Attachment and depression. Implications for family therapy.

The preceding discussion highlights the use of attachment theory in conceptualizing the interface between normal development and the manifestation of depression from infancy through adolescence. Additional research is needed to delineate better the specific nature of the association between attachment relationships and depression, particularly with regard to factors that mediate and moderate the link. The extant literature informs family-oriented clinical interventions with depressed young people with comorbid attachment problems, with or without a depressed parent. These family interventions are most likely to be effective if they incorporate developmentally informed conceptualizations and techniques and are targeted specifically to the problems of depressed youth and their families. The efficacy of such interventions remains to be determined through the implementation of treatment efficacy and effectiveness studies.

Interleukin 20: discovery, receptor identification, and role in epidermal function.

A structural, profile-based algorithm was used to identify interleukin 20 (IL-20), a novel IL-10 homolog. Chromosomal localization of IL-20 led to the discovery of an IL-10 family cytokine cluster. Overexpression of IL-20 in transgenic (TG) mice causes neonatal lethality with skin abnormalities including aberrant epidermal differentiation. Recombinant IL-20 protein stimulates a signal transduction pathway through STAT3 in a keratinocyte cell line, demonstrating a direct action of this ligand. An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis.

Anxiety and depression in mothers of children undergoing bone marrow transplant: symptom prevalence and use of the Beck depression and Beck anxiety inventories as screening instruments.

This study examined anxiety and depressive symptoms among 115 mothers of children undergoing bone marrow transplant and evaluated the ability of the Beck Anxiety Inventory (BAI; A. T. Beck, N. Epstein, et al., 1988) and the Beck Depression Inventory (BDI; A. T. Beck, 1978) to serve as screening tools for assessing generalized anxiety disorder (GAD), panic disorder (PD), and major depressive disorder (MDD). Mothers with BAI or BDI scores greater than or equal to 14 were administered a structured clinical interview. An additional 20% was randomly selected for interview to determine whether the scale cutoff was an accurate screening method. Among the 64 mothers interviewed, 20% received at least I of the 3 diagnoses. Although the BAI did not demonstrate predictive accuracy in assessing GAD and PD, the BDI did in assessing MDD. The results suggest that a subset of mothers may have an anxiety or depressive disorder and that investigators should use caution before using the BAI as a screening instrument for anxiety disorder.

General method for plasmid construction using homologous recombination.

We describe a general method for plasmid assembly that uses yeast and extends beyond yeast-specific research applications. This technology exploits the homologous recombination, double-stranded break repair pathway in Saccharomyces cerevisiae to join DNA fragments. Synthetic, double-stranded "recombination linkers" were used to "subclone" a DNA fragment into a plasmid with > 80% efficiency. Quantitative data on the influence of DNA concentration and overlap length on the efficiency of recombination are presented. Using a simple procedure, plasmids were shuttled from yeast into E. coli for subsequent screening and large-scale plasmid preps. This simple method for plasmid construction has several advantages. (i) It bypasses the need for extensive PCR amplification and for purification, modification and/or ligation techniques routinely used for plasmid constructions. (ii) The method does not rely on available restriction sites, thus fragment and vector DNA can be joined within any DNA sequence. This enables the use of multifunctional cloning vectors for protein expression in mammalian cells, other yeast species, E. coli and other expression systems as discussed. (iii) Finally, the technology exploits yeast strains, plasmids and microbial techniques that are inexpensive and readily available.

An islet-cell protein tyrosine phosphatase is a likely precursor to the 37-kDa autoantigen in type 1 diabetes: human and macaque sequences, tissue distribution, unique and shared epitopes, and predictive autoantibodies.

