Imaging Findings in Children Presenting with CNS Nelarabine Toxicity.

Nelarabine is a nucleoside analog critical for the treatment of patients with T-cell acute lymphoblastic leukemia/lymphoma. However, clinical peripheral and central neurologic adverse events associated with nelarabine administration have been reported. Neuroimaging of brain neurotoxicity has only been described in very few reports in pediatric patients so far. Six children with diagnosed T-cell acute lymphoblastic leukemia who clinically experienced possible, probable, or definite nelarabine-induced toxicity and underwent spine and/or brain MR imaging were reviewed. Neuroimaging findings showed a mixture of patterns including features of acute toxic leukoencephalopathy (seen in 6 cases), posterior reversible encephalopathy syndrome (2 cases), involvement of deep gray structures (1 case) and brainstem (2 cases), cranial and spinal neuropathy (2 cases each), and myelopathy (2 cases). Even though neuroimaging findings are nonspecific, the goal of this article was to alert the pediatric neuroradiologists, radiologists, and clinicians about the possibility of nelarabine-induced neurotoxicity and its broad neuroimaging spectrum.

Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPARbeta/delta ligand GW0742.

OBJECTIVE: To define the anti-inflammatory effects of PPARbeta/delta activation by use of the selective PPARbeta/delta ligand (GW0742) in a model of lipopolysaccharide (LPS)-induced pulmonary inflammation. METHODS: Male BALB/c mice were pretreated for three days with the PPARbeta/delta agonist, GW0742, prior to induction of LPS-mediated pulmonary inflammation. Bronchial alveolar lavage fluid (BALF) was analyzed for inflammatory cell influx and for levels of pro-inflammatory mediators. BALF-derived inflammatory cells were also collected for mRNA analysis. RESULTS: Pretreatment with GW0742 resulted in a significant decrease in leukocyte recruitment into the pulmonary space. Protein and mRNA levels of the pro-inflammatory cytokines IL-6, IL-1beta and TNFalpha in BALF were found to be significantly decreased in GW0742-treated animals (30 mg/kg). A significant decrease in granulocyte macrophage-colony stimulating factor (GM-CSF), a major regulator of neutrophil chemotaxis (via its downstream actions on TNFalpha and other cytokines/chemokines), activation and survival, was also noted in the BALF levels of GW0742-treated animals. CONCLUSIONS: The present study demonstrates that activation of PPARbeta/delta attenuates the degree of inflammation in a model of LPS-induced pulmonary inflammation and may therefore represent a novel therapeutic approach for the treatment of inflammation-mediated pathologies.

Purification of human respiratory syncytial virus by ultracentrifugation in iodixanol density gradient.

Ultracentrifugation in sucrose density gradient remains the most commonly used technique for hRSV purification. However, the high viscosity and hyper-osmotic property of sucrose can cause damage to the extremely labile virus leading to loss of infectivity. To overcome these limitations, an alternative purification technique was developed using iodixanol as gradient medium, incorporating MgSO(4) as a stabilizing agent and EDTA to disaggregate the virus prior to infectivity assay. Virus particles were banded at the 20-36% interface after purification of polyethylene glycol-concentrated viruses by rate zonal ultracentrifugation on a 20-52% discontinuous iodixanol gradient. The presence of the virus was confirmed by viral fusion glycoprotein content using ELISA. After further purification by buoyant density ultracentrifugation on a 20-52% continuous gradient, the virus was recovered in the region of density 1.15-1.19 g/ml and this was confirmed by the coincidence of the infectivity titre, viral genome and fusion glycoprotein peaks. Analysis of recovery rates showed that the use of iodixanol increased the virus yield up to 69%. Iodixanol was also found to be non-toxic to HeLa cells used in infectivity assay, eliminating the need of its downstream removal by dialysis.

Chronic boron or copper deficiency induces limb teratogenesis in Xenopus.

