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ABSTRACT: OBJECTIVE: To test the hypothesis that anti-islet autoantibody expression and random serum C-peptide obtained at diagnosis define phenotypes of pediatric diabetes with distinct clinical features. SUBJECTS: We analyzed 607 children aged <19 yr consecutively diagnosed with diabetes after exclusion of 13% of cases with secondary diabetes (e.g., cystic fibrosis related, steroid induced) and 7.3% of cases lacking measurement of C-peptide and/or autoantibodies. METHODS: Autoantibody positivity (A+) was defined as ≥1 positive out of GAD65, insulin, and ICA512 antibodies. Preserved beta-cell function (β+) was defined as random serum C-peptide at diagnosis ≥ 0.6 ng/mL. Body mass index (BMI) was measured at median 1.2 months after diagnosis. Characteristics at diagnosis and 2 yr (range 18-30 months) after diagnosis were compared among groups. RESULTS: Autoantibody expression and C-peptide at diagnosis defined the following groups: A+β- (52.1% of the children), A+β+ (32.8%), A-β+ (12.5%), and A-β- (2.6%). These four groups differed in gender, race/ethnicity, and clinical characteristics at diagnosis [i.e., age, pubertal development, obesity/overweight, diabetic ketoacidosis, glycemia, and hemoglobin A1c (HbA1c)] and at 2 yr (i.e., clinical diagnosis, treatment, and HbA1c) (all p < 0.0001). Among all β+ children, C-peptide >2 ng/mL was associated with lower HbA1c at onset (p = 0.0001) and, in the A+β+ subgroup, with higher frequency of achieving HbA1c < 7% at 2 yr (p = 0.03). All three patients (0.7% of total) with monogenic diabetes (maturity onset diabetes of the young, MODY) were A-β+ with C-peptide between 0.6 and 2 ng/mL. CONCLUSIONS: Anti-islet autoantibodies status and serum random C-peptide at diagnosis define four distinct phenotypes of pediatric diabetes with prognostic value.
Pediatric Diabetes 03/2013; · 2.16 Impact Factor
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ABSTRACT: BACKGROUND: Bronchiolitis obliterans (BO) is the major obstacle to long-term lung allograft viability. Its clinical correlate, BO syndrome (BOS), is defined as a decline of at least 20% in forced expiratory volume in 1 second (FEV(1)) from baseline. BOS is often diagnosed after significant organ dysfunction has occurred. Because BO is a small-airways disease, we hypothesized that a 20% decline in the 25% to 75% forced expiratory flow (FEF(25-75)) from baseline should occur before a decline in FEV(1) and should predict progression to BOS with high sensitivity and specificity. METHODS: Pulmonary function tests and records of pediatric lung transplantation patients at Texas Children's Hospital from 2002 to 2007 were reviewed. Declines in FEV(1) and FEF(25-75) from the best post-transplant baseline values were recorded and analyzed. Sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: Thirty-one patients were eligible for the study. In 11 BOS patients, the mean±standard deviation number of days from transplant until a 20% decline in FEV(1) was 896.5±400 compared with 728.0±475 (p = 0.022) until a 20% decline in FEF(25-75) was reached. The sensitivity, specificity, and positive predictive and negative predictive values of a 20% reduction in FEF(25-75) in determining BOS were 100%, 90.0%, 84.6%, and 100%, respectively. CONCLUSIONS: All patients who developed BOS had a decline in FEF(25-75) at or before the decline in FEV(1). The reduction in FEF(25-75) occurred statistically significantly earlier than the decline in FEV(1), by an average of 168.5 days. This decline in FEF(25-75) was also highly sensitive and specific for the diagnosis of BOS.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 10/2012; · 3.54 Impact Factor
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Jennifer A Rama,
Leland L Fan,
Albert Faro,
Okan Elidemir,
David L Morales,
Jeffrey S Heinle, E O'Brian Smith,
Matthew L Hazen,
Siby P Moonnumakal,
George B Mallory,
Marc G Schecter