BACKGROUND: We sought to identify novel islet-cell autoantigens to better understand the pathogenesis, prediction, and immunotherapy of type 1 diabetes. MATERIALS AND METHODS: Macaque and human islet cDNA libraries expressed in mammalian cells were screened with human diabetes sera. A positive clone was sequenced directly and after 5' rapid amplification of cDNA ends (RACE). Northern blotting and in situ hybridization revealed the tissue distribution of the corresponding protein. Antigen, expressed by in vitro translation, and tryptic peptides were analyzed by SDS-PAGE. For the immunoprecipitations, 183 diabetic, 60 prediabetic, and 91 control sera were used. Truncated antigens were used in immunoprecipitations for epitope mapping. Recombinant antigen expressed in transfected fibroblasts was used in competition assays. RESULTS: Sequencing yielded an 111-kDa, 1,013 amino acid, transmembrane protein (M1851) containing consensus protein tyrosine phosphatase (PTPase) sequence. M1851 was 77% identical in the intracellular domain, but only 31% identical extracellularly, to the islet-cell autoantigen ICA512. mRNA localized to brain, prostate, pancreatic islets, and adrenal medulla. After limited trypsinization, the in vitro translated antigen was 37 kDa. M1851 was recognized by 47% of prediabetes sera, 31% of new diabetes sera, but only 1% of healthy controls. Only 1/73 sera binding M1851 failed to bind ICA512, whereas 42/114 binding ICA512 did not bind M1851. M1851 reactivity was not fully displaced by ICA512 in 24/49 sera. Removing the C-terminal 27, 80, or 160 amino acids of M1851 decreased reactivity by 70%, 90%, and 100%, respectively. CONCLUSIONS: This new islet-cell PTPase is likely to be the precursor to the 37-kDa tryptic fragment antigen. It is structurally related to ICA512 but has distinct diabetes autoantibody epitopes located at the C terminus.

Adolescent cancer survivors. Psychosocial and familial adaptation.

Adolescent cancer survivors were compared with nondiseased control subjects on measures of adaptation, coping, body image, sexual adjustment, psychopathology, and family functioning. Cancer survivors reported no major difficulties in social competence, overall coping, and family communication. Although their school teachers reported no symptoms of psychopathology, the cancer survivors did report body image disturbances and adjustment difficulties. Further, the surviving adolescents were eager to present themselves favorably. Compared with nondiseased control families, families of survivors were characterized as somewhat inflexible. Implications for clinical practice include the careful monitoring of youth who have survived cancer as well as sensitivity to underlying concerns that the survivors and their families may avoid.

Parental psychopathology and children's adjustment to leukemia.

OBJECTIVE: The primary purpose of this study was to examine the relationship between parental psychopathology and psychosocial functioning of children in whom acute lymphocytic leukemia (ALL) has been diagnosed. METHOD: The sample consisted of 61 mother-child dyads. Twenty-one (34%) mothers met DSM-III-R criteria for at least one psychiatric disorder based on a Structured Clinical Interview for Diagnosis (SCID). RESULTS: Findings revealed that compared with children whose mothers did not meet DSM-III-R criteria for a psychiatric disorder, children with mothers who evidenced a psychiatric disorder self-reported more anxiety and a maladaptive attributional style and were reported by their mothers as evidencing more depression and a range of internalizing behavioral symptoms. CONCLUSIONS: Although our earlier research suggested that ALL children show relatively few symptoms of psychopathology, the present report reveals high rates of psychiatric difficulties in the mothers of ALL youth. These findings and their implications are discussed within a model that incorporates behavioral pediatrics and developmental psychopathology.

School reentry for the child with chronic illness.

Chronic illness affects up to 20% of children in the school-age population, 10% of whom are severely compromised. Reintegrating these children is a growing problem for schools, children and their families, and health care professionals, as it has become apparent that school adjustment is highly significant in the children's overall adjustment. This article focuses on the issues of reintegrating the chronically ill child into the school setting, the types of school problems encountered, the process of school reentry, with illustrative case material, and the implications for the school and family of returning the chronically ill child to school.

Cognitive development and learning in the pediatric organ transplant recipient.

