Retrospective evaluation and dating of non-accidental rib fractures in infants.

AIM: To describe the sequential appearance of healing rib fractures on initial and follow-up radiographs using published guidelines in approximating the age of rib fractures in infants with the aim of establishing a more objective method of dating rib fractures by measuring the thickness of the callous formation. MATERIALS AND METHODS: This was a retrospective analysis of initial and follow-up digital skeletal surveys of infants less than 12 months of age performed between January 2008 and January 2012 at the University of California Davis Children's Hospital. Six radiological features of rib fractures evaluating the appearance of the callous formation (C stage) and fracture line (F stage) were assessed. Patients with osteogenesis imperfecta, known vitamin D deficiency, and skeletal or metabolic dysplasia were not included in the study. Thereafter, callous thickness was measured and recorded for each stage. RESULTS: Sixteen infants (age range 1-11 months, seven males and nine females) with 23 rib fractures were analysed. The thickness of the callous formation follows a predictable pattern advancing one stage after a 2-week follow-up with progressive callous thickening starting from stage 2, peaks at around stage 4, and then tapers and remodels until it almost disappears when the fracture is healed at stage 6. CONCLUSION: It appears that rib fractures in infants follow a predictable pattern of healing. Measuring the thickness of the callous formation is a more objective way of guiding the radiologist in estimating the age of the fracture.

New limit on time-reversal violation in beta decay.

We report the results of an improved determination of the triple correlation DP·(p(e)×p(v)) that can be used to limit possible time-reversal invariance in the beta decay of polarized neutrons and constrain extensions to the standard model. Our result is D=[-0.96±1.89(stat)±1.01(sys)]×10(-4). The corresponding phase between gA and gV is ϕAV=180.013°±0.028° (68% confidence level). This result represents the most sensitive measurement of D in nuclear ß decay.

Measurement of Parity Violation in np Capture: the NPDGamma Experiment.

The NPDGamma experiment will measure the parity-violating directional gamma ray asymmetry A γ in the reaction [Formula: see text]. Ultimately, this will constitute the first measurement in the neutron-proton system that is sensitive enough to challenge modern theories of nuclear parity violation, providing a theoretically clean determination of the weak pion-nucleon coupling. A new beam-line at the Los Alamos Neutron Science Center (LANSCE) delivers pulsed cold neutrons to the apparatus, where they are polarized by transmission through a large volume polarized (3)He spin filter and captured in a liquid para-hydrogen target. The 2.2 MeV gamma rays from the capture reaction are detected in an array of CsI(Tl) scintillators read out by vacuum photodiodes operated in current mode. We will complete commissioning of the apparatus and carry out a first measurement at LANSCE in 2004-05, which would provide a statistics-limited result for A γ accurate to a standard uncertainty of ±5 × 10(-8) level or better, improving on existing measurements in the neutron-proton system by a factor of 4. Plans to move the experiment to a reactor facility, where the greater flux would enable us to make a measurement with a standard uncertainty of ±1 × 10(-8), are actively being pursued for the longer term.

Commissioning of the NPDGamma Detector Array: Counting Statistics in Current Mode Operation and Parity Violation in the Capture of Cold Neutrons on B 4 C and (27) Al.

The NPDGamma γ-ray detector has been built to measure, with high accuracy, the size of the small parity-violating asymmetry in the angular distribution of gamma rays from the capture of polarized cold neutrons by protons. The high cold neutron flux at the Los Alamos Neutron Scattering Center (LANSCE) spallation neutron source and control of systematic errors require the use of current mode detection with vacuum photodiodes and low-noise solid-state preamplifiers. We show that the detector array operates at counting statistics and that the asymmetries due to B4C and (27)Al are zero to with- in 2 × 10(-6) and 7 × 10(-7), respectively. Boron and aluminum are used throughout the experiment. The results presented here are preliminary.

MondoA, a novel basic helix-loop-helix-leucine zipper transcriptional activator that constitutes a positive branch of a max-like network.

