Self-regulation and social and behavioral functioning following childhood traumatic brain injury.

This study examined the impact of childhood traumatic brain injury (TBI) on self-regulation and social and behavioral functioning, and the role of self-regulation as a predictor of children's social and behavioral functioning. Participants included 65 children with moderate to severe TBI and 65 children without TBI, all between 6 and 11 years of age. Self-regulation and social and behavioral functioning were assessed 2 to 5 years following injury. Children with TBI displayed deficits in self-regulation and social and behavioral functioning, after controlling for socioeconomic status (SES), although the magnitude of the deficits was not related to injury severity. Self-regulation accounted for significant variance in children's social and behavioral functioning, after controlling for SES and group membership. Self-regulation may be an important determinant of children's social and behavioral functioning following TBI.     

Iowa's High School High Tech Goes to College Program: Preparing Students with Mild Disabilities for Careers in Technology

This paper describes an innovative approach to preparing high school students with mild disabilities for challenging careers in high tech industries, called High School High Tech (HSHT). Iowa's HSHT Goes to College program has three central elements, each of which is discussed in this paper: High School Preparation—assisting students in identifying a suitable high tech career goal; Higher Education Preparation and Supports—assisting students in selecting college/training programs that match their career goal, and in successfully completing their postsecondary programs; Workforce Entry Assistance—linking students with employers and launching their high tech careers. The paper concludes with a presentation of outcomes to date and recommendations for program enhancements. The information presented here is intended to assist education and rehabilitation professionals interested in establishing similar efforts across the nation.     

Regression of lymphomatous skin deposits in a chronic lymphocytic leukemia patient treated with the Toll-like receptor-7/8 agonist, imiquimod.

The identification of clinically relevant, active immunomodulatory agents is important for developing immunotherapeutic approaches to chronic lymphocytic leukemia (CLL) and other B-cell lymphomas that are not curable with conventional chemotherapy. In this investigation, the imidazoquinoline Toll-like receptor (TLR)-7/8 agonist, imiquimod, was found to mediate the clearance of a lymphomatous skin lesion in a CLL patient. Imidazoquinolines also activated TLR-7/8 signaling pathways, resulting in increased expression of costimulatory molecules on circulating tumor cells. These observations extend the therapeutic spectrum of imiquimod to cutaneous B-cell lymphomas and suggest the use of TLR-7/8 agonists in CLL immunotherapy.     

Trisomy 12 in Epstein-Barr virus-transformed lymphoblastoid cell lines of normal individuals and patients with nonhematologic malignancies

Karyotypes of 36 lymphoblastoid cell lines established by Epstein-Barr virus (EBV) transformation of peripheral blood lymphocytes (PBL) of eight normal individuals and 28 patients with various nonhematologic malignancies were analyzed. In seven lines (19.4%), cells with trisomy 12 were noted, with clonality in two of these lines. In two of 11 metaphases with such trisomy, chromosome 12 was involved in structural rearrangements [t(8;12)(q12;p12) and t(12;12)(q11;q24)]. No cells with trisomy 12 were observed in phytohemagglutinin (PHA)-stimulated PBL cultures of these individuals. In 250 individuals (normal and with nonhematologic malignancies) examined in our laboratory in the last 5 years, extra copies of chromosome 12 in PHA-stimulated PBL cultures were observed in only five of 23,216 cells (0.02%). There were no cases of clonality in these samples. The frequency of an extra chromosome 12 was comparable to that of the other chromosomes except 21 and X, whose frequency of occurrence was 0.08% and 0.09%, respectively. These findings should be considered random events in PHA-stimulated PBL. On the contrary, in lymphoblastoid cell lines established by EBV transformation, trisomy of chromosome 12 was the most frequent numerical abnormality. It was observed in 64.7% of all cases with chromosome gains and therefore could not be considered a random occurrence. The specificity of this phenomenon for EBV transformation is supported by the results of cytogenetic analysis of eight lymphoblastoid cell lines established by an alternative procedure in our laboratory [1]. In 400 cells analyzed not a single cell with trisomy 12 was observed. We suggest that EBV transformation might either randomly induce formation of such cells in immortalized B-cell populations or show potentially blastomogenic cells or proneness to their formation in certain individuals who could be predisposed to develop lymphoproliferative diseases, especially chronic lymphocytic leukemia (CLL) in which trisomy of chromosome 12 is the most common alteration.     

Effect of a low-protein diet on doxorubicin pharmacokinetics in the rabbit

Summary Malnutrition involving protein deficiency, which commonly occurs in cancer patients receiving anthracycline treatment, is considered to be a risk factor for the development of cardiotoxicity. Protein deficiency has been shown to impair the metabolism of drugs such as theophylline and acetaminophen. If protein deficiency also impairs anthracycline metabolism, it could explain at least in part the enchanced anthracycline toxicity associated with malnutrition. We tested this idea by determining the effect of a low- protein, isocaloric diet on doxorubicin pharmacokinetics in rabbits. The animals were randomized into two groups for 8–12 weeks. Rabbits in group 1 received a low-protein (5%), isocaloric diet, whereas those in group 2 received a normal-protein (15%) diet. Both groups (group 1,n=15; group 2,n=14) were given 5 mg/kg doxorubicin by i.v. bolus. After doxorubicin injection, blood samples were obtained over the next 52 h for the measurement of doxorubicin and doxorubicinol plasma concentrations by high-performance liquid chromatography (HPLC) with fluorometric detection. The low-protein diet significantly decreased doxorubicin clearance (48±3 vs 59±4 ml min^–1 kg^–1;P<0.05), prolonged the terminal climination half-life (28±2 vs 22±2 h;P<0.05), and increased the area under the plasma concentration/time curve extrapolated to infinity (1722±122 vs 1405±71 ng h ml^–1;P<0.05) as compared with the values determined for rabbits fed the standard rabbit chow (15% protein). The volume of distribution for doxorubicin was not altered by the low-protein diet. In addition, in rabbits fed the the low-portein diet, the terminal elimination half-life of the alcohol metabolite, doxorubicinol was prolonged (52±5 vs 40±2 h;P<0.05). Thus, a low-protein diet causes a reduction in the ability of rabbits to eliminate doxorubicin and possibly its alcohol metabolite doxorubicinol. If a similar alteration in anthracycline pharmacokinetics occurs in malnourished cancer patients, this phenomenon may contribute to their increased risk of developing cardiotoxicity associated with anthracycline therapy.Supported by the Department of Veterans Affairs and the American Heart Foundation