John J. Hutter

Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer.

Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 +/- 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg/m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10 micrograms/kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 micrograms/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 +/- 1.9 mm versus 13.1 +/- 1.5 mm for control subjects (p less than 0.01). End-systolic left ventricular posterior wall dimension at the 5-micrograms/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 +/- 2.4 mm versus 19.3 +/- 2.6 mm for control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Math Weaknesses in Survivors of Acute Lymphoblastic Leukemia Compared to Healthy Children

Difficulties in math are the most frequently reported area of academic deficit in survivors of acute lymphoblastic leukemia (ALL) and the most frequent academic complaint among parents of ALL survivors. However, previous studies that included measures of math skills have been limited by the use of only a single measure of math skills, most often a measure of written calculations, without any assessment of math reasoning or math application skills. Further, the nature of these math difficulties has not been adequately investigated. The purpose of this study was to examine the performance of ALL survivors using multiple measures of math skills. Performance was compared to a group of healthy controls matched for age and sex as well as to normative levels. Other measures of neuropsychological function were also administered, and the relationships between these measures and the math measures were explored. Converging evidence for math difficulties in ALL survivors compared to healthy controls and normative levels was found. While ALL survivors generally performed within the average range on measures of math skills, math performance was mostly related to memory function and dominant-hand psychomotor speed. By contrast, math performance of healthy children was mostly related to basic reading skills and visual-motor integration. These findings shed light on the nature of math difficulties in ALL survivors and have implications for intervention.

Behavioral Adjustment of Children and Adolescents With Cancer: Teacher, Parent, and Self-Report

PURPOSE/OBJECTIVES To describe behavioral adjustment in children and adolescents with acute lymphoblastic leukemia (ALL) and to determine whether behavioral adjustment is correlated with cognitive and academic abilities. DESIGN Descriptive, cross-sectional design. SETTING Two pediatric oncology treatment centers. SAMPLE 47 children and adolescents who had been receiving ALL therapy for at least one year or who were off therapy for no more than three years and their parents and teachers. Wechsler Intelligence Scale for Children-Revised (WISC-R) and Wide Range Achievement Test-Revised (WRAT-R) data were available on a subset of 17 subjects. METHODS Parent, teacher, and self-report Behavioral Assessment System for Children (BASC) ratings were used to measure behavioral adjustment. WISC-R measured cognitive abilities, and WRAT-R measured academic abilities. Demographic, family, and treatment-related data also were collected. MAIN RESEARCH VARIABLES Behavioral adjustment and cognitive and academic abilities. FINDINGS At least 20% of teacher ratings for somatization, learning problems, leadership, and study skills; parent ratings for somatization, adaptability, attention problems, withdrawal, anxiety, social skills, and depression; and self-report ratings for anxiety and attitude to school were in the at-risk range (i.e., presence of significant problems that require treatment). The majority of teacher BASC ratings were correlated significantly with WISC-R and WRAT-R scores. Self-report depression and social stress ratings were correlated significantly with some WISC-R and WRAT-R scores. Treatment-related experiences such as body image alterations and mental and emotional problems were associated with problematic behaviors, including depression, somatization, withdrawal, and social stress. CONCLUSIONS Youth with ALL are at risk for some behavioral adjustment problems, particularly anxiety, somatization, adaptability, attention, and withdrawal. Cognitive and academic abilities are associated with some dimensions of behavioral adjustment. IMPLICATIONS FOR NURSING Findings suggest the need for ongoing assessment of behavioral adjustment and cognitive and academic abilities of children with ALL. Behavioral interventions that target at-risk mannerisms, such as somatization, depression, anxiety, and social stress, are needed. Central nervous system treatment may contribute to behavioral adjustment problems, as well as to cognitive and academic problems. Strategies to improve academic abilities also may have a positive effect on behavioral adjustment.

OXIDATIVE CHANGES IN CEREBRAL SPINAL FLUID PHOSPHATIDYLCHOLINE DURING TREATMENT FOR ACUTE LYMPHOBLASTIC LEUKEMIA

Central nervous system (CNS) treatment contributes to improved long-term disease-free survival from childhood acute lymphoblastic leukemia (ALL) by sigificantly decreasing the rate of disease relapse. Methotrexate (MTX), a drug commonly used for CNS treatment, has been associated with cognitive and academic problems, white-matter changes, perfusion defects, and brain atrophy. This study investigated oxidative stress as a possible mechanism of chemotherapyinduced CNS injury. Unoxidized and oxidized components of phosphatidylcholine (PC), the most prevalent phospholipid in CNS cellular membranes, were measured in cerebral spinal fluid (CSF) samples obtained from 21 children diagnosed with low (n = 7), standard (n= 7), or high (n= 7) risk ALL. Children with high-risk ALL received the most MTX, especially during the most intensive phase of treatment (consolidation). Phospholipids were extracted from CSF samples obtained at diagnosis and during the induction, consolidation, and continuation treatment phases. Unoxidized and oxidized PC were measured by normalphase high-performance liquid chromatography at 2 ultraviolet wavelengths (206 and 234 nm, respectively). Data were analyzed by 2-way repeated-measures analysis of variance. Results support the hypotheses that the highest levels of oxidized PC would be observed during the most intensive phase of ALL therapy and in the high-risk ALL group. Findings provide preliminary evidence for chemotherapy-induced oxidative stress inCNSmembrane phospholipids.

