Biomedical subjects

Xiaoping Xiong

Publications and source records attributed to Xiaoping Xiong.

32 records · Page 2Linked to original sources

PubMed2004

Generation of high-yielding influenza A viruses in African green monkey kidney (Vero) cells by reverse genetics.

Influenza A viruses are the cause of annual epidemics of human disease with occasional outbreaks of pandemic proportions. The zoonotic nature of the disease and the vast viral reservoirs in the aquatic birds of the world mean that influenza will not easily be eradicated and that vaccines will continue to be needed. Recent technological advances in reverse genetics methods and limitations of the conventional production of vaccines by using eggs have led to a push to develop cell-based strategies to produce influenza vaccine. Although cell-based systems are being developed, barriers remain that need to be overcome if the potential of these systems is to be fully realized. These barriers include, but are not limited to, potentially poor reproducibility of viral rescue with reverse genetics systems and poor growth kinetics and yields. In this study we present a modified A/Puerto Rico/8/34 (PR8) influenza virus master strain that has improved viral rescue and growth properties in the African green monkey kidney cell line, Vero. The improved properties were mediated by the substitution of the PR8 NS gene for that of a Vero-adapted reassortant virus. The Vero growth kinetics of viruses with H1N1, H3N2, H6N1, and H9N2 hemagglutinin and neuraminidase combinations rescued on the new master strain were significantly enhanced in comparison to those of viruses with the same combinations rescued on the standard PR8 master strain. These improvements pave the way for the reproducible generation of high-yielding human and animal influenza vaccines by reverse genetics methods. Such a means of production has particular relevance to epidemic and pandemic use.

Animals↗

PubMed2004

Comparison of transcranial Doppler sonography with and without imaging in the evaluation of children with sickle cell anemia.

OBJECTIVE: High blood flow velocity in the middle cerebral artery or distal internal carotid artery, as measured by nonduplex transcranial Doppler sonography, predicts stroke in children with sickle cell anemia. However, velocities measured using the more widely available duplex transcranial Doppler imaging equipment may not be comparable. We sought to determine the magnitude and significance of the potential differences. SUBJECTS AND METHODS: We performed 55 paired examinations with duplex imaging and nonduplex nonimaging sonography machines on 53 children with sickle cell anemia. Examinations were performed consecutively by three sonographers blinded to the results of the opposing study. Velocities were measured in five clinically relevant vessels. RESULTS: Time-averaged mean maximum (TAMx) velocity measurements obtained with the duplex equipment were significantly lower than those made with the nonduplex equipment for all vessels except the posterior cerebral artery. The mean differences were 10.9% (p < 0.0001) in the middle cerebral artery, 12.7% (p = 0.002) in the anterior cerebral artery, 2.2% (p = 0.69) in the posterior cerebral artery, 21.0% (p < 0.0001) in the distal internal carotid artery, and 15.3% (p < 0.0001) at the bifurcation of the distal internal carotid artery. CONCLUSION: If TAMx velocities measured with duplex equipment are used to assign stroke risk in children with sickle cell anemia, we suggest that 180 cm/sec or more should be considered abnormal, and 153-179 cm/sec, as conditional. These values are 10% lower than those obtained from the nonduplex equipment used in the Stroke Prevention Trial in Sickle Cell Anemia study.

Adolescent↗

PubMed2004

The effects of hydrocephalus on intelligence quotient in children with localized infratentorial ependymoma before and after focal radiation therapy.

