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PubMed2003

Reconstitution of the latent T-lymphocyte response to Epstein-Barr virus is coincident with long-term recovery from posttransplant lymphoma after adoptive immunotherapy.

BACKGROUND: Adoptive transfer of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) has been used to treat EBV-induced posttransplant lymphoproliferative disease (PTLD) in solid-organ recipients. This study defines, in detail, the temporal relationship between adoptive transfer and the clinical response, EBV DNA load, and CTL response to EBV latent and lytic antigens in a patient with a subcutaneous PTLD presentation treated with adoptive transfer of autologous CTL. METHODS: A heart transplant patient developed multiple subcutaneous PTLD deposits and was treated with a total of six doses (20 x 106 CTL per dose) of cultured autologous polyclonal EBV-specific CTL by adoptive transfer. RESULTS: Complete regression occurred after the sixth CTL dose, and the patient has remained disease-free from 47 weeks to the present (136 weeks). Real-time polymerase chain reaction analysis showed a reduction in viral load after therapy. Enzyme-linked immunospot analysis using defined EBV CTL epitopes showed that the CTL precursor frequency (pCTL) toward a lytic antigen epitope was elevated early in the course of disease but tended to decrease to lower levels after long-term regression of PTLD. The most dramatic result was seen in relation to three latent CTL epitopes studied. Long-term regression of PTLD was characterized by high pCTL toward the latent antigens. CONCLUSIONS: Increased pCTL reactivity to latent EBV CTL epitopes is coincident with recovery from disease after adoptive transfer of autologous CTL. Furthermore, the results are compatible with the belief that activation of a sustained CTL response to EBV latent epitopes is protective and may be a characteristic of patients in long-term remission from PTLD.

DNA, Viral↗
PubMedDate not supplied

An adoption study of the etiology of teacher and parent reports of externalizing behavior problems in middle childhood.

Twin studies of externalizing behavior problems in middle childhood and early adolescence suggest that there is moderate-to-substantial genetic variance and modest-to-moderate shared environmental variance in these behaviors. The present study is novel in three ways: it is a sibling adoption study, it employs both teacher and parent ratings of children's behaviors averaged over five assessments, and it explores aggression and delinquency separately. The sample included 78 adoptive sibling pairs and 94 biologically related sibling pairs in the Colorado Adoption Project. Parents and teachers completed ratings of the children's externalizing behavior problems at ages 7, 9, 10, 11, and 12 years. Boys and adopted children were rated as being somewhat higher in externalizing behavior problems. Sex differences in delinquency were more pronounced in adoptive than in nonadoptive families. Teachers' ratings showed evidence for moderate heritability and no shared environment for aggression and showed modest shared environment for delinquency. Parents' ratings showed evidence for moderate amounts of heritability and shared environment for both aggression and delinquency.

Adoption↗
PubMed2002

Coping with birthparent loss in adopted children.

BACKGROUND: Relationships among adopted children's appraisals of birthparent loss, their coping strategies for managing such loss, and child and parent reports of child adjustment were investigated within the context of a stress and coping model of adoption adjustment. METHODS: Eighty-two 8-12-year-old adopted children and one of their parents participated. Children completed questionnaires assessing their negative affect about birthparent loss, their curiosity about birthparents, their use of coping strategies to manage birthparent-related distress, and their levels of depression, anxiety, and global self-worth. Parents reported on children's externalizing and internalizing behavior problems and social competence. RESULTS: Children who reported higher levels of negative affect about birthparent loss also reported higher levels of depression and lower self-worth. Curiosity about birthparents predicted parent-rated externalizing behavior. Behavioral avoidant coping was associated with greater self-reported anxiety and parent-rated externalizing behavior, whereas problem solving coping was associated with increased parent-rated social competence. CONCLUSIONS: The findings, though limited by issues of measurement and sampling, add to the knowledge base regarding adopted children's appraisal and coping behaviors, and provide partial support for a stress and coping model of adopted children's adjustment.

Adaptation, Psychological↗
PubMed2006

Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation.

