Biomedical subjects

Chin-Shang Li

Publications and source records attributed to Chin-Shang Li.

At least 19 recordsLinked to original sources

PubMed2025

Association of Genetic Predisposition to Inflammation With Cancer-Related Cognitive Impairment and Fatigue in Women Who Received Chemotherapy for Nonmetastatic Breast Cancer.

PURPOSE: Cancer-related cognitive impairment (CRCI) and cancer-related fatigue (CRF) are reported by approximately 75% of patients receiving chemotherapy for breast cancer and both have been linked to inflammation. We sought to test whether an inflammation polygenic risk score (iPRS) might be associated with CRCI and/or CRF. METHODS: Using data from the UK Biobank, we developed an iPRS for the INFLA-Score, a composite measure of C-reactive protein, white cell count, platelet count, and neutrophil-lymphocyte ratio. The iPRS was evaluated for association with CRCI and CRF among women with nonmetastatic breast cancer enrolled in two completed multisite clinical trials: URCC08106 and URCC10055. CRCI and CRF were measured before and after standard-of-care chemotherapy using the FACT-Cog and Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), respectively. Linear regression evaluated the change in FACT-Cog and MFSI scores; logistic regression evaluated binary outcomes of any versus no worsening of scores. Analyses were adjusted for patient and treatment factors. We also performed exploratory genome-wide analyses. RESULTS: The cohort included 802 women who received chemotherapy (anthracycline-based = 51.8%; previous surgery = 85.0%) at a median age of 55 years (range = 22-81). The iPRS was associated with a significant decrease in MFSI-SF score (β = -3.29 [95% CI, -6.25 to -0.34]; P = .029) and lower odds of decreased MFSI-SF score (odds ratio, 0.66 [95% CI, 0.47 to 0.93]; P = .016) following chemotherapy. This negative relationship was partially explained by a positive correlation of the iPRS with prechemotherapy MFSI-SF score (β = 4.33 [95% CI, 0.23 to 8.43]; P = .038). The iPRS was not associated with a change in FACT-Cog score (β = -1.12; P = .627), but single nucleotide polymorphism rs9365961 was (β = -10.05; P = 1.46 × 10-8). CONCLUSION: If validated, the iPRS could identify patients in need of supportive care interventions to reduce CRF.

Humans↗

PubMed2007

Therapy preference and decision-making among patients with severe sickle cell anemia and their families.

BACKGROUND: Patients with severe sickle cell anemia (SCA) may benefit from therapeutic intervention with hydroxyurea (HU), chronic red cell transfusion (CT), or stem cell transplantation (SCT). Determination of best treatment is complicated by the tradeoff between each treatment's risks and benefits and the lack of data comparing them to determine efficacy. We explored factors that influenced making decisions regarding interventions and examined the relations between treatment preference and health-related quality of life (HRQOL). METHODS: Children with severe SCA and their parents received brochures describing each treatment, discussed risk/benefits with a nurse-educator, and answered questions regarding HRQOL and the factors influencing treatment preference. Severe SCA was defined as >or=3 pain events requiring ER visits or hospitalizations within 12 months, >or=2 acute chest syndrome (ACS) events within 24 months, or a combination of the two. RESULTS: Thirty parents and 7 patients participated. HU was preferred by 21 parents and 4 children, CT by 5 parents and 1 child, and SCT by 3 parents and 1 child. One parent was undecided and one child preferred no treatment. Interviewees were most influenced by perceived efficacy and safety, but no factors differed significantly among treatment preference groups. HRQOL median scores (0-100 scale) for parents (56; range, 28-91) and children (61; range, 31-96) did not differ significantly among treatment preference groups. CONCLUSIONS: Patients with severe SCA and their parents can identify their treatment preferences. Improved understanding of their preferences and decision-making process will aid in the design of future clinical trials and in medical decision-making.

Adolescent↗

PubMed2006

Quantitative morphologic evaluation of white matter in survivors of childhood medulloblastoma.