Although organ transplantation is considered a viable treatment approach for end-stage organ disease, few empirical investigations have assessed the effects of transplantation on the cognitive development and learning of pediatric organ transplant recipients. This article reviews studies evaluating neurocognitive changes following organ transplantation in pediatric end-stage renal and liver disease. Despite numerous methodological problems inherent in the investigations examined, the findings of some studies are suggestive of potential neurocognitive benefits associated with organ transplantation. Recommendations are made regarding methodological improvements for future investigations assessing neurocognitive outcomes of organ transplantation.

Chemotherapy for acute lymphocytic leukemia: cognitive and academic sequelae.

Iatrogenic cognitive impairments have been reported for survivors of childhood leukemia after prophylactic central nervous system therapy with craniospinal radiation. To determine whether chemotherapy alone might be a source of central nervous system damage, we assessed in a cross-sectional design the cognitive and academic functioning of 48 children with acute lymphocytic leukemia who were at various stages in their treatment or who had completed treatment. The off-therapy patients who had completed a 3-year course of chemotherapy were more impaired in tasks of higher-order cognitive functioning than were those children whose leukemia had been newly diagnosed and those children whose diagnoses had been 1 year earlier. Off-therapy patients also had concomitant diagnosable learning disabilities in mathematics. We recommend appropriate liaison and special education placements, as well as continued evaluation of cognitive and leaning functioning of children treated for moderate-risk acute lymphocytic leukemia who receive chemotherapy alone.

Cognitive status of children treated with central nervous system prophylactic chemotherapy for acute lymphocytic leukemia.

Treatment-related cognitive impairments have been reported for survivors of childhood leukemia following prophylactic central nervous system (CNS) treatment with craniospinal radiation. We examined the neurocognitive status of 46 children with acute lymphocytic leukemia (ALL) to assess the impact of a regimen consisting of systemic chemotherapy and prophylactic CNS chemotherapy. By comparing three groups of ALL children (i.e., patients whose diagnosis was recent, patients 1 year postdiagnosis currently receiving CNS prophylactic chemotherapy, and off-therapy patients who had been treated with chemotherapy for 3 years) and their healthy siblings on measures of sequential and simultaneous processing, we were able to examine the effects of CNS prophylactic and systemic chemotherapy at various points during treatment. Results indicate that the children who had received a 3-year course of chemotherapy (off-therapy patients) were more impaired on tasks involving right-hemisphere simultaneous processing than were sibling controls or ALL children whose diagnosis was recent and whose treatment had just begun. Age at diagnosis did not interact with the effects of chemotherapy. These findings support the need for continued evaluation of cognitive functioning in ALL, children receiving CNS prophylactic chemotherapy to identify potential harmful neurocognitive sequelae of treatment.

Psychiatric and family functioning in children with leukemia and their parents.

The present study reports data from a cross-sectional investigation of the psychiatric and psychosocial functioning of 55 children diagnosed with acute lymphocytic leukemia and their families at three points in time: diagnosis (newly diagnosed), 1 year postdiagnosis, and 1 year after the completion of chemotherapy (off-therapy). Results reveal minimal psychopathology in these children and their parents based on self- and informant-reports and structured diagnostic interviews. These families appear to be functioning adequately and report more family cohesiveness and marital satisfaction after chemotherapy was completed. Coping strategies commonly used by children and their parents include problem-solving, a positive outlook, and good communication. Implications for psychiatric consultation are presented.

Training directors' opinions about the psychiatry resident in-training examination (PRITE).

