Late right ventricular reconstruction following valvotomy in pulmonary atresia with intact ventricular septum

Experience over two decades in the surgical management of pulmonary atresia with intact ventricular septum demonstrates that eventual right ventricular (RV) reconstruction is possible in the majority of patients surviving valvotomy in infancy. Ten of 17 operative survivors of early valvotomy have eventually received a patch graft to the RV outflow tract, with no reoperative deaths (mean follow-up, 7.4 years). RV systolic pressures, suprasystemic prior to reoperation, are near normal after outflow patch reconstruction. Serial cineangiograms show evidence of RV growth by measurement of tricuspid annulus diameter (TAD), and demonstrate a rate of growth [d(TAD)/d(body length)] greater than a normal rate derived from autopsy data. The mean TAD growth rate is significantly greater than that of patients with less favorable ventricle types treated with a systemic-pulmonary shunt alone. Measurement of TAD is a useful method for following RV growth, and may aid in selecting patients for RV reconstruction.     

Latency variability and temporal interrelationships of the auditory event-related potentials (N1, P2, N2, and P3) in normal subjects

Peak latency variation and the temporal interrelationships of the auditory event-related potential were investigated in 12 normal adults (ages 28-42). Measures of variation were based on both conventional averages and single trials. Estimates of N1, P2, N2 and P3 latencies were made on a trial-by-trial basis to target stimuli recorded from Fz, Cz and Pz scalp locations. Results showed that single-trial latency variability of the auditory ERP differed both among the various components and between subjects. Larger standard deviations were measured for the later N2 and P3 components than the earlier N1 and P2 components. Regression analyses between various component latencies indicated a strong covarying relationship between N2 and P3, with N2 accounting for up to 61% of the variance of P3 latency at Pz. Earlier N1 and P2 components added little to the overall prediction of either P3 or N2. For the other components, P2 accounted for 9-16% of the variance of N2, while N1 accounted for approximately 1% of the variance of N2; N1 accounted for 8-10% of the latency variation of P2. The correlations between single-trial peak latencies and RTs were positive but of low magnitude. The highest correlations between peak latency and RT were found for N2 (r = 0.33) and P3 (r = 0.24). The low correlations between the single-trial latencies of N1 and P3 suggest that the processes reflected by these components are independent and support a distinction between the earlier and the later components of the ERP. The close temporal coupling between N2 and P3 suggests that N2 may reflect cognitive properties in common to P3 in stimulus evaluation processes.     

Intraparenchymal fetal striatal transplants and recovery in kainic acid lesioned rats

Striatal kainic acid (KA) lesions induce behavioral and biochemical deficits which resemble symptoms encountered in patients suffering from Huntington's disease. In rats with KA lesions, fetal striatal transplants have shown to reverse the pervasive nocturnal hyperactivity induced by the lesion. In the present study 4.6 mm3 of fetal striatal tissue were delivered bilaterally into the anterodorsal portion of the lesioned caudate nucleus. Care was taken to deliver the transplant within the host parenchyma and away from the lateral ventricles. Locomotor behavior analyzed using the Digiscan animal activity monitors before and after the transplants demonstrated a reversal of the hyperactivity following transplants in 70% of lesioned animals. Microinjections of horseradish peroxidase delivered into the globus pallidus and substantia nigra of a small group of functionally recovered transplanted animals, did not reveal evidence for reinnervation between host nigra or pallidum and the transplant at 10 weeks post-transplantation. Other laboratories have reported anatomical connections by 6 months post-transplantation. Ventricular/brain ratios demonstrated that intraparenchymal transplants significantly reduced the ventricular dilation following KA lesion. These results suggest that functional recovery can be obtained when the transplant is immersed into the host's striatal parenchyma regardless of the existence of long-range anatomical connections.     

Recommended relative potency factors for 2,3,4,7,8-pentachlorodibenzofuran: the impact of different dose metrics.

The recent National Toxicology Program (NTP) cancer bioassays for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF) permit a reevaluation of the current TEF value of 4-PeCDF. The data also allow for the derivation of relative potency factors (RPFs) for cancer, which are based not only on administered dose but also on potentially more informative dose metrics, such as liver concentration, area under the liver concentration curve, and lifetime average body burden. Our analyses of these data indicate that chi-squared tests of observed versus predicted liver tumor incidence for 4-PeCDF reject the current TEF value of 0.5 value as too high. 4-PeCDF RPFs were derived using estimation methods that either did or did not assume parallelism of the 4-PeCDF and TCDD dose-response curves. The resulting parallelism-based RPFs for administered dose, liver concentration at terminal sacrifice, liver concentration AUC, and lifetime average body burden are 0.26, 0.014, 0.021, and 0.036, respectively. The administered dose RPF estimate is approximately one-half the current TEF value of 0.5. However, the use of administered dose fails to take into account pharmacokinetic differences between congeners and the generally acknowledged belief that body burden or some other measure of cumulative dose is more appropriate for estimating the health risk posed by persistent chemicals. The other three dose metrics do account for these important factors, and the corresponding RPFs are at least 10-fold lower than the current TEF for 4-PeCDF. In summary, our analyses support an administered dose TEF no greater than 0.25 and one in the 0.05-0.1 range for internal dose metrics such as lifetime average liver concentration or body burden.