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Biomedical subjects

O J David

Publications and source records attributed to O J David.

At least 19 recordsLinked to original sources
PubMed2003

Limited sampling strategies using Bayesian estimation or multilinear regression for cyclosporin AUC(0-12) monitoring in cardiac transplant recipients over the first year post-transplantation.

OBJECTIVE: The aim of this study was to develop routinely applicable limited sampling strategies for assessing cyclosporin (CsA) AUC(0-12 h), and possibly other exposure indices such as AUC(0-4 h) and C(max), in heart transplant patients over the first year post-transplantation. METHODS: First, the individual pharmacokinetics (PKs) of 14 adult heart-transplant patients receiving Neoral were assessed at three post-transplantation periods, at the end of the first week (W1), the third month (M3) and the first year (Y1). To fit blood concentrations, a PK model specially developed for oral CsA was applied. Second, two statistical methods were compared for AUC(0-12 h) estimation using a limited sampling strategy (maximum of three blood samples): multiple regression analysis (MR) and Bayesian estimation (BE). RESULTS: No significant difference was observed between the individual PK parameters at M3 and Y1, so population modelling was performed taking as a whole the concentration data collected at M3 and Y1. On the contrary, a significant difference ( P<0.05) was found for the C2/dose ratio between W1 and M3 and between W1 and Y1 (mean+/-SD =5.47+/-2.33; 7.78+/-1.05; 6.98+/-2.17 ml(-1 )for W1, M3 and Y1, respectively). Also, C(max)/dose and A were found significantly lower at W1 than at M3 ( P<0.01 and P<0.005, respectively), while lambda(1) was significantly higher at W1 than at both M3 and Y1 ( P<0.01). Using three sampling times (t0 h, t1 h and t3 h), BE allowed an accurate prediction of AUC(0-12 h) (mean bias =3.06+/-12.16%; +1.50+/-1.61%; and -0.20+/-11.42% at W1, M3 and Y1, respectively), AUC(0-4 h )and C(max). MR led to satisfactory estimation of AUC(0-12 h) using only two blood samples collected 2 h and 6 h post-dose (R=0.956-0.993; bias =-5.22 to +4.41; precision =6.38 to 9.90%), but this method is unable to estimate any other exposure index and requires strict respect of sampling times, contrary to BE. CONCLUSION: Neoral monitoring based on full or abbreviated AUC is possible using BE or MR in heart transplant patients over the first year post-transplantation. BE provides a good description of the individual PK profiles and thus might be useful not only in case of potential discrepancies between C2 and clinical findings, but also for clinical trials aimed at finding optimum PK monitoring in heart recipients.

Area Under Curve↗
PubMed2001

Limited sampling strategies for estimating cyclosporin area under the concentration-time curve: review of current algorithms.

Cyclosporin, the drug of first choice in transplantation surgery, is characterized by a low therapeutic index and variable absorption, so close monitoring of the drug is required to optimize the dosing. Predose blood cyclosporin levels are measured routinely for therapeutic monitoring, but this approach is not optimal because the area under the concentration-time curve (AUC) correlates better with clinical events. However, conventional methods of measuring AUC require many blood samples, which is not viable in a routine clinical setting. AUC monitoring can be simplified for use in a clinical setting by using a limited sampling strategy (LSS) that allows AUC to be estimated using a small number of blood samples collected at specific times. This article reviews the current literature on estimating cyclosporin AUC using LSS. Thirty-eight papers suggesting the use of specific time points were found. LSS has been developed for different transplant types, with different dosing regimens, and with different assays. Most authors suggested either two- or three-sample equations. Results from authors who validated their models suggest that equations defined on one transplant type may be applicable to other transplant types, to both adults and children, and to early or late after transplantation. Moreover, it seems that there is flexibility in the choice of equations available to clinicians. The number of samples to collect for accurate estimations is a matter of debate, but a wise choice can minimize the number. The choice of the optimal LSS and validation are discussed.

Algorithms↗
PubMed1989

Communication disturbances and hyperactive/conduct-disturbed behavior.

This study examines mother-child communication as one factor in the development of conduct-disturbed/hyperactive boys. Three groups of school-age children were compared: a group including conduct-disturbed/hyperactive boys who had a significant insult in their perinatal/developmental history; a group of conduct-disturbed/hyperactive boys in whom no insult could be found; and a group of normally active/non-conduct-disturbed/hyperactive boys. It was hypothesized that disturbed communication between mother and son would be found in boys who were conduct-disturbed/hyperactive, whether or not there was a probable organic cause for their dysfunction, and this hypothesis was confirmed. In addition, it was found that the communication patterns in children who had a probable organic etiology for their disturbance were different from those found in the group lacking an organic etiology. However, both of these groups exhibited communication patterns that were more disturbed than the communication from mother to son in the normally active, non-conduct-disturbed group.

Attention Deficit Disorder with Hyperactivity↗
PubMed1983

Predicting psychiatric admission from an emergency room. Psychiatric, psychosocial, and methodological factors.

The determinants of psychiatric hospitalization, especially nonspecific issues, have been studied extensively. The methodological problem of correlational non-cross-validated findings are seen as contributing to our uncertainties about the critical issues involved in the decision to admit. A cross-validated multiple regression analysis of determinants of hospitalization in an inner-city municipal hospital revealed two determinants of hospitalization: severity of schizophrenic symptoms and active suicidal and/or homicidal ideation. They accounted for one third of the variance without shrinkage. Quasi-experimental designs may be the most efficient means of studying the remaining unexplained variance.