Sets of adult male and female Xenopus laevis were administered a boron-deficient (-B) diet under low-boron culture conditions, a boron-supplemented (+B) diet under ambient boron culture conditions, a copper-deficient (-Cu) diet under low-copper culture conditions, or a copper-supplemented (+Cu) diet under ambient copper culture conditions, for 120 d. Adults from each group were' subsequently bred, and the progeny were cultured and bred. Results from these studies indicated that although pronounced effects on adult reproduction and early embryo-larval development were noted in the -B F1 generation, no effects on limb development were observed. No significant effects on reproduction, early embryogenesis, or limb development were noted in the +B group, irrespective of generation. Highly specific forelimb and hindlimb defects, including axial flexures resulting in crossed limbs and reduction deficits, were observed in -B F2 larvae, but not in the +B F2 larvae. As was noted in the boron-deficiency studies, significant effects on reproduction and early embryo development were observed in the -Cu F1 generation, but not in the +Cu F, generation. Unlike the effects associated with boron deficiency, maldevelopment of the hindlimbs (32 responders, n = 40) was found in the F1 generation.

Preliminary validation of a short-term morphological assay to evaluate adverse effects on amphibian metamorphosis and thyroid function using Xenopus laevis.

Short-term static-renewal studies were performed on Xenopus laevis embryos with 16 selected test materials from day 50 (stage 60) to day 64 (stage 66) (14-day test) to evaluate effects on tail resorption and thyroid function. Of the 16 test materials, nine were found to inhibit significantly the rate of tail resorption, four were found to stimulate metamorphosis and three had no appreciable effect on the rate of metamorphosis. In an effort to determine if the morphological effects observed were related to alteration in thyroid activity, measurement of triiodothyronine (T3) in the test organisms and coadministration studies using thyroxine (agonist) or propylthiouracil (antagonist) were performed based on the morphological response noted during tail resorption. Of the nine compounds found to inhibit the rate of tail resorption, six were found to reduce the levels of T3. In each case, the inhibitory response could be at least partially alleviated by the co-administration of thyroxine. Larvae exposed to the four stimulatory agents had somewhat elevated levels of T3 and were responsive to propylthiouracil antagonism. These results suggest that 12 of the 14 compounds tested in this study that altered the rate of tail resorption did so via the thyroid axis. Overall, the X. laevis model appeared to be a suitable system for evaluating the impact of environmental agents and chemical products on thyroid function.

A comparative study of smear layer removal using different salts of EDTA.

Three solutions of EDTA--a 15% concentration of the alkaline salt, a 15% concentration of the acid salt, and a 25% concentration of the alkaline salt--were evaluated for smear layer removal in root canal systems. All solutions were adjusted to pH 7.1 using either NaOH or HCl. When the EDTA solutions were alternately used for root canal irrigation with 5.25% NaOCl, they completely removed the smear layer in the middle and coronal thirds of canal preparations, but were less effective in the apical third. None of the EDTA solutions by themselves were effective at completely removing the smear layer at any level. The alkaline tetrasodium salt, pH adjusted with HCl, is more cost effective and performed equally as well as the more commonly used disodium salt.

Effect of calcium hydroxide and four irrigation regimens on instrumented and uninstrumented canal wall topography.

The topography of instrumented and uninstrumented canal walls exposed to calcium hydroxide and four different irrigation regimens was observed by scanning electron microscopy. After chemomechanical debridement, one tooth in each matched pair was medicated with calcium hydroxide. One week later, the teeth were irrigated and split longitudinally for evaluation. When no calcium hydroxide was used, predentin and pulpal debris covered the dentinal tubules of the uninstrumented surfaces in specimens irrigated with water or EDTA, but was absent on uninstrumented surfaces in specimens irrigated with NaOCl or NaOCl and EDTA. A typical smear layer was absent in instrumented specimens irrigated with NaOCl and EDTA, but covered the dentinal tubules of the instrumented surfaces of the EDTA irrigated specimens (partially) and the water or NaOCl irrigated specimens (completely). Calcospherites or their remnants were seen on the uninstrumented canal walls of specimens irrigated with NaOCl or NaOCl and EDTA, respectively. Calcium hydroxide use did not alter the surface topography in specimens irrigated with water, EDTA, or NaOCl, but seemed to erode the intertubular dentin in specimens irrigated with NaOCl and EDTA. All irrigants seemed to effectively remove most of the calcium hydroxide.