OBJECTIVE: The American College of Psychiatrists conducted research to validate the content outline of the Psychiatry Resident In-Training Examination (PRITE) and to assess what residency training directors think about the examination. METHOD: A mail survey was sent to the 218 psychiatry residency training directors who subscribe to the PRITE. RESULTS: The survey response rate was 70%. A majority of the respondents indicated agreement with the relative emphasis given to each content area in the PRITE (range = 52%-80% agreement). Eighty-one percent of the respondents were strongly in favor of continuing the practice of releasing the examination and the correct responses each year after the examinations have been scored. The majority of the respondents use results on the PRITE for individual resident evaluation and program evaluation (90% and 94%, respectively). Very few respondents use the PRITE results as the sole measure for assessing residents' cognitive competence or use it for marketing their residency programs. CONCLUSIONS: The survey provided strong support for the content areas covered in the PRITE and their relative emphases. The current practice of releasing PRITE items and answers (a main difference between the PRITE and the certification examination of the American Board of Psychiatry and Neurology) was well supported by the survey results. The stated purpose of the PRITE, to provide educationally useful feedback for individuals and groups in the form of comparisons with peers in specific areas of knowledge, was supported by a large majority of the respondents.

Organization and development of pediatric medical-psychiatric units. Part II: Clinical management issues.

Scant literature exists regarding combined medical-psychiatric units for pediatric populations. The present article is the second in a two-part series describing issues relevant to the organization and development of such a unit within a tertiary-care children's hospital. Case examples of medical-psychiatry patients are presented, together with summary patient statistics for the first 3 years of operation. Additionally, issues regarding the physical layout, treatment program, and staffing are discussed.

Organization and development of pediatric medical-psychiatric units. Part I: Administrative, financial, and political issues.

The growing literature regarding the development of medical-psychiatric units to facilitate diagnosis and treatment of patients with combined medical and psychiatric disorders is primarily limited to adult populations. Almost no published information is available concerning combined pediatric medical-psychiatric units. This article, the first in a two-part series, outlines the organization and development of a child and adolescent medical-psychiatric unit within a pediatric hospital. Various academic, administrative, political, financial, and clinical issues that must be considered during the developmental process are delineated and discussed. The second part of the series will address clinical management issues.

The significance of intracompartmental pressures in the diagnosis of chronic exertional compartment syndrome.

Chronic exertional compartment syndrome is one cause of pain in the lower extremity, a common disability in athletes. The significance of intracompartmental pressures in the diagnosis of chronic exertional compartment syndrome is somewhat controversial. The goal of this study was to review the compartment pressure tests in a group of patients that underwent fasciotomy for refractory exertional compartment syndrome and to compare these pressures with an asymptomatic control group. The results are presented and compared with those of previous studies.

Effects of methylphenidate on cardiovascular responses in attention deficit hyperactivity disordered adolescents.

The short-term dose effects of methylphenidate were examined on cardiovascular measures in 11 black male adolescents diagnosed as having attention deficit hyperactivity disorder (ADHD). In a double-blind, cross-over design with randomized order, the subjects received placebo and each of three methylphenidate doses (0.15, 0.3, and 0.5 mg/kg) for a period of 2 weeks per medication dosage. Significant main effects were found for diastolic and systolic blood pressure; however, pairwise comparisons revealed a significant linear increase in diastolic blood pressure only. Because of the unexpected increase in diastolic blood pressure, careful monitoring of black adolescents who are receiving methylphenidate is recommended.

A controlled trial of methylphenidate in black adolescents. Attentional, behavioral, and physiological effects.

The short-term effects of methylphenidate were examined on behavioral, laboratory, academic, and physiological measures in 11 black male adolescents diagnosed as having attention deficit disorder (ADD). In a double-blind, crossover design with randomized order, the subjects received placebo and each of three methylphenidate doses (0.15 mg/kg, 0.30 mg/kg, and 0.50 mg/kg) for a period of 2 weeks per medication dosage. Significant drug effects were found for the majority of measures. In general, the higher doses resulted in the most beneficial response in behavioral, academic, and laboratory measures of attention and impulsivity. However, a significant linear increase occurred in diastolic blood pressure. The results suggest that methylphenidate is an effective adjunct to the treatment of ADD in adolescents.