Neuropsychological and psychosocial effects of the FMR-1 full mutation: Case report of monozygotic twins discordant for the fragile X syndrome.

An extensive evaluation was conducted with 16-yr-old monozygotic twins concordant for the fragile X full mutation but discordant for mental retardation. The clearly affected twin had an IQ score of 47; 77% of her neuropsychological z scores were at least 2 SDs below average. Her sister had an IQ score of 105 and average neuropsychological performance. However, each girl demonstrated relative verbal strengths and visual-spatial weaknesses. Their parents rated each girl as having significant problems with attention, conduct, anxiety-withdrawal, and hyperactivity. The girls did not rate themselves as having significant anxiety. These findings are consistent with group data on females with fragile X and demonstrate the wide range of effects associated with the fragile X full mutation. This case report implicates the importance of a psychosocial phenotype of fragile X independent of cognitive ability level. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Late cytomegalovirus disease in marrow transplantation is predicted by virus load in plasma

Late occurrence of cytomegalovirus (CMV) disease after day 100 after bone marrow transplantation has become an increasing problem; whether a quantitative measurement of CMV DNA in plasma by polymerase chain reaction (P-PCR) could be predictive of such disease was investigated. In a prospective study, 117 subjects undergoing allogeneic marrow transplantation were followed for 120 days with weekly CMV blood cultures, with day 35 bronchoalveolar lavage CMV cultures, with weekly CMV P-PCR, and with clinical follow-up for an additional 1-2 years. Despite preemptive ganciclovir, CMV disease occurred in 9% of subjects, with a median time of onset of 176 days. Quantitative CMV P-PCR was associated with the late development of CMV disease (P = .01). Of 43 subjects with positive P-PCR results, 23% developed CMV disease, but no disease occurred in the 74 subjects with negative P-PCR (P < .001), despite the fact that 22% had CMV isolated from lung lavage fluid and 32% had CMV isolated from blood.     

Cytomegalovirus retinitis and viral resistance: 3. Culture results. CMV Retinitis and Viral Resistance Study Group

PURPOSE: The Strong Heart Study is a study of cardiovascular disease and its risk factors among American Indian men and women aged 45-74 yr representative of 13 communities from Arizona (AZ), Oklahoma (OK), and North/South Dakota (N/SD). This investigation sought to characterize the amount and type of physical activity and to determine the association between activity and lipids in this population. METHODS: Total physical activity (occupational plus leisure) was assessed with a validated questionnaire. RESULTS: Men and women from OK (21 +/- 19 and 16 +/- 15 h.wk-1; respectively) and N/SD (23 +/- 21 and 17 +/- 17 h.wk-1; respectively) had activity levels that were similar if not lower than the U.S. population with the AZ communities (17 +/- 21 and 10 +/- 14 h.wk-1; respectively) being substantially lower than the other two communities. Total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), and low density lipoprotein cholesterol (LDL-c) levels were lower than the U.S. population. CONCLUSIONS: For most of the population (diabetic men and nondiabetic men and women), activity was significantly associated (P < 0.05) with apolipoprotein (apo) AI after controlling for covariates. With levels of activity as low if not lower than the general U.S. population coupled with high prevalence of obesity and diabetes, efforts to increase physical activity in American Indians are warranted. Hopefully these increases in activity will result in favorable lipid changes as well as decreasing the risk of diabetes which is epidemic in these populations.     

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.     

Pressure waves in the aorta during isolated abdominal belt loading: the magnitude, phasing, and attenuation

While rupture of the aorta is a leading cause of sudden death following motor vehicle crashes, the specific mechanism that causes this injury is not currently well understood. Aortic ruptures occurring in the field are likely due to a complex combination of contributing factors such as acceleration, compression of the chest, and increased pressure within the aorta. The objective of the current study was to investigate one of these factors in more detail than has been done previously; specifically, to investigate the in situ intra-aortic pressure generated during isolated belt loading to the abdomen. Ten juvenile swine were subjected to dynamic belt loads applied to the abdomen. Intraaortic pressure was measured at multiple locations to assess the magnitude and propagation of the resulting blood pressure wave. The greatest average peak pressure (113.6 +/- 43.5 kPa) was measured in the abdominal aorta. Pressures measured in the thoracic aorta and aortic arch were 70 per cent and 50 per cent, respectively, that measured in the abdominal aorta. No macroscopic aortic trauma was observed. To the authors' knowledge the present study is the first one to document the presence, propagation, and attenuation of a transient pressure wave in the aorta generated by abdominal belt loading. The superiorly moving wave is sufficient to generate hydrostatic and intimal shear stress in the aorta, possibly contributing to the hypothesized mechanisms of traumatic aortic rupture.     

Teaching evidence-based interventions: Perceptions of influences on use in professional practice in school psychology.

