Somatic mosaicism in Fanconi anemia: Evidence of genotypic reversion in lymphohematopoietic stem cells

Somatic mosaicism has been observed previously in the lymphocyte population of patients with Fanconi anemia (FA). To identify the cellular origin of the genotypic reversion, we examined each lymphohematopoietic and stromal cell lineage in an FA patient with a 2815–2816ins19 mutation in FANCA and known lymphocyte somatic mosaicism. DNA extracted from individually plucked peripheral blood T cell colonies and marrow colony-forming unit granulocyte–macrophage and burst-forming unit erythroid cells revealed absence of the maternal FANCA exon 29 mutation in 74.0%, 80.3%, and 86.2% of colonies, respectively. These data, together with the absence of the FANCA exon 29 mutation in Epstein–Barr virus-transformed B cells and its presence in fibroblasts, indicate that genotypic reversion, most likely because of back mutation, originated in a lymphohematopoietic stem cell and not solely in a lymphocyte population. Contrary to a predicted increase in marrow cellularity resulting from reversion in a hematopoietic stem cell, pancytopenia was progressive. Additional evaluations revealed a partial deletion of 11q in 3 of 20 bone marrow metaphase cells. By using interphase fluorescence in situ hybridization with an MLL gene probe mapped to band 11q23 to identify colony-forming unit granulocyte–macrophage and burst-forming unit erythroid cells with the 11q deletion, the abnormal clone was exclusive to colonies with the FANCA exon 29 mutation. Thus, we demonstrate the spontaneous genotypic reversion in a lymphohematopoietic stem cell. The subsequent development of a clonal cytogenetic abnormality in nonrevertant cells suggests that ex vivo correction of hematopoietic stem cells by gene transfer may not be sufficient for providing life-long stable hematopoiesis in patients with FA.

Lymphocytes selected in allogeneic thymic epithelium mediate dominant tolerance toward tissue grafts of the thymic epithelium haplotype.

Athymic mice grafted at birth with allogeneic thymic epithelium (TE) from day 10 embryos before hematopoietic cell colonization reconstitute normal numbers of T cells and exhibit full life-long tolerance to skin grafts of the TE haplotype. Intravenous transfers of splenic cells, from these animals to adult syngeneic athymic recipients, reconstitute T-cell compartments and the ability to reject third-party skin grafts. The transfer of specific tolerance to skin grafts of the TE donor strain, however, is not observed in all reconstituted recipients, and the fraction of nontolerant recipients increases with decreasing numbers of cells transferred. Furthermore, transfers of high numbers of total or CD4+ T cells from TE chimeras to T-cell receptor-anti-H-Y antigen transgenic immunocompetent syngeneic hosts specifically hinder the rejection of skin grafts of the TE haplotype that normally occurs in such recipients. These observations demonstrate (i) that mice tolerized by allogeneic TE and bearing healthy skin grafts harbor peripheral immunocompetent T cells capable of rejecting this very same graft; and (ii) that TE selects for regulatory T cells that can inhibit effector activities of graft-reactive cells.

Intervenções de enfermagem na prevenção da pneumonia associada à ventilação mecânica

Relatório de Trabalho de Projeto apresentado para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Enfermagem Médico-cirúrgica

Activities of fenbendazole in comparison with albendazole against Echinococcus multilocularis metacestodes in vitro and in a murine infection model.

The current chemotherapeutic treatment of alveolar echinococcosis (AE) in humans is based on albendazole and/or mebendazole. However, the costs of treatment, life-long consumption of drugs, parasitostatic rather than parasiticidal activity of chemotherapy, and high recurrence rates after treatment interruption warrant more efficient treatment options. Experimental treatment of mice infected with Echinococcus multilocularis metacestodes with fenbendazole revealed similar efficacy to albendazole. Inspection of parasite tissue from infected and benzimidazole-treated mice by transmission electron microscopy (TEM) demonstrated drug-induced alterations within the germinal layer of the parasites, and most notably an almost complete absence of microtriches. On the other hand, upon in vitro exposure of metacestodes to benzimidazoles, no phosphoglucose isomerase activity could be detected in medium supernatants during treatment with any of these drugs, indicating that in vitro treatment did not severely affect the viability of metacestode tissue. Corresponding TEM analysis also revealed a dramatic shortening/retraction of microtriches as a hallmark of benzimidazole action, and as a consequence separation of the acellular laminated layer from the cellular germinal layer. Since TEM did not reveal any microtubule-based structures within Echinococcus microtriches, this effect cannot be explained by the previously described mechanism of action of benzimidazoles targeting β-tubulin, thus benzimidazoles must interact with additional targets that have not been yet identified. In addition, these results indicate the potential usefulness of fenbendazole for the chemotherapy of AE.