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ABSTRACT: BACKGROUND: Pediatric diffuse lung diseases comprise a heterogeneous group of rare lung disorders which may lead to end stage lung disease and referral for lung transplantation. Previous studies are limited by small numbers of patients with specific forms of diffuse lung disease. Children with all forms of diffuse lung disease who underwent lung transplantation at two pediatric centers were evaluated in terms of several pre- and post-transplant factors and compared to children with other end stage lung disorders. METHODS: A retrospective chart review was performed on all patients transplanted between October 1, 2002 and June 15, 2007 at Texas Children's Hospital and St. Louis Children's Hospital. Multiple pre-transplant characteristics and post-transplant morbidities and mortality were compared between diffuse lung disease, cystic fibrosis, and pulmonary vascular disease groups. RESULTS: There were 31 diffuse lung disease (DLD), 57 cystic fibrosis (CF), and 16 pulmonary vascular disease (PVD) patients included in our analysis. Patients with DLD had significantly higher pre-transplant morbidity including lower percent predicted of forced expiratory volume in first second (P = 0.013) and more patients with pulmonary hypertension (P = 0.001) and hypercapnia (P = 0.031). Compared to CF patients, more DLD and PVD patients required invasive ventilation (P = 0.001) and care in the pediatric intensive care unit (P = 0.001). After transplant, there was a difference among the three groups with regards to number of acute allograft rejections but statistical limitations preclude knowing between which group the difference lies. A difference in time to bronchiolitis obliterans was found between the PVD and CF groups but not when compared to the DLD patients. The three groups had similar time to post-transplant lymphoproliferative disease, rate of infections, and survival. CONCLUSION: Lung transplantation is as successful for patients with end stage diffuse lung disease as compared to other lung transplant candidates. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.
Pediatric Pulmonology 09/2012; · 2.53 Impact Factor
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ABSTRACT: OBJECTIVE: To examine the relationship between BMI and beta-cell function at diagnosis of autoimmune type 1 diabetes (T1D) in a large group of ethnically diverse children. METHODS: Cross-sectional analysis of 524 children (60.8% White, 19.5% Hispanic, 14.5% African-American, 5.2% other non-Hispanic; mean age = 9.8 yr [SD = 2.5]) with newly diagnosed autoimmune T1D. RESULTS: As much as 22.2% of children were overweight or obese. Median random serum C-peptide was 0.40 ng/mL (25th-75th percentiles = 0.3-0.8), with median glycemia of 366 mg/dL (25th-75th percentiles = 271-505). Median C-peptide was 0.3, 0.5, 0.7, and 0.85 ng/mL, respectively, in underweight, normal weight, overweight, and obese children (p < 0.0001, Kruskal-Wallis). In the final model (p < 0.0001), the odds of having preserved C-peptide (≥0.6 ng/mL) were increased by 2.4-fold (95% CI = 1.2-4.9, p < 0.015) and 4.1-fold (1.9-8.5, p < 0.0001), respectively, in overweight and obese compared to lean children; 1.3-fold per each year of age; 2.5-fold in girls compared to boys; 4-fold in children who presented without, compared to with, diabetes ketoacidosis (DKA); and decreased by 21% for each point increase in HbA1c. Tanner stage, race/ethnicity, glycemia, and number of anti-islet antibodies expressed were not independently associated with preserved C-peptide. The association between BMI and C-peptide levels was significant in children with and without preserved C-peptide. Excluding patients who presented with DKA and/or using BMI obtained 5 wk after diagnosis did not alter the results. CONCLUSION: Obese and overweight children compared to lean children have greater beta-cell function at the onset of autoimmune T1D. Prospective studies on the relationships among BMI, beta-cell function, and progression to clinical T1D are warranted.
Pediatric Diabetes 05/2012; · 2.16 Impact Factor
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ABSTRACT: Isoflavones, having chemical structures similar to estrogens, are believed to stimulate nitric oxide production and thus lower blood pressure. The efficacy of soy isoflavone supplementation to stimulate nitric oxide production and lower blood pressure in menopausal women with high normal blood pressure remains unknown.
The objective was to test the effect of soy isoflavone supplementation on nitric oxide production and blood pressure in menopausal women with high normal blood pressure.