Familial neurofibromatosis and juvenile chronic myelogenous leukemia

SummaryTwo male children with familial neurofibromatosis were observed to develop juvenile chronic myelogenous leukemia. These two cases add to previous reports which have described an increased incidence of non-lymphocytic leukemia in patients with neurofibromatosis. In particular, the rare entity juvenile chronic myelogenous leukemia would appear to be the form of non-lymphocytic leukemia that has a definite association with familial neurofibromatosis.

Hematologic Abnormalities in Severe Neonatal Necrotizing Enterocolitis: 25 Years Later

Necrotizing enterocolitis (NEC), the most common surgical emergency in newborns, remains a therapeutic challenge for clinicians. The hematological manifestations associated with NEC were first described 25 years ago. This review discusses current knowledge of the pathophysiology involved in disturbances in megakaryocytopoiesis, coagulation, leukopoiesis, and erythropoiesis that accompany the clinical entity NEC. The discussion includes current understanding of and potential strategies for treating the hematopoietic disturbances that occur secondary to NEC.

Prevalence of conditions associated with human immunodeficiency and hepatits virus infections among persons with haemophilia, 2001-2003

Summary.  Before the mid‐1980s, haemophilia often was unknowingly treated with contaminated plasma products, resulting in high rates of human immunodeficiency virus (HIV‐1), hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. To estimate the impact of these infections, a new cohort was established. All HCV‐seropositive patients, age 13–88 years, at 52 comprehensive haemophilia treatment centres were eligible. Cross‐sectional data collected during April 2001 to January 2004 (median June 2002) were analysed. Plasma HIV‐1 and HCV RNA were quantified by polymerase chain reaction. Highly active antiretroviral therapy (HAART) was defined as use of at least three recommended medications. Among 2069 participants, 620 (30%) had HIV‐1. Of 1955 with known HBV status, 814 (42%) had resolved HBV and 90 (4.6%) were HBV carriers. Although 80% of the HIV‐1‐positive participants had ≥200 CD4+ cells μL−1, only 59% were on HAART. HIV‐1 RNA was undetectable in 23% of those not taking antiretroviral medications. Most (72%) participants had received no anti‐HCV therapy. HCV RNA was detected less frequently (59%) among participants treated with standard interferon plus ribavirin (P = 0.0001) and more frequently among HIV‐1‐positive than HIV‐1‐negative participants (85% vs. 70%, P < 0.0001). HIV‐1‐positive participants were more likely to have pancytopenia and subclinical hepatic abnormalities, as well as persistent jaundice, hepatomegaly, splenomegaly and ascites. HAART recipients did not differ from HIV‐negative participants in the prevalence of ascites. The clinical abnormalities were more prevalent with older age but were not confounded by HBV status or self‐reported alcohol consumption. Eleven participants presented with or previously had hepatocellular carcinoma or non‐Hodgkin lymphoma. Although prospective analysis is needed, our data reveal the scale of hepatic and haematological disease that is likely to manifest in the adult haemophilic population during the coming years unless most of them are successfully treated for HIV‐1, HCV or both.

Opsomyoclonus and Neuroblastoma Response to ACTH

Children with neuroblastoma whose opsomyoclonus recurs or persists after initial surgery should be carefully evaluated for tumor. If no tumor is detectable, therapy with ACTH should be considered in patients whose sympto matology is severe enough to compromise normal development.

Two-dimensional echocardiography for evaluation of metastatic cardiac tumors in pediatric patients.

We have studied five patients with metastatic cancer in whom two-dimensional echocardiography (2DE) demonstrated cardiac or pericardial involvement. Echo studies may guide the clinician in instituting and/or modifying cardiac and cancer therapy in such patients.

Results of a thymic epithelial transplant in a child with Wiskott-Aldrich syndrome and central nervous system lymphoma.

Abstract A 3-year-old boy with Wiskott-Aldrich syndrome who was treated with transfer factor since early infancy developed primary central nervous system lymphoma. After an initial favorable response to radiation therapy, the lymphoma recurred but improved after chemotherapy. A thymic epithelial transplant was performed that resulted in clinical improvement in his eczema, a decrease in serum IgE, and an increase in E-rosette-positive cells in the peripheral blood. The transplant produced no improvement in antibody response to polysaccharide antigen, skin test reactivity, or in the level of thrombocytopenia. The duration of remission of the lymphoma after treatment with chemotherapy plus thymic epithelial transplantation was greater than that achieved with radiation therapy alone.