Can MR imaging challenge the commonly accepted theory of the pathogenesis of solitary enchondroma of long bone?

OBJECTIVE: It has been widely postulated that enchondromas arise from cartilage remnants that have been displaced from the growth plate into the metaphysis. However, this theory remains unproven. Based on the common occurrence of enchondromas on routine knee MR imaging (2.9 %), one would expect to find displaced cartilage in the metaphysis of skeletally immature individuals on routine knee MR examinations if the above theory was to be supported. MATERIALS AND METHODS: The electronic databases of a specialist orthopedic hospital and children's hospital were searched for skeletally immature patients who underwent MR imaging of the knee for a variety of indications. Individuals with Ollier disease or hereditary multiple exostoses were excluded. The MR images were subsequently reviewed by a musculoskeletal radiologist for evidence of displaced cartilage into the metaphysis. RESULTS: We reviewed 240 MR examinations of the knee that were performed in 209 patients. There were 125 MR studies in male and 115 MR examinations in female patients (age range: 5 months-16 years; median age: 13 years). In 97.1 %, the growth plates around the knee demonstrated a regular appearance. Seven cases (2.9 %) in six patients showed cartilage extension from the growth plate into the metaphysis, which remained in continuity with the growth plate. There were no cases of displaced cartilage into the metaphysis on MRI. CONCLUSIONS: Our study challenges the widely believed theory that enchondromas arise from displaced growth plate remnants.

Birth characteristics and childhood carcinomas.

BACKGROUND: Carcinomas in children are rare and have not been well studied. METHODS: We conducted a population-based case-control study and examined associations between birth characteristics and childhood carcinomas diagnosed from 28 days to 14 years during 1980-2004 using pooled data from five states (NY, WA, MN, TX, and CA) that linked their birth and cancer registries. The pooled data set contained 57,966 controls and 475 carcinoma cases, including 159 thyroid and 126 malignant melanoma cases. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: White compared with 'other' race was positively associated with melanoma (OR=3.22, 95% CI 1.33-8.33). Older maternal age increased the risk for melanoma (OR(per 5-year age increase)=1.20, 95% CI 1.00-1.44), whereas paternal age increased the risk for any carcinoma (OR=1.10(per 5-year age increase), 95% CI 1.01-1.20) and thyroid carcinoma (OR(per 5-year age increase)=1.16, 95% CI 1.01-1.33). Gestational age < 37 vs 37-42 weeks increased the risk for thyroid carcinoma (OR=1.87, 95% CI 1.07-3.27). Plurality, birth weight, and birth order were not significantly associated with childhood carcinomas. CONCLUSION: This exploratory study indicates that some birth characteristics including older parental age and low gestational age may be related to childhood carcinoma aetiology.

Plasma fibronectin supports neuronal survival and reduces brain injury following transient focal cerebral ischemia but is not essential for skin-wound healing and hemostasis.

Fibronectin performs essential roles in embryonic development and is prominently expressed during tissue repair. Two forms of fibronectin have been identified: plasma fibronectin (pFn), which is expressed by hepatocytes and secreted in soluble form into plasma; and cellular fibronectin (cFn), an insoluble form expressed locally by fibroblasts and other cell types and deposited and assembled into the extracellular matrix. To investigate the role of pFn in vivo, we generated pFn-deficient adult mice using Cre-loxP conditional gene-knockout technology. Here we show that pFn-deficient mice show increased neuronal apoptosis and larger infarction areas following transient focal cerebral ischemia. However, pFn is dispensable for skin-wound healing and hemostasis.

Parental educational attainment as an indicator of socioeconomic status and risk of childhood cancers.

BACKGROUND: Little has been reported on socioeconomic (SES) patterns of risk for most forms of childhood cancer. METHODS: Population-based case-control data from epidemiological studies of childhood cancer conducted in five US states were pooled and associations of maternal, paternal and household educational attainment with childhood cancers were analysed. Odds ratios (ORs) and 95% confidence intervals were estimated using logistic regression, controlling for confounders. RESULTS: Although there was no association with parental education for the majority of cancers evaluated, there was an indication of a positive association with lower education for Hodgkin's and Burkitt's lymphoma and Wilm's tumour, with the ORs ranging from 1.5 to >3.0 times that of more educated parents. A possible protective effect was seen for lower parental education and astrocytoma and hepatoblastoma, with ORs reduced by 30 to 40%. CONCLUSIONS: These study results should be viewed as exploratory because of the broad nature of the SES assessment, but they give some indication that childhood cancer studies might benefit from a more thorough assessment of SES.

