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J Parke

Publications and source records attributed to J Parke.

13 recordsLinked to original sources
PubMed2001

Population pharmacokinetic modeling of steady state carbamazepine clearance in children, adolescents, and adults.

Carbamazepine (CBZ) clearance decreases from childhood to adulthood and the factors determining this change could include age, size, autoinduction, or maturational changes. This study aims to describe the population pharmacokinetics of CBZ in children and young adults and test the hypothesis that CBZ clearance correlates with weight, surface area, and age. CBZ therapeutic drug monitoring data (sparse data) were collected from child and adult epileptics, and rich data were obtained from a bioequivalence study of CBZ in young adults. Population pharmaco-kinetic analysis was performed using NONMEM V. Forward stepwise, multiple regression was performed on the covariates. Bootstrap validation was performed. A total of 946 observations from 91 subjects, ages 0.7-37 years, were collected and analyzed. A one-compartment, first-order absorption and elimination model, with exponential interindividual error and additive residual error models was developed. The population model was: Clearance (Lhr-1) = ((2.24 x Surface area (m2)) + (0.047 x Dose (mg.kg-1)); Volume of distribution (L) = 0.37 x weight (kg); Absorption rate constant = 0.013 (hr-1). CBZ clearance increased with surface area and dose.

Adolescent↗
PubMed2000

Factors affecting oral cyclosporin disposition after heart transplantation: bootstrap validation of a population pharmacokinetic model.

OBJECTIVE: To determine factors affecting the population pharmacokinetics of oral cyclosporin (CsA) in cardiac allograft recipients during the first 3 weeks after surgery. METHODS: Data were obtained from routine trough monitoring and from two extra samples drawn during a dosing interval on a randomly selected day. Whole blood CsA concentrations were assayed using high-performance liquid chromatography (HPLC). Approximately equal numbers of patients were prescribed Sandimmun (SAN) or Neoral (NEO) CsA formulations. Parameter values of a one-compartment kinetic model with first-order absorption and elimination were sought together with the inter-patient and intra-patient variances using the NONMEM program. RESULTS: Improved fits resulted from using the following expression in the model to adjust apparent bioavailability as a function of post-operative day (POD): f= 0.2 + 10 x ABS (POD-5)/[(POD + 7) x 60]. The CsA clearance (CL/f) was found to be influenced by current body weight (WT). There was an absorption lag time of about 35 min with SAN, but zero lag time with NEO. Oral bioavailability (f) was increased by about 35% with concomitant diltiazem and about 18% with NEO. The CL/f was 10% higher during the daytime than at night. The final pharmacokinetic model was validated using 200 bootstrap samples of the original data. CONCLUSIONS: Using a validated population modelling approach, it was found that a number of factors influence the pharmacokinetics of CsA during the early postoperative period in cardiac transplant patients. These influences affecting oral bioavailability and clearance may need to be taken into account for maintaining appropriate concentrations of CsA in the bloodstream.

Adolescent↗
PubMed1999

A procedure for generating bootstrap samples for the validation of nonlinear mixed-effects population models.

A method is presented for automated preparation of bootstrap data samples and their presentation to NONMEM for use in the validation of population pharmacokinetic or pharmacodynamic models, which have been developed with relatively small numbers of subjects. The bootstrap sampling procedure involves the use of an MS-DOS batch file and a script file for use with the public-domain text processing program, AWK, which is a single EXE file (48k in size for the version used in this report). A UNIX version of AWK is also available and UNIX users can adapt the process to their needs. Its use obviates the need for expensive, high-end statistical packages and associated script files written using in-built programming languages. The method can easily be adapted to bootstrap sampling requirements in other biomedical modelling applications.

Computer Simulation↗
PubMed1998

NONMEM population pharmacokinetic modeling of orally administered cyclosporine from routine drug monitoring data after heart transplantation.

