Magnetoencephalography for clinical pediatrics: The effect of head positioning on measurement of somatosensory-evoked fields

OBJECTIVE: At present, whole-head MEG systems are designed to accommodate adult heads, thereby introducing a technical issue unique to pediatric MEG. It is known that magnetic field strength decreases as a function of 1/distance(2). For pediatric patients, we questioned whether re-positioning the head to minimize the distance between the expected source location and the MEG sensor array would significantly improve source measurement. METHODS: Somatosensory-evoked fields (SEFs) were recorded in 17 children (mean=4.96 years) with their head placed centrally in the MEG, and then re-positioned laterally to reduce the distance between the cortical source and sensors. Equivalent current dipole (ECD) source models were evaluated for changes in residual variance (RV), signal-to-noise ratio (SNR), moment (strength), and location. RESULTS: Re-positioning the head closer to the sensors resulted in a significant shift in the mediolateral dipole coordinate location, accompanied by a significant increase in the SNR, decrease in the dipole RV, and a reduction in size of ECD confidence volumes. CONCLUSIONS: We conclude that for clinical pediatric measurement of the SEF, repositioning of the head to minimize the distance between the expected SEF source location and the sensor array will significantly improve SEF source measurement and concomitant ECD source modeling. SIGNIFICANCE: These issues are relevant to all pediatric MEG settings involving healthy or clinical populations and underscores the need for future development of a MEG helmet specifically designed for pediatric populations.     

Somatosensory-evoked fields on magnetoencephalography for epilepsy infants younger than 4 years with total intravenous anesthesia.

OBJECTIVE: Patients must remain immobile for magnetoencephalography (MEG) and MRI recordings to allow precise localization of brain function for pre-surgical functional mapping. In young children with epilepsy, this is accomplished with recordings during sleep or with anesthesia. This paper demonstrates that MEG can detect, characterize and localize somatosensory-evoked fields (SEF) in infants younger than 4 years of age with or without total intravenous anesthesia (TIVA). METHODS: We investigated the latency, amplitude, residual error (RE) and location of the N20m of the SEF in 26 infants (mean age=2.6 years). Seventeen patients underwent TIVA and 9 patients were tested while asleep, without TIVA. RESULTS: MEG detected 44 reliable SEFs (77%) in 52 median nerve stimulations. We found 27 reliable SEFs (79%) with TIVA and 13 reliable SEFs (72%) without TIVA. TIVA effects included longer latencies (p<0.001) and lower RE (p<0.05) compared to those without TIVA. Older patients and larger head circumferences also showed significantly shorter latencies (p<0.01). CONCLUSIONS: TIVA resulted in reliable SEFs with lower RE and longer latencies. SIGNIFICANCE: MEG can detect reliable SEFs in infants younger than 4 years old. When infants require TIVA for MEG and MRI acquisition, SEFs can still be reliably observed.     

Genetic polymorphisms and functional characterization of the 5'-flanking region of the human CYP2C9 gene: in vitro and in vivo studies

OBJECTIVE: Genetic polymorphisms were identified in the 5'-flanking region of the human CYP2C9 gene, and their effects on the phenotype were evaluated on the basis of the luciferase reporter gene assay and the in vivo pharmacokinetics of phenytoin. METHODS: Genetic polymorphisms were screened by polymerase chain reaction-single-strand conformational polymorphism analysis, following sequencing with DNA samples obtained from 50 healthy volunteers and 133 adult epileptic patients. HepG2 hepatoma cells were cotransfected with various sequence patterns of 5'-flanking region-luciferase reporter gene constructs. Pharmacokinetic parameters of phenytoin in relation to the corresponding sequence patterns were estimated by the Bayesian method, and the results were compared with in vitro activities. RESULTS: Genetic analysis revealed the existence of 7 single nucleotide polymorphisms (SNPs). Allele frequencies of T-->C transition at position -1912 (T-1912C), C-1886G, C-1566T, G-1538A, C-1189T, G-982A, and A-162G were 0.019, 0.019, 0.077, 0.019, 0.579, 0.019, and 0.003, respectively. Some mutations occurred simultaneously, and a total of 6 sequence patterns (patterns 1-6) were observed. The luciferase reporter gene assay indicated that the presence of mutation(s) resulted in a reduction in luciferase activity of 41.4% (pattern 2) to 86.8% (pattern 5) compared with the activity of the wild-type construct. The calculated intrinsic clearance of phenytoin was also lower (up to a 40% reduction for pattern 2) when a mutation(s) was present. CONCLUSION: In addition to the two major mutations in the coding region (CYP2C9*2 and CYP2C9*3 ), mutations in the 5'-flanking region of the human CYP2C9 gene appear to contribute to the large interindividual variability in drug metabolism activity.     