During periods of immunosuppression, such as postallogeneic stem cell transplantation (SCT), patients are at significant risk for severe viral infections. Human adenovirus (HAdV) infection is a serious complication post-SCT, especially in children. Virus-specific T cells are essential for the clearance of HAdV, as antiviral chemotherapy has revealed limited success. We present feasibility data for a new treatment option using virus-specific donor T cells for adoptive transfer of immunity to patients with HAdV-infection/reactivation. Virus-specific donor T cells were isolated and infused into nine children with systemic HAdV infection after SCT. Isolation was based on gamma-interferon (IFN-gamma) secretion after short in vitro stimulation with viral antigen, resulting in a combination of CD4(+) and CD8(+) T cells. 1.2-50 x 10(3)/kg T cells were infused for adoptive transfer. Isolated cells showed high specificity and markedly reduced alloreactivity in vitro. Adoptive transfer of HAdV-specific immunity was successful in five of six evaluable patients, documented by a dose-independent and sustained in vivo expansion of HAdV-specific T cells, associated with a durable clearance/decrease of viral copies. T-cell infusion was well tolerated in all nine patients, except one case with graft-versus-host disease II of the skin. In conclusion, induction of a specific T-cell response through adoptive transfer was feasible and effective. When performed early in the course of infection, adoptive T-cell transfer may protect from HAdV-related complications.

Adenovirus Infections, Human↗
PubMed1985

Intellectual development within transracial adoptive families: retesting the confluence model.

The confluence model of intellectual development was estimated for a within-family sample of 321 children from 101 transracial adoptive families. Mental ages of the children and their parents, as well as birth or adoption intervals, were used in a nonlinear least-squares estimation procedure to obtain children's predicted mental ages. Contrary to an earlier report using these data, the confluence model performed quite well, accounting for up to 50% of the variance in mental age. When the relationship between chronological and mental age was taken into account, the predictive power of the model was reduced but not eliminated. The confluence model was also fitted separately to various subsamples. The model generated a good fit to the data from both biological and adopted children and fit the data from early-adopted children much better than the data from later-adopted children. Both findings were taken as evidence that the confluence model provides an environmental account of intellectual development within the family.

Adolescent↗
PubMed1997

Early intervention in adoptive families: supporting maternal sensitive responsiveness, infant-mother attachment, and infant competence.

Results from adoption studies suggest that adoptive families may experience special impediments with respect to the developmental progress and outcome of their children. Based on attachment theory, two early intervention programs were designed to support families in the Netherlands with an internationally adopted child. The intervention aimed at promoting maternal sensitive responsiveness, secure infant-mother attachment relationships, and infant exploratory competence. Ninety families with an interracially adopted infant (71 from Sri Lanka and 19 from Korea) were assigned to either a control group or one of two intervention groups. All of the children, 44 boys and 46 girls, were placed for adoption under the age of 5 months (M = 8 weeks). The first intervention group (N = 30) received a personal book, which focused on sensitive parenting. The second intervention group (N = 30) was provided with the same book as well as with three video-feedback sessions at their home. The control group (N = 30) did not receive intervention. In the control group sensitive responsiveness and security of attachment were comparable to outcomes from normative samples. The least intensive program, the personal book, did not bring about change in mothers or infants. In contrast, intervention effects were established upon maternal sensitive responsiveness, infant competence, and infant-mother attachment in the group that received both the book and video feedback.

Adoption↗
PubMed1994

Toward an organizational-relational model of open adoption.

Clinicians and social scientists have attempted to demonstrate the advisability of open versus closed adoption (communication and/or contact vs. no communication and/or contact between biological and adoptive parents) from a variety of theoretical perspectives. In our article, we seek a conceptual framework that will (a) elaborate how such divergent conclusions about openness versus confidentiality have heretofore been drawn, and (b) provide a comprehensive analysis of the behavior and experiences of all members of the adoption triad (birthparents, adoptive parents, adoptees). Employing structural aspects of organismic-developmental theory (Werner, 1957) and dynamic aspects of self-in-relation theory (Miller, 1976), we propose an organizational-relational approach to open adoption. Preliminary research findings are also provided.

Adaptation, Psychological↗
PubMed1996

Parents' sense of "entitlement" in adoptive and nonadoptive families.