Max is a common dimerization partner for a family of transcription factors (Myc, Mad [or Mxi]), and Mnt [or Rox] proteins) that regulate cell growth, proliferation, and apoptosis. We recently characterized a novel Max-like protein, Mlx, which interacts with Mad1 and Mad4. Here we describe the cloning and functional characterization of a new family of basic helix-loop-helix-leucine zipper heterodimeric partners for Mlx termed the Mondo family. MondoA forms homodimers weakly and does not interact with Max or members of the Myc or Mad families. MondoA and Mlx associate in vivo, and surprisingly, they are localized primarily to the cytoplasm of cultured mammalian cells. Treatment of cells with the nuclear export inhibitor leptomycin B results in the nuclear accumulation of MondoA and Mlx, demonstrating that they shuttle between the cytoplasmic and nuclear compartments rather than having exclusively cytoplasmic localization. MondoA preferentially forms heterodimers with Mlx, and this heterocomplex can bind to, and activate transcription from, CACGTG E-boxes when targeted to the nucleus via a heterologous nuclear localization signal. The amino termini of the Mondo proteins are highly conserved among family members and contain separable and autonomous cytoplasmic localization and transcription activation domains. Therefore, Mlx can mediate transcriptional repression in conjunction with the Mad family and can mediate transcriptional activation via the Mondo family. We propose that Mlx, like Max, functions as the center of a transcription factor network.

Induction of interleukin-8 release by lung epithelium with cystic fibrosis epithelial lining fluid is marginally affected by inhibitors of interleukin-1beta.

Interleukin-1beta (IL-1beta) and neutrophil elastase (NE) are present in the epithelial lining fluid (ELF) of patients with cystic fibrosis (CF). Both factors activate surrounding cells including lung epithelial cells, causing release of IL-8, a potent chemoattractant for neutrophils. Previous studies showed up-regulation of IL-8 release by lung epithelial cells as a function of NE in CF; however, few studies addressed the relationship between IL-1beta and activation of lung epithelial cells in CF lungs. Confluent layers of A549 cells, a type II-like human lung epithelial cell line, were incubated overnight with IL-1beta (0-5 ng/ml) or NE (100 nM), and supernatants were analyzed for IL-8 by enzyme-linked immunosorbent assay (ELISA). Both IL-1beta and NE led to a significant increase in IL-8: 12.8 +/- 2.8 ng/ml and 0.8 +/- 0.3 ng/ml, respectively. Next, bronchoalveolar lavage (BAL) samples were obtained from one healthy adult volunteer and six patients with CF and measured for IL-8 and IL-1beta concentrations by ELISA. Both IL-8 (range 169.00 +/- 56.57 to 1742.04 +/- 338.98 pg/ml) and IL-1beta (range 0-24.26 +/- 0.52 pg/ml) were detected in CF specimens, whereas neither was detected in the volunteer's specimen. Normal and CF BALs then were incubated overnight at a 1:10 dilution with confluent A549 cells. Analysis by ELISA of cell-free supernatants revealed increased IL-8 production from cells stimulated with CF BALs only. Similar experiments were performed with BAL supernatants that had been incubated with soluble IL-1 type II receptor, soluble IL-1 receptor antagonist, or a peptide inhibitor of NE. Addition of IL-1 inhibitors had a marginal effect on the amount of IL-8 release after incubation with CF BAL samples, whereas inhibition of NE had no effect. Our results indicate that other factors present in ELF in CF account for IL-8 release from lung epithelial cells.

Hemizygosity for the COP9 signalosome subunit gene, SGN3, in the Smith-Magenis syndrome.