In survivors of pediatric brain tumors, cranial radiation therapy can cause a debilitating cognitive decline associated with decreased volume in normal-appearing white matter (NAWM). We applied fractal geometry to quantify white matter (WM) integrity in the brain of medulloblastoma survivors. Fractal features of WM were evaluated by indices of fractal dimensions (FDs) of WM intensity and boundary on T1-weighted magnetic resonance images. The FD index of WM intensity was calculated by using a fractional Brownian motion model, and the FD index of WM boundary was calculated by using a box-counting method. Fractal features of WM on 116 magnetic resonance images of 58 patients with medulloblastoma were investigated at the start of therapy (Start TX) and approximately 2 years later (After TX). Patients were assigned to one of two groups based on change in NAWM volumes. Fractal features in patients with decreased NAWM volume were significantly greater After TX, whereas those in patients with increased NAWM volumes were not. Multiple linear regression analysis showed that fractal features were strongly correlated with NAWM volumes After TX in patients with decreased NAWM volume. These results demonstrated significant deficit in NAWM integrity and WM density changes in children treated for medulloblastoma. Multiple regression analysis illustrated that deficits in NAWM integrity in these children may partly explain the decrease in NAWM volume. We conclude that fractal geometry can be used to monitor the morphologic effects of neurotoxicity in brain tumor survivors.

Adolescent↗

PubMed2006

Computer-aided detection of therapy-induced leukoencephalopathy in pediatric acute lymphoblastic leukemia patients treated with intravenous high-dose methotrexate.

The purpose of this study was to use objective quantitative magnetic resonance imaging (MRI) methods to develop a computer-aided detection (CAD) tool to differentiate white matter (WM) hyperintensities into either leukoencephalopathy (LE) induced by chemotherapy or normal maturational processes in children treated for acute lymphoblastic leukemia without irradiation. A combined MRI set consisting of T1-weighted, T2-weighted, proton-density-weighted and fluid-attenuated inversion recovery images and WM, gray matter and cerebrospinal fluid proportional volume maps from a spatially normalized atlas were analyzed with a neural network segmentation based on a Kohonen self-organizing map (SOM). Segmented maps were manually classified to identify the most hyperintense WM region and the normal-appearing genu region. Signal intensity differences normalized to the genu within each examination were generated for four time points in 228 children. A second Kohonen SOM was trained on the first examination data and divided the WM into normal-appearing or LE groups. Reviewing labels from the CAD tool revealed a consistency measure of 89.8% (167 of 186) within patients. The overall agreement between the CAD tool and the consensus reading of two trained observers was 84.1% (535 of 636), with 84.2% (170 of 202) agreement in the training set and 84.1% (365 of 434) agreement in the testing set. These results suggest that subtle therapy-induced LE can be objectively and reproducibly detected in children treated for cancer using this CAD approach based on relative differences in quantitative signal intensity measures normalized within each examination.

Adolescent↗

PubMed2006

A regression spline model for developmental toxicity data.

Observed dose-response patterns of data from several developmental toxicity experiments appear to be nonlinear and should be characterized by an appropriate model to adequately fit this observed pattern. Information from these animal studies of ambient substances that are noncarcinogenic, yet potentially toxic, to humans is used by federal protection agencies (Environmental Protection Agency, Occupational Safety and Health Administration, Food and Drug Administration) to determine safe exposure levels, such as no observed adverse effects level and benchmark dose. We have developed a flexible regression linear B-spline model for application to developmental toxicity dose-response data from animal studies of these noncarcinogens. We apply our model to data from two CD-1 mice studies of the National Toxicology Program; the observed dose-response pattern from both appears nonlinear: (1) experiment of 131 pregnant mice allocated over five exposure levels (0, 0.025, 0.05, 0.10, and 0.15% diet) of diethylhexyl phthalate and (2) experiment of 111 pregnant mice exposed to five levels (0, 62.5, 125, 250, and 500 mg/kg/day) of diethylene glycol dimethyl ether. In each study, we measure litter response as the proportion of adversely affected fetuses. Upon applying our B-spline model to the data from both studies, we predict nonlinear dose-response, with improvement over the more typical logistic dose-response model in each of the two studies.

Animals↗

PubMed2006

White race as a risk factor for hypothyroidism after treatment for pediatric Hodgkin's lymphoma.