A randomized, double-blind, parallel, placebo-controlled 6-wk trial was conducted to assess the effects of daily supplementation with 80 mg soy hypocotyl isoflavones (in aglycone units) on nitric oxide metabolism and blood pressure in 24 menopausal women with 12 women per group. Changes in nitric oxide metabolism were assessed via a primed, constant-infusion protocol with [15N]arginine and [13C]- and [2H]citrulline. Changes in blood pressure and associated vascular hemodynamics were assessed via office and 24-h ambulatory blood pressure monitoring, forearm blood flow, and indexes of arterial compliance.
When compared with placebo and after control for pretreatment values, soy isoflavone supplementation had no effect on arginine flux, citrulline flux, nitric oxide synthesis, blood pressure, forearm blood flow, or estimates of arterial stiffness.
Daily supplementation with 80 mg soy hypocotyl isoflavones over a 6-wk period had no effect on nitric oxide metabolism or blood pressure and associated vascular hemodynamics in menopausal women with high normal blood pressure.
American Journal of Clinical Nutrition 05/2012; 95(6):1487-94. · 6.67 Impact Factor
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ABSTRACT: Noonan syndrome (NS) is a disorder of RAS- mitogen activated protein kinase (MAPK) pathway with clinical features of skeletal dysplasia. This pathway is essential for regulation of cell differentiation and growth including bone homeostasis. Currently, limited information exists regarding bone mineralization in NS.
Using dual-energy X-ray absorptiometry (DXA), bone mineralization was evaluated in 12 subjects (mean age 8.7 years) with clinical features of NS. All subjects underwent genetic testing which showed mutations in PTPN11 gene (N=8) and SOS1 gene (N=1). In a subgroup of subjects with low bone mass, indices of calcium-phosphate metabolism and bone turnover were obtained.
50% of subjects had low bone mass as measured by DXA. Z-scores for bone mineral content (BMC) were calculated based on age, gender, height, and ethnicity. Mean BMC z-score was marginally decreased at -0.89 {95% CI -2.01 to 0.23; p=0.1}. Mean total body bone mineral density (BMD) z-score was significantly reduced at -1.87 {95% CI -2.73 to -1.0; p=0.001}. Mean height percentile was close to - 2 SD for this cohort, thus total body BMD z-scores were recalculated, adjusting for height age. Adjusted mean total body BMD z-score was less reduced but still significant at -0.82 {95% CI -1.39 to -0.25; p=0.009}. Biochemical evaluation for bone turnover was unremarkable except serum IGF-I and IGF-BP3 levels which were low-normal for age.
Children with NS have a significantly lower total body BMD compared to age, gender, ethnicity and height matched controls. In addition, total BMC appears to trend lower in children with NS compared to controls. We conclude that the metabolic bone disease present resulted from a subtle variation in the interplay of osteoclast and osteoblast activity, without clear abnormalities being defined in the metabolism of either. Clinical significance of this finding needs to be validated by larger longitudinal studies. Also, histomorphometric analysis of bone tissue from NS patients and mouse model of NS may further elucidate the relationship between the RAS-MAPK pathway and skeletal homeostasis.
Molecular Genetics and Metabolism 04/2012; 106(2):237-40. · 3.19 Impact Factor
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ABSTRACT: Osteomyelitis is a common pediatric musculoskeletal infection. This infection can weaken the normal bone structure, resulting in the risk of a pathologic fracture. The purpose of this study was to evaluate the risk factors for pathologic fracture in children with Staphylococcus aureus osteomyelitis.
Seventeen children who were treated for a pathologic long-bone fracture secondary to Staphylococcus aureus osteomyelitis between January 2001 and January 2009 at a tertiary-care pediatric hospital were identified. These patients were compared with a control group consisting of forty-nine children with Staphylococcus aureus osteomyelitis without a fracture who were matched for age, sex, and methicillin susceptibility. A retrospective review of the clinical records, magnetic resonance imaging (MRI) studies, and microbiologic findings was performed.
Patients who developed a fracture presented with osteomyelitis at a mean age of 8.8 years (range, two to seventeen years). Fifteen of the seventeen patients had methicillin-resistant Staphylococcus aureus (MRSA) isolates, and two had methicillin-susceptible Staphylococcus aureus (MSSA). The mean time from disease onset to fracture was 72.1 days (range, twenty to 150 days). The duration of hospitalization, number of surgical procedures, duration of antibiotic treatment, and total number of complications differed significantly between the two groups. MRI studies at the time of admission demonstrated a significantly greater prevalence of subperiosteal abscess and greater circumferential size of such an abscess in the patients with a fracture. A sharp zone of abnormally diminished enhancement of the marrow was also more common in these patients. The USA300-0114 pulsotype was more commonly associated with an elevated likelihood of fracture.
