Nonfocal renal biopsies: adequacy and factors affecting a successful outcome.

PURPOSE: The purpose of this study was to evaluate factors affecting the success of ultrasound-guided core biopsy of kidneys and determine the optimum number of passes. METHODS: This retrospective study evaluated 484 nonfocal renal biopsies performed with 18-gauge side-notch biopsy needles. Number of biopsy passes, serum creatinine, body mass index, needle type, transplant age, kidney size, diabetic status, and operator were evaluated as predictors of the number of biopsy passes. RESULTS: Four hundred seventy-four biopsies (338 transplant, 136 native) were included with mean number of passes 2.87 (3.1 native vs 2.78 transplant; P = 0.002). Mean number of glomeruli yielded per pass was 6.9 (7.2 transplant vs 6.1 native; P = 0.0002) with 3 passes adequate for histological diagnosis in 84% of biopsies. Native kidney, increasing serum creatinine level, trainee biopsy operator, and use of a Temno needle were found to be independent predictors of having more than 3 biopsy passes on multivariate analysis. Age, sex, body mass index, diabetic status, and kidney size were not associated with the number of biopsy passes. CONCLUSIONS: The success of a nonfocal renal biopsy has many influencing variables, and in the absence of an on-site electron microscopy technologist to immediately evaluate biopsy samples, 3 passes with an 18-gauge needle would be adequate in 84% of kidneys to achieve a histological diagnosis, with 2 passes needed for transplant kidneys to meet the Banff 97 criteria.

Detection of urothelial tumors: comparison of urothelial phase with excretory phase CT urography--a prospective study.

PURPOSE: To compare contrast material-enhanced computed tomographic (CT) urography 60 seconds after injection of contrast material (urothelial phase [UP]) after intravenous administration of a diuretic with the standard 5-minute delayed excretory phase (EP) in a high-risk population for upper tract tumors. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Eighty CT urographic examinations in 77 patients known to have or at high risk for urothelial malignancy were included. After intravenous administration of a diuretic, dual-phase CT urography was performed at 60 seconds (UP) and 5 minutes (EP) after intravenous administration of contrast material. Two experienced abdominal radiologists independently interpreted each phase more than 1 month apart to minimize recall bias. Urinary tract distention and location and size of all lesions suspected of being urothelial tumors were recorded. Standard of reference was obtained from prospective study interpretation and surgical histopathologic findings. Generalized estimating equations for logistic regression were used to compare performance measures and adjust for the correlation of repeated measures within patients. RESULTS: There were 23 upper and 61 lower urinary tract tumors confirmed in 15 and 32 patients, respectively. For detection of bladder tumors, there was higher sensitivity for the UP than the EP (89.3% [109 of 122] vs 70.5% [86 of 122], respectively; P<.0001). For detection of upper tract tumors, there was higher sensitivity for the UP than the EP (82.6% [38 of 46] vs 69.6% [32 of 46], respectively; P=.0194). Distention of all upper urinary tract segments was better during the EP than the UP (P<.0001). CONCLUSION: UP CT urography after injection of a diuretic has a higher lesion detection rate than the EP for both upper and lower urinary tract tumors, which suggests its possible use as a single-phase protocol for evaluation of the entire urinary tract in patients at high risk for urothelial tumors.

Effect of Transdermal Estradiol and Insulin-like Growth Factor-1 on Bone Endpoints of Young Women With Anorexia Nervosa.

CONTEXT: Anorexia nervosa (AN) is prevalent in adolescent girls and is associated with bone impairment driven by hormonal alterations in nutritional deficiency. OBJECTIVE: To assess the impact of estrogen replacement with and without recombinant human insulin-like growth factor-1 (rhIGF-1) administration on bone outcomes. DESIGN: Double-blind, randomized, placebo-controlled 12-month longitudinal study. PARTICIPANTS: Seventy-five adolescent and young adult women with AN age 14 to 22 years. Thirty-three participants completed the study. INTERVENTION: Transdermal 17-beta estradiol 0.1 mg/day with (i) 30 mcg/kg/dose of rhIGF-1 administered subcutaneously twice daily (AN-IGF-1+) or (ii) placebo (AN-IGF-1-). The dose of rhIGF-1 was adjusted to maintain levels in the upper half of the normal pubertal range. MAIN OUTCOME MEASURES: Bone turnover markers and bone density, geometry, microarchitecture, and strength estimates. RESULTS: Over 12 months, lumbar areal bone mineral density increased in AN-IGF-1- compared to AN-IGF-1+ (P = 0.004). AN-IGF-1+ demonstrated no improvement in areal BMD in the setting of variable compliance to estrogen treatment. Groups did not differ for 12-month changes in bone geometry, microarchitecture, volumetric bone mineral density (vBMD), or strength (and results did not change after controlling for weight changes over 12 months). Both groups had increases in radial cortical area and vBMD, and tibia cortical vBMD over 12 months. Levels of a bone resorption marker decreased in AN-IGF-1- (P = 0.042), while parathyroid hormone increased in AN-IGF-1+ (P = 0.019). AN-IGF-1- experienced irregular menses more frequently than did AN-IGF-1+, but incidence of all other adverse events did not differ between groups. CONCLUSIONS: We found no additive benefit of rhIGF-1 administration for 12 months over transdermal estrogen replacement alone in this cohort of young women with AN.

