Stranded seed displacement, migration, and loss after permanent prostate brachytherapy as estimated by Day 0 fluoroscopy and 4-month postimplant pelvic x-ray.

PURPOSE: The aim of the study was to determine the incidence of local displacement, distant seed migration to the chest, and seed loss after permanent prostate brachytherapy (PPB) with stranded seeds (SSs) using sequential two-dimensional fluoroscopic pelvic and chest x-rays. METHODS AND MATERIALS: Between October 2010 and April 2014, a total of 137 patients underwent PPB and 4-month followup pelvic and chest x-ray imaging. All patients had exclusively SSs placed and an immediate postimplant fluoroscopic image of the seed cluster. Followup x-ray images were evaluated for the number, location, and displacement of seeds in comparison to Day 0 fluoroscopic images. Significant seed displacement was defined as seed displacement >1 cm from the seed cluster. Followup chest x-rays were evaluated for seed migration to the chest. RESULTS: Seed migration to the chest occurred in 3 of the 137 patients (2%). Seed loss occurred in 38 of the 137 patients (28%), with median loss of one seed (range, 1-16), and total seeds loss of 104 of 10,088 (1.0%) implanted. Local seed displacement was seen in 12 of the 137 patients (8.8%), and total seeds displaced were 0.15% (15/10,088). CONCLUSIONS: SS placement in PPB is associated with low rates of substantial seed loss, local displacement, or migration to the chest. Comparing immediate postimplant fluoroscopic images to followup plain x-ray images is a straightforward method to supplement quality assurance in PPB and was found to be useful in identifying cases where seed loss was potentially of clinical significance.

Differential recruitment of nuclear receptor coregulators in ligand-dependent transcriptional repression by estrogen receptor-α.

Estrogen receptors (ERs) are normally expressed in breast tissues and mediate hormonal functions during development and in female reproductive physiology. In the majority of breast cancers, ERs are involved in regulating tumor cell proliferation and serve as prognostic markers and therapeutic targets in the management of hormone-dependent tumors. At the molecular level, ERs function as ligand-dependent transcription factors and activate target-gene expression following hormone stimulation. Recent transcriptomic and whole-genome-binding studies suggest, however, that ligand-activated ERs can also repress the expression of a significant subset of target genes. To characterize the molecular mechanisms of transcriptional repression by ERs, we examined recruitment of nuclear receptor coregulators, histone modifications and RNA polymerase II docking at ER-binding sites and cis-regulatory regions adjacent to repressed target genes. Moreover, we utilized gene expression data from patient samples to determine potential roles of repressed target genes in breast cancer biology. Results from these studies indicate that nuclear receptor corepressor recruitment is a key feature of ligand-dependent transcriptional repression by Ers, and some repressed target genes are associated with disease progression and response to endocrine therapy. These findings provide preliminary insights into a novel aspect of the molecular mechanisms of ER functions and their potential roles in hormonal carcinogenesis and breast cancer biology.

Medicaid managed care in Chicago: changes in utilization.

In 1993, Illinois implemented Healthy Moms/Healthy Kids (HM/HK) in Chicago, a Medicaid managed care program for pregnant women and children. This study examines changes in immunizations for children (n = 134,072), prenatal care use for pregnant women (n = 5,151), and inpatient stays for mothers (n = 5,151) and newborns (n = 2,699) under the HM/HK program as compared with fee-for-service Medicaid in 1992 and 1993. HM/HK children were 10 percent more likely to receive any immunizations, and HM/HK pregnant women were 13 percent more likely to receive some prenatal care. Mothers' inpatient stays at delivery did not change under HM/HK. The length of newborn stays fell between 1992 and 1993, with both the HM/HK and the Medicaid 1993 comparison group deliveries associated with statistically shorter stays. During the early months of the program, improvements in the quantity of expected preventive care received were evident among children and women.

Specialty differences in the care of older patients with diabetes.