Staphylococcus aureus osteomyelitis is a serious infection that may predispose children to pathologic fractures. Protected weight-bearing and activity restriction are recommended in children with Staphylococcus aureus osteomyelitis who have the risk factors demonstrated in this study.
The Journal of Bone and Joint Surgery 01/2012; 94(1):34-42. · 3.27 Impact Factor
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Journal of pediatric gastroenterology and nutrition 11/2011; 54(1):109; author reply 109. · 2.18 Impact Factor
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ABSTRACT: To assess nutrition, physical activity and healthful knowledge in obese children with biopsy-proven non-alcoholic steatohepatitis (NASH or NA) compared to children without liver disease.
Children with biopsy-proven NASH comprised the NASH group. Age, sex and ethnicity matched control groups consisted of obese (OB) and lean (CO) children with no liver disease. Subjects were administered the School Physical Activity and Nutrition Survey and one blood draw was obtained.
Fifty-seven patients were enrolled with a mean age of 12.1 ± 2.1 years, and all were Hispanic. Even though the OB and NA had a similar increased body mass index (%), 35% of the NA group always read nutrition labels compared to none in the OB (P < 0.05), and more NA children felt their diet is "less healthy". NA consumed the least amount of fruits with only 25% having ≥ 1 fruit/d vs 45% in OB and 64.7% in CO (P < 0.05 NA vs CO). Only 15% of NA subjects performed light exercise vs 35% and 59% of OB and CO groups, respectively (P = 0.02). The mean physical activity score was lowest in the NA group (P < 0.05). Amongst the subjects with NASH, we found that 100% of patients with grade 2 or 3 fibrosis had a sedentary score > 2 compared to only 63.6% of those with grade 1 or no fibrosis (P < 0.05).
Children with NASH had increased se-dentary behavior, decreased activity, and fruit intake. Larger studies may determine the benefit of changing these behaviors as treatment for NASH.
World Journal of Gastroenterology 10/2011; 17(39):4396-403. · 2.47 Impact Factor
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ABSTRACT: Pediatric patients with hypertrophic cardiomyopathy (HCM) and restrictive physiology (RP) with poor outcomes have been identified, but data on their course are limited. Our goal was to delineate the clinical features and course of children with HCM and RP. An institutional review of 119 patients identified between 1985 and 2010 with the diagnosis of HCM was performed. The diagnosis of RP was based on >1 echocardiogram along with at least one of the following: left atrial enlargement without evidence of left ventricle dilation, E/E' ratio ≥ 10, and E/A ratio ≥ 3. Outcomes analysis was performed using Cox or Poisson regression when appropriate. RP was present in 50 (42%) patients. In patients without RP, 10-year freedom-from-death or aborted sudden cardiac death (aSCD), and death or heart transplant (HT), were 93.6 and 98.5%, respectively. In patients with RP, 10-year freedom-from-death or aSCD, and death or HT, were 59.0 and 71.2%, respectively. RP conferred a 3.5-fold increase in incidence rate of hospitalization (P = 0.01), a 3.8-fold increase in hazard of death or aSCD (P = 0.02), and a 5.7-fold increase in hazard of death or HT (P = 0.04). Assessment for RP is of paramount importance in children with HCM because those without RP have a good prognosis, and those with RP account for the majority of poor outcomes.
Pediatric Cardiology 09/2011; 33(1):141-9. · 1.30 Impact Factor
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ABSTRACT: The aim of the study was to determine the effectiveness of a school-initiated cognitive and behavioral program to reduce childhood obesity. Height, weight, body mass index (BMI), and BMI z scores were obtained at the beginning and end of the school year at an intervention school (n = 1022) and at a control school (n = 692). The prevalence of overweight and obesity was 18.9% and 30.4% versus 19% and 30.2%, respectively, in the intervention and control schools. The incidence of overweight increased in the control school, but the incidence of obesity, weight, and BMI z scores increased significantly in the intervention school, suggesting that implementation of any school-based obesity intervention programs requires careful planning to achieve goals.
