Health-related quality-of-life measures for children with asthma: reliability and validity of the Children's Health Survey for Asthma and the Pediatric Quality of Life Inventory 3.0 Asthma Module.

BACKGROUND: Economically disadvantaged African American youth are especially vulnerable to the effects of pediatric asthma and are at increased risk for difficulties in daily functioning. Measures of health-related quality of life (HRQoL) yield important information regarding the impact of pediatric chronic illness on daily functioning. It is essential to develop and validate measures of HRQoL to detect the impact of asthma on this vulnerable population. OBJECTIVE: To examine the psychometric properties of 2 asthma-specific measures of pediatric HRQoL in a sample of economically disadvantaged African American children diagnosed as having asthma. METHODS: One hundred twenty-seven caregivers completed questionnaires regarding their child's HRQoL, asthma symptoms, health care utilization, and school absences and regarding caregiver emotional distress. The severity of the child's asthma was measured via spirometry. RESULTS: The Children's Health Survey for Asthma and the Pediatric Quality of Life Inventory 3.0 Asthma Module demonstrated adequate internal consistency reliability and validity for the present sample. Lower HRQoL was associated with poorer adherence and more health care utilization, asthma symptom days, school absences, and caregiver distress. Only the Children's Health Survey for Asthma was significantly associated with severity, when defined as airway obstruction. CONCLUSIONS: This study supports the psychometric equivalence of 2 condition-specific measures of HRQoL in a population at high risk for asthma and asthma-related problems. The utility of each measure will depend on the needs of the researcher or physician. Both measures can inform the treatment course, help identify and address barriers to treatment adherence, and inform treatment interventions.     

Genome scan for loci involved in nonsyndromic cleft lip with or without cleft palate in families from West Bengal, India

In order to identify genes or regions involved in nonsyndromic cleft lip with or without cleft palate (CL/P) in families from India, we analyzed 38 multiplex families (DNA from 272 individuals, 82 affected with CL/P, 190 unaffected) for 285 genome-wide markers (average spacing 12.6 cM), including markers in six candidate loci or regions on chromosomes 2, 4, 6, 14, 17, and 19 that have been implicated in other studies of CL/P. LOD scores (two-point and multipoint), and model-free association (TDT) and linkage (NPL) statistics, were calculated between each of the markers and a hypothetical CL/P susceptibility locus. The most statistically significant two-point linkage results were with markers on chromosome 7 (LOD = 1.89 with D7S435, 7p15, 47 cM), chromosome 5 (LOD = 1.76 with D5S407, 5q11, 65 cM), chromosome 15 (LOD = 1.55 with D15S652, 15q26, 90 cM), and chromosome 20 (LOD = 1.46 with STS155130, 20q13, 54 cM). The most significant multipoint linkage result was on chromosome 5q, again near D5S407 (HLOD = 1.40). Regions on chromosomes 1p, 1q, 7q, 12q, 16q, 18q, and Xp also had a LOD or HLOD > or = 1.0. Of seven candidate markers and regions with previous positive reports in the literature (TGFA, MSX1, D4S175, F13A1, TGFB3, D17S250, and APOC2), none had a significant linkage result, but one (the APOC2 region) had a significant association result and three others (TGFA, MSX1, F13A1) had suggestive results. The results are consistent with the involvement of multiple loci in CL/P expression in this West Bengal population, which concurs with results found in other CL/P study populations.     

Phenotypic characterization of regulatory CD4+CD25+ T cells in rats

CD25 has become widely used as a marker for a subset of regulatory CD4(+) T cells present in the thymus and periphery of mice, rats and humans. However, CD25 is also expressed on conventionally activated T cells that are not regulatory and not all peripheral regulatory T cells express CD25. The identification of a stable and unique marker for regulatory T cells would therefore be valuable. This study provides a detailed account of the phenotype of CD4(+)CD25(+) regulatory T cells in rats. In the thymus, CD4(+)CD8(-)CD25(+) cells were found to have a more mature phenotype than the corresponding CD4(+)CD8(-)CD25(-) cells with respect to expression of Thy1 (CD90), CD53 and CD44, suggesting that CD25 expression, and perhaps commitment to regulatory function, might be a late event in thymocyte development. CD4(+)CD25(+) cells in both the thymus and periphery were found to have enriched and heterogeneous expression of activation markers such as OX40 (CD134) and OX48 (an antibody determined in this study to be specific for CD86). CD4(+)CD25(+) T cells were also found to have enriched expression of CD80, at both the mRNA and protein level. However, functional studies in vitro and in vivo showed that neither OX40 or CD86 were useful markers for the further subdivision of regulatory T cells. Our studies indicate that, at present, CD25 remains the most useful marker to enrich for regulatory CD4(+) T cells in rats and no further subdivision of the regulatory component of CD4(+)CD25(-)CD45RC(low) T cells has yet been achieved.     