OBJECTIVES: To determine differences in health status, quality of care, and resource utilization among older diabetic Medicare patients cared for by endocrinologists, internists, family practitioners, and general practitioners. METHODS: The authors analyzed 1,637 patients with diabetes age 65 years or older in the 1994 Medicare Current Beneficiary Survey, a database that links patient surveys to 12 months of Medicare claims data. MEASURES: Measures of morbidity were Basic and Instrumental Activities of Daily Living, health perception, Charlson Comorbidity Index score, and diabetic complications. Quality of care markers were measurement of ophthalmologic visit, lipid testing, glycosylated hemoglobin measurement, mammography, influenza vaccination, early hospital readmission, outpatient follow-up, and patient satisfaction. Resource utilization included reimbursement, relative value units, physician and emergency department visits, and hospitalizations. Age, gender, race, and education were adjusted for in multivariable analyses. RESULTS: Compared with patients of family practitioners, patients of endocrinologists and internists had more comorbidity and diabetic complications but similar health perception and deficiencies in activities of daily living. The patients of endocrinologists also had higher utilization of ophthalmologic screening, lipid testing, and glycosylated hemoglobin measurement than the patients of generalist physicians, but similar rates of influenza vaccination. Patients of endocrinologists and internists had higher total reimbursement than those of family practitioners and general practitioners. Patient satisfaction was generally similar. CONCLUSIONS: Older diabetic patients of endocrinologists had higher utilization of diabetes-specific process of care measures and had similar functional status despite more diabetic complications. However, they received a more costly style of care than patients of family practitioners and general practitioners. Future work needs to explore the optimal coordination of care of diabetic patients among different health providers.

Maternal minimum-stay legislation: cost and policy implications.

OBJECTIVES: Recently, most state legislatures and Congress have passed laws mandating insurance coverage for a minimum period of inpatient care following delivery. This study analyzed the likely cost implications of one state's law. METHODS: Hospital discharge records for Illinois women who gave birth (n = 167,769) and infants born (n = 164,905) during a 12-month period predating the law were analyzed. RESULTS: As a percentage of total spending on birth-related admissions and readmissions, the net effect of the law ranges from a savings of 0.1% to a cost of 20.2%. CONCLUSIONS: There may be large cost implications to this legislation, even with savings from avoided re-admissions.

Diabetes in the African-American Medicare population. Morbidity, quality of care, and resource utilization.

OBJECTIVE: To determine whether African-American Medicare recipients with diabetes are at increased risk for morbidity, poor quality of care, and high resource utilization. RESEARCH DESIGN AND METHODS: We analyzed 1,376 patients with diabetes who were > or = 65 years of age and in the 1993 Medicare Current Beneficiary Survey. Morbidity measures were the Katz Index of Activities of Daily Living, Instrumental Activities of Daily Living, overall health perception, Charlson Comorbidity Index score, and diabetic complications. Quality of care standards were glycosylated hemoglobin measurements, ophthalmological visits, lipid testing, mammography, influenza vaccination, readmission within 30 days of hospital discharge, and outpatient visits within 4 weeks of hospital discharge. We stratified Medicare reimbursement by type of service and adjusted for sex, education, and age in multivariable analyses. RESULTS: Compared with white patients, African-American patients had worse health perception and lower quality of care. They were more likely to visit the emergency department and had fewer physician visits per year. African-Americans had higher reimbursement for home health services, but total reimbursement was similar after case-mix adjustment. CONCLUSIONS: Improved access to preventive care for older African-Americans with diabetes may improve health perception and use of the emergency department. The potential effect on total reimbursement is unclear. Future policy interventions to improve quality of care among Medicare patients with diabetes should especially target African-Americans.

Social-emotional characteristics of preschool-aged children referred for Child Find screening and assessment: a comparative study.

Differences in parent ratings of social-emotional behavior among young children referred for Child Find screening and assessment and nonreferred children were examined. Participants included 64 preschool-aged children referred for Child Find screening and assessment (CF group) and 64 preschool-aged children without such referrals or identified disabilities (Comparison group). The Comparison group was matched to the CF group by gender and age, using a randomized block procedure. Social-emotional behavior of the participants was assessed using parent ratings on the Preschool and Kindergarten Behavior Scale (PKBS), a social skills and problem-behavior rating scale for use with children aged 3-6. PKBS scores were found to classify the participants into their respective groups with a substantial degree of accuracy. Significant differences were found between the two groups in social skills and problem behavior scores, with the CF participants evidencing greater social skills deficits and problem behavior excesses than the participants in the Comparison group. An inspection of frequency distributions of the two groups revealed that children referred for Child Find screening were approximately four times as likely to have significant social deficits, and approximately six times as likely to have significant problem-behavior excesses than their nonreferred comparison peers. New validity evidence for the PKBS is provided, along with recommendations for future research and clinical practice with the Child Find population.