Comparison of water-based foam and inert-gas mass emergency depopulation methods.

Current control strategies for avian influenza (AI) and other highly contagious poultry diseases include surveillance, quarantine, depopulation, disposal, and decontamination. Selection of the best method of emergency mass depopulation involves maximizing human health and safety while minimizing disease spread and animal welfare concerns. Proper selection must ensure that the method is compatible with the species, age, housing type, and disposal options. No one single method is appropriate for all situations. Gassing is one of the accepted methods for euthanatizing poultry. Whole-house, partial-house, or containerized gassing procedures are currently used. The use of water-based foam was developed for emergency mass depopulation and was conditionally approved by the United States Department of Agriculture in 2006. Research has been done comparing these different methods; parameters such as time to brain death, consistency of time to brain death, and pretreatment and posttreatment corticosterone stress levels were considered. In Europe, the use of foam with carbon dioxide is preferred over conventional water-based foam. A recent experiment comparing CO2 gas, foam with CO2 gas, and foam without CO2 gas depopulation methods was conducted with the use of electroencephalometry results. Foam was as consistent as CO2 gassing and more consistent than argon-CO2 gassing. There were no statistically significant differences between foam methods.

Postoutbreak disinfection of mobile equipment.

Current control strategies for avian influenza virus, exotic Newcastle disease, and other highly contagious poultry diseases include surveillance, quarantine, depopulation, disposal, and decontamination. Skid steer loaders and other mobile equipment are extensively used during depopulation and disposal. Movement of contaminated equipment has been implicated in the spread of disease in previous outbreaks. One approach to equipment decontamination is to power wash the equipment, treat with a liquid disinfectant, change any removable filters, and let it sit idle for several days. In this project, multiple disinfectant strategies were individually evaluated for their effectiveness at inactivating Newcastle disease virus (NDV) on mechanical equipment seeded with the virus. A small gasoline engine was used to simulate typical mechanical equipment. A high titer of LaSota strain, NDV was applied and dried onto a series of metal coupons. The coupons were then placed on both interior and exterior surfaces of the engine. Liquid disinfectants that had been effective in the laboratory were not as effective at disinfecting the engine under field conditions. Indirect thermal fog showed a decrease in overall virus titer or strength. Direct thermal fog was more effective than liquid spray application or indirect thermal fog application.

4D-Dynamic Contrast-Enhanced MRI for Preoperative Localization in Patients with Primary Hyperparathyroidism.

BACKGROUND AND PURPOSE: Our aim was to test the hypothesis that our recently introduced 4D-dynamic contrast-enhanced MR imaging with high spatial and temporal resolution has equivalent accuracy to 4D-CT for preoperative gland localization in primary hyperparathyroidism without requiring exposure to ionizing radiation. MATERIALS AND METHODS: Inclusion criteria were the following: 1) confirmed biochemical diagnosis of primary hyperparathyroidism, 2) preoperative 4D-dynamic contrast-enhanced MR imaging, and 3) surgical cure with >50% decrease in serum parathyroid hormone intraoperatively. 4D-dynamic contrast-enhanced studies were reviewed independently by 2 neuroradiologists to identify the side, quadrant, and number of abnormal glands, and compared with surgical and pathologic results. RESULTS: Fifty-four patients met the inclusion criteria: 37 had single-gland disease, and 17, multigland disease (9 with double-gland hyperplasia; 3 with 3-gland hyperplasia; and 5 with 4-gland hyperplasia). Interobserver agreement (κ) for the side (right versus left) was 0.92 for single-gland disease and 0.70 for multigland disease. Interobserver agreement for the quadrant (superior versus inferior) was 0.70 for single-gland disease and 0.69 for multigland disease. For single-gland disease, the gland was correctly located in 34/37 (92%) patients, with correct identification of the side in 37/37 (100%) and the quadrant in 34/37 (92%) patients. For multigland disease, the glands were correctly located in 35/47 (74%) patients, with correct identification of the side in 35/47 (74%) and the quadrant in 36/47 (77%). CONCLUSIONS: The proposed high spatial and temporal resolution 4D-dynamic contrast-enhanced MR imaging provides excellent diagnostic performance for preoperative localization in primary hyperparathyroidism, with correct gland localization of 92% for single-gland disease and 74% in multigland disease, superior to 4D-CT studies.