PURPOSE: Hypothyroidism frequently occurs after treatment for pediatric Hodgkin's lymphoma, but race has not been investigated as a risk factor for this delayed toxicity. The aim of this study was to determine whether race is an independent risk factor for hypothyroidism in survivors of pediatric Hodgkin's lymphoma. PATIENTS AND METHODS: To identify differences between black and white patients in the development of hypothyroidism after treatment for Hodgkin's lymphoma, we conducted a retrospective study of consecutively treated pediatric patients with newly diagnosed Hodgkin's lymphoma treated at St Jude Children's Research Hospital (Memphis, TN) from January 1980 through December 2002. Clinical or biochemical hypothyroidism was defined by an above normal thyroxine-stimulating hormone concentration or by the need for thyroid hormone replacement therapy. RESULTS: The 461 patients (388 white patients, 73 black patients) where followed for a median of 11.3 years (range, 1.8 to 24.9 years). Hypothyroidism developed in 196 (43%) of 461 patients after a median of 2.9 years (range, 0.7 to 11.3 years) after diagnosis of Hodgkin's lymphoma. Hypothyroidism developed in 47% of white patients but in only 21% of black patients (hazard ratio = 2.7; 95% CI, 1.6 to 4.6). After adjusting for other risk factors for hypothyroidism (thyroid radiation dose, sex, and nodular sclerosis histology), the risk of hypothyroidism in white patients was 2.5 times (95% CI, 1.5 to 4.3 times) the risk in black patients (P < .001). CONCLUSION: White patients have a higher risk of hypothyroidism after neck irradiation for pediatric Hodgkin's lymphoma than black patients.

Adolescent↗

PubMed2006

Natural history of thyroid nodules in survivors of pediatric Hodgkin lymphoma.

BACKGROUND: Survivors of Hodgkin lymphoma and other patients who receive neck irradiation are at increased risk of thyroid cancer. Ultrasonography provides an inexpensive and non-invasive method of thyroid screening, but the clinical significance of thyroid nodules detected by ultrasound screening is uncertain. PROCEDURE: We reviewed the demographics, clinical characteristics, method of detection, and outcome of patients who developed thyroid nodules after treatment for pediatric Hodgkin lymphoma at our institution. One radiologist reviewed all imaging studies. RESULTS: Sixty-seven children treated for Hodgkin lymphoma from 1962 to 2001 developed thyroid nodules. The study group represented 9,024 person-years of follow-up after the diagnosis of Hodgkin lymphoma and 581 person-years after diagnosis of a thyroid nodule. A median of 10.5 years (range, 0.2-24.8 years) elapsed between the diagnoses of Hodgkin lymphoma and thyroid nodule(s). All but one patient had received neck irradiation for Hodgkin lymphoma, with a median thyroid radiation dose of 35 Gy (range, 12-45 Gy). Thyroid nodules were found to be malignant in seven patients (10%), at a median of 16.2 years (range, 8.4-23.7 years) after diagnosis of Hodgkin lymphoma. Only one malignancy was found through screening ultrasonography. All patients with thyroid cancer remained disease-free at 0.4-16.2 years of follow-up. CONCLUSIONS: Thyroid nodules are common in Hodgkin lymphoma survivors treated with neck irradiation, but the majority of these lesions have an indolent clinical course and do not undergo malignant transformation. Only patients with a palpable mass or clinical symptoms need more extensive evaluation, including Doppler-flow ultrasonography and fine-needle aspiration.

Disease-Free Survival↗

PubMed2006

Distinguishing benign from malignant pulmonary nodules with helical chest CT in children with malignant solid tumors.