The literature suggests that problems with developing a sense of entitlement are unique to adoptive families, but this assumption has not been examined empirically. In this study, a questionnaire was constructed to define operationally those characteristics associated with the construct of entitlement, and was administered to adoptive and nonadoptive families with children averaging 11.5 years in age who presented either for mental health service or were recruited as a comparison-control sample. Factor analysis yielded four factors on which the four groups of subjects were compared. Results indicated that problems with entitlement are not specific to adoptive families. Instead, differences in sense of entitlement occurred primarily between clinic and nonclinic control families, regardless of whether the target child had been adopted. Findings are discussed in terms of methodological shortcomings in the adoption research literature and how problems in entitlement may be associated with other family characteristics.

Adolescent↗
PubMed2005

Protective influences of families for children adopted from the former Soviet Union.

PURPOSE: To (a) characterize the total competence of 9- to 12-year old children adopted from the former Soviet Union who have resided in the United States at least 5 years, and (b) evaluate risks and protective influences of adoptive families and their relationships to competence. DESIGN: Longitudinal, descriptive study. METHODS: In the previously reported phase, the families of 105 internationally adopted children and their families from 23 U.S. states were assessed via telephone interviews and postal survey. In this phase, 3.5 years later, 46 of the families from 16 states were located and reassessed. Measures included: Total Competence scale of the Child Behavior Checklist (CBCL), Family Environment Scale (FES), and demographic information. Multivariate regression analysis was conducted to determine which risk and protective factors contributed to competence scores of the adopted children. FINDINGS: Between Time 1 (mean age of children, 7.7 years) and Time 2 (mean age of children, 11 years), average scores on the Total Competence scale of the CBCL did not change significantly, despite impending challenges of early adolescence. Subdomain scores on the FES were more positive than norms. Results from the regression analysis showed that, of the risk and protective factors considered, only birth weight and the cohesion subscale of the FES were statistically significant in explaining variation in the competence score of the CBCL. CONCLUSIONS: Families continued to face challenges, but findings were consistent with other studies showing that, despite early adversities, these adopted children generally fared well developmentally with protective family environments of major importance.

Acculturation↗
PubMed1991

Interaction between genetic vulnerability and family environment: the Finnish adoptive family study of schizophrenia.

A nationwide Finnish sample of schizophrenics' offspring given up for adoption was compared blindly with matched controls, that is, adopted-away offspring of nonschizophrenic biologic parents. The adoptive families were investigated thoroughly by joint and individual interviews and psychologic tests. Biologic parents were also interviewed and tested. Among the 144 index and 178 control offspring, the percentage of both psychoses and other severe diagnoses (borderline syndrome and severe personality disorder) was significantly higher in the index adoptees than in the matched control adoptees. Of the 15 psychotic adoptees in the total sample to date, 13 are offspring of schizophrenics and 2 are control offspring. Both global clinical ratings and test data for the adoptive, rearing parents also correlate with the symptomatic status of the adoptees. A prospective, longitudinal study of adoptees at risk is being undertaken to explore the direction of effects between adoptees and adoptive parents.

Adoption↗
PubMed2007

MRSA in children from foreign countries adopted to Swedish families.

AIM: To determine if children adopted to Swedish families from countries with a high carrier rate of methicillin-resistant Staphylococcus aureus (MRSA) are infected or colonized with MRSA. METHODS: From January 2000 to May 2005, 23 adopted children from 6 countries were examined for MRSA at the University hospital in Lund after their arrival in Sweden. RESULTS: Thirteen of the 23 children (57%) were MRSA positive with a median age of the children at the time MRSA was detected of 6 (range 3-16) months. All MRSA positive children had a history of hospitalization in their native country before arriving in Sweden. The throat was the most frequent and persistent site where MRSA was seen while in sites such as the anterior nares and perineum, MRSA was found more intermittently. The MRSA-positive children were adopted into 13 Swedish families and in 3 families, 6 of 10 family members became MRSA positive. CONCLUSION: Children adopted from foreign countries to Swedish families and with a history of hospitalization in their native country were commonly colonized with MRSA. The throat was the most frequent site colonized and transmission of MRSA from adopted children to other family members occurred.

Adoption↗
PubMed1989

Adoption and identity: a case of anorexia nervosa.

