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Biomedical subjects

J T Wilson

Publications and source records attributed to J T Wilson.

At least 19 recordsLinked to original sources
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↗
PubMed1998

Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: guidelines for their use.

The Glasgow Outcome Scale (GOS) is the most widely used outcome measure after traumatic brain injury, but it is increasingly recognized to have important limitations. It is proposed that shortcomings of the GOS can be addressed by adopting a standard format for the interview used to assign outcome. A set of guidelines are outlined that are directed at the main problems encountered in applying the GOS. The guidelines cover the general principles underlying the use of the GOS and common practical problems of applying the scale. Structured interview schedules are described for both the five-point GOS and an extended eight-point GOS (GOSE). An interrater reliability study of the structured interviews for the GOS and GOSE yielded weighted kappa values of 0.89 and 0.85, respectively. It is concluded that assessment of the GOS using a standard format with a written protocol is practical and reliable.

Adolescent↗
PubMed1998

Analyzing outcome of treatment of severe head injury: a review and update on advancing the use of the Glasgow Outcome Scale.

The Glasgow Outcome Scale (GOS), two decades after its description, remains the most widely used method of analyzing outcome in series of severely head-injured patients. This review considers limitations recognized in the use of the GOS and discusses a new approach to assessment, using a structured questionnaire-based interview. Assignments can be made to an extended eight-point scale (GOSE) as well as the original five-point approach-in each case, with a high degree of interobserver consistency. The assignments are coherent with the principles of the World Health Organization classification of impairments, disabilities, and handicaps, and their validity is supported by strong associations with the results of neuropsychological testing and assessment of general health status. The need to allow for disability existing before injury, issues concerning the time of assessment after injury, and subdivisions of the scale into "favorable" and "unfavorable" categories are discussed. It is concluded that, in its improved structured format, the Glasgow Outcome Scale should remain the primary method of assessing outcome in trials of the management of severe head injury.

Craniocerebral Trauma↗
PubMed1998

Hollow visceral injury and blunt trauma.

BACKGROUND: The incidence of hollow viscus injury (HVI) after blunt trauma (BT) is variable, and differences between children and adults have not been well described. The purpose of this study is to determine the age-group-related incidence and characteristics of BT-associated HVI as well as the clinical markers and consequences of delayed diagnosis. METHODS: A 9-year trauma registry review of all patients with HVI. RESULTS: A large sample of patients (19,621) with BT were evaluated (2,550 < or = 14 years old; 17,070 > 14 years old). One hundred thirty-nine of 17,070 (0.8%) adults had HVI compared with 27 of 2,550 (1%) children. HVI occurred more frequently in the duodenum in children (11 of 27) compared with adults (17 of 139) (p < 0.05). Among patients with abdominal wall ecchymosis, 13.5% of children had HVI compared with 10.6% of adults. Delays in diagnosis of HVI occurred in 9 of 27 children compared with 10 of 139 adults (p < 0.0 5). Delayed diagnosis was associated with increased abdominal septic complications in both children (4 of 9) and adults (2 of 10) compared with diagnosis at presentation (p < 0.05). CONCLUSION: HVI occurs with a similar low frequency in both children and adults. Duodenal injuries are more common in pediatric BT patients. Abdominal wall ecchymosis is associated with increased HVI but is less predictive of HVI than previously described. Contrary to previous reports, delays in diagnosis are associated with increased morbidity.

Abdominal Injuries↗
PubMed1998

Assessing disability after head injury: improved use of the Glasgow Outcome Scale.

OBJECT: The Glasgow Outcome Scale (GOS) is widely used to assess outcome after head injury, but is recognized as having a number of shortcomings that are highlighted and investigated in this study. The authors pursued two goals: 1) investigating the practicality of using a standard set of questions as part of a structured interview to assign GOS scores, and 2) studying the role of preinjury problems in confounding postinjury assessment of disability. METHODS: Several of the major limitations of the GOS appear to arise from the use of a format that encourages impressionistic ratings. In the present study the authors examined the use of a standard interview for assessing the GOS covering five areas of social disability. Ratings were made for 80 head-injured patients. The results show that the rating based on the GOS provides an assessment of disability that is more complete than that given by an alternative scale of functional disability (Disability Rating Scale [DRS]) and much more complete than an assessment of physical disability (Barthel Activities of Daily Living [ADL] index). A measure of preinjury dependency was made revealing that, within this sample, 20% of patients required supervision in basic ADL before their injury. CONCLUSIONS: Assignment of GOS scores based on information obtained using a structured interview format provides a more comprehensive assessment of disability than using the DRS or the ADL index. There is a need to standardize attitudes about preinjury dependency in assessing disability after head injury.