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation syndrome associated with an interstitial deletion of chromosome band 17p11.2. The critical region is extremely gene-rich and spans approximately 1.5-2.0 Mb of DNA. Here we report the localization and partial characterization of the gene for subunit 3 of the COP9 signalosome, SGN3. SGN3 maps to the distal portion of the SMS critical interval, between SREBF1 and cCI17-638. We assessed the potential effect of haploinsufficiency of SGN3 in SMS patient lymphoblastoid cell lines through transfection studies and western analysis. Our results indicate that the COP9 signalosome assembles properly in these cells and appears to have normal expression and a kinase function intact. However, because the role of the COP9 signalosome in embryogenesis or differentiation is still uncertain, we cannot rule out the involvement of this gene in the Smith-Magenis syndrome.

Distribution and dynamics of laser-polarized (129)Xe magnetization in vivo.

The first magnetic resonance imaging studies of laser-polarized (129)Xe, dissolved in the blood and tissue of the lungs and the heart of Sprague-Dawley rats, are described. (129)Xe resonances at 0, 192, 199, and 210 ppm were observed and assigned to xenon in gas, fat, tissue, and blood, respectively. One-dimensional chemical-shift imaging (CSI) reveals xenon magnetization in the brain, kidney, and lungs. Coronal and axial two-dimensional CSI show (129)Xe dissolved in blood and tissue in the thorax. Images of the blood resonance show xenon in the lungs and the heart ventricle. Images of the tissue resonance reveal xenon in lung parenchyma and myocardium. The (129)Xe spectrum from a voxel located in the heart ventricle shows a single blood resonance. Time-resolved spectroscopy shows that the dynamics of the blood resonance match the dynamics of the gas resonance and demonstrates efficient diffusion of xenon gas to the lung parenchyma and then to pulmonary blood. These observations demonstrate the utility of laser-polarized (129)Xe to detect exchange across the gas-blood barrier in the lungs and perfusion into myocardial tissue. Applications to measurement of lung function, kidney perfusion, myocardial perfusion, and regional cerebral blood flow are discussed. Magn Reson Med 42:1137-1145, 1999.

Extracellular regulation of interleukin (IL)-1beta through lung epithelial cells and defective IL-1 type II receptor expression.

Interleukin (IL)-1beta is produced primarily by activated mononuclear phagocytic cells in the lung airway and functions as a potent proinflammatory cytokine. Release of IL-1beta in the airway microenvironment induces the production of proinflammatory factors from parenchymal airway cells, including IL-8. To study the regulation of lung epithelial cell responsiveness to IL-1beta, the human type II-like airway epithelial cell line A549 and primary normal human bronchial epithelial (NHBE) cells were assayed for IL-1-specific response modifiers. Specifically, the IL-1 type I receptor (IL-1RI), IL-1 type II receptor (IL-1RII), IL-1 receptor accessory protein (IL-1RAcP), and IL-1 receptor antagonist (IL-1Ra) were analyzed. Constitutive expression of IL-1RI, IL-1RAcP, and IL-1Ra was detected in both immortalized and primary human airway epithelial cells. Interestingly, a complete absence of IL-1RII expression was demonstrated under all study conditions in both A549 and NHBE cells. Both cell types were responsive to IL-1beta at concentrations as low as 50 to 500 pg/ml when measured by IL-8 release into cell supernatants. IL-1beta-induced chemokine production and release were inhibited by a 10- to 1,000-fold molar excess of recombinant IL-1RII or IL-1Ra, whereas IL-1RI was a less effective inhibitor. On the basis of our results, we propose that human lung epithelial cells lack the ability to downregulate IL-1beta activity extracellularly because of an inability to express IL-1RII. Release of extracellular IL-1 inhibitors, including soluble IL-1Ra and soluble IL-1RII, by other inflammatory cells present in the airway may be critical for regulation of IL-1beta activity in the airway microenvironment.

Functional analysis of different regions of the positive-acting CYS3 regulatory protein of Neurospora crassa.