Transition bei angeborenen Herzfehlern in der Schweiz

Die Chance, mit einem angeborenen Herzfehler erwachsen zu werden, liegt mittlerweile bei über 90 %. Trotz aller Erfolge der Medizin können Herzfehler auch nach erfolgreicher Korrektur nicht als geheilt betrachtet werden. Langzeitkomplikationen im Sinn von Herzrhythmusstörungen, Herzinsuffizienz, embolischen Ereignissen, Endokarditis, oder Reoperationen aufgrund residualer Befunde oder Klappendegenerationen sind häufig. Aus diesem Grund wird für eine Vielzahl angeborener Herzfehler eine lebenslange spezialisierte Betreuung empfohlen. Jugendliche mit Herzfehlern müssen darauf vorbereitet werden, im Erwachsenenalter Eigenverantwortung zu übernehmen. Dazu ist eine strukturierte Transition ein entscheidender Vorteil. Dadurch werden einerseits Jugendliche selbst auf ihre Erwachsenenrolle vorbereitet und andererseits kann ein adäquater Transfer der Betreuung vom Kinder- zum Erwachsenenmediziner gewährleistet werden. Jugendliche ohne Transfer und ohne spezialisierte Betreuung im Erwachsenenalter haben ein erhöhtes Risiko, kardiovaskuläre Komplikationen zu erleiden. Es wurde gezeigt, dass die Mortalität bei angeborenen Herzfehlern bei Erwachsenen mit spezialisierter Betreuung geringer ist als bei Patienten ohne entsprechende Betreuung. Am Beispiel des Zentrums für angeborene Herzfehler in Bern wird aufgezeigt, wie eine pflegegeleitete Transitionssprechstunde aufgebaut und erfolgreich umgesetzt werden kann.

Clinical practice guidelines for the psychosocial care of adults with cancer

Clinical practice guidelines are increasingly being developed in medical settings to provide evidence-based recommendations to guide the clinical care of patients. The development of Clinical practice guidelines for the psychosocial care of patients with medical illness is a newer initiative, and more complex as the target audience includes health care professionals from diverse backgrounds. In Australia, the National Breast Cancer Centre and National Cancer Control Initiative have collaborated to develop Clinical practice guidelines for the psychosocial care of adults with cancer, funded by the Australian Government Department of Health and Ageing. This paper outlines the development of these guidelines in the international context, gives an overview of their content, and describes strategies for their implementation and evaluation. Copyright (c) 2005 John Wiley C Sons, Ltd.

Merton's true self and the psychology of the dialogical self

Thomas Merton pursued a life-long quest to grasp the nature of the “true self.” This is the self that lives in and through Christ. Opposed to this is the false self that is expressive of infidelity. It is argued that the interaction between the true and false selves constitutes a dialogical process. The thesis of the essay is that this interaction expresses the dynamics associated with what some psychologists refer to as the “dialogical self.” The dialogical self is a model of the inner life that draws attention to the interpretive process required to deal with the many voices that get internalized in an engagement with the world.

Lifetime suicide risk in major depression: sex and age determinants

Background: Recent work has demonstrated that the lifetime suicide risk for patients with DSM IV Major Depression cannot mathematically approximate the accepted figure of 15%. Gender and age significantly affect both the prevalence of major depression and suicide risk, Methods: Gender and age stratified calculations were made on the entire population of the USA in 1994 using a mathematical algorithm. Sex specific corrections for under-reporting were incorporated into the design. Results: The lifetime suicide risks for men and women were 7% and 1%, respectively. The combined risk was 3.4%. The male:female ratio for suicide risk in major depression was 10:1 for youths under 25, and 5.6:1 for adults. Conclusions: Suicide in major depression is predominantly a male problem, although complacency towards female sufferers is to be avoided. Diagnosis of major depression is of limited help in predicting suicide risk compared to case specific factors. The male experience of depression that leads to suicide is often not identified as a legitimate medical complaint by either sufferers or professionals. Increasing help-accessing by males is a priority. Clinical implications: Patients with a history of hospitalisation; comorbidity, especially for substance abuse; and who are male, require greater vigilance for suicide risk. It may be that for males che threshold for diagnosing and treating major depression needs to be lowered. Limitations: This research is based on a mathematical algorithm to approximate a life-long longitudinal study that identifies community cases of depression. Our findings therefore rely on the validity of the statistics used. Extrapolation is limited to populations with an actual suicide rate of 17/100,000 or less and a lifetime prevalence of major depression of 17% or more. (C) 1999 Elsevier Science B.V. All rights reserved.