Adolescent↗
PubMed1997

Implementation of natural attenuation at a JP-4 jet fuel release after active remediation.

After eighteen months of active remediation at a JP-4 jet-fuel spill, a residual of unremediated hydrocarbon remained. Further site characterization was conducted to evaluate the contribution of natural attenuation to control exposure to hazards associated with the residual contamination in the subsurface. Activities included the detailed characterization of ground-water flow through the spill; the distribution of fuel contaminants in groundwater; and the analysis of soluble electron acceptors moving into the spill from upgradient. These activities allowed a rigorous evaluation of the transport of contaminants from the spill to the receptor of groundwater, the Pasquotank River. The transport of dissolved contaminants of concern, that is benzene, toluene, ethyl benzene, xylene isomers (BTEX) and methyl-tertiary-butyl ether (MTBE), into the river from the source area was controlled by equilibrium dissolution from the fuel spill to the adjacent groundwater, diffusion in groundwater from the spill to permeable layers in the aquifer, and advective transport in the permeable layers. The estimated yearly loading of BTEX compounds and MTBE into the receptor was trivial even without considering biological degradation. The biodegradation of hydrocarbon dissolved in groundwater through aerobic respiration, denitrification, sulfate reduction, and iron reduction was estimated from changes in ground-water chemistry along the flow path. The concentrations of target components in permanent monitoring wells continue to decline over time. Long term monitoring will ensure that the plume is under control, and no further active remediation is required.

Biodegradation, Environmental↗
PubMed1997

SPECT, CT, and MRI in head injury: acute abnormalities followed up at six months.

Neuroimaging with single photon emission computed tomography (SPECT) using the cerebral blood flow tracer 99Tc(m)-HMPAO has been used to study acute functional alterations after head injury and residual abnormalities at six month follow up in 32 patients. Comparison has been made with anatomical abnormalities defined acutely with CT and on follow up with MRI. SPECT showed slightly more abnormalities than CT in the acute phase (49 regions of abnormally low tracer uptake on SPECT and 45 lesions on CT). Twenty two of the acute SPECT abnormalities were in normal regions on CT. At follow up MRI showed more abnormalities than SPECT (30 on SPECT and 48 on MRI). Ten of the SPECT deficits were in regions with normal MRI. Comparison of the intensity of late and early SPECT deficits showed that only four early deficits deteriorated whereas 28 improved. Only five of 27 lesions seen on both acute SPECT and CT resolved compared with 16 of 22 lesions seen on SPECT but not on CT. Regions of abnormally high tracer uptake were detected in the acute stage in five of the patients. No high focal uptake was evident on follow up. Ten patients with a residual SPECT abnormality and eight with residual MRI lesions were graded clinically in the upper band of good recovery.

Adolescent↗
PubMed1996

Multiple intradural spinal lipomata with intracranial extension.

An intradural, intramedullary lipoma originating within the upper cervical cord with significant extension into the posterior fossa is reported in an infant. Two additional lipomas were found in the lumbar region. This constellation of findings represents the first description of multiple intradural, intramedullary spinal lipomas with extensive intracranial involvement.

Cerebral Ventricle Neoplasms↗
PubMed1995

Spinal anesthesia for repair of meningomyelocele in neonates.

The use of spinal anesthesia for meningomyelocele repair in neonates has received minimal attention. Spinal anesthesia may lessen the stress response to surgery and decrease postoperative respiratory complications. We therefore examined the efficacy of spinal anesthesia in 14 neonates requiring repair of lumbar or sacral meningomyelocele. All neonates were positioned prone with a small chest roll. Hyperbaric 0.5% tetracaine with epinephrine was injected into the caudal end of the meningomyelocele sac. If necessary, supplemental tetracaine was administered directly into the intrathecal space by the surgeon during the operation. Blood pressure, heart rate, and oxyhemoglobin saturation were measured throughout surgery. Neonates were monitored with transthoracic impedance apnea monitors, electrocardiogram (ECG), and pulse oximetry for 36 h after surgery. Spinal anesthesia was successful in all cases. Seven patients received one supplemental tetracaine injection; one patient received two supplemental injections. Arterial blood pressure decreased an average of 5 mm Hg with the largest decrease being 10 mm Hg. Two postoperative respiratory events occurred in the first 8 h after surgery. Both neonates had received intraoperative midazolam for sedation. Neurologic function was assessed pre- and postoperatively. Twelve patients had no change in neurologic function after surgery, while two infants demonstrated improved function. We conclude that spinal anesthesia can be safely used for meningomyelocele repair.