Journal of pediatric gastroenterology and nutrition 08/2011; 54(1):113-6. · 2.18 Impact Factor
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ABSTRACT: Balloon aortic valvuloplasty (BAV) is the primary therapy for congenital aortic stenosis (AS). Few reports describe long-term outcomes. In this study, a retrospective single-institution review was performed of patients who underwent BAV for congenital AS. The following end points were evaluated: moderate or severe aortic insufficiency (AI) by echocardiography, aortic valve replacement, repeat BAV, surgical aortic valvotomy, and transplantation or death. From 1985 to 2009, 272 patients who underwent BAV at ages 1 day to 30.5 years were followed for 5.8 ± 6.7 years. Transplantation or death occurred in 24 patients (9%) and was associated with depressed baseline left ventricular shortening fraction (LVSF) (p = 0.04). Aortic valve replacement occurred in 42 patients (15%) at a median of 3.5 years (interquartile range 75 days to 5.9 years) after BAV and was associated with post-BAV gradient ≥25 mm Hg (p = 0.02), the presence of post-BAV AI (p = 0.03), and below-average baseline LVSF (p = 0.04). AI was found in 83 patients (31%) at a median of 4.8 years (interquartile range 1.4 to 8.7) and was inversely related to post-BAV gradient ≥25 mm Hg (p <0.04). AI was associated with depressed baseline LVSF (p = 0.02). Repeat valvuloplasty (balloon or surgical) occurred in 37 patients (15%) at a median of 0.51 years (interquartile range 0.10 to 5.15) and was associated with neonatal BAV (p <0.01), post-BAV gradient ≥25 mm Hg (p = 0.03), and depressed baseline LVSF (p = 0.05). In conclusion, BAV confers long-term benefits to most patients with congenital AS. Neonates, patients with post-BAV gradients ≥25 mm Hg, and patients with lower baseline LVSF experienced worse outcomes.
The American journal of cardiology 07/2011; 108(7):1024-8. · 3.58 Impact Factor
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Ashok Balasubramanyam,
Ivonne Coraza, E O'Brian Smith,
Lynne W Scott,
Payal Patel,
Dinakar Iyer,
Addison A Taylor,
Thomas P Giordano,
Rajagopal V Sekhar,
Pamela Clark,
Edith Cuevas-Sanchez,
Swarna Kamble,
Christie M Ballantyne,
Henry J Pownall
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ABSTRACT: HIV patients on antiretroviral therapy (ART) have a unique dyslipidemia [elevated triglycerides and non-high-density lipoprotein-cholesterol (HDL-C), low HDL-C] with insulin resistance (characterized by hypoadiponectinemia).
The aim was to test a targeted, comprehensive, additive approach to treating the dyslipidemia.
We conducted a randomized, double-blind, placebo-controlled, 24-wk trial of lifestyle modification, fenofibrate, and niacin in multiethnic HIV clinics at an academic center.
Hypertriglyceridemic adult patients were stratified on three combinations of ART classes. Subjects retained at the first measurement (2 wk) after entry were included in the analysis (n = 191).
Subjects were randomized into five treatment groups: usual care (group 1); low-saturated-fat diet and exercise (D/E; group 2); D/E + fenofibrate (group 3); D/E + niacin (group 4); or D/E + fenofibrate + niacin (group 5).
We measured changes in fasting triglycerides, HDL-C, and non-HDL-C (primary), and in insulin sensitivity, glycemia, adiponectin, C-reactive protein, energy expenditure, and body composition (secondary). Data were analyzed as a factorial set of treatment combinations using a mixed repeated measures model, last observation carried forward, and complete case approaches (groups 2-5), and as an unstructured set of treatments (groups 1-5).
Fenofibrate improved triglycerides (P = 0.002), total cholesterol (P = 0.02), and non-HDL-C (P = 0.003), whereas niacin improved HDL-C (P = 0.03), and both drugs decreased the total cholesterol-to-HDL-C ratio (P = 0.005-0.01). The combination of D/E, fenofibrate, and niacin provided maximal benefit, markedly reducing triglycerides (-52% compared to usual care; P = 0.003), increasing HDL-C (+12%; P < 0.001), and decreasing non-HDL-C (-18.5%; P = 0.003) and total cholesterol-to-HDL-C ratio (-24.5%; P < 0.001). Niacin doubled adiponectin levels.
