Search PubMed⌕ Search

Biomedical subjects

J T Wilson

Publications and source records attributed to J T Wilson.

At least 19 recordsLinked to original sources
PubMed2003

Role of the research-subject locator (RSL) in the performance of a pediatric drug trial.

This article examines the feasibility, effectiveness, and ethical constraints relevant to appropriate financial compensation of the pediatric house officer who functions as a research-subject locator (RSL). When carefully trained and supervised, the RSL can facilitate timely enrollment of research subjects in pediatric drug trials, augment the house officer training experience, and advocate for children to increase therapeutic options available for pediatric care. When monitored within the clinical trial schema, the RSL has no direct link to the study outcome and thus performs within ethical standards for subject enrollment and study participation.

Child↗
PubMed2002

Concordance between tramadol and dextromethorphan parent/metabolite ratios: the influence of CYP2D6 and non-CYP2D6 pathways on biotransformation.

Cytochrome P4502D6 (CYP2D6) activity has been shown to be a determinant of both the pharmacokinetics and pharmacodynamics of tramadol in adults. This study evaluated the association between CYP2D6 activity, as determined by dextromethorphan (DM) urinary metabolite ratio, and tramadol biotransformation in 13 children (7-16 years). CYP2D6 genotype was determined by XL-PCR and PCR/RFLP. Phenotype was assessed by HPLC quantitation of DM and its metabolites from a 12- to 24-hour urine collection following a single oral dose of DM. There was only a modest correlation between tramadol/M1 (metabolite 1) plasma concentration or AUC and the DM/dextrorphan (DX) urinary molar ratio in the study cohort; however, when subjects were segregated based on the number of functional CYP2D6 alleles, a much stronger relationship was observed for subjects with two functional alleles, with essentially no relationship evident in those individuals with one functional allele. Further evaluation of these data suggested that the CYP2D6-mediated metabolite (M1) is formed to a lesser extent, and the formation of the non-CYP2D6 product (M2) is more pronounced in subjects with one versus two functional alleles. Thus, the number of functional CYP2D6 alleles and the availability of alternative cytochromes P450 capable of metabolizing tramadol may explain the poor association between DM, a well-characterized CYP2D6 probe, and tramadol in a population of CYP2D6 extensive metabolizers.

Adolescent↗
PubMed2001

Prospective study of morbidity after tonsillectomy in children.

Post-operative morbidity was prospectively studied in 384 children after tonsillectomy or adenotonsillectomy, using visual analogue scores to record symptom levels, and questionnaires to monitor satisfaction scores from the children and their families. Assessments were performed between the 7th and 14th day post-operatively. Two hundred children were assessed before the introduction of a pre-admission programme which consisted of an instructional videotape session in the ward and an advice booklet. Department practice was also changed to provide a bottle of paracetamol on discharge routinely for each child. Following these changes in practice a further 184 children were assessed. The provision of relatively simple measures in the programme increased parental satisfaction rates (P<0.05) and reduced GP contact rates (35--17%, P<0.05) post-operatively. The actual levels of morbidity were unchanged despite the provision of analgesia.

Acetaminophen↗
PubMed2001

Spatial normalization of lesioned HMPAO-SPECT images.

We investigated the effect of nonlinear alignment on SPECT images with lesions. Linear alignment produces reliable results but the introduction of nonlinear methods can improve matching by accounting for global brain shape. We examined the hypothesis that nonlinear alignment can introduce unwanted image distortions when lesions are present. We set out to quantify possible distortions by constructing artificial lesions in order to obtain images with controllable characteristics. We examined the use of basis functions (in SPM96 and SPM99) and other nonlinear models (in AIR3.08) designed to achieve optimum alignment between image and template. We found that the use of models with high degrees of nonlinearity will result in unwanted deformations and that the safest way to align images with lesions is to use 12-point linear affine transformations. Masking was examined as a remedy to distortions caused by nonlinear methodologies and produced significantly improved results.