In the filamentous fungus Neurospora crassa during conditions of sulfur limitation, CYS3, a major positive-acting regulatory protein, turns on the expression of an entire set of genes which encode permeases and enzymes involved in the acquisition of sulfur from environmental sources. CYS3 functions as a homodimeric protein and possesses a b-Zip domain that confers sequence-specific DNA binding. Expression of various hybrid GAL4-CYS3 fusion proteins in yeast was used to detect regions involved in gene activation. An amino-terminal serine/threonine-rich domain of CYS3 alone strongly activated expression of beta-galactosidase, the yeast reporter. Moreover, mutant CYS3 proteins with amino-acid substitutions in this region that showed increased expression in Neurospora also displayed an enhanced activation potential in yeast. The cys-3 gene of the exotic N. crassa Mauriceville strain and of N. intermedia were cloned and demonstrated to be functional for gene activation and for sulfur-mediated regulation by complementation of a loss-of-function cys-3 mutation. The amino-terminal serine/threonine-rich region is highly conserved in these two CYS3 proteins, in agreement with the possibility that it serves as the activation domain. Surprisingly, an extended promoter region of the cys-3 gene in the Mauriceville strain and in N. intermedia was very well conserved with that of the standard N. crassa gene, including the presence of three CYS3-binding sites possibly involved in autogenous control. Results are presented which indicate that synthesis of the CYS3 regulatory protein is highly regulated and can be detected in the nucleus of cells subjected to sulfur de-repression, but is not found in the nucleus or the cytoplasm of S-repressed cells. The amino-acid substitutions of the CYS3 protein present in a temperature-sensitive cys-3 mutant and in a second-site revertant of a cys-3 null mutation are presented and are shown to affect their DNA-binding activities.

Quantitative rheumatology: a survey of outcome measurement procedures in routine rheumatology outpatient practice in Canada.

OBJECTIVE: To assess the extent to which quantitative clinical measurement is performed by rheumatologists in the longitudinal followup of patients with rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and fibromyalgia (FM) in routine outpatient practice in Canada. METHODS: A cross sectional postal survey was conducted using an 18 item self-administered questionnaire sent to Canadian Rheumatology Association members. RESULTS: Rheumatologists (response rate 85%) were more likely to longitudinally follow patients with RA and AS than those with OA or FM. There was a high degree of variability in the methods used to monitor patients longitudinally. Many measures used in clinical research were used infrequently in routine clinical practice. In general, the major health status measures surveyed were not used in clinical monitoring. There was a high level of agreement (>80%) that the characteristics required of an outcome measure for use in clinical practice should include simplicity, brevity, ease of scoring, reliability, validity, and sensitivity to change. CONCLUSION: The majority of Canadian rheumatologists perform outcome measurement during the longitudinal followup of their outpatients with RA, AS, OA, and FM. However, the process lacks standardization. High performance health status measures, developed for clinical research, have not been widely adopted in rheumatology practices. There is agreement on the characteristics required by Canadian rheumatologists for measurement procedures used in routine clinical care. Quantitative measurement in clinical practice using standardized procedures is an attainable, but as yet, unrealized opportunity.

Relationship between reason for placement and medical findings among children in foster care.