Cyberbullying and Adolescents.

PURPOSE OF REVIEW: Cyberbullying is an aggressive behavior involving a type of electronic communication intending to harm a victim that can have profound effects on adolescents. This review examines the epidemiology, issues from cyberbullying, presentation to care of its victims and proposed interventions to this behavior. RECENT FINDINGS: There are a variety of physical and psychological effects on victims of cyberbullying that can include recurrent abdominal pain, headaches and difficulty with sleep. In addition, victims have higher rates of anxiety, depression, suicidal ideation and a lower level of well-being. Unfortunately, victims may remain silent, so screening for cyberbullying is encouraged in a variety of settings. Interventions can be designed at the level of the victim (and perpetrator), family, school and other support networks. Prevention of cyberbullying can be a focus for providers of healthcare. SUMMARY: Cyberbullying can have profound biopsychosocial effects on its victims. There are strategies currently in use and under development to identify and intervene on behalf of those affected by these behaviors.

Suboptimal bone microarchitecure in adolescent girls with obesity compared to normal-weight controls and girls with anorexia nervosa.

BACKGROUND: Despite their higher areal bone mineral density (aBMD), adolescents with obesity (OB) have an increase in fracture risk, particularly of the extremities, compared with normal-weight controls. Whereas bone parameters that increase fracture risk are well characterized in anorexia nervosa (AN), the other end of nutritional spectrum, these data are lacking in adolescents with obesity. OBJECTIVE: Our objective was to compare bone parameters in adolescent girls across the nutritional spectrum, to determine whether suboptimal bone adaptation to increased body weight may explain the increased fracture risk in OB. METHODS: We assessed bone endpoints in 153 adolescent girls 14-21 years old: 50 OB, 48 controls and 55 AN. We used (i) DXA to assess aBMD at the lumbar spine, proximal femur and whole body, and body composition, (ii) high resolution peripheral quantitative CT (HRpQCT) to assess bone geometry, microarchitecture and volumetric BMD (vBMD), and (iii) finite element analysis to assess failure load (a strength estimate) at the distal radius and tibia. All aBMD, microarchitecture and FEA analyses were controlled for age and race. RESULTS: Groups did not differ for age or height. Areal BMD Z-scores at all sites were highest in OB, intermediate in controls and lowest in AN (p < 0.0001). At the radius, cortical area and thickness were higher in OB compared to AN and control groups (p = 0.001) while trabecular area did not differ across groups. Compared to controls, OB had higher cortical porosity (p = 0.003), higher trabecular thickness (p = 0.024), and higher total, cortical and trabecular vBMD and rod BV/TV (p < 0.04). Plate BV/TV did not differ in OB vs. controls, but was higher than in AN (p = 0.001). At the tibia, total, cortical, and trabecular area and cortical thickness were higher in OB vs. controls and AN (p < 0.005). OB also had higher cortical porosity (p < 0.007) and lower trabecular thickness (p < 0.02) than the other two groups. Trabecular number, total and trabecular vBMD, and rod BV/TV were higher in OB vs. controls and AN (p < 0.02), while cortical vBMD and plate BV/TV did not differ in OB vs. the other two groups. Finally, failure load (a strength estimate) was higher in OB at the radius and tibia compared to controls and AN (p < 0.004 for all). However, after adjusting for body weight, failure load was lower in OB vs. controls at both sites (p < 0.05), and lower than in AN at the distal tibia. CONCLUSION: Not all bone parameters demonstrate appropriate adaptation to higher body weight. Cortical porosity and plate BV/TV at the radius and tibia, and cortical vBMD and trabecular thickness at the tibia are particularly at risk. These effects may contribute to the higher risk for fracture reported in OB vs. controls.