This study examined perceptions of school psychologists regarding their use of evidence-based interventions in school settings after completing a graduate course in school-based psychosocial interventions. Ninety-four individuals who completed the course during the 10 years prior to the study were asked to complete a survey that focused on personal and organizational factors affecting the implementation of evidence-based interventions through assessment of (a) the extent of their use of interventions in professional school psychology practice, (b) perceptions of facilitators to implementation, and (c) perceptions of barriers to implementation. Fifty-four responded (a 57% response rate); analyses were conducted on the responses of 34 individuals who indicated that they were currently school psychologists working in schools. Results indicated that school psychologists’ personal beliefs about the interventions influenced their decisions to implement them. Several evidence-based interventions were less likely to be used in urban practice settings. Training in evidence-based interventions should address the personal and contextual issues that are related to implementation, as well as the procedures of the interventions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experience with reduction mammaplasty following breast conservation surgery and radiation therapy

Little is known about the outcome of breast reduction in the previously radiated breast. With the increased popularity of breast conservation in the management of breast cancer, it is inevitable that more women with breast cancer who have had a breast radiated will be seeking breast reduction. Although it would be expected that reduction of the radiated breast would be more challenging and would yield less-pleasing results, it has been unclear whether reduction in the radiated breast could be safely performed without interfering with mammography and cancer surveillance. Our experience using different techniques in three patients demonstrates that such reductions can be effectively and safely done if certain principles are followed. Pedicles should be designed to be broader and shorter than usual, and breast flaps should be undermined or elevated either minimally or not at all.     

Molecular analysis of T-cell receptor repertoire in bone marrow transplant recipients: evidence for oligoclonal T-cell expansion in graft-versus-host disease lesions

We have analyzed the T-cell receptor (TCR) V beta repertoire using polymerase chain reaction (PCR) in a cohort of eight patients receiving allogeneic bone marrow transplantation (BMT) from related and unrelated donors at the City of Hope. Results of PCR studies from graft-versus-host disease (GVHD) skin lesions show a bias in the usage of TCR V beta families, whereas examination of peripheral blood (PB) withdrawn at the same time did not reveal a similar phenomenon. In one such family, TCR V beta 2 is predominantly expressed in 7 of 7 biopsy specimens examined. V beta 2 TCR expression from these patients was analyzed more extensively using a combination of individual TCR gene cloning, followed by sequence analysis. We found evidence of oligoclonal expansion of single V beta 2-bearing TCRs in GVHD lesions, and in the PB of some patients after diagnosis of GVHD. In contrast, GVHD-negative biopsy samples showed no evidence for clonotypic TCR amplification. Sequence-specific TCR CDR3 region probes were derived from analysis of the predominant expressed TCR in GVHD lesions, and used to probe Southern blots of amplified V beta 2 TCR mRNA from PB and tissue from BMT recipients and their respective donors. In most cases the probes are highly specific in detecting TCR expression from GVHD lesions alone, although in several instances expression could be detected in PB after GVHD diagnosis. These data provide supporting evidence for the hypothesis that acute GVHD is associated with expansion of T-cell clones expressing antigen-specific TCRs that may contribute to the disease pathology.     

T cell vaccination induces T cell receptor Vbeta-specific Qa-1-restricted regulatory CD8(+) T cells

Vaccination of mice with activated autoantigen-reactive CD4(+) T cells (T cell vaccination, TCV) has been shown to induce protection from the subsequent induction of a variety of experimental autoimmune diseases, including experimental allergic encephalomyelitis (EAE). Although the mechanisms involved in TCV-mediated protection are not completely known, there is some evidence that TCV induces CD8(+) regulatory T cells that are specific for pathogenic CD4(+) T cells. Previously, we demonstrated that, after superantigen administration in vivo, CD8(+) T cells emerge that preferentially lyse and regulate activated autologous CD4(+) T cells in a T cell receptor (TCR) Vbeta-specific manner. This TCR Vbeta-specific regulation is not observed in beta2-microglobulin-deficient mice and is inhibited, in vitro, by antibody to Qa-1. We now show that similar Vbeta8-specific Qa-1-restricted CD8(+) T cells are also induced by TCV with activated CD4(+) Vbeta8(+) T cells. These CD8(+) T cells specifically lyse murine or human transfectants coexpressing Qa-1 and murine TCR Vbeta8. Further, CD8(+) T cell hybridoma clones generated from B10.PL mice vaccinated with a myelin basic protein-specific CD4(+)Vbeta8(+) T cell clone specifically recognize other CD4(+) T cells and T cell tumors that express Vbeta8 and the syngeneic Qa-1(a) but not the allogeneic Qa-1(b) molecule. Thus, Vbeta-specific Qa-1-restricted CD8(+) T cells are induced by activated CD4(+) T cells. We suggest that these CD8(+) T cells may function to specifically regulate activated CD4(+) T cells during immune responses.     

Recombinant modified vaccinia virus Ankara-simian immunodeficiency virus gag pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer

The utility of modified vaccinia virus Ankara (MVA) as a vector for eliciting AIDS virus-specific cytotoxic T lymphocytes (CTL) was explored in the simian immunodeficiency virus (SIV)/rhesus monkey model. After two intramuscular immunizations with recombinant MVA-SIVSM gag pol, the monkeys developed a Gag epitope-specific CTL response readily detected in peripheral blood lymphocytes by using a functional killing assay. Moreover, those immunizations also elicited a population of CD8+ T lymphocytes in the peripheral blood that bound a specific major histocompatibility complex class I/peptide tetramer. These Gag epitope-specific CD8+ T lymphocytes also were demonstrated by using both functional and tetramer-binding assays in lymph nodes of the immunized monkeys. These observations suggest that MVA may prove a useful vector for an HIV-1 vaccine. They also suggest that tetramer staining may be a useful technology for monitoring CTL generation in vaccine trials in nonhuman primates and in humans.