Evaluation of laser Doppler flowmetry in renal transplantation

Renal grafts are presently evaluated based on the surgeon's observation of the organ microcirculation. Effectiveness of organ microcirculation has traditionally been accomplished through evaluation of the appearance of the graft. Laser doppler flowmetry (LDF) has been suggested as a possible means to determine graft effectiveness. Renal grafts in 46 transplants were studied using LDF and the technique was evaluated. It was found to be a useful technique for monitoring effectiveness of grafts.     

Plasma 5'-nucleotidase activities increase in women with hyperemesis gravidarum

OBJECTIVES: To investigate plasma activities of 5'-nucleotidase, a key enzyme in the production of adenosine and evaluate the relationship between changes in 5'-nucleotidase activities and pregnancy-related hormones, estrogen, progesterone and human chorionic gonadotropin (hCG) in women with hyperemesis gravidarum. DESIGN AND METHODS: Plasma 5'-nucleotidase activities and estradiol, progesterone and hCG levels were measured in 21 women with hyperemesis gravidarum and normal pregnancies, matched for age, parity and gestational week. RESULTS: In women with hyperemesis gravidarum, plasma 5'-nucleotidase activities averaged 8.1 +/- 0.6 IU/L, which were significantly increased compared to those in normal pregnant women (5.5 +/- 0.5 IU/L)(p < 0.05). The increases in plasma 5'-nucleotidase activities were accompanied by elevations of plasma estradiol, progesterone and hCG levels. CONCLUSIONS: The increase of plasma 5'-nucleotidase activities may be at least partly attributed to elevations of pregnancy-related hormones, suggesting changes in purine metabolism in women with hyperemesis gravidarum.     

Expression of P-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene

To evaluate whether mutations in the human multidrug resistance (MDR)-1 gene correlate with placental P-glycoprotein (PGP) expression, we sequenced the MDR-1 cDNA and measured PGP expression by Western blotting in 100 placentas obtained from Japanese women. Nine single nucleotide polymorphisms (SNPs) were observed with an allelic frequency of 0.005 to 0.420. Of these SNPs, G2677A (allelic frequency = 0.18) and G2677T (0.39) in exon 21 were associated with an amino acid conversion from Ala to Thr and to Ser, respectively. Sixty-one of 65 samples (93.8%), which had a C3435T allele, also had a mutant G2677(A,T) allele, suggesting an association between the two SNPs. Correlations of mutations with expression levels were observed; individuals having the G2677(A,T) and/or T-129C (p < 0.05) allele had less placental PGP. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based genotyping tests were developed for the detection of these SNPs. The PCR, in which genomic DNAs obtained from healthy subjects (n = 48) are used as samples, was successful. The frequency of mutations in placental cDNA was identical with that in genomic DNA. When genotype results were compared between Caucasians and Japanese, ethnic differences in the frequency of polymorphism in the MDR-1 gene were suspected. Although it remains to be determined whether these SNPs influence the pharmacokinetic and dynamic properties of clinically useful drugs that are substrates of PGP, the polymorphism of the MDR-1 gene presented here may provide useful information in in vivo study of these issues.