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X Xiong

Publications and source records attributed to X Xiong.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of ionizing radiation on the human brain: white matter and gray matter T1 in pediatric brain tumor patients treated with conformal radiation therapy.

OBJECTIVE: To test a hypothesis that fractionated radiation therapy (RT) to less than 60 Gy is associated with a dose-related change in the spin-lattice relaxation time (T1) of normal brain tissue, and that such changes are detectable by quantitative MRI (qMRI). METHODS: Each of 21 patients received a qMRI examination before treatment, and at several time points during and after RT. A map of brain T1 was calculated and segmented into white matter and gray matter at each time point. The RT isodose contours were then superimposed upon the T1 map, and changes in brain tissue T1 were analyzed as a function of radiation dose and time following treatment. We used a mixed-model analysis to analyze the longitudinal trend in brain T1 from the start of RT to 1 year later. Predictive factors evaluated included patient age and clinical variables, such as RT dose, time since treatment, and the use of an imaging contrast agent. RESULTS: In white matter (WM), a dose level of greater than 20 Gy was associated with a dose-dependent decrease in T1 over time, which became significant about 3 months following treatment. In gray matter (GM), there was no significant change in T1 over time, as a function of RT doses < 60 Gy. However, GM in close proximity to the tumor had an inherently lower T1 before therapy. Neither use of a contrast agent nor a combination of chemotherapy plus steroids had a significant effect on brain T1. CONCLUSION: Results suggest that T1 mapping may be sensitive to radiation-related changes in human brain tissue T1. WM T1 appears to be unaffected by RT at doses less than approximately 20 Gy; GM T1 does not change at doses less than 60 Gy. However, tumor appears to have an effect upon adjacent GM, even before treatment. Conformal RT may offer a substantial benefit to the patient, by minimizing the volume of normal brain exposed to greater than 20 Gy.

Adolescent↗
PubMed2001

Effect of therapeutic ionizing radiation on the human brain.

We test a hypothesis that fractionated radiation therapy within a therapeutic dose range is associated with a dose-related change in normal brain, detectable by quantitative magnetic resonance imaging. A total of 33 patients were examined by quantitative magnetic resonance imaging to measure brain tissue spin-lattice relaxation time (T1) before treatment, and at various times during and after radiation therapy. A T1 map was generated at each time point, and radiation therapy isodose contours were superimposed on the corresponding segmented T1 map. Changes in white matter and gray matter T1 were analyzed as a function of radiation therapy dose and time since treatment, controlling for patient age and tumor site. In white matter, a dose level of more than 20 Gy was associated with a dose-dependent decrease in T1 over time, which became significant 6 months after treatment. There was no significant change in T1 of gray matter over time, at radiation therapy doses of less than 60 Gy. However, GM in close proximity to the tumor had a lower T1 before therapy. Our results represent the first radiation dose-response data derived from pediatric brain in vivo. These findings confirm that white matter is more vulnerable to radiation-induced change than is gray matter, and suggest that T1 mapping is sensitive to radiation-related changes over a broad dose range (20 to 60 Gy). Human white matter T1 is not sensitive to radiation therapy of less than 20 Gy, and gray matter T1 is unchanged over the dose range used to treat human brain tumor. The reduction of gray matter T1 near the tumor could result from compression of cortical parenchyma near the growing tumor mass, or from tumor cell invasion directly into the parenchyma. If brain T1 is a surrogate for radiation effect, reducing the volume of normal white matter receiving more than 20 Gy could be an important treatment planning goal.

Adolescent↗
PubMed2001

Tumor volume or dynamic contrast-enhanced MRI for prediction of clinical outcome of Ewing sarcoma family of tumors.