OBJECT: The goal of this study was to determine the influence of hydrocephalus on intelligence quotient (IQ) in children with infratentorial ependymoma before and after the administration of focal radiation. METHODS: Measurements of ventricular size, including Evans index (EI), cella media index (CMI), frontal horn diameter (FHD), and ventricular angle, were performed using magnetic resonance imaging at the time of diagnosis and again at 3, 6, 9, and 12 months after the initiation of radiation therapy. Of the 59 patients (median age at time of radiation treatment, 4.1 years), the clinical diagnosis established in 50 (85%) was hydrocephalus and 23 (39%) required placement of a cerebrospinal fluid (CSF) shunt. Extent of resection was gross or near total in 50 (85%). Before and after radiation treatment, IQ was measured using age-appropriate testing. The correlation between multiple ventricular measurements and IQ was investigated using standard regression techniques and a generalized linear model. Patients with a higher EI (p = 0.04), CMI (p = 0.001), and FHD (p = 0.0002) at the time of diagnosis were more likely to have lower IQ scores before radiation treatment. Patients with higher CMI (p = 0.04) and FHD (p = 0.01) at the time of diagnosis were more likely to exhibit an increase in IQ score after radiotherapy. The rate of change in IQ after radiation treatment was positively correlated with the CMI intercept (p = 0.015) and negatively correlated with the rate of FHD change (p = 0.006). CONCLUSIONS: Changes in IQ score before and after radiation treatment are significantly influenced by the extent and treatment of hydrocephalus at the time of diagnosis. Hydrocephalus is an important factor to include when analyzing the effects of treatment. Patients who undergo a second surgery for ependymoma are more likely to require the placement of a CSF shunt (p = 0.0001).

Adolescent↗

PubMed2004

Abnormal hippocampal development in children with medulloblastoma treated with risk-adapted irradiation.

BACKGROUND AND PURPOSE: Children with medulloblastoma demonstrate post-treatment neurocognitive deficits in a number of areas, including memory performance. However, there is no definitive understanding of the neuropathology underlying these functional deficits. Previous literature has reported that hippocampal integrity is crucial to the acquisition of new episodic memories. Therefore, we hypothesized that longitudinal hippocampal volume measurements are abnormal in patients with medulloblastoma and thereby provide a possible substrate for explaining memory dysfunction. METHODS: Twenty-five pediatric patients underwent 159 serial MR imaging examinations (mean = six examinations per patient) for up to 5 years after irradiation and chemotherapy treatment for medulloblastoma. Right and left hippocampal volumes were obtained by manually tracing 1.5-mm contiguous coronal sections through the structure. Random coefficient models were used to examine longitudinal change in hippocampal volume as a function of time after diagnosis. RESULTS: Both right and left hippocampal volumes initially decreased after treatment. This abnormal volume pattern continued until approximately 2-3 years after diagnosis, when hippocampal volumes returned toward a normal positive growth pattern. Volume loss occurred predominately in the posterior regions. Female sex, low parental education, shunt placement, and positive seizure history all had a significant negative impact on hippocampal volume. CONCLUSION: Pediatric medulloblastoma survivors demonstrate an abnormal pattern of hippocampal volume development after treatment. Radiation dose mapping may expand our understanding of region-specific changes in hippocampal volume. Further exploration of the relationships between radiation therapy, memory dysfunction, and hippocampal pathology in this population is warranted.

Amnesia↗

PubMed2003

Brain imaging findings in pediatric patients with sickle cell disease.

PURPOSE: To determine prevalence of imaging abnormalities in the brain of children with sickle cell disease (SCD) and to identify clinical and methodological factors that influence prevalence estimate. MATERIALS AND METHODS: Magnetic resonance (MR) imaging and MR angiographic findings for 185 patients with SCD examined at St Jude Children's Research Hospital since 1993 were reviewed. At least two readers independently reviewed images. Standard MR imaging criteria were used to identify lacunae, loss of white matter volume, encephalomalacia, or leukoencephalopathy. Patients were assigned grades to indicate limited or extensive abnormalities. Standard MR angiographic criteria were used to identify arterial tortuosity (limited vasculopathy) and stenosis or occlusion (extensive vasculopathy). Findings were evaluated as a function of patient clinical status (including stroke) and diagnosis. Recent methods (T1- and T2-weighted MR imaging plus fluid-attenuated inversion recovery [FLAIR] at 3-mm section thickness) were compared with older methods (T1- and T2-weighted MR imaging without FLAIR at 5-mm section thickness). RESULTS: At mean age of 10 years, overall prevalence of infarction, ischemia, or atrophy in patients with SCD was 44% (82 of 185), and prevalence of vasculopathy was 55% (102 of 185), without evidence of a significant referral bias. Twenty-six of 27 patients with clinical stroke had abnormal findings at imaging, but even if patients with stroke were excluded, 35% (56 of 158) had a "silent infarction" (MR imaging-visible injury without clinical stroke), and 49% (78 of 158) had abnormal findings at MR angiography. Patients with clinically severe disease had more abnormalities at MR imaging (P <.001) and MR angiography (P <.004) than did patients with milder disease. Severe vasculopathy was more prevalent in patients with hemoglobin SS than in those with hemoglobin SC (P <.001). Recent imaging methods showed more abnormalities than did older methods (P <.01). With newer methods, 43% (29 of 67) of patients had extensive abnormalities, whereas with older methods, 28% (33 of 116) had extensive abnormalities. CONCLUSION: Prevalence of ischemic brain injury in pediatric patients with SCD is substantially higher than was previously reported, in part because of improvements in imaging methods.