Reliability of children's self-reported internalizing symptoms over short to medium-length time intervals.

OBJECTIVE: To determine whether children between the ages of 8 and 12 years are able to reliably report internalizing symptoms over short to medium-length time intervals as measured by an objective self-report instrument of internalizing symptoms. METHOD: The Internalizing Symptoms Scale for Children (ISSC) was group-administered initially to 131 children and at subsequent intervals of 2 weeks, 4 weeks, and 12 weeks. RESULTS: Pearson product-moment correlations for the ISSC total scores of the participants were computed across the various retest intervals. At 2 weeks, the correlation was .84. At 4 weeks, the correlation was .76. After 12 weeks, the correlation was .74. CONCLUSIONS: These data indicate that children between 8 and 12 years old can reliably report their experience over short to medium-length intervals. These findings provide strong support for the ISSC as a research and clinical instrument for the assessment of internalizing symptoms in children between 8 and 12 years of age, which may ultimately prove beneficial in the identification and treatment of childhood internalizing disorders. Limitations and recommendations for future research are discussed.

Social-emotional behavior of preschool-age children with and without developmental delays.

Differences in parent and teacher ratings of social-emotional behavior among young children with developmental delays and those without significant developmental problems were examined. Participants included 198 preschool-age children identified as having a developmental delay (DD group) and 198 preschool-age children without significant developmental problems (Comparison group) who were matched to the DD group by age and gender, using a randomized block procedure. Parent and teacher perceptions of social-emotional behavior of the participants were assessed using the Preschool and Kindergarten Behavior Scale (PKBS), a social skills and problem behavior rating scale for the use with young children. PKBS scores were found to classify the participants into their respective groups with a substantial degree of accuracy. Statistically significant differences in social skills and problem behavior scores between the two groups were found, with the DD participants evidencing greater social skills deficits and problem behavior excesses than the Comparison group. Individuals in the DD group were found to be four to five times more likely to have significant social skills deficits and problem behavior excesses than individuals in the Comparison group. The critical social-emotional behaviors separating the two groups appeared to be social interaction and independence skills, and socially withdrawn and isolated behavior patterns. New validity evidence for the PKBS is discussed, as are future needs pertaining to research and clinical practice in the area of social-emotional behavior of young children with developmental delays.

The absence of the transcription activator TFE3 impairs activation of B cells in vivo.

TFE3 is a ubiquitously expressed member of the TFE3/mi family of basic helix loop helix zipper transcription factors. TFE3 binds to muE3 sites located in the immunoglobulin heavy-chain (IgH) intronic enhancer, heavy-chain variable region promoters, the Ig kappa intronic enhancer, and regulatory sites in other genes. To understand the role of TFE3 in Ig expression and lymphoid development, we used embryonic stem (ES) cell-mediated gene targeting and RAG2-/- blastocyst complementation to generate mice which lack TFE3 in their B and T lymphocytes. TFE3- ES cells fully reconstitute the B- and T-cell compartments, giving rise to normal patterns of IgM+ B220+ B cells and CD4+ and CD8+ T cells. However, TFE3- B cells show several defects consistent with poor B-cell activation. Serum IgM levels are reduced twofold and IgG and IgA isotypes are reduced three- to sixfold in the TFE3- chimeras even though in vitro, the TFE3- splenocytes secrete normal levels of all isotypes in response to lipopolysaccharide activation. Peripheral TFE3- B cells also show reduced surface expression of CD23 and CD24 (heat-stable antigen).

Medicare beneficiaries covered by Medicaid buy-in agreements.

About 13 percent of Medicare beneficiaries receive some assistance from Medicaid. States "buy in" Medicare coverage for these low-income beneficiaries. For those eligible, states also provide benefits beyond those covered by Medicare. Buy-in beneficiaries are different from other Medicare beneficiaries in many ways. They have lower incomes, which is consistent with the policy intent. They use more health services in general but do not appear to receive timely, appropriate care relative to several disease-specific standards. As policymakers consider restructuring Medicare and Medicaid, careful attention needs to be paid to the effects of changes on these beneficiaries.