PURPOSE: To retrospectively assess whether computed tomographic (CT) findings can indicate the benign or malignant nature of pulmonary nodules in pediatric patients with malignant solid primary tumors. MATERIALS AND METHODS: With institutional review board approval, waived parental and patient consent, and HIPAA compliance, the authors determined the incidence of malignancy among 81 pulmonary nodules that were sampled at biopsy within 3 weeks after chest CT (January 1999 to September 2003) in 41 young patients with malignant solid tumors. Three radiologists independently and retrospectively reviewed these scans and the available previously obtained scans, classifying nodules as benign, malignant, or indeterminate on the basis of their number, unilateral versus bilateral distribution, size, margins (indistinct vs distinct), calcification, growth, and associated adenopathy. These classifications were compared with nodule histologic type, and interreviewer agreement was assessed. RESULTS: The median patient age was 14.8 years (mean, 13.7 years; range, 5-21 years). Twenty-four of the 41 patients (58%) had at least one biopsy-proved malignant nodule. Four (10%) patients had both benign and malignant nodules; 17 (42%) had only benign nodules. Reviewer 1 classified 65% (39 of 60) of nodules correctly; reviewer 2, 57% (37 of 65); and reviewer 3, 67% (43 of 64). Interreviewer agreement was slight to moderate (kappa </= 0.43, P </= .03). In contrast to findings in adults, sharply defined nodules in younger individuals were more likely to be malignant (P = .03) and nodule size was not associated with malignancy (P >/= .32). CONCLUSION: The frequency of benign nodules and the inconsistency of predictions based on CT features suggest the need for better predictors of pulmonary nodules being malignant or benign, so as to reduce unnecessary thoracotomy in pediatric patients with solid malignancy. .

Adolescent↗

PubMed2006

Angiogenesis inhibitors in a murine neuroblastoma model: quantitative assessment of intratumoral blood flow with contrast-enhanced gray-scale US.

PURPOSE: To quantify intratumoral ultrasonographic (US) contrast agent flow at gray-scale imaging as a measure of functional tumor vascularity in an orthotopic murine neuroblastoma model treated with angiogenesis inhibitors. MATERIALS AND METHODS: After Institutional Animal Care and Use Committee approval, retroperitoneal neuroblastomas were established in mice with unmodified NXS2 cells (n = 13) or with cells engineered to overexpress an angiogenesis inhibitor--either tissue inhibitor of matrix metalloproteinase-3 (n = 22) or a truncated soluble form of the vascular endothelial growth factor receptor-2 (truncated soluble fetal liver kinase-1; n = 13). When tumors were approximately 600 mm3, contrast material-enhanced gray-scale US was performed, and the imaging was recorded on cine clips. Regions of interest within tumors were analyzed off-line to determine postcontrast change in signal intensity (SI) from baseline to initial peak (deltaSI), rate of SI increase from baseline to initial peak (RSI), and contrast material washout. The Mann-Whitney test was used to evaluate potential differences in these US parameters between treatment groups. The mean intratumoral endothelial cell (CD34) and pericyte (smooth muscle actin [SMA]) counts at immunohistochemical analysis were also evaluated. Spearman correlation test was used to investigate the relation between US parameters and these histologic markers. RESULTS: The deltaSI and RSI were lower in tumors overexpressing an angiogenesis inhibitor than in control tumors (all P < .03). Contrast material washout did not differ between groups. For the entire cohort, the RSI correlated with the immunohistochemical assessment of tumor vascularity (SMA and CD34 counts) (P < .003). CONCLUSION: Quantification of intratumoral flow of a US contrast agent at gray-scale imaging shows promise for monitoring tumor vascular response to antiangiogenic therapy.

Albumins↗

PubMed2005

Effects of EPI readout bandwidth on measured activation map and BOLD response in fMRI experiments.

The purpose of this study was to evaluate the effects of echo planar imaging (EPI) readout bandwidth and its interaction with data processing procedures on the measured blood oxygenation level dependent (BOLD) response and activation in fMRI experiments. Seventeen healthy subjects were scanned during a brief visual stimulation paradigm with two EPI pulse sequences having 'high' (1953 Hz/pixel) and 'low' (780 Hz/pixel) readout bandwidth. Functional data were analyzed with a general linear model including temporal filtering and a basic correlation model following (1) no preprocessing, (2) realignment, or (3) realignment and spatial smoothing. A range of statistical thresholds were used to generate activation maps. Despite slightly higher BOLD signal detected with the high bandwidth sequence from matched ROIs in the primary visual cortex, results showed that the low bandwidth pulse sequence was more sensitive under most conditions evaluated. That is, the low bandwidth sequence detected greater numbers of activated voxels with lower cluster average BOLD signal (e.g., low bandwidth detected 1.4 times more voxels, with average BOLD signal 30% lower compared to high bandwidth for P = 0.05 (corrected) with the 3rd preprocessing procedure using the general linear model). However, there was significant interaction between bandwidth and data preprocessing procedures. Of particular interest, the sensitivity advantage of the low bandwidth pulse sequence decreased for the smoothed data as the activation threshold became less conservative. For the frequently used threshold of P = 0.001 (uncorrected) and cluster size of at least 5 voxels, the bandwidth advantage became insignificant. These findings demonstrate that the effects of bandwidth should be considered carefully in the design, analysis, and interpretation of BOLD fMRI studies.