A scanning electron microscopic study of in vivo ultrasonic root-end preparations.

The purpose of this in vivo study was to evaluate root-ends for cracks after root resection and again after ultrasonic root-end preparation in patients undergoing endodontic surgery. Endodontic surgery was performed on 25 roots from 20 patients. In vivo vinyl polysiloxane impressions were made after root resection and again after ultrasonic root-end preparations. Epoxy resin casts were made from the impressions and scanning electron micrographic examination of the root-end replicas was performed. There was no evidence of cracks after root resection. One incomplete canal crack was evident after ultrasonic root-end preparation.

Evaluation of diamond-coated ultrasonic instruments for root-end preparation.

Ultrasonic instrumentation has been associated with cracking of the dentin in the area of the root-end preparation. The purpose of this study was to evaluate root-end preparations for cracking and to describe cavosurface morphology after the use of diamond-coated instruments. Forty teeth were inspected for intradentin cracks, incomplete canal cracks, and complete canal cracks before and after preparation with a stainless steel CT-5 ultrasonic instrument and again after root-end preparation with an S12D/90 degrees diamond-coated instrument. Six teeth had polyvinylsiloxane impressions taken of the root ends after preparation with the CT-5 and again after preparation with the diamond-coated instrument. Replicas were made, split, sputter-coated, and inspected using the scanning electron microscope. This study indicates that use of the diamond-coated instrument for root-end preparation does not result in significant root-end cracking and that it can remove cracks created by a prior instrument's use. The use of the diamond-coated instrument resulted in a heavily abraded, debris-covered cavosurface that may affect the apical seal.

The topography of root ends resected with fissure burs and refined with two types of finishing burs.

OBJECTIVES: This study compared the surface topography of roots resected with #57, Lindeman, and Multi-purpose burs. Further comparisons were made after refinements with either a multifluted carbide or an ultrafine diamond finishing bur. STUDY DESIGN: Three groups of single-rooted human teeth were resected with each resection bur, and resin replicas of the root ends were made. Root ends from each resection bur group were finished with either a multifluted carbide or an ultrafine diamond finishing bur, and the root ends were replicated. All replicas were evaluated at a magnification of x20 for smoothness and surface irregularities. Data analysis was done with the Wilcoxon signed rank test and the chi-square test at a significance level of p < 0.05. RESULTS: The Multi-purpose bur produced a smoother and more uniplanar surface than the #57 bur and caused less damage to the root than either the #57 or the Lindeman bur. The multifluted carbide finishing bur tended to improve the smoothness of the root end, while the ultrafine diamond tended to roughen the surface. CONCLUSIONS: The Multi-purpose bur produced the smoothest and most uniplanar resected root-end surface with the least root shattering. The multifluted carbide finishing bur produced a smoother surface than the ultrafine diamond bur.

The application of a risk-approach model to reduce mortality in infancy.

OBJECTIVES: To examine the utility of a risk-approach model in identifying infants at greater risk of postneonatal mortality (PNM) and to determine whether there is a relationship between PNM and linkage of at-risk infants to primary health care. METHODS: The Sheffield Birth Score instrument was applied to 90,846 newborn infants to determine high-score (HS) and low-score (LS) infant risk groups. Health care visit data were collected on all HS infants who were referred for primary pediatric care. Mortality rates were calculated for both HS and LS infant groups and for HS infants who were linked and not linked to care. RESULTS: The HS infant group was at significantly greater risk of PNM (p < 0.0001). The linked group had a lower PNM rate (p < 0.05), and linked/not-linked group differences were noted for 11 of 20 variables. When these 11 variables and the linked/not-linked variable were entered into a logistic regression analysis, linkage was the only significant variable (p < 0.01) in predicting PNM. CONCLUSIONS: The Sheffield Birth Score differentiated at birth those infants who were at greater risk of PNM. The lower incidence of PNM among linked HS infants suggests a promising argument for early pediatric intervention. Further research to clarify specific factors that influence health care participation decisions is suggested.