Prostate cancer, race, and socioeconomic status: inadequate adjustment for social factors in assessing racial differences.

BACKGROUND: This paper reviews the state of the art in analyzing race, social factors, and economic factors in cancer research, with an emphasis on prostate cancer and the role of socioeconomic status (SES) in racial differences in mortality. It analyzes the quality of articles in the literature that assess the role of SES in cancer mortality. METHODS: English-language titles were identified using MEDLINE with publication dates from mid-1985 through July 1994. Articles in the references of these articles were also included in the final selection, based originally on title and ultimately on content, dating back to 1978. Articles that included SES information and distinguished between whites and African-Americans were chosen, resulting in a final selection of 21 articles. Articles are summarized with consideration of five criteria considered minimal requirements of a well-designed study of the role of race in cancer mortality: (1) SES measure(s) should be on an individual level, not census level; (2) SES should be controlled for when making comparisons between whites and blacks; (3) SES should include at least (individual level) measures of income and education; (4) sample sizes are sufficient for the relevant populations; and (5) specific cancer sites should be studied separately. RESULTS: Of the articles reviewed, only two meet the minimum standards, neither of which studied prostate cancer. It is not clear whether observed racial differences in prostate cancer are directly attributable to race or reflect underlying social factor differences between whites and African-Americans. CONCLUSIONS: In the future, specific characteristics of SES should be measured at the individual level; there is a need for expansion and standardization of data in terms of social and economic content; other methodological advances are needed in modeling to take into consideration the influence of SES in outcome research related to cancer.

v-Abl activates c-myc transcription through the E2F site.

The v-abl oncogene of Abelson murine leukemia virus encodes a deregulated form of the cellular nonreceptor tyrosine kinase. v-Abl activates c-myc transcription, and c-Myc is an essential downstream component in the v-Abl transformation program. To explore the mechanism by which v-Abl activates c-myc transcription, a cotransfection assay was developed. We show that transactivation of a c-myc promoter by v-Abl requires the SH1 (tyrosine kinase) and SH2 domains of v-Abl; the C-terminal domains are not required for transactivation. The assay also identified the E2F site in the c-myc promoter as a v-Abl-responsive element. In addition, multimerized E2F sites were shown to be sufficient to confer v-Abl-dependent activation on a minimal promoter. This is the first identification of a v-Abl response element for transcriptional activation. v-Abl tyrosine kinase-dependent changes in proteins binding the c-myc E2F site were also demonstrated, including induction of a complex containing DP1, p107, cyclin A, and cdk2. Identification of v-Abl-dependent changes in E2F-binding proteins provides an important link between v-Abl, transcription, cell cycle regulation, and control of cellular growth.

TFE3 contains two activation domains, one acidic and the other proline-rich, that synergistically activate transcription.

TFE3 is a basic-helix-loop-helix-zipper (bHLHZIP) domain-containing protein that binds mu E3 sites in regulatory elements in the immunoglobulin heavy chain gene. The protein is a transcriptional activator that is expressed in vivo as two alternately spliced isoforms with different activating properties: TFE3L contains an N-terminal acidic activation domain; TFE3S lacks this activation domain and is a dominant negative inhibitor of TFE3L. We show that TFE3L and TFE3S contain a second, C-terminal activation domain rich in proline residues. This pro-rich activation domain has activity in a Gal4 fusion assay comparable to the N-terminal acidic activation domain present in TFE3L. The TFE3 pro-rich activation domain contains regions of strong homology with the related proteins microphthalmia and TFEB, suggesting that these regions are important for function. Using two different assays, we show that the N- and C-terminal activation domains of TFE3 act synergistically. This synergism explains in part the ability of TFE3S to act as a dominant negative. Our domain analysis of TFE3 is incorporated into a general structural model for the TFE3 protein that predicts that the activation domains of TFE3 will be widely separated in space.

Genetic analyses of tattered, an X-linked dominant, developmental mouse mutation.