Social aspects of pharmaceutical innovation: heart disease

This study examines the invention, innovation, introduction and use of a new drug therapy for coronary heart disease and hypertension; beta-blockade. The relationships between drug introductions and changes in medical perceptions of disease are analysed, and the development and effects of our perception of heart disease through drug treatments and diagnostic technology is described. The first section looks at the evolution of hypertension from its origin as a kidney disorder, Bright's disease, to the introduction and use of effective drugs for its treatment. It is shown that this has been greatly influenced by the introduction of new medical technologies. A medical controversy over its nature is shown both to be strongly influenced by the use of new drugs, and to influence their subsequent use. The second section reviews the literature analysing drug innovation, and examines the innovation of the beta-blocking drugs, making extensive use of participant accounts. The way in which the development of receptor theory, the theoretical basis of the innovation,was influenced by the innovation and use of drugs is discussed, then the innovation at ICI, the introduction into clinical use, and the production of similar drugs by other manufacturers are described. A study of the effects of these drugs is then undertaken, concentrating on therapeutic costs and benefits, and changes in medical perceptions of disease. The third section analyses the effects of other drugs on heart disease, looking at changes in mortality statistics and in medical opinions. The study concludes that linking work on drug innovation with that on drug effects is fruitful, that new drugs and diagnostic technology have greatly influenced medical perceptions of the nature and extent of heart disease, and that in hypertension, the improvement in drug treatment will soon result in much of the population being defined as in need of it life-long.

Brain structural changes associated with chronicity and antipsychotic treatment in schizophrenia

Accumulating evidence suggest a life-long impact of disease related mechanisms on brain structure in schizophrenia which may be modified by antipsychotic treatment. The aim of the present study was to investigate in a large sample of patients with schizophrenia the effect of illness duration and antipsychotic treatment on brain structure. Seventy-one schizophrenic patients and 79 age and gender matched healthy participants underwent brain magnetic resonance imaging (MRI). All images were processed with voxel based morphometry, using SPM5. Compared to healthy participants, patients showed decrements in gray matter volume in the left medial and left inferior frontal gyrus. In addition, duration of illness was negatively associated with gray matter volume in prefrontal regions bilaterally, in the temporal pole on the left and the caudal superior temporal gyrus on the right. Cumulative exposure to antipsychotics correlated positively with gray matter volumes in the cingulate gyrus for typical agents and in the thalamus for atypical drugs. These findings (a) indicate that structural abnormalities in prefrontal and temporal cortices in schizophrenia are progressive and, (b) suggest that antipsychotic medication has a significant impact on brain morphology. © 2009 Elsevier B.V. and ECNP.

Parental confidence in managing food allergy:development of the Food Allergy Self-Efficacy Scale for parents (FASE-P)

Background: Food allergy is often a life-long condition that requires constant vigilance in order to prevent accidental exposure and avoid potentially life-threatening symptoms. Parents’ confidence in managing their child’s food allergy may relate to the poor quality of life anxiety and worry reported by parents of food allergic children. Objective: The aim of the current study was to develop and validate the first scale to measure parental confidence (self-efficacy) in managing food allergy in their child. Methods: The Food Allergy Self-Efficacy Scale for Parents (FASE-P) was developed through interviews with 53 parents, consultation of the literature and experts in the area. The FASE-P was then completed by 434 parents of food allergic children from a general population sample in addition to the General Self-Efficacy Scale (GSES), the Food Allergy Quality of Life Parental Burden Scale (FAQL-PB), the General Health Questionnaire (GHQ12) and the Food Allergy Impact Measure (FAIM). A total of 250 parents completed the re-test of the FASE-P. Results: Factor and reliability analysis resulted in a 21 item scale with 5 sub-scales. The overall scale and sub-scales has good to excellent internal consistency (α’s of 0.63-0.89) and the scale is stable over time. There were low to moderate significant correlations with the GSES, FAIM and GHQ12 and strong correlations with the FAQL-PB, with better parental confidence relating to better general self-efficacy, better quality of life and better mental health in the parent. Poorer self-efficacy was related to egg and milk allergy; self-efficacy was not related to severity of allergy. Conclusions and clinical relevance: The FASE-P is a reliable and valid scale for use with parents from a general population. Its application within clinical settings could aid provision of advice and improve targeted interventions by identifying areas where parents have less confidence in managing their child’s food allergy.