A comparison of canal centering ability of four instrumentation techniques.

The purpose of this study was to compare three engine driven (nickel-titanium) NiTi instrument systems with hand files for their effect on canal transportation. Mesial roots of mature lower first molars with separate canals were paired on the basis of curvature and morphology. Canal lengths were standardized to 11 mm from orifice to apical foramen. Profile, Lightspeed, McXIM, and Flex-R hand filing techniques respectively were randomly assigned to one of the four canals of each tooth pair. The roots were mounted and sectioned at 1 mm, 3 mm, and 5 mm from working length using a modified Bramante technique. All sections were video imaged preoperatively after instrumentation to size #30 and after final instrumentation to size #40. The images were computer analyzed for changes in canal area and centering at each stage of instrumentation. Preparation time was also recorded. Data were analyzed using ANOVA. The NiTi systems remained better centered in the canal than stainless steel hand files. There were no significant differences among the NiTi systems at any level. The difference between hand filing and the NiTi techniques was more pronounced at size #40 than at size #30. The NiTi systems were all significantly faster than hand filing. No significant differences in preparation were found between the NiTi systems when canals were instrumented to the size nearest #40.

Demineralization of resected root-ends with methylene blue dye.

OBJECTIVES: This study evaluated the ability of methylene blue solutions of different concentration, pH, and time exposure to remove the smear layer from resected root-ends. STUDY DESIGN: Resected root-ends were treated with either 2% methylene blue dye for intervals of 5 to 11 minutes or 1% methylene blue for 7 to 9 minutes and examined with a scanning electron microscope for smear layer removal. Two minute applications of saline solution and 50% citric acid served as controls. RESULTS: All methylene blue solutions were found to be ineffective in removing the smear layer at all time intervals tested. An experimental solution of 1% methylene blue in 50% citric acid was found to predictably remove the smear layer during a 2 minute application and retained all the favorable staining characteristics of the dye. Fifty percent citric acid solutions applied for 3 minutes appeared to overdemineralize the root-end and gave poorer results than 2 minute applications. CONCLUSIONS: Smear layer removal was pH dependent. Methylene blue solutions are clinically unsuitable for smear layer removal.

Evaluation for cracks associated with ultrasonic root-end preparation of gutta-percha filled canals.

Many clinicians use ultrasonics for root-end preparations. The purpose of this study was to evaluate resected root-end surfaces of bilaterally matched human teeth for cracks before and after ultrasonic root-end preparation. Twenty matched pairs of extracted single rooted teeth were divided into two experimental groups. In group 1, root-end resection was performed on uninstrumented teeth. In group 2, root-end resection was performed after the canals were instrumented and filled with gutta-percha. All teeth in both groups received root-end preparations using ultrasonic instrumentation at low power. Two examiners evaluated the root-ends after root-end resection and again after root-end preparation using zoom magnification of 20x to 63x. The number, types, and location of cracks were mapped. There were no significant differences when gutta-percha filled roots were compared to uninstrumented roots with regard to the number or type of cracks after root-end resection or root-end preparation. In addition, there were no significant differences in the number or type of cracks following root resection and ultrasonic root-end preparation when compared to teeth with root resection alone.

Comparison of dentinal crack incidence and of post removal time resulting from post removal by ultrasonic or mechanical force.

The purpose of this study was to compare the frequency of canal and intradentin cracks after intraradicular post removal using ultrasonic instrumentation or the Gonan post removal system. Sixty cadaver teeth were divided into 4 groups of 15 teeth each: group 1, ultrasonic removal; group 2, Gonan post removal system; group 3, cemented posts not removed; and group 4, no posts. Groups 1 and 2 were contralateral matched pairs. Para Posts were placed in groups 1, 2, and 3 to 7 mm apical to the cementoenamel junction and luted with ZnPO4 cement. The time required for post removal in groups 1 and 2 was recorded. The teeth were extracted, sectioned, and examined. Canal and intradentin cracks were mapped, and their frequency was recorded at each level. There were statistically more cracks present in the ultrasonic group than the no post group. There were no other differences that reached statistical significance. It took significantly longer for post removal using the ultrasonic tip versus the Gonan system.