Artifacts↗
PubMed2001

Tophaceous gout of the spine mimicking epidural infection: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Tophaceous gout uncommonly affects the axial skeleton. The clinical presentations of gout of the spine range from back pain to quadriplegia. Gout that presents as back pain and fever may be difficult to distinguish from spinal infection. We present a case of a patient with tophaceous gout of the lumbar spine who was initially diagnosed with and treated for an epidural infection. The clinical and diagnostic features of tophaceous gout of the spine are reviewed. CLINICAL PRESENTATION: A 70-year-old man presented with a 2-day history of fever and back pain. A physical examination revealed that he had flank tenderness and evidence of polyarthritis affecting the elbows, knees, and right first metatarsophalangeal joint. A magnetic resonance imaging scan of the patient's lumbar spine showed an extensive area of abnormal gadolinium enhancement of the paramedian posterior soft tissues from L3 to S1 with an area of focal enhancement extending into the right L4-L5 facet joint. INTERVENTION: A laminectomy was performed at L4-L5, and a chalky white material in the facet joint was found eroding into the adjacent pars intra-articularis. Light and polarizing microscopy confirmed the presence of gouty tophus. No evidence of infection was found. CONCLUSION: Gouty arthritis of the spine is rare. Thirty-seven previous cases have been reported. When the clinical presentation includes acute back pain and fever, differentiation of spinal gout from spinal infection may be difficult. The clinical suspicion of spinal gout may lead to the correct diagnosis by a less invasive approach than exploration and laminectomy.

Aged↗
PubMed2001

Evaluation of occult acetaminophen hepatotoxicity in hospitalized children receiving acetaminophen. Pediatric Pharmacology Research Unit Network.

The safety of repeated doses of acetaminophen in ill children with the potential of reduced glutathione stores has been questioned. This study measured hepatic transaminases in children and adolescents (n=100) who received > or = 6 therapeutic doses of acetaminophen over a 48-hour period of hospitalization. Acetaminophen-protein adducts were measured in a cohort of subjects with hepatic transaminase elevation (n=8) and in those (n=10) receiving concurrent drug therapy with agents that induce the cytochrome P450 enzymes involved in acetaminophen metabolism. Acetaminophen-protein adducts were not detected in this cohort of 18 subjects. Based on this pilot study, the routine use of acetaminophen at therapeutic doses in ill, hospitalized children and adolescents appears safe.

Acetaminophen↗
PubMed2001

Single-dose pharmacokinetics of bupropion in adolescents: effects of smoking status and gender.

Sustained-release (SR) bupropion (Zyban) is approved as a smoking cessation aid for adults. Since smoking often begins in adolescence, we determined the single-dose pharmacokinetics of bupropion SR in 75 adolescent subjects ranging from 13 to 18 years old. Subjects self-reported their smoking status. Urinary cotinine concentration was used to verify smoking status. Thirty-seven subjects (18 males, 19 females) were classified as cigarette smokers and 38 were nonsmokers (19 males, 19 females). Fasted subjects received one tablet (150 mg) of bupropion SR, and plasma samples were collected before (0) and 1/2, 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours after dosing. Plasma samples were analyzed for bupropion and its three major metabolites (hydroxybupropion and the aminoalcohol isomers, erythrohydrobupropion plus threohydrobupropion, expressed as a composite) by solid-phase extraction, followed by LC/MS/MS. Factorial analysis of variance (ANOVA) was used to evaluate the effects of smoking and gender on pharmacokinetic parameters. Smokers and nonsmokers differed significantly (p < 0.05) in age and urinary cotinine (p < 0.01) concentration but did not differ significantly in mean weight, height, body surface area, or body mass index. The pharmacokinetic (PK) parameters for bupropion and hydroxybupropion did not differ between smokers and nonsmokers, but differences were found between male and female subjects. Mean values for area under the plasma concentration versus time curve (AUC0-->infinity), volume of distribution (Vd beta) normalized to body weight, maximum plasma concentration (Cmax), and elimination half-life (t1/2 beta) for bupropion were significantly (p < 0.05) greater in females than males, while clearance of bupropion normalized to body weight (CL/f) did not differ between males and females. Females also exhibited significantly (p < 0.05) larger values for hydroxybupropion mean AUC0-->infinity and Cmax than males. The mean ratio of hydroxybupropion to bupropion AUC for adolescents was approximately 4 to 5, which is lower than that previously reported for adults. In conclusion, smoking status does not affect the single-dose pharmacokinetics of bupropion SR in adolescents. However, females differ from males in several potentially important PK parameters for bupropion and its major metabolite, hydroxybupropion.

Adolescent↗
PubMed2001

The pharmacokinetics of irbesartan in hypertensive children and adolescents.

An open-label study was conducted to characterize the pharmacokinetics and antihypertensive response to irbesartan in children (1-12 years) and adolescents (13-16 years) with hypertension. Patients received single once-daily oral doses of irbesartan 2 mg/kg (maximum of 150 mg once daily) for 2 to 4 weeks (+/- nifedipine or hydrochlorothiazide). Plasma irbesartan concentrations were determined by a validated high-performance liquid chromatography/fluorescence method from blood samples taken predose, up to 24 hours after dosing on Day 1, and up to 48 hours after the final dose. The plasma concentration-time profiles were similar between the 6- to 12-year and the 13- to 16-year age groups and to that previously determined from a study of adult subjects receiving approximately 2 mg/kg (i.e., 150 mg) oral irbesartan once daily. Mean reductions in systolic/diastolic blood pressure were 16/10 mmHg at Day 28 with irbesartan monotherapy (n = 8). Irbesartan was well tolerated and may be a treatment option for pediatric hypertensive patients.