Bagging model with cost sensitive analysis on diabetes data

Diabetes patients might suffer from an unhealthy life, long-term treatment and chronic complicated diseases. The decreasing hospitalization rate is a crucial problem for health care centers. This study combines the bagging method with base classifier decision tree and costs-sensitive analysis for diabetes patients' classification purpose. Real patients' data collected from a regional hospital in Thailand were analyzed. The relevance factors were selected and used to construct base classifier decision tree models to classify diabetes and non-diabetes patients. The bagging method was then applied to improve accuracy. Finally, asymmetric classification cost matrices were used to give more alternative models for diabetes data analysis.

Stress Urinary Incontinence in Female Athletes

Objective: The purpose of this study is to educate allied health professionals and female athletes of the anatomy of the pelvic floor, and the pathology, etiology, and prevalence of stress urinary incontinence in female athletes. Background: Urinary incontinence is not a life-threatening or dangerous condition, but it is socially embarrassing, may cause the individual to remove herself from social situations, and decrease quality of life. While typically associated with parous women who had vaginal delivery, research has shown prevalence of the condition in physically active women of all ages. Stress urinary incontinence has shown to lead to withdrawal from participation in high-impact activities such as gymnastics, aerobics, and running. It may be considered a barrier for life-long athletics participation in women. Description: An in-depth introduction to the cause and origin of stress urinary incontinence including review of the female pelvic floor anatomy and prevalence of stress urinary incontinence in the female athletic population. Clinical Advantages: Athletic trainers and other allied health professionals will develop an understanding of the multiple mechanisms that cause stress urinary incontinence. Clinician competency of the dynamics and mechanism of urinary incontinence prepares the individual to learn diagnostics, prevention, pharmacological intervention, and treatment of this pathology.

A comprehensive assessment of self -report experiences of adoptive parents of special needs children in Florida

Adoption of special needs children is now seen as a life long event whereby the adoptive child and family have unique needs. The need for postplacement resources throughout the life cycle of the adoption process is evident. This exploratory-descriptive research employed a random stratified cross-sectional design. The purpose of the study was to describe, identify, examine, and assess the relative influence of identified empirically and conceptually relevant variables of self-report experiences of adoptive parents of special needs children. Primary areas of exploration included: (1) adoptive children and families' characteristics, (2) postplacement service needs, utilization and satisfaction, and (3) adoptive parents' perceptions of their adoption experiences. A proportionate stratified random mail survey was used to obtain 474 families who had adopted special needs children from the 15 geographic districts which make up the state adoption social service agency in Florida. A 144-item survey questionnaire was used to collect basic information on demographic data, service provision, and adoption experiences. Four research questions were analyzed to test the effect the predictor variables had on willingness to adopt another special needs child, successful adoption, satisfying experience, and realism about problems. All four research questions revealed that the full model and the child's antecedent and the adoptive parents' intervening variable blocks were significant in explaining the variance in the dependent variables. The child's intervening variables alone were only significant in explaining the variance for one of the dependent variables. The results of the statistical analysis on the fifth research question and the three hypotheses determined that (1) only one postplacement service, crisis intervention, had a statistically significant impact on the adoptive parents' perceived level of satisfaction with the adoption experience; (2) adoptive parents who rate their adoption as successful are more likely to express a desire to adopt another special needs child; (3) the more adequate information on the child the adoptive parents perceived that they had prior to placement, the more they perceived they were realistic about the problems they would encounter; and (4) six specific postplacement services were found to be significant in predicting successful adoptions--crisis intervention, outpatient drug/alcohol treatment, maintenance subsidy, physical therapy, special medical equipment, and family counseling. Implications for the social work field and future research are discussed. ^

Anthony Hall, 1947 View

Anthony Hall was named for Libby C. Anthony who was a matron of girls as well as assistant in domestic economy. She was the first Treasurer for the National League of Afro-American Women and a life long resident of Jefferson City, Missouri. This three story brick building was completed in 1940 and served as a dormitory for Freshman and sophomore young women. It was renovated in 2007. It is now a co-ed residence hall for upperclassmen.