Paediatric germ cell tumours and congenital abnormalities: a Children's Oncology Group study.

METHODS: Maternally reported congenital abnormalities (CAs) were examined in a case-control study of 278 cases of paediatric germ cell tumours (GCTs) and 423 controls. RESULTS AND CONCLUSIONS: Germ cell tumours were significantly associated with cryptorchidism in males (OR=10.8, 95% CI: 2.1-55.1), but not with any other specific CA in either sex.

Inactivation of avian influenza virus using four common chemicals and one detergent.

Five disinfectant chemicals were tested individually for effectiveness against low pathogenic avian influenza virus (LPAIV), A/H7N2/Chick/MinhMa/04, on hard, nonporous surfaces. The tested agents included acetic acid, calcium hydroxide, sodium carbonate, sodium hydroxide, and a powdered laundry detergent without bleach. Multiple common chemicals including acetic acid (1 and 3%), sodium hydroxide (2%), and calcium hydroxide (1%) effectively inactivated LPAIV on a metal surface. The laundry detergent without bleach, sodium carbonate (4%), and the lower concentration of sodium hydroxide (1%) were not able to consistently inactivate LPAIV on hard, nonporous surfaces.

Perinatal risk factors for hepatoblastoma.

We confirmed the strong association of hepatoblastoma with very low birth weight (relative risk <1000 g vs >or=2000 g=25.6; 95% confidence interval: 7.70-85.0) and demonstrated independent associations with congenital abnormalities and maternal Asian race in a population-based Minnesota study that included 36 cases and 7788 controls.

Childhood cancer in the offspring born in 1921-1984 to US radiologic technologists.

We examined the risk of childhood cancer (<20 years) among 105 950 offspring born in 1921-1984 to US radiologic technologist (USRT) cohort members. Parental occupational in utero and preconception ionising radiation (IR) testis or ovary doses were estimated from work history data, badge dose data, and literature doses (the latter doses before 1960). Female and male RTs reported a total of 111 and 34 haematopoietic malignancies and 115 and 34 solid tumours, respectively, in their offspring. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Leukaemia (n=63) and solid tumours (n=115) in offspring were not associated with maternal in utero or preconception radiation exposure. Risks for lymphoma (n=44) in those with estimated doses of <0.2, 0.2-1.0, and >1.0 mGy vs no exposure were non-significantly elevated with HRs of 2.3, 1.8, and 2.7. Paternal preconception exposure to estimated cumulative doses above the 95th percentile (82 mGy, n=6 cases) was associated with a non-significant risk of childhood cancer of 1.8 (95% CI 0.7-4.6). In conclusion, we found no convincing evidence of an increased risk of childhood cancer in the offspring of RTs in association with parental occupational radiation exposure.

Drosophila homolog of the myotonic dystrophy-associated gene, SIX5, is required for muscle and gonad development.

SIX5 belongs to a family of highly conserved homeodomain transcription factors implicated in development and disease. The mammalian SIX5/SIX4 gene pair is likely to be involved in the development of mesodermal structures. Moreover, a variety of data have implicated human SIX5 dysfunction as a contributor to myotonic dystrophy type 1 (DM1), a condition characterized by a number of pathologies including muscle defects and testicular atrophy. However, this link remains controversial. Here, we investigate the Drosophila gene, D-Six4, which is the closest homolog to SIX5 of the three Drosophila Six family members. We show by mutant analysis that D-Six4 is required for the normal development of muscle and the mesodermal component of the gonad. Moreover, adult males with defective D-Six4 genes exhibit testicular reduction. We propose that D-Six4 directly or indirectly regulates genes involved in the cell recognition events required for myoblast fusion and the germline:soma interaction. While the exact phenotypic relationship between D-Six4 and SIX4/5 remains to be elucidated, the defects in D-Six4 mutant flies suggest that human SIX5 should be more strongly considered as being responsible for the muscle wasting and testicular atrophy phenotypes in DM1.

Acute immunologic pulmonary alveolitis.

Acute immunologic injury of rat lung has been induced by the intrabronchial injection of heterologous antibody and the intravenous injection of radiolabeled antigen. Within 4 h an acute hemorrhagic neutrophil-rich exudate develops in alveolar and interstitial areas and then gradually fades. Lung injury in this model can be quantitated by measurements of increased vascular permeability and extractable hemoglobin. By the use of immunofluorescent techniques, alveolar and interstitial deposits of antigen and antibody have been demonstrated, but not the third component of complement (C3). Although not found in relation to immune complexes, C3 is nevertheless present in damaged lung as measured by accumulation of radiolabeled C3 from the circulation. Ablation experiments indicate the requirement for both circulating neutrophils and C3 for the development of lung injury. These studies provide definition for the development of lung damage induced by immune complexes.