A combination of fenofibrate and niacin with low-saturated-fat D/E is effective and safe in increasing HDL-C, decreasing non-HDL-C and hypertriglyceridemia, and ameliorating hypoadiponectinemia in patients with HIV/ART-associated dyslipidemia.
The Journal of clinical endocrinology and metabolism 05/2011; 96(7):2236-47. · 6.50 Impact Factor
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Sean E Hesselbacher,
Robert Ross,
Matthew B Schabath, E O'Brian Smith,
Sarah Perusich,
Nadia Barrow,
Pamela Smithwick,
Manoj J Mammen,
Harvey Coxson,
Natasha Krowchuk,
David B Corry,
Farrah Kheradmand
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ABSTRACT: Emphysema is largely an under-diagnosed medical condition that can exist in smokers in the absence of airway obstruction. We aimed to determine the sensitivity and specificity of pulmonary function tests (PFTs) in assessing emphysema using quantitative CT scans as the reference standard. We enrolled 224 ever-smokers (current or former) over the age of 40. CT of thorax was used to quantify the low attenuation area (% emphysema), and to measure the standardized airway wall thickness. PFTs were used individually and in combination to predict their ability to discriminate radiographic emphysema. Significant emphysema (>7%) was detected in 122 (54%) subjects. Twenty six (21%) emphysema subjects had no evidence of airflow obstruction (FEV(1)/FVC ratio <70%), while all subjects with >23% emphysema showed airflow obstruction. The sensitivity and specificity of spirometry for detecting radiographic emphysema were 79% and 75%, respectively. Standardized airway wall thickness was increased in subjects with airflow obstruction, but did not correlate with emphysema severity. In this cohort of lifetime ever-smokers, PFTs alone were inadequate for diagnosing emphysema. Airway wall thickness quantified by CT morphometry was associated with airflow limitation, but not with emphysema indicating that the heterogeneous nature of lung disease in smokers may represent distinct phenotypes.
International Journal of Environmental Research and Public Health 05/2011; 8(5):1324-40. · 1.61 Impact Factor
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ABSTRACT: Inflammatory bowel disease (IBD) has a wide spectrum and variability among different ethnic groups. We aimed to evaluate disease characteristics in the pediatric Hispanic population, which has not been well studied.
We identified patients <18 years old seen at Texas Children's Hospital (TCH) and diagnosed with IBD between 2004 and 2009. We compared them with their White, African American, and "other" counterparts with regard to their demographics, disease characteristics, and initial therapy.
There were a total of 399 patients with IBD: 211 (52.9%) White, 67 (16.8%) African American, 53 (13.3%) Hispanic, and 68 (17%) "other." Crohn's disease (CD) was the most common IBD type among all groups; however, Hispanics had the highest proportion of patients with ulcerative colitis (UC) and IBD-unclassified (IBD-U). There was male predominance in all groups except African Americans. Hispanics had the highest percentage of Medicaid coverage (P < 0.01) and none of the Hispanics had a first-degree relative with IBD. They had a younger age at diagnosis but a similar duration of symptoms prior to diagnosis. Hispanics had less failure to thrive and a higher body mass index (BMI) Z-score. Hispanics with CD more often received systemic steroids while those with UC and IBD-U were more often treated with local steroids (P < 0.01), oral 5-aminosalicylate (P < 0.01), and less often received immunomodulators or biologics (P = 0.05).
We demonstrate differences in disease characteristics between Hispanics and other ethnicities with IBD. Further epidemiologic studies are needed, including longer-term follow-up, to better define the burden of illness in Hispanics.
Inflammatory Bowel Diseases 03/2011; 18(3):546-54. · 4.86 Impact Factor
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Francene M Steinberg,
Michael J Murray,
Richard D Lewis,
Margaret A Cramer,
Paula Amato,
Ronald L Young,
Stephen Barnes,
Karen L Konzelmann,
Joan G Fischer,
Kenneth J Ellis,
Roman J Shypailo,
J Kennard Fraley, E O'Brian Smith,
William W Wong
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ABSTRACT: Soy isoflavones are naturally occurring phytochemicals with weak estrogenic cellular effects. Despite numerous clinical trials of short-term isoflavone supplementation, there is a paucity of data regarding longer-term outcomes and safety.