BACKGROUND: The identification of risk factors that predict poor clinical outcome at the time of diagnosis could lead to intensified early therapy and improved outcome for pediatric patients with Ewing sarcoma family of tumors (ESFT). OBJECTIVE: To compare the effectiveness of static magnetic resonance (MR) imaging measurements of tumor volume with variables obtained by dynamic contrast-enhanced MR imaging (DEMRI) in predicting ESFT outcome. METHODS: MR examinations that included DEMRI were retrospectively reviewed. The analyses included 45 examinations of 21 patients with ESFT (performed from 1992 to 1996). Tumor volumes were measured on the static MR images, and the regions of interest were selected for DEMRI analysis. The relationships of static MR imaging and DEMRI variables with the probability of progression-free survival (PFS) and disease-free survival (DFS) were determined. RESULTS: Larger tumor volume at the time of diagnosis predicted poorer PFS and DFS estimates. No DEMRI variable predicted outcome. CONCLUSION: Determination of tumor volume by static MR imaging at the time of diagnosis is a simple and reliable method of predicting the clinical outcome of patients with ESFT. DEMRI is not as reliable a technique as static MR imaging for predicting the outcome of these patients.

Adolescent↗
PubMed2001

Gestational diabetes mellitus: prevalence, risk factors, maternal and infant outcomes.

OBJECTIVES: To study prevalence, risk factors, and maternal and infant outcomes of women with gestational diabetes mellitus (GDM). METHODS: A retrospective cohort study was performed based on 111563 pregnancies delivered between 1991 through 1997 in 39 hospitals in northern and central Alberta, Canada. Multivariate logistic regression was used to estimate the odds ratios with 95% confidence intervals, and to control for confounding variables. RESULTS: The prevalence of GDM was 2.5%. Risk factors for GDM included age >35 years, obesity, history of prior neonatal death, and prior cesarean section. Teenage mothers and women who drank alcohol were less likely to have GDM. Mothers with GDM were at increased risk of presenting with pre-eclampsia, premature rupture of membranes, cesarean section, and preterm delivery. Infants born to mothers with GDM were at higher risk of being macrosomic or large-for-gestational-age. CONCLUSIONS: Specific conditions predispose to GDM which itself is associated with a significantly increased risk of maternal and fetal morbidity.

Adolescent↗
PubMed2001

Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain.

Etk/BMX, a member of the Btk family of tyrosine kinases, is highly expressed in cells with great migratory potential, including endothelial cells and metastatic carcinoma cell lines. Here, we present evidence that Etk is involved in integrin signalling and promotes cell migration. The activation of Etk by extracellular matrix proteins is regulated by FAK through an interaction between the PH domain of Etk and the FERM domain of FAK. The lack of Etk activation by extracellular matrix in FAK-null cells could be restored by co-transfection with wild-type FAK. Disrupting the interaction between Etk and FAK diminished the cell migration promoted by either kinase. Furthermore, inhibiting Etk expression in metastatic carcinoma cell lines with an antisense oligonucleotide blocks integrin-mediated migration of these cells. Taken together, our data indicate the essential role of the interaction of the PH domain of Etk and the FERM domain of FAK in integrin signalling.

Animals↗
PubMed2001

Preeclampsia and cerebral palsy in low-birth-weight and preterm infants: implications for the current "ischemic model" of preeclampsia.

OBJECTIVE: One of the prevailing hypotheses for the pathogenesis of preeclampsia is the "ischemic model." It assumes that reduced uteroplacental perfusion is the primary step and the point of convergence of diverse pathogenic processes in the development of preeclampsia. One might expect a fetus under such "ischemic conditions" to be at an increased risk of later development of cerebral palsy (CP). The objective of this study was to test the hypothesis that maternal preeclampsia increases the risk of CP in preterm and low-birth-weight infants. METHODS: A meta-analysis was performed based on published articles identified by searching computerized databases (MEDLINE, EMBASE, CINAHL, Current Contents, Biological Abstracts, and Dissertation Abstracts) from 1966 through 1999. Ten observational studies on the association between preeclampsia and CP were identified based on prespecified inclusion criteria. Two independent reviewers extracted data and assessed the methodological quality of eligible articles. Odds ratios (OR) of CP for preeclampsia from individual studies were pooled. MAIN OUTCOME MEASURE: Cerebral palsy. RESULTS: In case-control studies, preeclampsia was associated with a statistically significant decreased risk of CP [pooled adjusted OR, 0.50; 95% confidence interval (CI), 0.33-0.81; p < 0.01). In cohort studies, preeclampsia was associated with a nonstatistically significant reduced risk of CP (pooled OR, 0.91; 95% CI, 0.35-2.41; p > 0.05). CONCLUSIONS: Preeclampsia may be associated with a decreased risk of CP in preterm and low-birth-weight infants. This challenges the currently held belief that reduced uteroplacental perfusion is the unique pathophysiological process in preeclampsia.