Anemia, Sickle Cell↗

PubMed2003

Prospective brain imaging evaluation of children with sickle cell trait: initial observations.

PURPOSE: To determine whether sickle cell trait (hemoglobin AS) is associated with abnormalities in the brain of asymptomatic children. MATERIALS AND METHODS: Magnetic resonance (MR) imaging and MR angiography were performed prospectively in 26 siblings (eight girls, 18 boys; mean age, 10.5 years) of patients with sickle cell disease. Two neuroradiologists, blinded as to whether a child had hemoglobin AS or AA, reviewed images obtained in siblings. With MR imaging, lacunae, loss of white matter volume, encephalomalacia, or leukoencephalopathy was identified. With MR angiography, arterial stenosis, occlusion, or tortuosity was identified. Images with definite or possible abnormalities were mixed with randomly selected images and were referred to a third neuroradiologist for a completely blinded review. In cases in which all neuroradiologists concurred, a score was assigned that indicated the sibling had an abnormality. MR angiographic findings were assigned a score for tortuosity with a new quantitative scale. RESULTS: Among 26 siblings screened, 21 children had sickle cell trait. Among these 21 children, two had mild abnormalities at MR imaging (sample prevalence rate, 10% [95% CI: 1%, 29%]), and four had arterial tortuosity (sample prevalence rate, 19% [95% CI: 5%, 42%]). When children with sickle cell trait were compared with 31 control subjects without the trait, arterial tortuosity was significantly more common in children with sickle cell trait (P =.014). Among children with sickle cell trait, percentage of hemoglobin S was significantly greater in children who had tortuosity than percentage of hemoglobin S in children who had normal blood vessels at MR angiography (P <.03). CONCLUSION: Findings suggest that greater percentage of hemoglobin S is associated with mild vasculopathy. This vasculopathy may explain some of the excess risk of stroke among African Americans.

Adolescent↗

PubMed2003

Brain injury in children with sickle cell disease: prevalence and etiology.

Our objective was to evaluate the relationship between brain injury by magnetic resonance imaging (MRI) and vasculopathy by magnetic resonance angiography (MRA) in children with hemoglobin SS, the most serious form of sickle cell disease. We reviewed imaging for all 146 SS patients imaged at St. Jude Children's Research Hospital since 1993. Standard MRI criteria were used to identify cystic infarction, leukoencephalopathy, encephalomalacia, or atrophy. Standard MRA criteria were used to identify arterial tortuousity (limited vasculopathy), and stenosis or occlusion (extensive vasculopathy). At an average age of 10 years, the estimated prevalence of infarction, ischemic damage, or atrophy in SS patients was 46%, and of vasculopathy was 64%. Only 28% of patients were normal by both modalities, and patients abnormal by MRA often were abnormal by MRI (p < 0.00001). Patients with cystic infarction had limited vasculopathy, whereas patients with encephalomalacia had stenosis or occlusion (p < 0.0001). Large arteries were affected in 31% of brain injury patients, whereas small arteries are inferred to be abnormal in up to 69% of patients with brain injury. The degree of vasculopathy is closely related to the degree of brain injury, implying that vasculopathy is prodromal to most forms of brain injury in hemoglobin SS.