Prognostic indicators of changes in bone density measures in adolescent girls with anorexia nervosa-II.

INTRODUCTION: Adolescents with anorexia nervosa (AN) have low bone mineral density (BMD). Baseline predictors of temporal BMD changes (DeltaBMD) in AN, including 1) gastrointestinal peptides regulating food intake and appetite that have been related to bone metabolism and 2) bone turnover markers, have not been well characterized. We hypothesized that baseline levels of nutritionally regulated hormones and of bone turnover markers would predict DeltaBMD overall. METHODS: In a prospective observational study, lumbar and whole-body BMD was measured at 0, 6, and 12 months in 34 AN girls aged 12-18 yr and 33 controls. Baseline body mass index, lean mass, nutritionally regulated hormones [IGF-I, cortisol, ghrelin, leptin, and peptide YY (PYY)], bone formation, and resorption markers were examined to determine nutritional and hormonal predictors of bone density changes. RESULTS: In a regression model, baseline ghrelin and PYY predicted changes in spine bone measures; and baseline ghrelin, cortisol, and PYY predicted changes in whole-body bone measures independent of baseline nutritional status. CONCLUSIONS: Neuroendocrine gastrointestinal-derived peptides regulating food intake are independent predictors of changes in bone mass in AN.

Weight gain and restoration of menses as predictors of bone mineral density change in adolescent girls with anorexia nervosa-1.

CONTEXT: Adolescents with anorexia nervosa (AN) have low bone mineral density. However, the effect of disease recovery, first, on bone density measures assessed using the Molgaard approach, which differentiates between reported low bone density resulting from short bones (based on height Z-scores) and that resulting from thin bones [based on measures of bone area (BA) for height] or light bones [based on measures of bone mineral content (BMC) for BA]; and second, on height-adjusted bone density measures, has not been well characterized. We hypothesized that menstrual recovery and weight gain (> or =10% increase in body mass index) would predict an increase in these measures of bone density. METHODS: In a prospective observational study, lumbar and whole-body (WB) bone density was measured at 0, 6, and 12 months in 34 AN girls aged 12-18 yr and 33 controls. Using Ward's modification of the Molgaard approach, we determined measures of BMC for BA and BA for height at the lumbar spine and WB and also determined spine bone mineral apparent density and WB BMC adjusted for height. RESULTS: Girls with AN had lower spine BMC for BA Z-scores (P = 0.0009), and lower WB BA for height Z (P < 0.0001), compared with controls. Menstrual recovery and weight gain in AN (AN-recovered) (median 9 months) resulted in a stabilization of BMD measures, whereas BMD continued to decrease in AN who did not gain weight and recover menses (AN-not recovered). AN-recovered also predicted greater increases in spine BMC for BA and WB BA for height, compared with AN-not recovered (P < 0.05). CONCLUSIONS: Even short-term weight gain with menstrual recovery is associated with a stabilization of BMD measures.

Acylated ghrelin and leptin in adolescent athletes with amenorrhea, eumenorrheic athletes and controls: a cross-sectional study.

OBJECTIVES: Neuroendocrine factors may predict which athletes develop amenorrhea and which athletes remain eugonadal. Specifically, ghrelin and leptin have been implicated in regulation of GnRH secretion, with ghrelin having inhibitory and leptin, facilitatory effects. We hypothesized that adolescent athletes with amenorrhea (AA) would have higher ghrelin and lower leptin levels than eumenorrheic athletes (EA) and would predict levels of gonadal steroids. DESIGN: Cross-sectional. SUBJECTS AND MEASUREMENTS: We enrolled 58 girls, 21 AA, 19 EA and 18 nonathletic controls 12-18 years old. Fasting blood was drawn for active ghrelin, leptin, E(2) and testosterone. Athletes were > 85% of ideal body weight for age based on body mass index (BMI). RESULTS: AA girls had lower BMI than EA and controls (P = 0.003). Log ghrelin was higher in AA than in EA and controls (P < 0.0001), and remained higher after controlling for BMI Z-scores. Leptin was lower in AA than in the other groups (P < 0.0001), however, the differences did not persist after controlling for BMI Z-scores. Testosterone was lower in AA than in EA and controls (P = 0.002) and log E(2) trended lower in AA (P = 0.07). We observed inverse associations of log active ghrelin with testosterone (P = 0.01), and positive associations of leptin with testosterone and log E(2) (P = 0.02 and 0.009). CONCLUSION: Higher ghrelin levels, even after controlling for BMI, and lower leptin in AA compared with EA and controls, and their inverse and positive associations, respectively, with gonadal steroids suggest endocrine perturbations that may explain why hypogonadism occurs in some but not all athletes.