Contribution of stabilizing agents present in intravenous immunoglobulin preparations to modulation of mononuclear cell proliferation in vitro.

Intravenous immunoglobulin (IVIG) preparations have been shown to suppress lymphocyte proliferation in vitro. This study aimed to investigate the effects of an IVIG produced by fractionation/DEAE-Sephadex adsorption on lymphocyte proliferation in vitro, with particular reference to contributions of the stabilizing agents present in the IVIG to the modulation of mononuclear cell proliferation. It was found that glycine significantly inhibited stimulation by the mitogenic lectin phytohaemagglutinin (PHA; 58% inhibition, P < 0.01). Glucose and human albumin also reduced the response to PHA but to a lesser extent (20% and 30%, respectively). In further experiments the effects of sucrose and maltose, two disaccharides used as stabilizing agents in IVIG preparations, were studied. Three doses were used (2.5 mM, 25 mM and 250 mM), representing levels likely to be found in vivo after infusion of IVIG at immunotherapeutic doses, on four different proliferative stimuli. Maltose was found to inhibit proliferation to PHA, anti-CD3 and PMA in a dose responsive manner. Sucrose also inhibited proliferation to these stimuli, but a dose response was not observed. For both sugars, only the highest dose (250 mM) inhibited the proliferative response of mononuclear cells to PMA and a calcium ionophore (ionomycin). The repurified IgG component of the IVIG preparation did not inhibit PBMC responses to PHA in this system. Kinetic analyses, in which the sugars were added 24 h after proliferative stimuli, indicated that both sugars still inhibited responses to PHA, and, to a lesser extent, PMA, but only maltose inhibited the anti-CD3 response. These findings show that stabilizing agents currently found in commercial IVIG preparations make a significant contribution to modulating mononuclear cell proliferation and need to be considered when assessing the immunomodulatory role of IVIG in vitro.

Evaluation of cracks associated with ultrasonic root-end preparation.

The purpose of this study was to evaluate the integrity of resected root-end surfaces of extracted human teeth after using ultrasonic tips at low or high frequencies for root-end preparation. Thirty bilaterally matched pairs of single-rooted human teeth had root-end resections using a low-speed diamond saw and were examined for root-end cracks. The matched pairs of teeth were then divided into two experimental groups, with one member of each pair being placed in each group. In group 1, root-end preparations were made with an ultrasonic tip on the lowest frequency setting. The preparations in group 2 were done on the highest power setting. Two investigators again examined the resected root-ends using a stereomicroscope at x20 to x63 and recorded the numbers, types, and location of the cracks. Three types of cracks were observed: canal cracks, intradentin cracks, and cemental cracks. There were significantly more root-ends with cracks after ultrasonic root-end preparation than after root-end resection only. In root-ends that had any cracks, significantly more canal cracks per root occurred when the ultrasonic tip was used on the high-frequency setting for root-end preparation than when the ultrasonic tip was used on the low power setting.

The quality of training for nursing assistants:.

Training of personnel is held to be critical to the quality of care for frail elders. This article reports the evaluations of 48 experienced nursing assistants (NAs) on the quality of their training, its relevance to their work, and gaps or needed changes. Findings are from in-depth interviews with NAs conducted as part of a larger study of workforce satisfaction.

Infiltrate of chronic lymphocytic leukemia appearing as a periapical radiolucent lesion.

This report presents a case of a mandibular premolar with a vital pulp and a periapical radiolucent lesion in a patient with a history of chronic lymphocytic leukemia. Biopsy of the lesion revealed an infiltrate of chronic lymphocytic leukemia in the mandible, which is quite rare. This lesion may have portended a worsening of the patient's condition and downgrading of her prognosis.