Race disparities in genetic alterations within Wilms tumor specimens

BackgroundWilms tumor (WT) affects Black children disproportionately. Genetic aberrations within WT specimens that contribute to this disparity have not been reported.MethodsThe Therapeutically Applied Research to Generate Effective Treatments (TARGET) database was queried for WT patient and genomic features. Clinical and genetic variables were compared by race.ResultsWithin the discovery set (enriched for adverse events; N = 94 White, 19 Black, 14 Other/unreported patients), Black children were more likely to present with advanced stage disease (p = 0.019). Within the validation set (primarily a random sampling of NWTS-5; N = 360 White, 92 Black, 72 Other/Unreported), Black children appeared older at diagnosis (p = 0.050), had decreased median follow-up time (p<0.0005) and were over-represented (17.4%) relative to the concurrent U.S. Census (12.8%). Among the 37 target genes sequenced, ACTB (p = 0.030) and DICER1 (p = 0.026) mutations were more common in Black patient specimens, whereas DGCR8 (p = 0.041) mutations were more common in White patient specimens. White patient specimens were more likely to contain one or multiple targeted mutations (p = 0.026).ConclusionWithin the TARGET database, Black children were over-represented and harbored WT specimens containing more frequent ACTB and DICER1 mutations. In contrast, WT from White children contained overall more mutations in targeted genes and specifically in DGCR8.Level of EvidenceIII.     

The role of bone marrow microRNA (miR) in erythropoietic dysfunction after severe trauma

BackgroundPrevious data has shown that severe traumatic injury is associated with bone marrow dysfunction, which manifests as persistent injury-associated anemia. This study sought to identify whether the expression of erythropoiesis-related microRNAs were altered in the bone marrow of trauma patients to determine if these microRNAs play a role in persistent injury-associated anemia.MethodsBone marrow was collected from severely injured trauma patients who underwent fracture fixation as well as patients who underwent elective hip replacement. There were 27 trauma patients and 10 controls analyzed. Total RNA and microRNA were isolated from CD34-positive cells using the RNeasy Plus Mini kit, and genome-wide microRNA expression patterns were assayed. Genes with significant expression differences were found using BRB-ArrayTools with a significance of P < .01.ResultsThere were marked differences in expression of 108 microRNAs in the trauma group when compared with hip replacement patients. Four of these microRNAs play a role in regulating erythropoiesis: microRNA-150, microRNA-223, microRNA15a, and microRNA-24. These microRNAs were all upregulated significantly, with trauma/hip replacement fold changes of 1.7, 1.8, 1.2, and 1.2 respectively, and all act to suppress or regulate erythropoiesis.ConclusionAssessment of the bone marrow microRNA profile in trauma patients compared to those undergoing elective hip replacement revealed the differential expression of microRNA-150, microRNA-223, microRNA-15a, and microRNA-24. These microRNAs all play a role in decreased erythroid progenitor cell growth and provide important insight to the erythropoietic dysfunction seen after trauma.     

Medical complications during acute rehabilitation following spinal cord injury--current experience of the Model Systems

OBJECTIVES: To examine the frequency of common secondary medical complications during acute rehabilitation in persons with new spinal cord injury (SCI). DESIGN: Survey and analysis of data in the National SCI Statistical Center (NSCISC) database. SETTING: Eighteen Model System SCI Centers located in urban, public medical centers around the United States. SUBJECTS: A total of 1,649 persons with new SCI entered into the NSCISC database between 1996 and mid-1998. RESULTS: Since 1992, the number of days from injury to admission to rehabilitation has steadily decreased, resulting in the increased potential to develop common secondary medical complications during rehabilitation hospitalization. Pressure ulcers occur with high frequency and were found to have developed in 23.7% of patients during rehabilitation. In addition, autonomic dysreflexia and atelectasis/pneumonia also occur with relative frequency during rehabilitation. Conversely, deep vein thrombosis and pulmonary embolism have decreased, most likely because of greater awareness of their potential to develop, as well as improved methods of prophylaxis. Cardiopulmonary arrest and gastrointestinal hemorrhage occur with relatively small frequency. The frequency of renal complications is difficult to gauge because of the decreasing number of patients who have any renal testing performed during rehabilitation hospitalization. CONCLUSION: The continued declining lengths of acute care hospitalization after SCI have resulted in the occurrence in the rehabilitation setting of medical complications that were previously seen in acute care. Greater awareness and attention to these conditions are necessary to reduce their occurrence, so that obstacles to recovery and functional improvement after SCI are minimized.     

Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.      

Basketball Injuries: An Overview

A college wrestler's weight, body brief fat, and hormone levels were measured during 2 years of competition. Marked weight loss during the initial season was associated with lower serum levels of testosterone and several other hormones, as well as a decrease in reported sexual activity. All values returned to normal after the season. The following year, with less weight loss, the wrestler had only a transient decrease in testosterone and prolactin and reported no decline in sexual activity. Body fat greater than 5% seemed essential to maintaining normal endocrine function.     

The relationship between CR3 deficiency and neutrophil actin assembly

Polymorphonuclear leukocytes (PMN) with a deficiency of the complement receptor type 3 (CR3) membrane glycoprotein family have impairments in the ability to adhere to surfaces as well as chemotactic and phagocytic defects, processes that require a functional contractile apparatus. PMN from the patient with neutrophil actin dysfunction (NAD) displayed similar functional characteristics to those with CR3 deficiency suggesting the two disorders may be the same disease. In order to evaluate the relationship between CR3 deficiency and actin assembly, actin filament assembly was measured in PMN from six previously reported homozygotes (two severe and four moderate CR3-deficient patients) as well as five heterozygotes for CR3 deficiency. PMN from all patients had normal unstimulated concentrations of F-actin and after exposure to the chemotactic peptide FMLP (5 x 10(-7) mol/L for 5 to 40 seconds at 25 degrees C) assembled actin normally. Pretreatment of normal PMN with concentrations of monoclonal anti-alpha CR3 antibody, capable of blocking PMN adherence, also failed to impair FMLP- induced actin filament assembly. CR3 glycoprotein expression was measured in PMNs from the mother, father, and older sister of the NAD patient (N Engl J Med 291:1093, 1974). Actin filament assembly was recently shown to be defective in PMNs from all three family members. The total concentrations of the alpha and beta CR3 subunits were below normal in PMN detergent extracts from the mother (25% of simultaneous controls) and older sister (56% of control). PMN surface expression of these two subunits was also found to be depressed (mother, 50%; older sister, 63% of control). These findings suggest these two NAD family members are heterozygote carriers for CR3 deficiency as well as NAD. Simultaneous studies of the father, however, demonstrated normal total concentrations of both the alpha and beta CR3 subunits (126% of controls) as well as normal surface expression of both subunits after phorbol myristate acetate stimulation and incubation at 37 degrees C (mean, 112% of controls) but slightly lower than normal levels after FMLP stimulation (mean, 83%). These findings indicate that CR3 deficiency generally is not associated with defective actin filament assembly and support the conclusion that NAD represents a unique kindred in which PMN actin function differs from previously reported genotypes of CR3 deficiency.     

Optimum blood collection intervals for B-type natriuretic peptide testing in patients with heart failure

Patients with congestive heart failure have increased concentrations of B-type natriuretic peptide (BNP) in blood. We determined the frequency of serial BNP measurements that exceeded the biologic variation of BNP of 100% as a function of days between blood collections. Samples collected 7 days apart were associated with the highest frequency (50%) of statistically different results (increased or decreased) compared with daily collections, where increased or decreased results occurred less often (22%).     

Primary low-grade B-cell lymphoma of the urinary bladder: case report and literature review

The first recorded case of lymphoma of the bladder was reported by Eve and Chaffey in 1885. Malignant lymphoma of the bladder can be classified into one of three different clinical groups: 1) Primary lymphoma localized to the bladder; 2) Lymphoma presenting in the bladder as the first sign of disseminated disease (non-localized lymphoma); 3) Recurrent bladder involvement by lymphoma in patients with a history of malignant lymphoma (secondary lymphoma). Primary extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT type) of the urinary bladder, first described by Kempton et al in 1990, is the most common primary bladder lymphoma and associated with an excellent prognosis. We present a patient with gross hematuria who was found to have a primary bladder lymphoma and review the relevant literature.