The population pharmacokinetics of cyclosporine (CsA) in adult recipients of cardiac transplants were determined from sparse, retrospective drug monitoring data accumulated for at least 3 months after surgery. All were receiving oral CsA twice daily, and morning trough levels in whole-blood were measured by high-performance liquid chromatography. Additional data included height, weight, gender, age, ethnicity, hematocrit, total bilirubin, and concurrent drug use. Population modeling was performed using NONMEM on 36 randomly selected patients, assuming a one-compartment model with first-order absorption and elimination. Improved fits were obtained by incorporating the following expression in the model to adjust oral bioavailability as a function of postoperative day (POD): F = 0.2 + 10 x ABS (POD - 7)/([POD + 10] x 60). Interpatient variability (CV%) in clearance (CL) was 20.2%. There was a mean bias of 8.5% at the average CsA concentration of 250 ng/ml when the predictive performance was assessed statistically in a reserved subset of 33 patients who received cardiac transplants. For the entire population (n = 69 patients), the average CsA CL and terminal half-life (T1/2) were, respectively: CL (l/h) = 0.256 x weight (kg); T1/2 = 11.0 hours, or CL (l/h) = 0.184 x weight (kg); T1/2 = 14.7 hours, if there was concomitant diltiazem administration. These results compared favorably with those reported elsewhere for studies of postcardiac transplant kinetics using the traditional multiple blood sampling approach.

Administration, Oral↗
PubMed1996

Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2)

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly, mental retardation (MCA/MR) syndrome associated with deletion of chromosome 17 band p11.2. As part of a multi-disciplinary clinical, cytogenetic, and molecular approach to SMS, detailed clinical studies including radiographic, neurologic, developmental, ophthalmologic, otolaryngologic, and audiologic evaluations were performed on 27 SMS patients. Significant findings include otolaryngologic abnormalities in 94%, eye abnormalities in 85%, sleep abnormalities (especially reduced REM sleep) in 75%, hearing impairment in 68% (approximately 65% conductive and 35% sensorineural), scoliosis in 65%, brain abnormalities (predominantly ventriculomegaly) in 52%, cardiac abnormalities in at least 37%, renal anomalies (especially duplication of the collecting system) in 35%, low thyroxine levels in 29%, low immunoglobulin levels in 23%, and forearm abnormalities in 16%. The measured IQ ranged between 20-78, most patients falling in the moderate range of mental retardation at 40-54, although several patients scored in the mild or borderline range. The frequency of these many abnormalities in SMS suggests that patients should be evaluated thoroughly for associated complications both at the time of diagnosis and at least annually thereafter.

Abnormalities, Multiple↗
PubMed1996

Audio-teleconferencing as a medium for distance learning: its application for continuing education in optometry.

This paper describes a highly successful pilot program of four audio-teleconferences that was offered in 1993 to optometrists based in rural and regional areas of Queensland. The program represents the first application of such technology for this purpose, either within Australia or overseas. It accessed the facilities of eight of a network of 38 open learning centres across Queensland and comprised an integrated package of three workshops, each of 3 hours duration, covering issues relating to the eye disease, glaucoma, and a stand-alone workshop covering general practice/legal issues. A 'complex directed conference model' of audio-teleconferencing was used, with each workshop incorporating a slide presentation and companion workbook that described individual pre-workshop preparatory activities and was structured to provide a focus for group discussions during the workshop. The program demonstrated audio-teleconferencing to be both a cost- and educationally-effective medium for the delivery of continuing education to a widely distributed audience.

Australia↗
PubMed1996

RANZCP guidelines for psychotropic drugs: application to hospital inpatients. Royal Australian and New Zealand College of Psychiatrists.

The objective of this study was to monitor compliance with the Royal Australian and New Zealand College of Psychiatrists (RANZCP) guidelines for psychiatric drug use, in the forensic section of a psychiatric institution in Queensland. The author performed an audit of the charts and medical records of 65 patients in three forensic hospital wards at the John Oxley Memorial Hospital, a 73-bed forensic/secure section of the Wolston Park Hospital Complex. It was found that many patient records were lacking some relevant documentation. There was a higher rate of prescription for multiple psychotropic drugs than is recommended for patients at discharge from inpatient units. This quality assurance exercise has provided a basis for discussion to find ways to more closely comply with the RANZCP Guidelines for Psychotropic Drugs in Psychiatric Practice. No benchmarks are available for equivalent continuing inpatients in a similar setting. It has been shown that, for continuing inpatients in a forensic hospital, there is poor compliance with Draft Clinical Indicator No. 2.1 for Pilot Test (developed jointly by the RANZCP and the ACHS). Perhaps the threshold for this indicator needs to be raised in this clinical setting. The situation may be clarified when the proposed follow-up audit has taken place. There were no patients receiving doses in excess of currently-accepted limits, that is, Clinical Indicator (CI) No. 2.2 was 0, and there were 31 patients (47.7%) concurrently receiving two or more antipsychotic drugs and CI no.2.3 had a value of 31.