Anorexia nervosa, as a retreat from and subsequent avoidance of intolerable maturational turmoil, can provide a vivid insight, especially as body weight is restored to normal within treatment, into the sexual and identity conflicts that have previously characterized the adolescence of the individual. When the adolescent has been adopted into the family then the challenge of developing biological (genetic) identity is especially great to the individual and his adoptive parents. A rare case of anorexia nervosa in a male adoptee is presented against this background. Our patient's dependent and smothering bond with his adoptive mother, which was loving but highly conditional, left him with no room for negotiation when it was threatened by his emerging sexual and other impulsivity and new assertiveness. Understanding and treatment of such cases can also help to shed light on the particular challenges that face many adoptive parents when their adopted children experience the thrust of puberty and enter adolescence.

Adoption↗
PubMed1999

Adoption: a forgotten paediatric speciality.

OBJECTIVE: To study the medical, emotional, and developmental profile of children being considered for permanent substitute care. DESIGN: A retrospective analysis of 100 adoption/permanency medicals. SETTING: All children considered by the adoption and permanency panel in Greenwich, south east London, between 1994 and 1998. OUTCOME MEASURES: Analysis of medical reports completed using the British Agencies for Adoption and Fostering form C (under 5 years) or form D (over 5 years). These include the details of a physical examination, including vision, hearing, height, and weight; emotional and behavioural concerns expressed by the foster carer and school progress. RESULTS: These children have complex needs. Only 31 of the 100 children were considered unlikely to have significant medical, developmental, or emotional problems. CONCLUSIONS: Adoption medical work is becoming more specialised. Healthcare commissioners should establish minimum standards for the doctors involved in this work. As the NHS moves towards becoming a more primary care led organisation, this small service must not be forgotten. The NHS devotes few resources and little training to adoption. The medical input required to support adoption and fostering services should be recognised as a specialist paediatric service and adequately resourced.

Adolescent↗
PubMed2000

Adoptive transfer of acute lung injury.

In this study, we describe a novel adoptive transfer protocol to study acute lung injury in the rat. We show that bronchoalveolar lavage (BAL) cells isolated from rats 5 h after intratracheal administration of lipopolysaccharide (LPS) induce a lung injury when transferred to normal control recipient rats. This lung injury is characterized by increased alveolar-arterial oxygen difference and extravasation of Evans blue dye (EBD) into lungs of recipient rats. Recipient rats receiving similar numbers of donor cells isolated from healthy rats do not show adverse changes in the alveolar-arterial oxygen difference or in extravasation of EBD. The adoptive transfer-induced lung injury is associated with increased numbers of neutrophils in the BAL, the levels of which are similar to the numbers observed in BAL cells isolated from rats treated for 5 h with LPS. As an indicator of BAL cell activation, donor BAL cell inducible nitric oxide synthase (iNOS) expression was compared with BAL cell iNOS expression 48 h after adoptive transfer. BAL cells isolated 5 h after LPS administration expressed iNOS immediately after isolation. In contrast, BAL cells isolated 48 h after adoptive transfer did not express iNOS immediately after isolation but expressed iNOS following a 24-h ex vivo culture. These findings indicate that the activation state of donor BAL cells differs from BAL cells isolated 48 h after adoptive transfer, suggesting that donor BAL cells may stimulate migration of new inflammatory cells into the recipient rats lungs.

Adoptive Transfer↗
PubMed2004

Failed adoptive immunotherapy with tumor-specific T cells: reversal with low-dose interleukin 15 but not low-dose interleukin 2.