Anesthesia, Spinal↗
PubMed1995

U83836E reduces secondary brain injury in a rabbit model of cryogenic trauma.

Oxygen-derived free radicals have been implicated in secondary brain injury after head trauma. Although oxygen-free radicals may be derived from multiple sources, the activation and accumulation of neutrophils in areas of brain injury is a potential source of deleterious inflammatory mediators, including free radicals, which may exacerbate the primary insult. Neutrophils may also impede the cerebral microcirculation by congestion and occlusion of postcapillary venules. The lazaroid U83836E is a potent-free radical scavenger that inhibits lipid peroxidation. U83836E was studied in a cryogenic model of cerebral injury in pretreatment paradigm. Fifteen rabbits received a unilateral cryogenic brain lesion. Six animals received U83836E, and nine animals received vehicle only. Arterial blood gases, hematocrit, temperature, and mean arterial pressure were controlled in physiologic range throughout the experiment. Intracranial pressure was continuously monitored. Lesion size was determined by triphenyltertrazolium chloride staining and planimetric image analysis. Neutrophil aggregation and oxygen-free radical generation was assessed in whole blood by impedance aggregometry and simultaneous luminol-mediated chemiluminescence, respectively. Myeloperoxidase assay was used to determine neutrophil accumulation within the brain. Elevations in intracranial pressure from baseline values were significantly greater in the untreated (control) animals at all time points (p < 0.0001). Mean lesion size (% hemisphere +/- SEM) was significantly reduced in animals receiving U83836E (4.41 +/- 0.64, n = 6) when compared with controls (15.09 +/- 2.28, n = 9, p < 0.001). A reduction in both the release of oxygen-free radicals and in neutrophil aggregation following the cryogenic injury in the U83836E animals correlated with a smaller lesion volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Pharmacotherapy of depression in children.

Depression can interfere with the overall functioning of children and adolescents. It can impair normal cognitive and social development. The use of antidepressant medications in children and adolescents has grown in the past decade. Newer antidepressant agents, the selective serotonin reuptake inhibitors, appear very promising, but their safety and efficacy have not been established for children. This review focuses on depression and the design of studies for its treatment with newer antidepressant drugs in children.

Adolescent↗
PubMed1995

Neuropsychological consequences of two patterns of brain damage shown by MRI in survivors of severe head injury.

Two subgroups of patients were identified from 48 patients with traumatic head injury who had MRI during the acute stage: (a) those with severe diffuse injury--six patients with lesions in both the corpus callosum and the brain stem; (b) those with severe focal injury--16 patients with extensive frontotemporal lesions. Most patients with diffuse injury were in a coma on admission to hospital, whereas most patients with focal injury were out of coma. Duration of post-traumatic amnesia was prolonged in both groups. Patients were followed up at six months after injury, when a battery of neuropsychological tests was given. Patients with both diffuse and focal patterns of injury were impaired by comparison with controls on a range of measures, including tests of memory and attention. The findings contrast with the view that diffuse injury is of much greater importance than focal injury in determining outcome after head injury.

Adolescent↗
PubMed1995

Primary diffuse chiasmatic germinomas: differentiation from optic chiasm gliomas.

Primary germ cell tumors confined to the optic nerves and chiasm without suprasellar extension are uncommon. These tumors appear similar to chiasmatic gliomas on both computed tomography and magnetic resonance imaging, potentially resulting in treatment errors if the diagnosis is based on radiologic criteria alone. Unlike chiasmatic gliomas, suprasellar germinomas characteristically present with a clinical triad of endocrine abnormalities, diabetes insipidus, and visual complaints. We report the case of a 9-year-old boy who presented with a 5-month history of fatigue, 16-pound weight gain, polydipsia, polyuria, visual complaints, and intermittent headache. Imaging studies demonstrated findings consistent with a glioma of the chiasm with infiltration into the optic tracts. At surgery, the chiasm and optic tracts were diffusely enlarged with no other suprasellar abnormalities. Biopsy specimens were characteristic of germ cell tumor. Based on this result, the patient received a treatment regimen different from that used at our institution for chiasmatic gliomas. We feel it is imperative to biopsy chiasmatic lesions that radiologically appear to be gliomas if symptoms do not adhere to the classical clinical presentation.

Biopsy↗