Suppression of immune complex-induced inflammation by the chemotactic factor inactivator.

Small amounts (10(-10) mol) of purified human chemotactic factor inactivator (CFI) suppress leukocytic infiltration, permeability changes, and hemorrhage associated with acute immune complex-induced injury in rats. The reversed passive dermal Arthus reaction and acute immune complex-induced alveolitis in rats have served as the model systems of inflammation. The mechanism of inhibition does not appear to relate to interference with formation and deposition of immune complexes, or with fixation of complement in vitro or iv vivo. Human CFI inhibits in vitro the chemotactic activity generated in complement-activated rat serum. The inhibitory effects of human CFI are not seen if it is first heat inactivated. The data provide the first direct support for the conclusion that CFI has anti-inflammatory activity.

Evidence for the role of platelet-activating factor in immune complex vasculitis in the rat.

These studies were designed to determine the role of platelet-activating factor (PAF) in the pathogenesis of immune complex (IgG) induced dermal vasculitis in the rat. In vitro, very low (pM and nM) concentrations of PAF "primed" rat neutrophils for enhanced O2-. responses to IgG immune complexes while higher concentrations were directly stimulatory. The PAF receptor antagonist, L-652,731, blocked responses (O2-. production and enzyme release) of rat neutrophils stimulated with PAF but did not block responses triggered by immune complexes, formyl chemotactic peptide or opsonized zymosan particles. When L-652,731 was added to the antibody employed in the reversed passive Arthus reaction, the injury resulting from immune complex-induced vasculitis was significantly attenuated. In order to determine if in vivo protection provided by L-652,731 was related to neutrophils, we developed a new model in which rats are systemically depleted of neutrophils by cyclophosphamide and then locally reconstituted with intact neutrophils in a manner that allows restoration of immune complex-induced vascular injury. With this model, we demonstrated that the effects of neutrophil reconstitution are substantially diminished if the cells are pretreated with L-652,731 and then washed. By priming neutrophils with substimulatory concentrations of PAF, we have also provided in vivo evidence that neutrophil priming can increase the magnitude of vascular injury. These data provide evidence that vascular injury associated with immune complex dermal vasculitis is related to availability of PAF receptors on neutrophils, suggesting a mechanism through which PAF may function as a mediator in the pathogenesis of immune complex vasculitis.

Intravascular activation of complement and acute lung injury. Dependency on neutrophils and toxic oxygen metabolites.

Intravascular activation of the complement system with cobra venom factor results in acute lung injury, which has been quantitated by increases in lung vascular permeability. Cobra venom factor preparations devoid of phospholipase A2 activity retain full lung-damaging capacity. The lung injury is associated with the preceding appearance of chemotactic activity in the serum coincident with the development of a profound neutropenia. The chemotactic activity is immunochemically related to human C5a. Morphologic studies have revealed discontinuities in the endothelial cell lining of lung alveolar capillaries, damage and/or destruction of endothelial cells in these areas, plugging of pulmonary capillaries with neutrophils that are in direct contact with vascular basement membrane, the presence of fibrin in alveolar spaces and in areas adjacent to damaged endothelial cells, and intraalveolar hemorrhage. Lung injury is dramatically attenuated in animals that have been previously neutrophil depleted. Teh intravenous injection of superoxide dismutase or catalase also provides significant protection from the pulmonary damage. Very little protection from the pulmonary damage. Very little protection is afforded by pretreatment of rats with antihistamine. These studies suggest that intravascular activation of the complement system leads to neutrophil aggregation and activation, intrapulmonary capillary sequestration of neutrophils, and vascular injury, which may be related to production of toxic oxygen metabolites by complement-activated neutrophils.

In vivo damage of rat lungs by oxygen metabolites.

