Is routine pelvic surveillance imaging necessary in patients with Wilms tumor?

BACKGROUND:

It is unclear whether routine pelvic imaging is needed in patients with Wilms tumor. Thus, the primary objective of the current study was to examine the role of routine pelvic computed tomography (CT) in a cohort of pediatric patients with Wilms tumor.

METHODS:

With institutional review board approval, the authors retrospectively identified 110 patients who had Wilms tumor diagnosed between January 1999 and December 2009 with surveillance imaging that continued through March 2011. The authors estimated overall survival (OS), event‐free survival (EFS), and dosimetry from dose length product (DLP) conversion to the effective dose (ED) for every CT in a subgroup of 80 patients who had CT studies obtained using contemporary scanners (2002‐2011). Metal‐oxide‐semiconductor field‐effect transistor (MOSFET) dosimeters were placed within organs of anthropomorphic phantoms to directly calculate the truncal ED. ED_DLP was correlated with ED_MOSFET to calculate potential pelvic dose savings.

RESULTS:

Eighty patients underwent 605 CT examinations that contained DLP information, including 352 CT scans of the chest, abdomen, and pelvis; 123 CT scans of the chest and abdomen; 102 CT scans of the chest only; 18 CT scans of the abdomen and pelvis; 9 CT scans of the abdomen only; and 1 CT that was limited to the pelvis. The respective 5‐year OS and EFS estimates were 92.8% ± 3% and 2.6% ± 4.3%. Sixteen of 110 patients (15%) developed a relapse a median of 11.3 months (range, 5.0 months to 7.3 years) after diagnosis, and 4 patients died of disease recurrence. Three patients developed pelvic relapses, all 3 of which were symptomatic. The estimated ED savings from sex‐neutral CT surveillance performed at a 120‐kilovolt peak without pelvic imaging was calculated as 30.5% for the average patient aged 1 year, 30.4% for the average patient aged 5 years, 39.4% for the average patient aged 10 years, and 44.9% for the average patient aged 15 years.

CONCLUSIONS:

Omitting pelvic CT from the routine, off‐therapy follow‐up of patients with Wilms tumor saved an average 30% to 45% of the ED without compromising disease detection. Cancer 2013. © 2012 American Cancer Society.     

A GAP-43-like protein in cat visual cortex

We have purified a protein that changes in relative concentration during the development of the kitten visual cortex. It resembles GAP-43 (a neuronal protein that is expressed at elevated levels during periods of development and regenerative axon growth) in the following respects: (1) it is an acidic protein (pI = 4.7) whose electrophoretic mobility on SDS-PAGE is similar to, but lower than rat GAP-43, suggesting that the cat protein is larger; (2) its electrophoretic mobility varies with the acrylamide concentration in a manner that is characteristic of GAP-43; (3) its concentration in kitten forebrain is elevated during early postnatal development; (4) the sequence of ten consecutive amino acids from a chemically generated fragment matches the expected sequence from GAP-43; and (5) its amino-acid content also matches GAP-43. We conclude that our purified protein is cat GAP-43. Immunoblots with an antibody prepared against rat GAP-43 suggested that the concentration of GAP-43 in the visual cortex declines with age.     

Identification and localization of adrenergic receptors in cat visual cortex

The concentration and location of adrenergic receptors in cat visual cortex have been determined by radioligand binding techniques using [3H]prazosin (alpha 1-adrenergic receptors), [3H]yohimbine (alpha 2-adrenergic receptors) and [3H]dihydroalprenolol (beta-adrenergic receptors). Saturable high affinity binding sites for all of these ligands were found. The beta-adrenergic receptor population was resolved into beta 1- and beta 2-sites that were present in the ratio 35:65. The laminar distributions of the alpha 1-, alpha 2- and beta-adrenergic receptors were different. The alpha 1- and beta-adrenergic receptors were very similarly localized, being seen in upper layers (I, II and III) and lower layers (layers V and VI). The labelling in upper layers was greater than that in lower layers, more so for alpha 1-adrenergic receptors than beta-adrenergic receptors. alpha 2-Adrenergic receptors were seen in a single band that occupied layer II and III but did extend to the pial surface. These results indicate that the effect of norepinephrine on neuronal activity in cat visual cortex will depend upon the layer in which it is released. Our results provide a basis for further physiological studies of the role of norepinephrine in the processing of visual information.     