OBJECTIVE: To determine the reasons for placement of children in foster care, the prevalence of medical findings during initial placement, and the relationship between reason for placement and medical findings. The association between placement reasons and parental substance abuse also was explored. METHODS: Population-based analysis of medical records of 749 children examined at the Child Protection Center in San Francisco from October 1, 1991, to December 31, 1992. Health evaluations consisted of a clearance examination of children during entry into foster care and a comprehensive examination 3 weeks later. Reasons for foster placement included abandonment, neglect, no available caretaker, physical abuse, sexual abuse, and failed placement. RESULTS: Nearly 50% of children in our study were < 6 years of age. Neglect (30%), physical abuse (25%), and no available caretaker (24%) were the most frequent placement reasons, followed by abandonment (9%), failed placement (7%), and sexual abuse (5%). Substance abuse was documented in 30% of parents, 51% when the placement reason was neglect. Medical findings were identified in 60% of children. Among 0 to 6-year-olds, 27% had upper respiratory illnesses, 23% had developmental delay, and 21% had skin conditions; for children 7 to 12 years of age, 32% failed vision screening, 12% had dental caries, and 11% had upper respiratory illnesses; and among 13- to 18-year-olds, 31% failed vision screening and 12% had positive tuberculin skin tests. For younger children, skin conditions were associated with neglect, no available care taker, and failed placement, and developmental delay with neglect and abandonment. For adolescents, history of psychiatric illness was associated with neglect and failed placement. Marks of abuse for all age groups were limited to children who had been physically abused. Three or more diagnoses were identified for approximately 20% of children who had been neglected or abandoned or had failed placement, compared with 10% of children who had been either physically or sexually abused. CONCLUSIONS: Specific medical findings associated with reasons for placement provide health professionals with additional information to assess more accurately the health care needs of children entering foster care. As important, screening tests revealed high rates of vision problems and exposures to tuberculosis, warranting earlier and more comprehensive screening. Finally, children who have endured variations of neglect or failed placement may have more health problems than anticipated previously.

Alpha 1-antitrypsin and protease complexation is induced by lipopolysaccharide, interleukin-1beta, and tumor necrosis factor-alpha in monocytes.

Local regulation of alpha1-antitrypsin (alpha1-AT) may have importance in maintenance of the protease-antiprotease balance in the microenvironment of inflammatory cells. We therefore studied whether lipopolysaccharide (LPS), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNFalpha) affect the pericellular concentration of alpha1-AT in human peripheral blood mononuclear cells (PBMC). PBMC taken from normal healthy volunteers were treated with LPS, IL-1beta, and TNFalpha, and the concentration of human alpha1-AT in conditioned supernatants was measured. When compared with unstimulated control supernatants (147 +/- 19 ng/ml), LPS (439 +/- 66 ng/ml; p < or = 0.001), IL-1beta (263 +/- 37 ng/ml; p < or = 0.01), and TNFalpha (316 +/- 59 ng/ml; p < or = 0.05) induced a 2- to 3-fold increase of alpha1-AT. Up-regulation of alpha1-AT protein correlated with an increase in alpha1-AT mRNA, suggesting a simultaneous increase in alpha1-AT synthesis. Despite the increase in alpha1-AT concentration, functional antiprotease activity could not be detected. Furthermore, protease activity was present in all samples, with the amount of activity being inversely related to the amount of alpha1-AT measured in supernatants. These findings suggest that local inflammatory conditions up-regulate alpha1-AT production by monocytes which complex with a protease derived from the PBMC population.

Insight, neurocognitive function and symptom clusters in chronic schizophrenia.

Only recently has there been interest in the systematic study of insight in schizophrenia. The present investigation was designed to evaluate the specific relationship between psychopathological symptoms, neurocognitive deficits and awareness of illness in chronic schizophrenia. Fifty-eight outpatients with the DSM-III-R diagnosis of schizophrenia were rated on David's Schedule for Assessing Insight, the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale and the Wisconsin Card Sorting Test (WCST). Results indicate that there is a significant association among these variables and that approximately 44% of the variance in the dependent variable could be explained by this combination of independent variables. Notably, however, negative symptoms were only moderately inversely correlated with awareness of illness, and they were not associated with scores on the WCST. Moreover, neither negative symptoms nor per cent perseverative errors contributed significantly to the prediction of insight in schizophrenia. These findings argue against the notion that unawareness of illness is the product of neuropsychological dysfunction in the frontal lobes. Instead, the most significant associations and predictors of insight were related to the positive symptoms of schizophrenia.

Brain MRI with laser-polarized 129Xe.