Adolescent↗

PubMed2003

Predicting intellectual outcome among children treated with 35-40 Gy craniospinal irradiation for medulloblastoma.

Fifty children diagnosed with medulloblastoma completed 188 psychological evaluations using the Wechsler Intelligence Scales for Children (D. Wechsler, 1974, 1991) over a 7-year study period following 35-40 Gy postoperative craniospinal irradiation. Random coefficient models were used to predict the trend in the children's intellectual performance as a function of time since diagnosis, with both patient and treatment variables as parameters of this function. A quadratic model demonstrated a delay prior to decline in performance for older patients, whereas the younger patients showed an immediate loss of performance with a plateau at approximately 6 years postdiagnosis. A steeper decline was found for those with higher baseline performance. Clinicians may use the proposed predictive model to identify those patients who are at risk of significant intellectual decline.

Adolescent↗

PubMed2003

Sequential conditional probability ratio tests for normalized test statistic on information time.

Sequential conditional probability ratio tests (SCPRTs) provide monitoring procedures with a unique property that a decision reached at early stopping is unlikely to be reversed should the trial continue to the planned end (Xiong, X., 1995, Journal of the American Statistical Association 90, 1463-1473; Tan, M., Xiong, X., and Kutner, M. H., 1998, Biometrics 54, 682-95). It actually provides a probability statement of a conclusion reversal, should the proposed interim analysis plan be used. To broaden its scope of applications, in this article we develop the SCPRT in terms of Brownian motion, which is applicable to most clinical trials with various endpoints. In addition, we utilize the unique structure of the SCPRT to derive a class of adaptive sequential tests that retain the significance level and power in the presence of a nuisance parameter. We illustrate the proposed methods with examples in clinical trials.

Biometry↗

PubMed2003

Risk factors for the development of obesity in children surviving brain tumors.

Hypothalamic obesity, a syndrome of intractable weight gain due to hypothalamic damage, is an uncommon but devastating complication for children surviving brain tumors. We undertook a retrospective evaluation of the body mass index (BMI) curves for the St. Jude Children's Research Hospital brain tumor population diagnosed between 1965 and 1995 after completion of therapy to determine risk factors for the development of obesity. Inclusion criteria were: diagnosis less than 14 yr of age, no spinal cord involvement, ambulatory, no supraphysiologic hydrocortisone therapy (>12 mg/m(2) x d), treatment and follow-up at St. Jude Children's Research Hospital, and disease-free survival greater than 5 yr (n = 148). Risk factors examined were age at diagnosis, tumor location, histology, extent of surgery, hydrocephalus requiring ventriculoperitoneal shunting, initial high-dose glucocorticoids, cranial radiation therapy, radiation dosimetry to the hypothalamus, intrathecal chemotherapy, and presence of endocrinopathy. Analyses were performed both between groups within a risk factor and against BMI changes for age in normal children older than 5.5 yr (the age of adiposity rebound). Risk factors were: age at diagnosis (P = 0.04), radiation dosimetry to the hypothalamus (51-72 Gy, P = 0.002 even after hypothalamic and thalamic tumor exclusion), and presence of any endocrinopathy (P = 0.03). In addition, risk factors when compared with BMI slope for the general American pediatric population included: tumor location (hypothalamic, P = 0.001), tumor histology (craniopharyngioma, P = 0.009; pilocytic astrocytoma, P = 0.043; medulloblastoma, P = 0.039); and extent of surgery (biopsy, P = 0.03; subtotal resection, P = 0.018). These results verify hypothalamic damage, either due to tumor, surgery, or radiation, as the primary cause of obesity in survivors of childhood brain tumors. In particular, hypothalamic radiation doses of more than 51 Gy are permissive. These results reiterate the importance of the hypothalamus in energy balance, provide risk assessment criteria for preventative measures before the development of obesity in at-risk patients, and suggest therapeutic strategies to reduce the future development of obesity.