Isolation of a gene encoding an integral membrane protein from the vicinity of a balanced translocation breakpoint associated with DiGeorge syndrome

Deletions within 22q11 have been associated with a wide varietyof birth defects embraced by the acronym CATCH22 and includingthe DiGeorge syndrome, Shprintzen syndrome (velocardiofacialsyndrome) and congenital heart disease. It is not known howmany genes contribute to this phenotype. Previous studies haveshown that a balanced translocation disrupts sequences withinthe shortest region of deletion overlap for DiGeorge syndrome.A P1 clone was isolated which spans this breakpoint and usedto isolate a cDNA encoding a transmembrane protein expressedin a wide variety of tissues. This gene (called IDD) is notdisrupted by the translocation, but maps within 10 kb of thebreakpoint. Mutation analysis of five affected cases with nopreviously identified chromosome 22 deletion was negative, buta potential protein polymorphism was discovered. No deletionsor rearrangements were detected in these patients followinganalysis with markers closely flanking the breakpoint, datawhich emphasize that large (i. e. over 1 Mb) interstitial deletionsare the rule in DiGeorge syndrome. The proximity of IDD to thebalanced translocation breakpoint and its position within theshortest region of deletion overlap indicate that this genemay have a role, along with other genes, in the CATCH22 haploinsufficiencysyndromes.     

The effect of varying stimulus intensity on NMDA-receptor activity in cat visual cortex

1. A study was made of the relative contribution of N-methyl-D-aspartate (NMDA) and non-NMDA receptors to the visual responses of cells in different layers of the cat visual cortex at different levels of excitatory drive (which was varied by altering the stimulus contrast). 2. Receptive fields were mapped for 121 cells in area 17 of cat cortex. Cells were characterized to determine the optimal visual stimulus, the brightness of which was then varied relative to background luminance to construct a contrast-response (C-R) curve for each cell. Curves were made during control conditions and during application of agonists (NMDA and quisqualate) and/or antagonists [(D)-2-amino-5-phosphonovaleric acid (D-APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)] to examine the excitatory amino acid components of the visual response. 3. Threshold responses were obtained with stimuli between 1/60 and 1.8 X background luminance. The cell response, measured by firing rate, was linearly related to stimulus contrast over 1-2 decades and saturated at higher contrasts. 4. Application of APV reduced the slope of the linear portion of the C-R curve for cells located in layers II and III (average reduction, 59% of control). APV did not decrease the threshold to stimulation. The "just suprathreshold" responses to stimulation were reduced by the same proportion as the saturation responses for individual cells. The principal effect was therefore to reduce the gain of the C-R curve in these layers. 5. Application of APV reduced the spontaneous activity of cells located in layers IV, V, and VI with little if any effect on the gain of the C-R curve. This suggests a tonic background level of NMDA-receptor activation in these layers, which is not directly related to the visual response. 6. Low levels of NMDA increased the gain of the C-R curve in layers II/III and V/VI. On the other hand, low levels of quisqualate increased the overall level of firing without affecting the gain of the C-R curve. NMDA did not increase the gain of the curve in layer IV. 7. These experiments show that visual stimuli that produce just suprathreshold responses activate NMDA receptors. The degree of activation is proportionally the same for small responses and large responses for an individual cell. Rather than finding a threshold for NMDA-receptor activation, a continuous range of NMDA-receptor influence was observed over the entire response range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ascertainment correction for Markov chain Monte Carlo segregation and linkage analysis of a quantitative trait

Although extended pedigrees are often sampled through probands with extreme levels of a quantitative trait, Markov chain Monte Carlo (MCMC) methods for segregation and linkage analysis have not been able to perform ascertainment corrections. Further, the extent to which ascertainment of pedigrees leads to biases in the estimation of segregation and linkage parameters has not been previously studied for MCMC procedures. In this paper, we studied these issues with a Bayesian MCMC approach for joint segregation and linkage analysis, as implemented in the package Loki. We first simulated pedigrees ascertained through individuals with extreme values of a quantitative trait in spirit of the sequential sampling theory of Cannings and Thompson [Cannings and Thompson [1977] Clin. Genet. 12:208-212]. Using our simulated data, we detected no bias in estimates of the trait locus location. However, in addition to allele frequencies, when the ascertainment threshold was higher than or close to the true value of the highest genotypic mean, bias was also found in the estimation of this parameter. When there were multiple trait loci, this bias destroyed the additivity of the effects of the trait loci, and caused biases in the estimation all genotypic means when a purely additive model was used for analyzing the data. To account for pedigree ascertainment with sequential sampling, we developed a Bayesian ascertainment approach and implemented Metropolis-Hastings updates in the MCMC samplers used in Loki. Ascertainment correction greatly reduced biases in parameter estimates. Our method is designed for multiple, but a fixed number of trait loci.