Objective: To derive a model describing carbamazepine (CBZ) clearance in children, in terms of individual patient characteristics.
Methods: One hundred and eighteen steady-state serum carbamazepine concentration measurements were gathered during normal routine
care of 72 compliant out-patients (2.3–16.3 years old). Levels were obtained from patients receiving monotherapy (55%), concomitant
valproate (26%), or concomitant inducers (phenytoin, phenobarbitone; 19%). A one-compartment model was used to fit the data
with the computer programme Nonlinear Mixed Effects Model (NONMEM).
Results: Weight, age and concomitant medication were all important determinants of clearance. The final model for clearance (l · h−1) was: CL = [0.7(WT)0.4] · M, where WT is patient weight (kg) and M is a scaling factor for concomitant medication, with a value of 1 for patients
on CBZ monotherapy or concomitant valproate and 1.4 for those receiving concomitant inducers. For the purposes of this analysis,
bioavailability (f) was assumed to be complete, i.e., f is thus included in the term CL.
Conclusions: CBZ clearance decreased with increasing age. As age and weight were correlated, either variable was a satisfactory predictor.
The influence of both the inducers and valproate on CBZ clearance was as expected. This model, which describes clearance in
terms of patient-specific details, can be used when predicting the maintenance dose required to achieve a target mean steady-state
CBZ concentration in children.
Received: 10 May 1997 / Accepted: 16 February 1998 相似文献
A new and easily accessible concordance of nucleotide substitutions in the hypervariable segments of the human mitochondrial DNA (mtDNA) control region has been constructed. The concordance indexes all population-specific mtDNA sequences in a standardized format. The first edition of the concordance includes 1,440 sequences representing 762 mtDNA types from over 65 populations for hypervariable region 1, and 520 sequences representing 260 mtDNA types from over 26 populations for hypervariable region 2. Investigators are invited to submit new sequences to the database, and details for doing so are given in the text. 相似文献
An association between mitochondrial DNA (mtDNA) mutations 11778G>A and 14484T>C and mtDNA haplogroup J suggests that this
haplogroup harbors substitutions capable of modifying the phenotype of Leber's disease. Our knowledge of the compilation of
substitutions in haplogroup J is based on only a small number of complete mtDNA sequences, however. We constructed phylogenetic
networks for mtDNA haplogroup TJ that were based on the sequence of the complete coding region and the hypervariable segment
I, respectively, in 28 Finnish samples. The networks revealed a subdivision of the haplogroup into subclusters T1, T2, J1,
and J2, while comparison of the two networks suggested nine fast evolving nucleotide sites in the hypervariable segment I.
Genotypes of patients harboring 11778G>A or 14484T>C were obtained from the literature and were then placed in the network.
Only four substitutions were found to be common to the patients, but none of these was unique to haplogroup J. If increased
penetrance of the 11778G>A and 14484T>C mutations in patients belonging to haplogroup J is assumed, combinations of ancient
substitutions must be implicated.
Received: September 29, 2000 / Accepted: November 10, 2000 相似文献
A questionnaire on climacteric symptoms was sent to every woman living in the city of Linköping, Sweden (120,000 inhabitants) who was born in 1928 or 1930. Of the 1246 women concerned, 1118 (90%) responded. At the time of the survey, 252 women (23%) were pre-menopausal. In the total sample, 10B had undergone hysterectomy and/or bilateral oophorectomy. The median age at natural menopause was 51 yr.
Climacteric symptoms were reported by 75% of the women, the predominating complaints being sweating attacks and hot flushes. Vaginal dryness and tenderness were experienced by 30% of the post-menopausal women, the discomfort tending to become more common as the duration of the post-menopausal period lengthened.
After the menopause, every third woman experienced periods of depression more often than previously. Depression was positively correlated to the severity of the vasomotor symptoms.
Fifty percent of the women expressed interest in receiving oestrogen treatment, although only 7% were using oestrogens at the time of the survey. This discrepancy is probably due to widespread apprehension in Swedish society - shared by the doctors - in regard to ‘hormonal treatment’. 相似文献
We tested the hypothesis that sequential movements are represented in the correlated activity of motor cortical neurons. We
simultaneously recorded multiple single neurons in the motor cortex while monkeys performed a two-segment movement sequence.
Before any movement began the correlated spike firing between pairs of neurons differed when these sequences were planned
as whole (planned) as compared to when they were planned one segment at a time (unplanned) even when the firing rates of these
neurons did not distinguish between the two conditions. Moreover, the correlation strength was significantly larger when the
directional preferences of the neurons matched the direction of the final segment of the sequence. Our results suggest that
spatially distributed groups of MI neurons form dynamic correlation structures that distinguish different forms of sequential
action.
Electronic Publication 相似文献
The identification of the insulin minimal model (MM) for the estimation of insulin secretion rate (ISR) and physiological indexes (e.g. beta-cell sensitivity) requires the knowledge of C-peptide (CP) kinetics. The four parameters of the two-compartment model of CP kinetics in a given individual can be derived either from an additional bolus experiment or, more frequently, from a population model. However, in both situations, the CP kinetics is uncertain and, in MM identification, it should be treated as such. This paper shows how to handle CP kinetics uncertainty by using a Bayesian methodology. In seven subjects, MM indexes and ISR were estimated together with their confidence intervals, using either the bolus data or the population model to assess CP kinetics. The two main results that arise from the application of the new methodology are: (i) the use of the population model in place of the bolus data to determine CP kinetics does not affect, on average, the point estimates of ISR profile and MM parameters but only the confidence intervals which becomes wider (less than 50%); (ii) in both the bolus and population situation neglecting the uncertainty of CP kinetics, as done in MM literature so far, introduces no bias, on average, on point estimates of MM indexes but only an underestimation of confidence intervals. 相似文献
Human Y-chromosomal binary polymorphisms have been considered to preserve the paternal genetic legacy and provide evidence
on human evolution and the genetic relationships among and demographic history of different populations. To reveal the genetic
origin and immigration of the Fujian Han, 13 binary markers on the Y chromosome were used to screen Fujian Han by allele-specific
polymerase chain reaction. The results indicated that the M9G marker was highly prevalent (96.20%), suggesting a significant genetic drift. In addition, M122C frequency was only 22.78%, and M45A and M103T were default. The distinctive haplogroup frequencies (H1, H5, and H6/7/8) imply that the haplogroup pattern is a relatively ancestral and interim type.
Received: October 13, 2001 / Accepted: December 3, 2001 相似文献