Commitment of Persons with Psychiatric Disorders↗
PubMed1982

Mental retardation and "nontoxic" lead levels.

The authors studied the blood lead concentrations of children with IQs of 55-84, divided according to the presence (N = 48) or absence (N = 35) of a probable etiology for their retardation, and of 40 control children. The mean lead level of the retarded children with unknown etiologies was 25.03 micrograms/dl, which was significantly higher than those of the other two groups; 54% of the group with unknown etiologies had levels above 25 micrograms/dl, compared with 15% of the retarded children with probable etiologies and 17% of the control children. In the group of retarded children with unknown etiologies there was a significant negative correlation between lead levels and IQ.

Child↗
PubMed1977

Lead and hyperactivity: lead levels among hyperactive children.

Previous work has demonstrated an association between hyperactivity and increased body lead burdens in school-age children. In the present study it is shown that within a group of hyperactive children those for whom an organic etiology is present have lead burdens lower than in those for whom no apparent cause could be found. These data lead us to reject the notion that hyperactivity per se is responsible for the acquisition of elevated lead levels, and further strengthen the suspicion that for some children lower lead level absorption may be implicated in the development of the hyperkinetic disorder.

Central Nervous System Diseases↗
PubMed1976

Lead and hyperactivity. Behavioral response to chelation: a pilot study.

Lead-chelating medication was used to treat 13 hyperkinetic school children whose blood and urine lead levels were in an elevated but "nontoxic" range. Six children with histories of etiologically relevant perinatal or developmental complications showed relatively little improvement. Seven other children with unremarkable histories, and for whom a lead etiology could thus be entertained, showed marked improvement. The authors conclude that lead may play an important role in the etiology of some cases of hyperactivity; lead-chelating agents may have a major place in the treatment of hyperactivity; and the medical workup of hyperactivity should include lead level measurements and careful consideration of other possible etiological factors.

Child↗
PubMed1974

Association between lower level lead concentrations and hyperactivity in children.

Hyperactive children were compared with a nonhyperactive control group on two measures that reflect the presence of body lead and on a lead exposure questionnaire. The overall hypothesis that was tested was that a relationship exists between hyperactivity in children and a concommitant condition of increased body lead stores. Operationally, the hypothesis was reduced to a comparison of the hyperactive group and control group on the following measures: (1) blood lead levels; (2) post-penicillamine urine lead levels; (3) scores on a lead exposure questionnaire. The designation hyperactive or nonhyperactive was arrived at by using three different measurements: a doctor's diagnosis; a teacher's rating scale; a parent questionnaire. Hyperactive children had significantly higher values on all three measures than did the controls. More than half the hyperactive children had blood lead levels in the range considered to be raised but not toxic, and 60% of post-penicillamine urine levels were in the "toxic" range. It is concluded that there is an association between hyperactivity and raised lead levels, that a large body-lead burden may exact consequencies that have hitherto been unrealized; that the definition of what is a toxic level for blood lead needs reevaluation and that physicians should look for raised lead levels in children with hyperactivity.

Attention↗
PubMedDate not supplied

Childhood lead poisoning: a re-evaluation.

Long recognized as an environmental toxin of fearsome lethality, lead effects are commonly described as extremely serious, particularly as regards the central nervous system. It is postulated here that this represents only part of the pathologic spectrum. Ohter lead-related conditions, as yet unrecognized, may include a wide range of central nervous system dysfunctions that although severe, are not so acutely dramatic or widely destructive as the classic encephalopathic or preencephalopathic states. These conditions remain etiologically unrecognized primarily because of (1) the variable nature of onset, (2) the variable nature of the manifestations, (3) the relative subtlety of the dysfunctions, and most importantly, (4) the absence of consistant, unequivocal evidence demonstrating the relationship of lower blood lead levels with pathologic effects. This last is seen as pivotal, and an extensive examination of the reasons for its absence is presented. It is postulated that biological variability, a concept widely used in medicine but rarely invoked in the researching of lead toxicity, is a crucial ingredient in lead research. It is further asserted that the grevious lack of etiologic recognition will continue until that factor is incorporated into research designs.

Central Nervous System Diseases↗
PubMedDate not supplied

Blood lead stability.

Blood lead levels, the single most useful and authoritative index of lead toxicity, has heretofore been faulted for the following weaknesses: (1) it is too responsive to evanescent environmental changes, thereby putting its stability into question; (2) it does not provide sufficient insight into a total body burden; and (3) it may be normal at a time when toxicity is still occurring or has occurred recently. Each "weakness" is addressed herein, and hopefully, put into a useful perspective, i.e., at a clinical research and treatment level, none of the above is severe enough, if extant at all, to outweigh its manifold usefulness.

Analysis of Variance↗
PubMedDate not supplied

The relationship of hyperactivity to moderately elevated lead levels.

Controversy exists with respect to whether moderately elevated lead levels are toxic in certain children with various central nervous system dysfunctions. One way of addressing this controversy is to remove the lead; if the condition is ameliorated a presumption of toxicity becomes reasonable. Such a strategy is reported herein. Children with an operationally defined central nervous system dysfunction (hyperactivity) and moderately elevated lead levels were treated with a lead chelating agent in a random allocation double blind treatment regimen. The finding of statistically significant and obvious behavioral improvement reported by three separate evaluators (i.e., parent, teacher, and treating physician) of the child suggests that the presumption of a toxic relationship between moderately elevated lead levels and hyperactivity is supported.

Analysis of Variance↗