Adult↗

PubMed2005

BOLD responses to visual stimulation in survivors of childhood cancer.

Children surviving certain cancers have a high incidence of cognitive deficits caused by central nervous system (CNS) disease or treatments directed at the CNS. To establish the feasibility of using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study cognitive deficits in survivors of childhood cancer, we tested the hypothesis that this population has the same BOLD response to visual stimulation as healthy subjects. We used BOLD fMRI to measure spatial and temporal patterns of brain activity after brief visual stimulation in 16 survivors of childhood cancer, 11 age-similar healthy siblings of survivors, and 16 healthy adults. Functional data for the survivors were analyzed with two general linear models, one used a canonical hemodynamic response function (HRF) and the other used a Fourier set as basis functions. The measured BOLD signal and brain activation patterns were similar in the survivors with both models. The BOLD signal for survivors was qualitatively similar in timing and shape, but there were significant quantitative differences as compared with healthy subjects. The activation was normally located in the primary visual cortex in 13 survivors, but the activation volume was significantly smaller in brain tumor survivors than in other groups. These findings demonstrate the feasibility of using BOLD fMRI to investigate brain function in survivors of childhood cancer. However, fMRI studies in this population must take into account effects of quantitative differences in their BOLD responses as compared to healthy subjects.

Adolescent↗

PubMed2005

Granulocyte-macrophage colony stimulating factor and immunosuppression in the treatment of pediatric acquired severe aplastic anemia.

BACKGROUND: Immunosuppressive therapy (IS) is effective in the treatment of patients with acquired severe aplastic anemia (SAA). An enhanced myeloid response and decreased infection risk may be possible with the addition of a hematopoietic cytokine. Published data on the combination of cytokines and IS in patients with SAA are limited. The addition of G-CSF to IS shortens the time to neutrophil count recovery, but may not improve overall survival. Because GM-CSF acts differently than G-CSF, its use in combination with IS may be different. PROCEDURE: A retrospective chart review was performed on patients diagnosed with SAA and treated with IS and GM-CSF at St. Jude Children's Research Hospital. Hematologic recovery, prognostic factors, and infection data were collected. RESULTS: Eighteen patients were included in this study. The median age at diagnosis was 7.2 years (range 1.8-17.0). Ten patients (56%) had a complete response, four (22%) a partial response, and four (22%) no response. Median time to erythrocyte and platelet transfusion independence were 90 (18,243) and 64 days (18-243), and to discontinuation of treatment 287 days (90-730). Median time to partial (ANC > 500) and full (ANC > 1,500) neutrophil recovery were 41 and 51 days, respectively. Seventeen documented discrete infections occurred in six patients over 36 patient years. CONCLUSIONS: GM-CSF, in addition to IS, may shorten time to neutrophil count recovery, may be beneficial in decreasing infection rates, and may improve platelet response in patients with SAA. However, consistent with studies utilizing G-CSF, GM-CSF probably does not affect overall response rate. To fully answer whether or not cytokine therapy is of added value to IS in pediatric patients, a multi-institutional randomized trial is needed.

Adolescent↗

PubMed2005

Sickle cell hepatopathy: clinical presentation, treatment, and outcome in pediatric and adult patients.

