Despite the marked improvement in the overall survival (OS) for patients diagnosed with Wilms' tumor (WT), the outcomes for those who experience relapse have remained disappointing. We describe the ...outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and were reported to the Center for International Blood and Marrow Transplantation Research. The 5-year estimates for event-free survival (EFS) and OS were 36% (95% confidence interval (CI); 29-43%) and 45% (95 CI; 38-51%), respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. As attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus HDT followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. As disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy.
Plasmodium falciparum is a protozoan parasite responsible for the most severe forms of human malaria. All the clinical symptoms and pathological changes seen during human infection are caused by the ...asexual blood stages of Plasmodium. Within host red blood cells, the parasite undergoes enormous developmental changes during its maturation. In order to analyse the expression of genes during intraerythrocytic development, DNA microarrays were constructed and probed with stage‐specific cDNA. Developmental upregulation of specific mRNAs was found to cluster into functional groups and revealed a co‐ordinated programme of gene expression. Those involved in protein synthesis (ribosomal proteins, translation factors) peaked early in development, followed by those involved in metabolism, most dramatically glycolysis genes. Adhesion/invasion genes were turned on later in the maturation process. At the end of intraerythrocytic development (late schizogony), there was a general shut‐off of gene expression, although a small set of genes, including a number of protein kinases, were turned on at this stage. Nearly all genes showed some regulation over the course of development. A handful of genes remained constant and should be useful for normalizing mRNA levels between stages. These data will facilitate functional analysis of the P. falciparum genome and will help to identify genes with a critical role in parasite progression and multiplication in the human host.
Students referred by general education teachers to school study teams (SSTs) were evaluated for learning disabilities (LD) eligibility. We classified children as LD on the basis of a WISC-III Full ...Scale IQ of 82 or higher and a 22-point discrepancy between IQ and any WRAT-R achievement score. Research decisions were then contrasted with actual school-based decisions regarding the child as LD. Over half of the students referred to SSTs were certified by the schools as LD, yet less than half of these school-certified students with LD evidenced the aptitude-achievement discrepancy required by the state. Examination of the cases called LD by the schools revealed that children were classified as LD on the basis of low absolute achievement, regardless of whether or not a discrepancy existed. Moreover, in cases where a discrepancy was found but the school did not classify the child as LD, that child evidenced significantly higher achievement, despite exhibiting the requisite 22-point discrepancy. The school-identified students with LD constituted an extremely heterogeneous group, including students with mental retardation along with a substantial number who failed to qualify for any special education services. Findings are discussed in terms of the discrepancy between criteria specified in state regulations and what the committee members at the school site seemed to use in classifying children with LD.
Nonmelanotic skin cancer, primarily basal and squamous cell carcinoma, represents a major health concern in both the United States and the world. Primary care physicians must be able to recognize ...these cancers and perform the appropriate diagnostic tests to confirm their clinical suspicion. Several biopsy techniques are available for the physician to use in their office, and once diagnosis is confirmed, a variety of treatment modalities exist that provide excellent cure rates. Nevertheless, primary prevention with the use of sunscreen, protective clothing, and wide-brimmed hats is necessary to reduce the incidence of this costly disease.
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