Causes of Isolated Aortic Insufficiency in an Urban Population in the 1990s: A Review of 56 Surgical Pathology Cases

Until recently, the cause of isolated aortic insufficiency (AI) was usually thought to be inflammatory or rheumatic in most cases. However, at our institution we have noted a high prevalence of myxomatous degeneration (MD) in aortic valves removed for AI. In this study we report anatomic observations on valves from 56 consecutive patients with isolated AI undergoing aortic valve replacement surgery. Fifty-six consecutive aortic valves removed at our institution from 1994 to 1996 for isolated AI and/or aortic aneurysm were reviewed. Anatomic features were compared with clinical history and echocardiographic data. The anatomic results were also compared to 22 age-matched control aortic valves obtained at autopsy. In 13/56 cases (23%), a specific valvular cause of AI was determined (infectious endocarditis, seven cases; chronic rheumatic disease, four cases; congenital bicuspid valve, two cases). Of the remaining (idiopathic) 43 cases, 18 (42%) had severe isolated MD defined as >50% expansion of the spongiosa and disruption of the fibrosa by the deposition of acid mucopolysaccharides in the absence of severe calcification, fibrosis, or other pathologic findings. Only 1/22 aortic valves from the autopsy controls had severe MD. Eighteen of the 56 patients also had a clinical history of aortic dilatation/aneurysm of which 12 were confirmed to be dilated by echocardiographic criteria. Of these 12, five (42%) had MD of the aortic valve only, three (25%) had both MD and cystic medial degeneration (CMD) of the aorta, two (17%) had CMD of the aorta only, and two (17%) had no specific diagnosis. Isolated MD of the aortic valve is the most common cause of isolated AI in our patient population. Furthermore, in a subset of non-Marfan’s patients with both AI and dilatation of the aortic root/aortic aneurysm the incidence of MD is even higher (67%). These results suggest that there is overlap between MD and CMD in non-Marfan’s patients and that both entities may be part of a spectrum of a generalized connective tissue disorder.     

Cell-free fetal DNA and intact fetal cells in maternal blood circulation: implications for first and second trimester non-invasive prenatal diagnosis

Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development.     

Incidence of delirium and associated mortality in hematopoietic stem cell transplantation patients.

Delirium has been associated with a high risk of mortality in medical patients. Despite the high incidence of delirium in patients who undergo hemapoietic stem cell transplantation (HSCT), delirium as a risk factor for death has not been examined in this population. Thirty adult patients undergoing HSCT who were admitted to the University of Iowa Blood and Marrow Transplantation Program inpatient unit were assessed prospectively from 1 to 2 weeks before transplantation, throughout their inpatient stay, and at 100 days after transplantation. The Delirium Rating Scale and Memorial Delirium Assessment Scale were used twice weekly during the inpatient period to assess delirium severity and occurence. Patients' self-reports of medical history, computerized medical records, and neuropsychological and psychiatric assessments were used to identify pretransplantation risk factors. The incidence of delirium (Delirium Rating Scale score >12 or Memorial Delirium Assessment Scale score >or=8) was 43% and occurred with highest frequency in the first 2 weeks after transplantion. The presence of delirium at any point during hospitalization after transplantation and transplant type (allogeneic) were highly predictive of mortality (p < .0005; odds ratios, 14.0 and 14.4). In conclusion, this study highlights the importance of monitoring for delirium during the acute recovery period after transplantation and suggests that early or even prophylactic treatment for delirium should be studied. Studies to determine the factors that connect delerium soon after transplantation to mortality are highly warranted.     

Detection of somatic mutations in man: evaluation of the microtitre cloning assay for T-lymphocytes

A method of detecting 6-thioguanine-resistant lymphocytes bythe cloning of T-lymphocytes in microtitre wells is evaluatedfor its usefulness in population monitoring. Factors shown toaffect the cloning efficiency of lymphocytes include the strainand irradiation level of the lymphoblastoid feeder cells andthe use of a pre-incubation period in bulk culture without mitogenicstimulus before plating at limiting dilutions. Cord blood sampleshave markedly lower mutant frequencies than adult blood samples.The adult range was 8.0 x 10^–7 to 1.8 x 10^–5. Sevenmales and seven females aged between 23 and 47 years were sampled.No effect of sex or age was found. Individual samples whichwere divided at collection and treated separately did not varyfrom each other, but repeat samples taken at different timesshowd up to a 2-fold variation. The application of this methodin population monitoring is discussed.     

Short term dynamic psychotherapy goes to Hollywood: the treatment of performance anxiety in cinema

This article uses characters in popular films to demonstrate the theory and application of short term dynamic psychotherapy (STDP) in the treatment of performance anxiety. The reader is taught to identify affect phobias that are hypothesized to underlie performance anxiety. Similar in function to external phobias, affect phobias or internal phobias involve the avoidance of feelings (e.g., fear about feeling anger, shame about showing grief, pain about closeness), which thwarts adaptive responding and generates numerous behavioral problems. STDP treatment focuses on the restructuring of defenses, conflicted affects, and attachments. The resolution of the affect phobia requires systematic desensitization of affective responses (i.e., exposure and desensitization of underlying conflicted feelings). When patients learn to access adaptive forms of feelings, performance anxiety can often be resolved.