Adolescent↗
PubMed1991

Brachial plexus birth injury.

Brachial plexus birth injuries occur at a frequency of 1-2 per 1000 births. Many of these injuries spontaneously resolve. Should spontaneous recovery not occur within the first 4-6 months of life, the prognosis for attaining movement and function of the affected appendage is significantly impaired. The child demonstrates a lifelong disfiguring and functional handicap. With advances in technology, diagnosis and microsurgical techniques, surgical exploration of the brachial plexus has been revived. A multidisciplinary approach has provided dynamic results. At present only one institution in the United States utilizes this innovative protocol. This article addresses the collaborative perioperative nursing implications for a child with brachial plexus birth injury.

Birth Injuries↗
PubMed1991

Role of height and glycosylated hemoglobin in abnormal nerve conduction in pediatric patients with type I diabetes mellitus after 4-9 yr of disease.

OBJECTIVE: To determine the role of height and glycosylated hemoglobin in abnormal nerve conduction in pediatric patients with insulin-dependent (type I) diabetes mellitus. RESEARCH DESIGN AND METHODS: Sixty-six pediatric patients (aged 6.3-18.2 yr) with a duration of diabetes from 4 to 8.5 yr but free of clinical neuropathy were evaluated for abnormal nerve conduction. RESULTS: Mean HbA1 values for 1 and 2 yr before study were available. Electroneurographic findings were significantly different from control subjects in upper and lower extremities and included all five measured velocities, three sensory latencies, and one amplitude. Stepwise regression analysis identified an adverse effect of height on latency (5 of 6) and of mean HbA1 concentration on decreasing velocity (4 of 5). The data analysis from 52 patients who were restudied and who had a duration of diabetes from 5.3 to 9.6 yr confirmed that all velocity values slowed; one of five values did so significantly. The coefficients associated with mean HbA1 concentration usually increased in both upper- and lower-extremity velocity analyses at the follow-up examination. The change in peroneal motor velocity between the first and last examinations was significantly related to the increasing time interval between examinations. CONCLUSIONS: Prospective evaluation of nerve conduction parameters in pediatric patients with diabetes should include both height (the most significant independent variable in latency analysis) and mean glycemic control (the most consistent variable in velocity analyses) as variables in the assessment of the natural history of evolving peripheral neuropathy.

Body Height↗
PubMed1988

Myosin and Ca2+-sensitive streaming in the alga Chara: detection of two polypeptides reacting with a monoclonal anti-myosin and their localization in the streaming endoplasm.

A monoclonal antibody to the heavy chain of myosin from mouse 3T3 cells was used to detect and localize related proteins in the green alga Chara. Proteins of 200,000 and 110,000 Mr reacted on immunoblots of proteins precipitated rapidly with trichloroacetic acid to minimize proteolysis. Immunofluorescence of whole cells localized these proteins to organelles of the streaming endoplasm, to a system of endoplasmic strands and to the subcortical actin bundles. Except that fewer endoplasmic strands and organelles were found and the strands were tangled, the localization pattern was similar in cells rapidly perfused to remove the bulk of the streaming endoplasm. Actin was confined almost entirely to the system of subcortical actin bundles in both whole and perfused cells. Myosin that was associated with the tangled endoplasmic strands but not that associated with the organelles or actin bundles was removed by concentrations of Ca2+ inhibiting ATP-dependent streaming in perfused cells. ATP extracted both organelles and endoplasmic strands but left a continuous pattern of myosin immunostaining along the actin bundles. The findings are discussed in relation to the possible existence of two forms of myosin and of separate mechanisms moving the bulk endoplasm and individual organelles.

Actins↗
PubMed1967

Terminal carcinoma.

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Neoplasm Metastasis↗