The intrapulmonary instillation into rat lung of enzymes that generate oxygen metabolites results in acute lung injury. The injection of xanthine oxidase and xanthine produces acute lung injury that, in the presence of superoxide dismutase, but not in the presence of catalase, can be significantly diminished, suggesting that O2- has the capacity to injure the lung. Instillation of a generator of H2O2, namely glucose oxidase, will, in sufficient quantities, produce acute injury that is not neutrophil-dependent. When either a low dose of glucose oxidase alone or lactoperoxidase alone is employed, little lung injury occurs. However, instilling the combination of the two enzymes produces severe, acute injury that can be blocked in a dose-dependent manner by catalase, but not by superoxide dismutase. Purified human leukocytic myeloperoxidase, but not horseradish peroxidase, will substitute for lactoperoxidase in the model of lung injury. The lung damaging effects of these enzymes cannot be attributed to the presence of contaminating proteases. Acute lung injury produced by the instillation of glucose oxidase and lactoperioxidase progresses to interstitial fibrosis. These studies represent a direct application of generators of oxygen metabolites to the in vivo induction of lung injury. The data suggest that rat lung is susceptible to injury by a variety of oxygen metabolites, including O2-, H2O2 and its lactoperoxidase or myeloperoxidase-produced derivatives. The studies also indicate that lung injury produced by oxygen metabolites can result in interstitial pulmonary fibrosis.

Acute lung injury in rat caused by immunoglobulin A immune complexes.

Mouse IgG and IgA, with reactivity to dinitrophenol conjugated to carrier protein, have been isolated from myeloma proteins by means of a variety of affinity techniques. The IgA was predominantly in the dimeric form. The in vitro and in vivo biological activities of IgA-containing immune complexes were assessed in the rat. IgA-containing immune complexes were demonstrated, in a dose-dependent manner in vitro, to activate neutrophils and to generate O.-2. In addition, these immune complexes showed evidence of complement activation in vitro, by the use of immunofixation techniques. When IgA was instilled into the airways of rats and antigen was injected intravenously, acute lung injury occurred, as reflected by increases in lung permeability and morphological changes consisting of blebbing of endothelial cells, intra-alveolar hemorrhage, and fibrin deposition. The lung changes were directly proportional to the amount of IgA instilled into the airways and failed to occur if intravenous injection of antigen was omitted. Lung injury did not occur in animals that received an intravenous injection of antigen in the absence of an airway injection of IgA. Lung injury related to IgA-containing immune complexes was complement dependent but neutrophil independent. In companion studies with mouse IgG-containing immune complexes, acute lung injury also occurred and had morphological features similar to those associated with IgA-induced lung injury except that, in the case of IgG immune complex-induced damage, neutrophils were more evident. Acute lung injury induced by IgG-containing immune complexes, whether of mouse or rabbit origin, was complement and neutrophil dependent. The similarities and differences between IgG- and IgA-associated acute immune complex-induced injury of rat lung were reinforced by the use of morphometry techniques. Studies with another monoclonal IgA antibody-containing antigen-binding activity to phosphorylcholine also demonstrated the ability of IgA antibody to cause acute lung injury in the rat. Neither antibody alone nor antigen (phosphorylcholine linked to bovine serum albumin) alone produced evidence of lung injury. These studies indicate for the first time that immune complexes containing IgA have lung-damaging properties and that the pathogenic mechanisms are different from those associated with IgG-associated immune complex-induced acute lung injury.

Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice.

Human antigen-specific CD4+ T cells become autoreactive after treatment with various DNA methylation inhibitors, including 5-azacytidine, procainamide, and hydralazine. This suggests a mechanism that could contribute to the development of some forms of autoimmunity. In this report we have asked whether T cells treated with DNA methylation inhibitors can induce autoimmunity. Murine CD4+ T cells were treated with 5-azacytidine or procainamide and were shown to respond to syngeneic antigen-presenting cells, similar to CD4+ human T cell clones treated with these drugs. Functional characterization demonstrated that cells treated with either drug spontaneously lysed syngeneic macrophages and secreted IL-4, IL-6, and IFN-gamma. Adoptive transfer of 5-azacytidine- or procainamide-treated cells into unirradiated syngeneic recipients induced an immune complex glomerulonephritis and IgG anti-DNA and antihistone antibodies. These experiments demonstrate that T cells treated with either of two distinct DNA methyltransferase inhibitors are sufficient to induce a lupus-like disease. It is possible that the lysis of macrophages, together with the release of cytokines promoting B cell differentiation, contributes to the autoantibody production and immune complex deposition. These results suggest that environmental agents that inhibit DNA methylation could interact with T cells in vivo to produce a lupus-like illness, a mechanism that could have relevance to drug-induced and idiopathic lupus.