Adoptive immunotherapy with tumor-specific T cells has emerged as a valid approach for prevention or treatment of diseases, such as melanoma and EBV-associated lymphoma. As interleukin (IL) 15 promotes survival of CD8(+) memory CTLs, we hypothesized that it could be used to enhance antitumor immunity in vivo through the maintenance of adoptively transferred memory CTL. To test this, we treated mice bearing P1A(+) tumors with adoptively transferred T cells possessing a transgenic Valpha8(+) T-cell receptor specific for the P1A tumor antigen (called P1CTL). Mice were then randomized to receive daily low-dose IL-15 (0.5 microg/day) or PBS. Mice receiving the transgenic P1CTL and IL-15 experienced a significantly delayed tumor relapse or complete tumor regression (P < 0.002 compared with PBS), with a striking persistence of the CD8(+) Valpha8(+) P1CTL compared with mice receiving the CD8(+) Valpha8(+) P1CTL and PBS vehicle (26.3 versus 5.1% P < 10(-5)). Animals exhibiting complete tumor regression had a significant population of CD8(+) Valpha8(+) P1CTL (46%) that persisted with IL-15 treatment until 140 days after adoptive transfer and successfully defended them against tumor rechallenge without IL-15. Low-dose IL-2 afforded no protection over vehicle and resulted in lower percentages of T cells with an activated memory phenotype, lower Bcl-2 expression, and lower ex vivo antitumor cytotoxicity compared with mice treated with IL-15. Collectively, the data support the notion that exogenous low-dose IL-15 therapy can enhance and even reverse the limited efficacy of adoptively transferred tumor-specific T-cell therapy and may do so in a fashion that is superior and distinct from exogenous IL-2 therapy.

Animals↗
PubMed2002

Early puberty in adopted children.

Early puberty is frequently observed in adopted children. In various studies, early puberty has been associated with decreased final height. In Europe, studies were undertaken to treat early puberty in adopted children with GnRH agonist. This article reviews the current understanding of early puberty in adopted children, including prevalence, background and treatment options. Data from the European studies are briefly described. Besides auxological aspects, psychological items are addressed as well. Studies on the psychological effect of early puberty in adopted children are reported. Future issues include further study in the mechanism of early puberty in adopted children, evaluation of final height results of the growth studies and quality of life assessments in this specific group of children.

Adoption↗
PubMed2002

Tissue distribution of target antigen has a decisive influence on the outcome of adoptive cancer immunotherapy.

Adoptive transfer of allogeneic T cells has unmatched efficacy to eradicate leukemic cells. We therefore sought to evaluate in kinetic terms interactions between T cells and allogeneic leukemic cells. T cells primed against the model B6(dom1) minor histocompatibility antigen were adoptively transferred in irradiated B10 (B6(dom1)-positive) and congenic B10.H7(b) (B6(dom1)-negative) recipients, some of which were also injected with EL4 leukemia/lymphoma cells (B6(dom1)-positive). A key finding was that the tissue distribution of the target epitope dramatically influenced the outcome of adoptive cancer immunotherapy. Widespread expression of B6(dom1) in B10 recipients induced apoptosis and dysfunction of antigen-specific T cells. Furthermore, in leukemic B10 and B10.H7(b) hosts, a massive accumulation of effector/memory B6(dom1)-specific T cells was detected in the bone marrow, the main site of EL4 cell growth. The accumulation of effector/memory cells in recipient bone marrow was EL4 dependent, and its kinetics was different from that observed in recipient spleen. We conclude that strategies must be devised to prevent apoptosis of adoptively transferred T cells confronted with a high antigen load and that local monitoring of the immune response at the site of tumor growth may be mandatory for a meaningful assessment of the efficacy of adoptive immunotherapy.

Animals↗
PubMed2004

Study of oral tolerance and its indirect effects in adoptive cell transfer experiments.

Parenteral exposure to antigens to which oral tolerance had been previously induced results in the inhibition of immune responses to other unrelated antigens. Herein we tested whether indirect effects of oral tolerance could be adoptively transferred. Anti-Ova- and antihemoglobin-specific responsiveness as well as oral tolernace to Ova were transferred to irradiated, but not to normal, nonirradiated recepients. Irradiation, thus, facilitated adoptive transfer of oral tolerance. However, the inhibitory (indirect) effects upon the unrelated immunogen were not adoptively transferred, even to irradiated recepients. In addition, we studied adoptively transferred CFSE-labeled spleen cells by flow cytometry in recipient spleen, inguinal lymph nodes, and bone marrow, both in irradiated and nonirradiated recipients, 1, 3, or 5 days after cell transfer. Comparing the percent and absolute number of CFSE-labeled cells in each organ displayed significant differences in the dynamics of decay of adoptively transferred cells from tolerant or immune donors.

Administration, Oral↗