Cerebral Palsy↗
PubMed2001

Molecular modeling and biochemical characterization reveal the mechanism of hepatitis B virus polymerase resistance to lamivudine (3TC) and emtricitabine (FTC).

Success in treating hepatitis B virus (HBV) infection with nucleoside analog drugs like lamivudine is limited by the emergence of drug-resistant viral strains upon prolonged therapy. The predominant lamivudine resistance mutations in HBV-infected patients are Met552IIe and Met552Val (Met552Ile/Val), frequently in association with a second mutation, Leu528Met. The effects of Leu528Met, Met552Ile, and Met552Val mutations on the binding of HBV polymerase inhibitors and the natural substrate dCTP were evaluated using an in vitro HBV polymerase assay. Susceptibility to lamivudine triphosphate (3TCTP), emtricitabine triphosphate (FTCTP), adefovir diphosphate, penciclovir triphosphate, and lobucavir triphosphate was assessed by determination of inhibition constants (K(i)). Recognition of the natural substrate, dCTP, was assessed by determination of Km values. The results from the in vitro studies were as follows: (i) dCTP substrate binding was largely unaffected by the mutations, with Km changing moderately, only in a range of 0.6 to 2.6-fold; (ii) K(i)s for 3TCTP and FTCTP against Met552Ile/Val mutant HBV polymerases were increased 8- to 30-fold; and (iii) the Leu528Met mutation had a modest effect on direct binding of these beta-L-oxathiolane ring-containing nucleotide analogs. A three-dimensional homology model of the catalytic core of HBV polymerase was constructed via extrapolation from retroviral reverse transcriptase structures. Molecular modeling studies using the HBV polymerase homology model suggested that steric hindrance between the mutant amino acid side chain and lamivudine or emtricitabine could account for the resistance phenotype. Specifically, steric conflict between the Cgamma2-methyl group of Ile or Val at position 552 in HBV polymerase and the sulfur atom in the oxathiolane ring (common to both beta-L-nucleoside analogs lamivudine and emtricitabine) is proposed to account for the resistance observed upon Met552Ile/Val mutation. The effects of the Leu528Met mutation, which also occurs near the HBV polymerase active site, appeared to be less direct, potentially involving rearrangement of the deoxynucleoside triphosphate-binding pocket residues. These modeling results suggest that nucleotide analogs that are beta-D-enantiomers, that have the sulfur replaced by a smaller atom, or that have modified or acyclic ring systems may retain activity against lamivudine-resistant mutants, consistent with the observed susceptibility of these mutants to adefovir, lobucavir, and penciclovir in vitro and adefovir in vivo.

Acyclovir↗
PubMed2001

[Uvulopalatopharyngoplasty for the treatment of obstructive sleep apnea syndrome in 70 cases].

OBJECTIVE: To elevate the effect of uvulopalatopharyngoplasty (UPPP) and minimize the postoperative complications. METHOD: The data of 70 patients with obstructive sleep apnea syndrome diagnosed with polysomnography were analyzed. RESULT: 15 cases (21%) reported unchanged snoring and apnea and hyponea index. 55 cases improved after UPPP for at least 6 months. The complications included hypertensive crisis (2 cases), respiratory embarrassment (4 cases) in period of paretic UPPP. After UPPP, The complications included local hemorrhage (1 case), wound dehiscence (2 cases), temporal velopalatal insufficiency (9 cases), one had suffocation after extraction of endotracheal tube. CONCLUSION: Our results indicate that the strategies of improving the effect and avoiding the complications include: Excision of the lateral pharyngeal wall in retropalatal region and fat tissue in soft palate. Protection of palatosalpingeus and palatostaphylinus. Part preservation of uvula. Confirmation of the obstructive region. Choice of the anesthesia and preventive tracheotomy. Modified tracheotomy were safe and convenient when exchanging trachea canula.