BACKGROUND: Standard diagnostic criteria and therapy are lacking for sickle cell hepatopathy, an uncommon complication of sickle cell disease. Here we propose diagnostic and therapeutic guidelines based on our experience and on reported cases. METHODS: We defined sickle hepatopathy by a total serum bilirubin concentration >13 mg/dl not explained by severe acute hemolysis, viral hepatitis, extrahepatic obstruction, or hepatic sequestration. We reviewed the records of all children with sickle hepatopathy seen at our institution during the past 20 years and the reported cases from the literature. Patients were categorized into two groups based on whether hepatic dysfunction at presentation was mild (Group I) or severe (Group II). RESULTS: Seven patients were identified from our institution and 37 patients from the literature. The 44 patients were evenly divided between the two groups. Group I patients had a significantly lower mean age (11.8 years vs. 24.5 years, P = 0.0001), maximum bilirubin level (36.2 mg/dl vs. 76.8 mg/dl, P = 0.0008), and frequency of treatment with exchange transfusions (P = 0.03). Overall, mortality was 4% in Group I and 64% in Group II (P = 0.0001). Gender and recurrence rate did not differ. Among Group II patients, only two of nine who received exchange transfusion died, whereas 12 of 13 who did not receive exchange transfusion died (P = 0.0015). CONCLUSIONS: Sickle cell hepatopathy is an uncommon complication characterized by extreme hyperbilirubinemia and either mild or severe hepatic dysfunction. Children and adults can present with either form; however, adults have a higher frequency of the severe form. Exchange transfusion may be the only effective management for initial episodes of severe sickle cell hepatopathy.

Adolescent↗

PubMed2005

Chronic transfusion therapy for children with sickle cell disease and recurrent acute chest syndrome.

The objective was to study the effects of chronic transfusion therapy (CTX) on the prevention of new episodes of acute chest syndrome (ACS) in children with sickle cell disease (SCD) and recurrent or unusually severe ACS. A retrospective chart review was performed of patients given CTX for recurrent or severe ACS. Frequency, median severity score, and median hospital stay for ACS episodes were determined. Differences in these values before and during CTX were analyzed. Twenty-seven patients were identified. Before treatment, the ACS incidence was 1.3 episodes per patient-year; during treatment, it decreased to 0.1 episodes per patient-year (P < 0.0001). The median severity score for ACS episodes was 0.8 (range 0-5) before CTX and 0.5 (0-3) during CTX (P = 0.84). The median hospital stay was 5 days (range 3-15 days) before CTX and 3 days (2-7 days) during CTX (P = 0.38). CTX significantly reduces the incidence of ACS events among patients with a history of recurrent or severe episodes but does not significantly decrease their severity. The effectiveness of CTX should be prospectively compared with that of hydroxyurea and stem cell transplantation.

Adolescent↗

PubMed2005

A quantitative MR imaging assessment of leukoencephalopathy in children treated for acute lymphoblastic leukemia without irradiation.

PURPOSE: Intravenous methotrexate (IV-MTX), an effective treatment for acute lymphoblastic leukemia (ALL), has a significant toxic effect on the central nervous system, with leukoencephalopathy (LE) being the most common form. The purpose of this study was to use objective quantitative MR imaging to prospectively assess the temporal evolution of LE extent and intensity. METHODS: Forty-five children (low-risk, 10 mol/L/12F; mean age, 5.0 years at diagnosis; standard/high-risk, 11 mol/L/12F; mean age, 9.2 years at diagnosis) treated for ALL on a single institutional protocol were evaluated longitudinally to assess the extent of LE (proportion of white matter impacted) through tissue segmentation and the relative intensity of LE through relative elevations in T1 and T2 relaxation rates. One-sided Wilcoxon-Mann-Whitney tests were used to assess differences in quantitative measures at 4 different points in therapy both within and between risk arms. RESULTS: The proportion of white matter affected in both patient groups increased significantly with additional courses of IV-MTX, whereas the intensity of LE also increased steadily; however, both the intensity and extent of LE declined significantly approximately 1.5 years after completion of IV-MTX. Increases in the T1 and T2 relaxation rates above normal-appearing white matter were significantly correlated with each other and were dependent on the proportion of white matter affected. CONCLUSION: Higher doses and more courses of IV-MTX were associated with increased intensity and extent of LE. There was a significant reduction in both the intensity and extent of LE after completion of therapy. The impact of these changes on neurocognitive functioning and quality of life in survivors remains to be determined.

Antimetabolites, Antineoplastic↗

PubMed2004

Tolerance to vancomycin in pneumococci: detection with a molecular marker and assessment of clinical impact.