Administration, Oral↗
PubMed2001

Assessing outcome in head injury trials.

It is often suggested that one reason that neuroprotection trials in head injury have not shown benefit is the insensitivity of the outcome measures employed. The review considers strengths and weaknesses of the main approaches to assessing outcome in head injury trials. Determination of a response to neuroprotection requires a measure that is both sensitive to differences in outcome and is also influenced by brain injury. Sets of tests have been proposed for use in clinical trials that include scales of disability and handicap and measures of neuropsychological impairment. The Glasgow Outcome Scale (GOS) covers the whole spectrum of outcome after head injury and is the most popular primary endpoint for head injury trials. Although the GOS is a simple scale, small changes in the distribution of outcome can be detected with appropriate sample sizes. Late outcome in survivors can be influenced by various personal and environmental factors in addition to initial brain pathology. Other rating scales and questionnaires do not appear to offer significant advantages over the GOS, but can be used to supplement the information collected. Neuropsychological tests have properties that make them attractive as outcome measures, although there are practical difficulties with using tests. Neuropsychological assessment is potentially a powerful way of testing specific hypotheses concerning the effects of treatment. All current outcome measures have limitations; choice of the most appropriate endpoint will depend both on the properties of the measures available, and on the anticipated effects of treatment.

Activities of Daily Living↗
PubMed2000

Emotional and cognitive consequences of head injury in relation to the glasgow outcome scale.

OBJECTIVE: There is current debate over the issue of the best way of assessing outcome after head injury. One criticism of scales of disability and handicap such as the Glasgow outcome scale (GOS) is that they fail to capture the subjective perspective of the person with head injury. The aims of the study were to investigate aspects of the validity of structured interviews for the GOS, and address the issue of the relation between the GOS and subjective reports of health outcome. METHODS: A total of 135 patients with head injury were assessed using the GOS and an extended GOS (GOSE) and other measures of outcome and clinical status at 6 months after injury. RESULTS: There were robust correlations between the GOS and measures of initial injury severity (particularly post-traumatic amnesia) and outcome assessed by disability scales (particularly the disbility rating scale (DRS)); however, associations with cognitive tests were generally modest. There were also strong correlations with self report measures of health outcome: both the GOS and GOSE were related to depression measured by the Beck depression inventory, mental wellbeing assessed by the general health questionnaire, and to all subscales of the short form-36. The GOS scales were also strongly associated with frequency of reported symptoms and problems on the neurobehavioural functioning inventory. CONCLUSIONS: The GOS and GOSE show consistent relations with other outcome measures including subjective reports of health outcome; they thus remain useful overall summary assessments of outcome of head injury.

Adolescent↗
PubMed2000

Analysis of HMPAO SPECT scans in head injury using Statistical Parametric Mapping.

The paper examines the ability of Statistical Parametric Mapping (SPM) to contribute towards the quantitative analysis of HMPAO SPECT images containing lesions. A validation study is described in which SPECT images were created that contained synthetic lesions and were analysed with SPM. The study established a set of guidelines concerning the alignment, smoothing, and statistical analysis of images. These were then applied to analysis of SPECT scans from head injured patients. A demonstration is given of the use of SPM to identify localised blood flow abnormalities associated with cognitive deficits after head injury. Correlations between blood flow abnormalities and a test of visual memory are illustrated.

Journal Article↗
PubMed2000

Acetaminophen controlled-release sprinkles versus acetaminophen immediate-release elixir in febrile children.

Current acetaminophen (APAP) formulations approved for antipyretic use in children require up to five doses/day, which compromise compliance and risk breakthrough fever over 4 hours after dosing. A total of 112 evaluable febrile children received oral APAP-equivalent doses of either one dose of APAP controlled release (CR) as sprinkles on applesauce or one dose q 4 hours x 2 of APAP immediate-release (IR) elixir in an 8-hour, double-blind, double-dummy, randomized, multicenter study. Prior or concurrent antibiotic use did not significantly affect either the magnitude or the pattern of temperature reduction during the 8-hour observation period. Significantly greater aural temperature reductions were found with APAP-CR than with APAP-IR at 4 and 5 hours. However, the 8-hour AUCs of temperature reduction were not significantly different between treatments. Pharmacokinetic/pharmacodynamic modeling of APAP was performed in 8 patients with values in both treatments similar to previous results, except for expected differences in AUC0-infinity. Similar 8-hour temperature reduction for APAP-CR (one dose) and APAP-IR (two doses) demonstrates the efficacy of APAP-CR as an antipyretic in children 2 to 11 years of age. A decrease in the number of APAP daily doses and the prolonged antipyretic effect of APAP-CR may assist those who care for febrile children at home.