Tattered (Td) is an X-linked dominant mouse mutation that causes prenatal lethality in affected males. To map the locus, we analyzed 199 normal male and affected female progeny from a backcross of Td and Mus castaneus. Pedigree analysis of these animals suggests a gene order of cen-DXWas70-(Td, DXMit26, Gata1, Tcfe3)-(Cybb, Otc)-tel, where Tcfe3 is a transcription factor homologous to a gene involved in the murine microphthalmia (mi) mutation [Hodgkinson et al. Cell 74, 395-404, 1993]. To evaluate Tcfe3 as a candidate for Td, heterozygous tattered females were crossed to xid males to obtain females in which > 95% of B cells expressed genes solely from the Td X Chromosome (Chr). Fluorescent activated cell sorting (FACS) analysis and Western blotting of isolated splenocytes from Td/xid double heterozygotes rule out Tcfe3 as a likely candidate for the Td mutation.

A role for c-Abl in c-myc regulation.

c-Abl, a nonreceptor tyrosine kinase, appears to play a role in cell cycle progression, cell proliferation and differentiation. Mice homozygous for a mutation in c-abl (ablml), show pleiotropic abnormalities, including neonatal death, developmental defects, susceptibility to infection and dehydration (Schwartzberg et al., 1991). However, the exact substrates of c-Abl and the signal transduction pathways it might initiate are not known. We have examined how c-Abl affects c-myc expression by studying ablml mice. Quantitative riboprobe analyses demonstrated that in the heart, liver, thymus, brain, testes, intestines and lung, there were no differences in the steady-state level of c-myc RNA between the ablml mice and littermate controls. However, in adrenal glands, kidneys and splenic B cells, c-myc RNA levels were decreased approximately 50% compared to littermate controls. Induction of c-myc mRNA following activation of splenic B cells with LPS is also defective in ablml splenocytes. Finally, we show that c-Abl can directly transactivate c-myc transcription. These results suggest that c-Abl is involved in the normal transcription regulation of c-myc in selected tissues and that decreased c-myc RNA could be one cause of abnormalities in the ablml mice.

The alliance of adaptive behavior and social competence: an examination of relationship between the scales of Independent Behavior and the Social Skills Rating System.

This study examined the relationship between ratings of adaptive behavior and social competence in a population of 208 students in kindergarten through third grade with a variety of disabilities using the Scales of Independent Behavior (SIB; Bruininks, Woodcock, Weatherman, & Hill, 1984) and the Social Skills Rating System (SSRS; Gresham & Elliott, 1990). Moderate yet statistically significant relationships between the SIB adaptive behavior scores and the SSRS social competence scores were found, with strongest correlations occurring between the SSRS and the Social and Communication subscale (r = .51) and Work Skills subscale (r = .60) on the SIB. Weak to near zero correlations were found between the SIB adaptive behavior scores and SSRS Problem Behaviors scores. This investigation provides new evidence for the concurrent criterion-related validity of both the SIB and the SSRS.

Yin-yang 1 activates the c-myc promoter.

Previous studies on the murine c-myc promoter demonstrated that a ubiquitously present protein, common factor 1 (CF1), bound at two sites located -260 and -390 bp from the P1 transcription start site. CF1 has been purified to near homogeneity and shown to be identical to the zinc finger protein Yin-yang 1 (YY1) as judged by similarity of molecular weight and other biochemical properties, immunological cross-reactivity, and the ability of recombinant YY1 to bind to CF1 sites. In cotransfection experiments, YY1 is a strong activator of transcription from c-myc promoter-based reporters. Furthermore, in murine erythroleukemia cells, overexpressed YY1 causes increased levels of c-myc mRNA initiated from both major transcription initiation sites of the endogenous c-myc gene.

Transcriptional repressor ZF5 identifies a new conserved domain in zinc finger proteins.

We have cloned a cDNA encoding a new murine C2H2 zinc finger protein, ZF5. The 51.3 kD protein contains five GL1-Kruppel type zinc fingers at the C-terminus. At its N-terminus, ZF5 has a 41 amino acid region which was found to be homologous to the N-termini of several other zinc finger proteins. This region defines a new motif within zinc finger proteins which we have named the Zinc finger N-terminal (ZiN) domain. ZF5 binds to two sites in the c-myc promoter and to the -50 bp site of the herpes simplex thymidine kinase promoter. ZF5 is a transcriptional repressor and its repression domain is located N-terminal to the zinc finger domains. A single 4 kb ZF5 mRNA is expressed widely.