BACKGROUND: Vancomycin is often added to therapy for meningitis caused by Streptococcus pneumoniae. Tolerant bacteria without classic resistance that escape killing by multiple antibiotics have been reported sporadically. We determined the prevalence of tolerance to vancomycin in pneumococci and its effect on the outcome of meningitis. METHODS: Archival samples of 215 nasopharyngeal (NP) and 113 meningitis isolates were tested for the killing efficacy of vancomycin. Specific DNA sequence changes in a transporter locus were identified for tolerant isolates. Similar tests were conducted prospectively on 517 NP isolates from healthy children. RESULTS: In archival isolates, tolerance to vancomycin was detected in 3.7% of NP and 10.6% of invasive isolates. Patients with meningitis caused by tolerant isolates had a worse estimated 30-day survival than did patients with meningitis caused by nontolerant isolates (49% vs. 86%; P = .048); 62.5% of tolerant archival NP isolates harbored a specific sequence change for pep27 and vex2 (P = .021). Prospective analysis of 517 carriage isolates indicated that 8.1% were tolerant to vancomycin and that 82.1% of tolerant isolates harbored the specified marker gene sequences (P = .001). CONCLUSIONS: Tolerance to vancomycin exists in the population of pneumococci. Tolerant isolates are associated with meningitis of increased mortality, and these isolates can be tracked by specific marker sequences in 2 genes.

Alleles↗

PubMed2004

Oral glutamine supplementation decreases resting energy expenditure in children and adolescents with sickle cell anemia.

OBJECTIVES: To determine the effects of orally administered glutamine on the resting energy expenditure (REE) and nutritional status of children and adolescents with sickle cell anemia. METHODS: Twenty-seven children and adolescents (13 boys, 14 girls), 5.2 to 17.9 years old (median 11.0 years), received orally administered glutamine (600 mg/kg per day) for 24 weeks. Measures of REE and other nutritional parameters were compared at baseline and 24 weeks. RESULTS: After 24 weeks, the patients' median REE (kcal/d) decreased by 6% (P = 0.053) as indicated by the Harris Benedict equations and by 5% (P = 0.049) as indicated by the modified equations. Patients with less than 90% ideal body weight had even greater declines in REE after 24 weeks (P < 0.03 and 0.02, respectively). Improvements in nutrition parameters and in two amino acids in the plasma were observed. CONCLUSIONS: After 24 weeks of orally administered glutamine, children and adolescents with sickle cell anemia had a decrease in REE and improvement in nutritional parameters. Those who were underweight had a greater decrease in REE than those of normal body weight. Lowering REE may be an effective way to improve the growth of these children and adolescents.

Administration, Oral↗

PubMed2003

Identification of hemochromatosis gene polymorphisms in chronically transfused patients with sickle cell disease.

Three polymorphic gene mutations in the human hemochromatosis (HFE) gene (C282Y, H63D, S65C) are associated with non-transfusion-related iron overload in Caucasians. More recently, these mutations have also been identified in African-Americans. However, the prevalence of HFE gene mutations in African-Americans with sickle cell disease (SCD) has not been described. The presence of these mutations in this population is particularly important, because patients with SCD may be placed on chronic red cell transfusion therapy and are thus at further risk for iron overload. Thus, we attempted to establish the gene mutation prevalence in African-Americans with SCD, to compare this frequency with published gene frequencies in African-Americans, and to evaluate their significance with regard to transfusion-related iron overload. Eighty-nine African-American patients with SCD, all of whom were receiving chronic red cell transfusion therapy, were screened by DNA analysis for the three HFE gene mutations. Two patients were heterozygous for the C282Y HFE mutation (2.3%), six were heterozygous for the H63D mutation (6.8%), none carried the S65C mutation (0.0%), and no homozygous or compound heterozygous subjects were identified. The prevalence of C282Y and H63D in the SCD population was similar to that observed in the general African-American population. In addition, there was no increased mutation prevalence when comparing those SCD patients on chronic transfusion therapy who had ferritin levels greater than 2,500 ng/mL and those less than 2,500 ng/mL. This study represents the first identification of the known HFE gene mutations by DNA analysis in the SCD population. We conclude that the presence of recognized HFE coding region mutations do not seem to have an impact on the degree of iron overload in patients with SCD receiving chronic transfusion therapy.

Adolescent↗