Acetaminophen↗
PubMed1999

Validation of statistical parametric mapping (SPM) in assessing cerebral lesions: A simulation study.

Simulated abnormalities were introduced in a normal SPECT with known and controllable characteristics (abnormality size and depth) in an attempt to provide validation for the analysis of SPECT lesion studies using SPM. Two simulations were carried out. The first determined the minimum hypoperfusion depth detectable using SPM by altering mean local intensity while keeping the size of the lesion constant. This was done by changing the mean local intensity in percentile increments of 10 down to -100 and up to 50. The second simulation determined the cluster size that SPM can detect by keeping the mean intensity of the lesion constant while altering its size from 4 voxels to 63,000 voxels in a total brain volume of 300, 000 voxels. Both simulations determined which method of normalization is most appropriate, what level of grey matter thresholding should be used, and at what statistical probability peak threshold (u) the results should be determined. Proportional scaling was found to be the most appropriate normalization method. ANCOVA was useful where very large abnormalities were present and normalization external to SPM was not available. In those cases, ANCOVA was used in conjunction with measurement of an unaffected part of the brain (in this case medial occipital lobe). For better results statistical probability peak threshold was set to p(u) = 0. 01 and grey matter threshold was set to a value below 0.5. SPM produced best results when the abnormality represented a decrease of about -50% from the normal or more and detected other decreases in an acceptable manner.

Analysis of Variance↗
PubMed1999

Anaphase aberrations in the embryos of the marine tubeworm Pomatoceros lamarckii (Polychaeta: Serpulidae): a new in vivo test assay for detecting aneugens and clastogens in the marine environment.

The marine environment receives a wide variety of chemical inputs, many of which have the potential to damage DNA or interfere with the process of cell division. Here we describe a new assay based on the early embryo and larval stages of a planktonic spawning, tube dwelling marine worm, Pomatoceros lamarckii, which for experimental purposes has the advantage of producing large numbers of ripe gametes throughout the majority of the year. One of the most promising end-points is the use of dividing cells to detect anaphase aberrations such as lagging chromosomes, tripolar anaphases, acentric fragments and chromosome bridges. Apart from the reference mutagens mitomycin C and cyclophosphamide and the well-documented spindle poison colchicine, we tested the fungicide carbendazim, a primary metabolite of the fungicide benomyl, and thiabendazole, a pesticide and antihelminthic drug; both of which are known to act as aneugens in other test systems. In addition we tested sodium hypochlorite, a widely used oxidizing agent and disinfectant, di-butylphthalate, a commercial plasticizer and suspected aneugen, and sodium chloride, a recognized non-genotoxin. Significant increases in the frequency of anaphase abnormalities occurred with most test compounds at relatively low concentrations, confirming the sensitivity of the new assay. Sodium chloride yielded a negative response except at the highest non-relevant concentrations, where some chromatid stickiness was observed. In addition, the developmental consequences of exposure to these compounds were assessed in 4-8 cell embryos and at 48 h once the embryos had metamorphosed into free swimming larvae. Mitotic inhibition and anaphase aberrations were found to be a more sensitive indicator of genotoxic exposure than larval development, although there was a suggestion of a possible mechanistic link between aneugenicity/clastogenicity and larval fitness. The new test assay provides a rapid and inexpensive method for screening chemicals and effluents destined for release into the marine environment for potential gamete effects.

Animals↗
PubMed1998

Evaluation of the comet assay as a method for the detection of DNA damage in the cells of a marine invertebrate, Mytilus edulis L. (Mollusca: Pelecypoda).

