGKalpha-mediated phosphatidic acid generation allows dissociation of the enzyme from the plasma membrane and return to the cytosol, as demonstrated using a pharmacological inhibitor and a catalytically inactive version of the enzyme. The NH(2)-terminal domain of the protein is shown to be responsible for receptor-induced translocation and phosphatidic acid-mediated membrane dissociation. After examining induction of the T cell activation marker CD69 in cells expressing a constitutively active form of the enzyme, we present evidence of the negative regulation that DGKalpha exerts on diacylglycerol-derived cell responses. This study is the first to describe DGKalpha as an integral component of the signaling cascades that link plasma membrane receptors to nuclear responses.

Animals↗
PubMed2001

Hydrolysis of an organophosphate ester by manganese dioxide.

Amorphous manganese dioxide facilitates the hydrolysis of p-nitrophenyl phosphate to p-nitrophenol and orthophosphate despite insignificant adsorption of p-nitrophenyl phosphate or p-nitrophenol to the manganese dioxide. At pH 8, the orthophosphate product is released into solution; at pH 4 and pH 6, some remains adsorbed. The rate of hydrolysis is an order of magnitude more rapid than the same reaction facilitated by iron oxides. Because manganese dioxides are ubiquitous components of soils and sediments, this suggests the possibility of significant abiotic pathways for the formation of bioavailable orthophosphate from phosphate ester precursors.

Biological Availability↗