Adult↗
PubMed2000

Spatiotemporal expression of BDNF in the hippocampus induced by the continuous intracerebroventricular infusion of beta-amyloid in rats.

The beta-amyloid protein (Abeta) is the major component of senile plaques found in the brain in Alzheimer's disease (AD). Its neurotoxic properties in vivo, however, are not well defined. Since the expression of neurotrophin genes is considered an important component of the intrinsic neuroprotective response to insults, we analyzed the gene expression of neurotrophins in the brains of rats which received a continuous infusion of Abeta-(1-42) into the cerebroventricle. Northern blot analysis revealed a significant increase in brain-derived neurotrophic factor (BDNF) expression in the hippocampus but no change in the cerebral cortices. The alteration peaked on days 3-7 and returned to the basal level on day 14 after the start of Abeta-(1-42) infusion. No significant changes in nerve growth factor or neurotrophin-3 mRNA expression were observed. The infusion of Abeta-(1-40) and (25-35) also triggered the expression of BDNF mRNA, whereas neither Abeta-(40-1) nor (1-16) had any effect. In situ hybridization histochemistry revealed that the expression mainly occurred in the hilus and granular layer of the dentate gyrus and to a lesser extent in the pyramidal neurons of the CA1 region. These results demonstrate that the continuous intracerebroventricular infusion of Abeta induces selective and spatiotemporal expression of BDNF mRNA in the hippocampus.

Alzheimer Disease↗
PubMed2000

Cloning, characterization, and functional studies of human and mouse glycoprotein VI: a platelet-specific collagen receptor from the immunoglobulin superfamily.

Injuries to the vessel wall and subsequent exposure of collagen from the subendothelial matrix result in thrombus formation. In physiological conditions, the platelet plug limits blood loss. However, in pathologic conditions, such as rupture of atherosclerotic plaques, platelet-collagen interactions are associated with cardiovascular and cerebral vascular diseases. Platelet glycoprotein VI (GPVI) plays a crucial role in collagen-induced activation and aggregation of platelets, and people who are deficient in GPVI suffer from bleeding disorders. Based on the fact that GPVI is coupled to the Fc receptor (FcR)-gamma chain and thus should share homology with the FcR chains, the genes encoding human and mouse GPVI were identified. They belong to the immunoglobulin (Ig) superfamily and share 64% homology at the protein level. Functional evidence demonstrating the identity of the recombinant protein with GPVI was shown by binding to its natural ligand collagen; binding to convulxin (Cvx), a GPVI-specific ligand from snake venom; binding of anti-GPVI IgG isolated from a patient; and association to the FcR-gamma chain. The study also demonstrated that the soluble protein blocks Cvx and collagen-induced platelet aggregation and that GPVI expression is restricted to megakaryocytes and platelets. Finally, human GPVI was mapped to chromosome 19, long arm, region 1, band 3 (19q13), in the same region as multiple members of the Ig superfamily. This work offers the opportunity to explore the involvement of GPVI in thrombotic disease, to develop alternative antithrombotic compounds, and to characterize the mechanism involved in GPVI genetic deficiencies. (Blood. 2000;96:1798-1807)

Amino Acid Sequence↗
PubMed2000

Sample size calculation for planning group sequential longitudinal trials.

Procedures are developed in this paper for sample size calculations for planning a group sequential longitudinal trial with various correlation structures, using a test statistic based on generalized estimating equations (Lee, Kim and Tsiatis) and group sequential boundaries based on type I error spending functions (Lan and DeMets).

Adolescent↗
PubMed2000

In vitro evaluation of hepatitis B virus polymerase mutations associated with famciclovir resistance.