Astrocytoma↗

PubMed2003

Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial.

Hypothalamic obesity is a devastating complication in children surviving brain tumors and/or cranial irradiation. These subjects are thought to exhibit autonomic dysregulation of the beta-cell, with insulin hypersecretion in response to oral glucose tolerance testing (OGTT). We report the results of a randomized, double-blind, placebo-controlled trial of octreotide therapy for pediatric hypothalamic obesity. Eighteen subjects [weight, 100.6 +/- 5.6 kg; body mass index (BMI), 37.1 +/- 1.3 kg/m(2)] received octreotide (5-15 microg/kg x d s.c.) or placebo for 6 months. With octreotide, Delta weight (mean +/- SEM) was +1.6 +/- 0.6 vs. +9.1 +/- 1.7 kg for placebo (P < 0.001). Delta BMI was -0.2 +/- 0.2 vs. +2.2 +/- 0.5 kg/m(2), respectively (P < 0.001). OGTT documented Delta insulin response (peak - basal) of -417 +/- 304 pM after octreotide vs. +216 +/- 215 pM after placebo (P = 0.034). Improvement in physical activity by parent report was noted with octreotide, but not placebo (P = 0.03). For the octreotide group, changes in quality of life positively correlated with changes in insulin response (P = 0.041). Complications and adverse events were mild and self-limited. These data demonstrate the beneficial effects of octreotide in pediatric hypothalamic obesity. Octreotide suppressed insulin, and stabilized weight and BMI. Improved quality of life correlated with the degree of insulin suppression. Octreotide was safe and well tolerated.

Adolescent↗

PubMed2003

Cognitive impairment in children with hemoglobin SS sickle cell disease: relationship to MR imaging findings and hematocrit.

BACKGROUND AND PURPOSE: Children with hemoglobin SS sickle cell disease are known to suffer cognitive impairment if they have silent infarct, but recent evidence suggests that patients with hemoglobin SS sickle cell disease may be impaired even if they are free of infarction. We test a hypothesis that cognitive impairment in children with hemoglobin SS sickle cell disease is associated with low hematocrit and MR imaging abnormalities. METHODS: A cohort of 49 patients was examined, all of whom had hemoglobin SS sickle cell disease but no history of clinical stroke. The Wechsler scales, which are standardized and age-adjusted, were used to assess cognitive function. Patients also underwent MR imaging examination of the brain, and hematocrit was measured in a subset of 45 patients. MR images were evaluated by at least two readers, and abnormal imaging findings were evaluated by at least three readers. Any lesion was sufficient to be classified as abnormal, with lesions defined to include lacunar infarction, encephalomalacia, or leukoencephalopathy. Hematocrit data were used if obtained within 3 months of psychometric testing and if there were no confounding events in the patients' charts. Wechsler test scores were then evaluated in relation to imaging findings and hematocrit values. RESULTS: Patients with imaging abnormalities had more cognitive impairment than did patients with normal imaging findings in verbal intelligence quotient (P <.02) and verbal comprehension (P <.01). Patients with low hematocrit had cognitive impairment shown by many performance measures, including full-scale intelligence quotient (P <.006), verbal comprehension (P <.006), and freedom from distractibility (P <.02). Multivariate analysis showed that MR imaging and hematocrit were independent predictors of full-scale intelligence quotient. CONCLUSION: Focal brain injury, revealed by MR imaging, is associated with cognitive impairment, but our data suggest that diffuse brain injury may also contribute to impairment. These findings show that impairment is multifactorial and suggest that chronic brain hypoxia is part of the pathophysiology of sickle cell disease.

Adolescent↗

PubMed2002

Acute effects of irradiation on cognition: changes in attention on a computerized continuous performance test during radiotherapy in pediatric patients with localized primary brain tumors.