Our aim was to evaluate the clinical outcomes of soy hypocotyl isoflavone supplementation in healthy menopausal women as a secondary outcome of a trial on bone health.
A multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg aglycone equivalent soy hypocotyl isoflavones plus calcium and vitamin D on the health of 403 postmenopausal women. At baseline and after 1 and 2 y, clinical blood chemistry values were measured and a well-woman examination was conducted, which included a mammogram and a Papanicolaou test. A cohort also underwent transvaginal ultrasound measurements to assess endometrial thickness and fibroids.
The baseline characteristics of the groups were similar. After 2 y of daily isoflavone exposure, all clinical chemistry values remained within the normal range. The only variable that changed significantly was blood urea nitrogen, which increased significantly after 2 y (P = 0.048) but not after 1 y (P = 0.343) in the supplementation groups. Isoflavone supplementation did not affect blood lymphocyte or serum free thyroxine concentrations. No significant differences in endometrial thickness or fibroids were observed between the groups. Two serious adverse events were detected (one case of breast cancer and one case of estrogen receptor-negative endometrial cancer), which was less than the expected population rate for these cancers.
Daily supplementation for 2 y with 80-120 mg soy hypocotyl isoflavones has minimal risk in healthy menopausal women. This trial was registered at clinicaltrials.gov as NCT00665860.
American Journal of Clinical Nutrition 02/2011; 93(2):356-67. · 6.67 Impact Factor
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ABSTRACT: The clinical measures of gastric residuals and abdominal distention are often used to guide feeding in preterm infants, but there are few data demonstrating their usefulness. Similarly, techniques are now available to investigate gastrointestinal (GI) function noninvasively and safely, but their ability to predict attainment of full gavage feedings and/or feeding volume in preterm infants is unclear.
We sought to determine prospectively the potential relationships of attainment of full gavage feedings and feeding volume with clinical measures and noninvasive GI tests.
Fifty preterm infants were followed prospectively. Daily tally was taken of gavage feeding intake, gastric residual volumes (GRVs; milliliters per day, number of GRVs >50% of the previous feeding volume, and number of GRVs >2 ml/kg), and abdominal distention. Infants underwent repeated measurement of lactase activity, GI permeability, fecal calprotectin concentration, and gastric emptying.
The number of GRVs >2 ml/kg tended to decrease with postnatal age (p = 0.06). Lactase activity and feeding volume in milliliters per kilogram per day prior to achieving full feedings were correlated (p = 0.007, β = 0.164). There was no correlation between feeding outcomes and GRV (ml/day), GRV >50%, GRV >2 ml/kg, small bowel, colonic, or whole bowel permeability, fecal calprotectin concentration, gastric emptying, or abdominal distention.
GRV is unreliable in predicting attainment of full gavage feeding. Lactase activity is related to feeding volume. However, other noninvasive GI tests utilized were not predictive. These data cast doubt upon the utility of GRV in guiding feeding therapy. Randomized trials of different GRV management protocols are needed.
Neonatology 01/2011; 99(1):38-44. · 2.66 Impact Factor
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ABSTRACT: KL-6 is a glycoprotein expressed by pulmonary epithelial cells, and its serum level has been used as a marker of disease activity in a variety of respiratory illnesses. Previously, we showed that KL-6 was elevated in lung transplant recipients diagnosed with BOS. In this study, we followed serum KL-6 levels and lung functions prospectively in lung transplant recipients who were within the first five-yr post-transplant and had no evidence of BOS at the time of study entry. Mean peak KL-6 levels were 596.16 ± 309.32 U/mL in the nine recipients who developed BOS compared to 352.41 ± 140.68 in 36 recipients who did not (p = 0.05). Six of the nine patients with BOS had an absolute rise in KL-6 above baseline level >200 U/mL compared to two of the 37 who had the same increase in KL-6 but did not develop BOS. Using the 200 U/mL elevation of KL-6 from baseline as a threshold for a positive test would produce a sensitivity of 67%, specificity of 95%, PPV of 75%, and a NPV of 92%. In addition, mean KL-6 levels of patients during acute rejection were not significantly elevated compared to the prerejection mean KL-6 levels (p = 0.71). We conclude that serum KL-6 is a relatively specific marker of BOS in lung transplant recipients.