Several mutations (V521L, P525L, L528M, T532S, and V555I) in the gene for hepatitis B virus (HBV) polymerase have been identified in HBV isolated from patients that displayed break-through viremia during famciclovir treatment. To determine whether these mutations cause phenotypic resistance to famciclovir, we compared the inhibition constants (K(i)) of penciclovir triphosphate (PCVTP, the active metabolite of famciclovir) for recombinant wild-type and mutant HBV polymerases containing these mutations. In in vitro enzymatic assays, the V555I mutation displayed the most resistance (with K(i) increased by 6.2-fold) to PCVTP. The V521L and L528M mutations showed moderately decreased sensitivity to PCVTP (K(i) increased by >3-fold). We also analyzed the cross-resistance profiles of these variants for adefovir and lamivudine, two other antiviral agents that also inhibit DNA replication by HBV polymerase. All 5 famciclovir-associated mutations were sensitive to adefovir diphosphate (ADVDP) in in vitro enzymatic assays (<2.3-fold decreased sensitivity). The V521L, L528M, and T532S mutations were also sensitive to lamivudine triphosphate (LAMTP); however, the P525L and V555I mutations displayed moderately decreased sensitivity to LAMTP in enzymatic assays (3.6-fold decreased sensitivity). The lamivudine-resistant mutations M552I, M552V, and L528M+M552V, which were previously shown to display 8- to 25-fold resistance to LAMTP, were less resistant (< or = 3.1-fold) to PCVTP.

2-Aminopurine↗
PubMed2000

Accuracy of MR imaging for detecting epiphyseal extension of osteosarcoma.

BACKGROUND: Too few patients are receiving epiphyseal-sparing limb salvage procedures for osteosarcoma. OBJECTIVE: To determine how magnetic resonance (MR) imaging can best predict the epiphyseal extension of osteosarcoma. MATERIALS AND METHODS: Forty children underwent complete pretreatment static and dynamic contrast-enhanced MR imaging (DEMRI). Static MR images [T1-weighted and short tau inversion recovery (STIR)] of the epiphyses were read in three ways: (1) for suspicion of any abnormality (tumor or edema), (2) for suspicion of tumor, excluding suspected edema, and (3) validating the second method by using a scale to rate the likelihood of tumor. Presentation imaging was compared to histopathologic findings after chemotherapy and resection. The receiver operating characteristic (ROC) method was used to analyze the scaled ratings of static MR and DEMRI values. RESULTS: At delayed resection, 20 of 40 children with osteosarcoma had confirmed epiphyseal tumor; however, 32 epiphyses were abnormal on STIR and 28 abnormal on T1. Differentiating suspected tumor from edema increased the accuracy to an Az (area under the ROC curve) of 0.94 for both T1-weighted and STIR static sequences. T1-weighted MR had better specificity and STIR better sensitivity at any given rating. DEMRI was slightly less accurate (Az = 0.90). CONCLUSION: Static MR imaging most accurately detected epiphyseal extension of osteosarcoma when readers distinguished suspected tumor from edematous or normal tissue.

Adolescent↗
PubMed2000

Subtle white matter volume differences in children treated for medulloblastoma with conventional or reduced dose craniospinal irradiation.

Medulloblastoma is the most common malignant brain tumor in children, and approximately seventy percent of average-risk patients will achieve long-term survival. Craniospinal irradiation (CSI), combined with chemotherapy and surgery, is currently the mainstay of treatment but places children who survive at risk for serious neurocognitive sequelae. These sequelae are intensified with a younger age at treatment, greater elapsed time following treatment, and an increased radiation dose. Many newer treatment approaches have attempted to address this problem by reducing the dose of the CSI component of radiation therapy while maintaining the current survival rates. This study evaluates longitudinal MR imaging during therapy to assess the impact of the two CSI doses (conventional [36 Gy] and reduced [23.4 Gy]) on normal appearing white matter volumes (NAWMV) evaluated in a single index slice. Twenty-six children and young adults at least three years of age enrolled on an institutional protocol for newly diagnosed, previously untreated primary medulloblastoma had at least four MR examinations over a minimum nine month period following CSI. These serial volumes were evaluated as a function of time since CSI in three analyses: 1) all subjects, 2) subjects stratified by age at CSI, and 3) subjects stratified by CSI dose. The first analysis demonstrated that medulloblastoma patients treated with CSI have a significant loss of NAWMV in contradistiction to normally expected maturation. Stratifying the patients by age at CSI found no significant differences in the rate of NAWMV loss. The final analysis stratified the patients by CSI dose and revealed that the rate of NAWMV loss was 23% slower in children receiving reduced-dose. Serial quantitative MR measures of NAWMV may provide a neuroanatomical substrate for assessing functional impact of CSI on normal brain function following treatment for medulloblastoma.