The feasibility of brain MRI with laser-polarized 129Xe in a small animal model is demonstrated. Naturally abundant 129Xe is polarized and introduced into the lungs of Sprague-Dawley rats. Polarized xenon gas dissolves in the blood and is transported to the brain where it accumulates in brain tissue. Spectroscopic studies reveal a single, dominant, tissue-phase NMR resonance in the head at 194.5 ppm relative to the gas phase resonance. Images of 129Xe in the rat head were obtained with 98-microliter voxels by 2D chemical shift imaging and show that xenon is localized to the brain. This work establishes that nuclear polarization produced in the gas phases survives transport to the brain where it may be imaged. Increases in polarization and delivered volume of 129Xe will allow clinical measurements of regional cerebral blood flow.

Evidence that cutaneous carcinogen-initiated epithelial cells from mice are quiescent rather than actively cycling.

The basal layer of the epidermis and hair follicles is composed of actively cycling, transit-amplifying cells and quiescent cells including stem cells. To determine which population is the target of carcinogenic chemicals, we treated CD-1 female mice topically with 5-fluorouracil (5-FU), an agent known to kill cycling but not quiescent cells, to probe the origin of the neoplastic lesions. We first determined that 5-FU kills cycling cells in the epidermis. Treatment of mice at 59 days of age (when in anagen 1) with topical 5-FU delayed hair regrowth by 10 days compared to vehicle-treated controls, suggesting that 5-FU killed the cells in anagen. Moreover, 5-FU suppressed the usual hyperplastic response of the epidermal cells to treatment with 12-O-tetradecanoylphorbol-13-acetate. 5-FU reduced the number of epidermal basal cells counted in cross-sections of skin and suppressed DNA synthesis. Approximately 50% of mice treated with 5-FU developed, within 1 week of treatment, a sloughing of the epidermis persisting for 3 weeks, followed by complete healing. Despite the evidence of cell killing in the epidermis and lower hair follicles, in a carcinogenesis experiment where 5-FU or vehicle was applied following tumor initiation with 7,12-dimethylbenz[a]anthracene, the papilloma and carcinoma responses were virtually identical whether or not the mice were treated with 5-FU, suggesting that the tumors arose from quiescent, rather than actively cycling, epidermal cells. When 5-FU was applied before initiation, the papilloma but not the carcinoma responses were slightly but significantly reduced relative to controls. These results are consistent with the hypothesis that the quiescent rather than the rapidly proliferating cells are the targets of tumor initiation.

Nurses transition from hospital to home: bridging the gap.

Practice transition between health care settings is often fraught with frustration, stress, and even traumatic learning experiences for nurses. As the need for qualified infusion therapists in home care increases, more acute care nurses are making the transition from hospital to home. This article is designed to profile the differences between the care settings and offer suggestions to smooth the change from hospital to home care.

Is the incidence of ovarian ectopic pregnancy increasing?

Although tubal pregnancy is increasing, ovarian ectopic pregnancy has remained a rare event. However, North American reports suggest an increasing incidence relative to both tubal and term pregnancies. We report an unexpected increase in our practice with five primary ovarian pregnancies over the past year. Current understanding of the aetiological factors, pathogenesis and implications for management are outlined.

Depression in schizophrenia: a comparison of three measures.

Depression, as a feature of schizophrenia, is well established. However, clarifying the exact nature of this relationship has been problematic. The clinical measures routinely utilized to evaluate depression have not been specifically designed for use in schizophrenia, and it is well recognized that a variety of depressive symptoms overlap with other features common to this illness, e.g. negative symptoms, neuroleptic induced side effects. The present study compared three commonly used measures of depression (Hamilton Depression Rating Scale (Ham-D), Calgary Depression Scale (CDS) and the depression subscale of the Positive and Negative Syndrome scale (PANSS-D) in a group of outpatients with schizophrenia, evaluating the degree of association between the scales. Additionally, the relationship between each of the depression measures, negative symptoms and extrapyramidal symptoms (EPS) was calculated. Results revealed that all three measures of depression were significantly correlated, although the CDS was unique in its ability to distinguish between depression, negative symptoms and EPS. It is concluded that the CDS, when compared with the HAM-D and the PANSS-D, is the most suitable measure of depression in schizophrenia.