Pediatric Transplantation 11/2010; 14(7):903-8. · 1.48 Impact Factor
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Mousumi Moulik,
John P Breinholt,
William J Dreyer,
Debra L Kearney,
Jack F Price,
Sarah K Clunie,
Brady S Moffett,
Jeffrey J Kim,
Joseph W Rossano,
John Lynn Jefferies,
Karla R Bowles, E O'Brian Smith,
Neil E Bowles,
Susan W Denfield,
Jeffrey A Towbin
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ABSTRACT: This study sought to evaluate the outcome and prevalence of viral endomyocardial infection after cardiac transplantation.
Viral myocardial infection causes heart failure, but its role after cardiac transplantation is unclear. We hypothesized that viral infection of the cardiac allograft reduces graft survival.
Between June 1999 and November 2004, 94 pediatric cardiac transplant patients were screened for the presence of viral genome in serial endomyocardial biopsies (EMBs) using polymerase chain reaction (PCR) assays. Graft loss, advanced transplant coronary artery disease (TCAD), and acute rejection (AR) were compared in the PCR-positive (n = 37) and PCR-negative (n = 57) groups, using time-dependent Kaplan-Meier and Cox regression analyses. From November 2002 to November 2004, intravenous immunoglobulin therapy (IVIG) was administered to patients with PCR-positive EMBs. The outcomes of the IVIG-treated, PCR-positive patients (n = 20) were compared with IVIG-untreated, PCR-positive patients (n = 17).
Viral genomes were detected in EMBs from 37 (39%) patients; parvovirus B19, adenovirus, and Epstein-Barr virus (EBV) were the most common. The PCR-positive group (n = 37, 25% graft loss at 2.4 years) had decreased graft survival (p < 0.001) compared with the PCR-negative group (n = 57, 25% graft loss at 8.7 years) and developed advanced TCAD prematurely (p = 0.001). The number of AR episodes was similar in both groups. On multivariate analysis, presence of viral genome was an independent risk factor for graft loss (relative risk: 4.2, p = 0.015). The time to advanced TCAD after becoming PCR-positive was longer in the IVIG-treated patients (p = 0.03) with a trend toward improved graft survival (p = 0.06).
Viral endomyocardial infection is an independent predictor of graft loss in pediatric cardiac transplant recipients. This effect appears to be mediated through premature development of advanced TCAD. IVIG therapy in this subgroup may improve survival and merits further investigation.
Journal of the American College of Cardiology 08/2010; 56(7):582-92. · 14.16 Impact Factor
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ABSTRACT: We aimed to prospectively and longitudinally measure lung function in a cohort of children with bronchopulmonary dysplasia (BPD) during their first 3 years of life.
Forty-four children with BPD with a mean (+ or - SD) gestational age of 25.6 (+ or - 1.7) weeks and birth weight of 0.767 (+ or - 0.2) kg underwent serial measurements of lung function (maximum flow at functional residual capacity [V(max)FRC] and functional residual capacity [FRC]) at 6, 12, and 24 months after initial discharge from the neonatal care unit.
Compared with normative data, children with BPD had low partial expiratory airflow, measured by V(max)FRC, with mean z score (+ or - SD) of -1.92 (+ or - 1.04), -1.79 (+ or - 1.5), and -1.67 (+ or - 1.5) at 6, 12, and 24 months, respectively. Over time there was no significant improvement in z scores (P = .66), and 45% of the patients had a z score value of less than -2 (2 SDs below the mean) at the end of the study. FRC measurements steadily and significantly increased over time. Partial expiratory flow showed no correlation with gestational age, birth weight, or length of mechanical ventilation. Mean FRC was significantly higher in children who were using bronchodilators and inhaled steroids but showed no correlation with clinical symptoms. Bronchodilator response was initially present in 30% of the patients and declined to 20% at the end of the study.
During the first 3 years of life, children with mostly moderate-to-severe BPD continue to show significant abnormalities with airflow limitation according to lung-function testing.
PEDIATRICS 06/2010; 125(6):e1441-7. · 4.47 Impact Factor