PURPOSE: To assess sustained attention, impulsivity, and reaction time during radiotherapy (RT) for pediatric patients with localized primary brain tumors. METHODS AND MATERIALS: Thirty-nine patients (median age 12.3 years, range 5.9-22.9) with primary brain tumors were evaluated prospectively using the computerized Conners' continuous performance test (CPT) before and during conformal RT (CRT). The data were modeled to assess the longitudinal changes in the CPT scores and the effects of clinical variables on these changes during the first 50 days after the initiation of CRT. RESULTS: The CPT scores exhibited an increasing trend for errors of omission (inattentiveness), decreasing trend for errors of commission (impulsivity), and slower reaction times. However, none of the changes were statistically significant. The overall index, which is an algorithm-based weighted sum of the CPT scores, remained within the range of normal throughout treatment. Older patients (age >12 years) were more attentive (p < 0.0005), less impulsive (p < 0.07), and had faster reaction times (p < 0.001) at baseline than the younger patients. The reaction time was significantly reduced during treatment for the older patients and lengthened significantly for the younger patients (p < 0.04). Patients with a shunted hydrocephalus (p < 0.02), seizure history (p < 0.0006), and residual tumor (p < 0.02) were significantly more impulsive. Nonshunted patients (p < 0.0001), those with more extensive resection (p < 0.0001), and patients with ependymoma (p < 0.006) had slower initial reaction times. CONCLUSION: Children with brain tumors have problems with sustained attention and reaction time resulting from the tumor and therapeutic interventions before RT. The reaction time slowed during treatment for patients <12 years old. RT, as administered in the trial from which these data were derived, has limited acute effects on changes in the CPT scores measuring attention, impulsiveness, and reaction time.

Adolescent↗

PubMed2002

Radiation dose-volume effects on growth hormone secretion.

PURPOSE: Growth hormone (GH) deficiency is a known consequence of central nervous system irradiation. The relationship between the dose to the hypothalamus and the time to onset of clinically significant GH deficiency is unknown. Conformal radiotherapy (CRT) techniques allow for a more accurate determination of hypothalamic dosimetry. We correlated the dosimetry of the hypothalamus and the peak GH value after CRT in children with localized primary brain tumors. METHODS AND MATERIALS: The arginine tolerance/L-dopa test was performed before (baseline) and repeated 6 and 12 months after CRT in 25 children (median age 4.8 years) with ependymoma (n = 15) or low-grade (n = 8) or high-grade (n = 2) astrocytoma. None had evidence of GH deficiency (arginine tolerance/L-dopa peak GH level >10 ng/mL [10 microg/L]) at baseline. Peak GH levels were modeled as a function of time after CRT and volume of the hypothalamus receiving a dose within the specified intervals of 0-20 Gy, 20-40 Gy, and 40-60 Gy. The model was used to predict the change in the peak GH levels over time (0-12 months) and fit under the assumption that the integral effect of irradiation was a linear sum of the products of the volume receiving a particular dose and the impact of that dose. RESULTS: The peak GH level declined during the 0-12 months after CRT (p < 0.0001). GH deficiency was observed in 11 children at 6 months and a total of 20 children at 12 months. As expected, the effect of the dose interval 0-20 Gy was smaller than the 20-40-Gy dose interval; the largest effect was noted with the dose interval 40-60 Gy. The peak GH level may be predicted using the following estimating equation within the time limit of 0-12 months: GH(t)=Exp[ln(bGH)-(0.00058V(0-20 Gy)+0.00106V(20-40 Gy)+0.00156V(40-60 Gy))x t], where bGH is the baseline peak GH level, V(0-20 Gy), V(20-40 Gy), and V(40-60 Gy) is the percent-volume of the hypothalamus irradiated from 0 to 20 Gy, 20 to 40 Gy, and 40 to 60 Gy, respectively, and t is time after irradiation. When included in the model, the rate of decline in the peak GH response also was influenced by hydrocephalus and tumor location. CONCLUSION: The peak GH response within 12 months after CRT depends on hypothalamic dose-volume effects and may be predicted on the basis of a linear model that sums the effects of the entire distribution of dose. The modeled effects may be used to optimize radiotherapy and minimize and treat GH deficiency.

Adolescent↗