Adolescent↗
PubMed2000

Anemia during pregnancy and birth outcome: a meta-analysis.

To determine the relationship between maternal anemia [hemoglobin (Hgb) < 10-11 g/dL] and various birth outcomes, a meta-analysis was conducted based on published literature identified by MEDLINE and manual search from 1966 through 1999. Odds ratios (OR) from selected studies were pooled according to the gestational age at anemia diagnosis. The meta-analysis shows that maternal anemia during early pregnancy was associated with slightly increased preterm birth [pooled adjusted OR (aOR): 1.32, 95% confidence interval (CI): 1.01-1.74], and nonstatistically significant increased low birth weight [pooled aOR: 1.39 (0.70-2.74)], and was not associated with fetal growth restriction [pooled aOR: 1.01 (0.73-1.38)]. However, there was a nonstatistically significant inverse relationship between anemia during late pregnancy and preterm birth [pooled aOR: 0.92 (0.54-1.84)] and low birth weight [pooled aOR: 0.80 (0.64-1.00)]. Anemia was not statistically significantly associated with hypertensive disorders of pregnancy regardless of stage of pregnancy [pooled OR: 0.80 (0.53-1.20)]. The relationship between anemia and perinatal mortality was inconclusive. A few studies indicated that severe maternal anemia (Hgb < 8-8.5 g/dL) was associated with increased risk of poor outcomes. We conclude that early pregnancy anemia is associated with slightly increased risk of preterm birth. The trend toward an inverse association of anemia determined during late pregnancy with preterm birth and low birth weight may reflect the benefit of plasma volume expansion.

Adult↗
PubMed2000

Association of preeclampsia with high birth weight for age.

OBJECTIVE: The purpose of this study was to examine the effect of gestational hypertension and preeclampsia on fetal growth. STUDY DESIGN: A retrospective cohort study was conducted on the basis of 97,270 pregnancies delivered between 1991 and 1996 in 35 hospitals in northern and central Alberta, Canada. Univariate and multivariate logistic analyses were performed to examine the impact of preeclampsia and gestational hypertension on high-birth-weight (> or =4200 g), large-for-gestational-age, low-birth-weight (<2500 g), and small-for-gestational-age babies. RESULTS: The rate of high-birth-weight fetuses in women with gestational hypertension (7. 3%) was higher than in those with normal blood pressure (5.6%). After we controlled for confounders, the adjusted odds ratio of high birth weight was 1.44 (95% confidence interval, 1.21-1.70) in women with gestational hypertension. Preeclampsia was also associated with a statistically nonsignificant (P =.054) increased risk of high birth weight (adjusted odds ratio, 1.40; 95% confidence interval 0. 99-1.98). The rate of large-for-gestational-age babies was significantly higher in women with gestational hypertension (4.5%) and preeclampsia (4.7%) than in those with normal blood pressure (2. 2%), with adjusted odds ratios of 1.50 (95% confidence interval, 1. 22-1.85) for gestational hypertension and 1.87 (95% confidence interval, 1.31-2.67) for preeclampsia. Concurrently, women who had gestational hypertension were also at higher risk of having low-birth-weight (adjusted odds ratio, 2.4; 95% confidence interval, 2.13-2.93) and small-for-gestational-age (adjusted odds ratio, 2.04; 95% confidence interval, 1.68-2.48) babies. Women with preeclampsia were also at markedly higher risk of having low-birth-weight (adjusted odds ratio, 4.14; 95% confidence interval, 3.32-5.15) and small-for-gestational-age (adjusted odds ratio, 2.56; 95% confidence interval, 1.92-3.41) babies. CONCLUSIONS: There is a significant association of preeclampsia and gestational hypertension with large-for-gestational-age infants, in addition to a significant association with low-birth-weight and small-for-gestational-age infants. This study challenges the currently held belief that reduced uteroplacental perfusion is the unique pathophysiologic process in preeclampsia.

Birth Weight↗