The potential application of the comet assay for monitoring the effect of DNA damaging agents on the marine mussel, Mytilus edulis (an important pollution indicator organism), was explored. A detailed investigation of the baseline levels of single-strand breaks in isolated gill cells, and how they were affected by age/size of animal, time since collection, feeding regime, in vivo vs. in vitro exposure conditions, and by antioxidant supplementation was undertaken. The level of cometing in untreated controls was found to be highly variable over time (fluctuations between low and very high DNA damage occurred over just 14 days post collection). No difference was observed between age/size and feeding regime of the animals. On exposure to 0, 100, 500 and 1000 microM H2O2, it was observed that the in vitro exposure produced a markedly more homogeneous dose response compared to the in vivo studies (where gill cells were exposed as a tissue). An important finding of our research was the effect of prior supplementation of the animals' diet with 1 mg/ml alpha-tocopherol acetate (vitamin E compound), which resulted in a marked reduction in the levels of DNA damage expressed by the negative controls, without influencing the actual response to H2O2 (0, 5, 25, and 100 microM) and N-nitrosodimethylamine, NDMA (0, 5, 25, and 100 mM). The effect of vitamin E supplementation was to increase the sensitivity of the comet assay at the lower end of the dose range. This study demonstrated the potential application of the comet assay to the gill cells of the mussel, M. edulis. Although preliminary findings suggest that antioxidant supplementation can improve the sensitivity of the assay by lowering the baseline damage in untreated animals, our conclusion is that the assay has more potential for use in an in vitro context for the screening of agents destined for release or disposal into the marine environment.

Animals↗
PubMed1998

Integrated pharmacokinetic-pharmacodynamic model for acetaminophen, ibuprofen, and placebo antipyresis in children.

A descriptive profile for antipyretic drug action has been documented for children. However, a linked pharmacokinetic-pharmacodynamic (PK/PD) model is central to the understanding of antipyretic drug action in febrile children. This was examined for previously reported data from 178 febrile children who received a single oral dose of acetaminophen (APAP) (12.5 mg/kg), ibuprofen (IBU) (5 or 10 mg/kg), or placebo. Rectal temperatures and plasma levels (microgram/ml) of APAP and IBU were measured for up to 12 hr after drug administration. Nonlinear regression analyses were applied to these measurements and yielded simultaneous solutions of an integrated one-compartment PK, link, and Sigmoid Emax effect model in 102/153 febrile children given APAP or IBU. The PK parameters (tlax, k alpha, beta, T1/2 beta, AUC0-infinity, Vd/F, and Clp/F) were not different than those reported previously, except the APAP k alpha was significantly lower. The link component yielded keos of 0.58 +/- 0.06 (mean +/- SE), 0.70 +/- 0.11 and 0.57 +/- 0.11 hr-1 for APAP, IBU05, and IBU10, respectively; the Sigmoid Emax component yielded EC50s (microgram/ml) and sigmoidicity (gamma) of 4.63 +/- 0.39 and 3.98 +/- 0.42 for APAP, 11.33 +/- 1.35 and 3.97 +/- 0.58 for IBU05 and 12.83 +/- 1.89 and 4.27 +/- 0.63 for IBU10. On visual inspection of the efficacy-time profiles of the febrile children, a number of them had an apparent linear function (slope; delta degree C/hr) and/or a sinusoidal cyclic function "confounding" standard approaches to PD analysis. Thus, the temperature profiles of 91/102 children given APAP or IBU required the addition of a slope (delta degree C/hr) and/or a sinusoidal cyclic function to the Sigmoid Emax component to fit the data satisfactorily. All 22 children given a placebo also required a slope and/or a cyclic function in their PD model. The residual delta degree Cs (observed-predicted) of the placebo group were not significantly different from 0. Thus, no placebo antipyretic effect was observed. Dose dependency of IBU AUC0-infinity was confirmed; doubling the dose from 5 to 10 mg/kg increased the AUC0-->infinity by only 1.5-fold. The confounding effect of initial temperature (Tempi) on antipyretic efficacy in all treatment groups except placebo was also confirmed to expose nonlinear pharmacodynamics. A significant (p = 0.03) contribution of Tempi (but not age) on the value of the slope function was found. There was no consistent effect of age or Tempi on the cyclic component of the integrated model of antipyresis. In addition, a multiple linear relationship of age and Tempi was observed with a large number of the PK, link, and PD variables in those who received IBU. Dose, age, and Tempi interacted with beta in a significant multiple linear relationship with AUC0-infinity. The effects of IBU dose, age, and Tempi are pervasive and cascade down the chain of events leading to the PD response. The etiology of pyresis may create the slope function, the magnitude of which may be partially due to the underlying disease. In some cases, the cyclic function may be explained by temperature regulation. Regardless of their cause, both confound analysis of drug action and make the simple, unmodified Sigmoid Emax effect model less than satisfactory for interpretation of antipyretic drug effects. The influence of Tempi on the magnitude of antipyretic drug response is also a finding with major impact on PD investigations of antipyretic medications. In children receiving IBU, dose and age are also confounders, in addition to Tempi. A multiplicity of covariables must be taken into account when developing appropriate dosing regimens for these antipyretics in febrile children.

Acetaminophen↗