Optimizing lithium treatment in bipolar disorder: a review of the literature and clinical recommendations.

While the past decade has witnessed a major proliferation of putative treatments for bipolar disorder, one medication--lithium--has proven its effectiveness through 50 years of clinical experience and scientific scrutiny. Unfortunately, because the generic compound, lithium, lacks the financial support of its newer, patented comparators, it is often neglected by clinicians who are exposed to continuing medical education (CME) and residency training programs that are heavily weighted towards the newer treatments. This article critically examines the medical literature on lithium's efficacy, anti-suicidal properties, and adverse effects. The authors present research-based recommendations for maximizing lithium's benefits and minimizing adverse effects associated with lithium in patients with bipolar disorder.

Impact of physiologic estrogen replacement on anxiety symptoms, body shape perception, and eating attitudes in adolescent girls with anorexia nervosa: data from a randomized controlled trial.

OBJECTIVE: Anorexia nervosa is characterized by low weight, aberrant eating attitudes, body image distortion, and hypogonadism. Anxiety is a common comorbid condition. Estrogen replacement reduces anxiety in animal models, and reported variations in food intake across the menstrual cycle may be related to gonadal steroid levels. The impact of estrogen replacement on anxiety, eating attitudes, and body image has not been reported in anorexia nervosa. We hypothesized that physiologic estrogen replacement would ameliorate anxiety and improve eating attitudes without affecting body image in anorexia nervosa. METHOD: Girls 13-18 years old with anorexia nervosa (DSM-IV) were randomized to transdermal estradiol (100 µg twice weekly) with cyclic progesterone or placebo patches and pills for 18-months, between 2002 and 2010. The State-Trait Anxiety Inventory for Children (STAIC), the Eating Disorders Inventory-2 (EDI-2), and the Body Shape Questionnaire (BSQ-34) were administered. 72 girls completed these measures at baseline (n=38 [girls receiving estrogen] and n=34 [girls receiving placebo]) and 37 at 18 months (n=20 [girls receiving estrogen] and n=17 [girls receiving placebo]). The primary outcome measure was the change in these scores over 18 months. RESULTS: Estrogen replacement caused a decrease in STAIC-trait scores (-3.05 [1.22] vs. 2.07 [1.73], P=.02), without impacting STAIC-state scores (-1.11 [2.17] vs. 0.20 [1.42], P=.64). There was no effect of estrogen replacement on EDI-2 or BSQ-34 scores. Body mass index (BMI) changes did not differ between groups, and effects of estrogen replacement on STAIC-trait scores persisted after controlling for BMI changes (P=.03). Increases in serum estradiol were significantly associated with decreases in STAIC-trait scores (Spearman ρ = -0.45, P=.03). CONCLUSIONS: Estrogen replacement improved trait anxiety (the tendency to experience anxiety) but did not impact eating attitudes or body shape perception. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00088153.

Adolescent girls with anorexia nervosa have impaired cortical and trabecular microarchitecture and lower estimated bone strength at the distal radius.

CONTEXT: Adolescents with anorexia nervosa (AN) have low areal bone mineral density (aBMD) at both cortical and trabecular sites, and recent data show impaired trabecular microarchitecture independent of aBMD. However, data are lacking regarding both cortical microarchitecture and bone strength assessment by finite element analysis (FEA) in adolescents with AN. Because microarchitectural abnormalities and FEA may predict fracture risk independent of aBMD, these data are important to obtain. OBJECTIVE: Our objective was to compare both cortical and trabecular bone microarchitecture and FEA estimates of bone strength in adolescent girls with AN vs normal-weight controls. DESIGN, SETTING, AND SUBJECTS: We conducted a cross-sectional study at a clinical research center that included 44 adolescent girls (21 with AN and 23 normal-weight controls) 14 to 22 years old. MAIN OUTCOME MEASURES: We evaluated 1) aBMD (dual-energy x-ray absorptiometry) at the distal radius, lumbar spine, and hip, 2) cortical and trabecular microarchitecture at the ultradistal radius (high-resolution peripheral quantitative computed tomography), and 3) FEA-derived estimates of failure load at the ultradistal radius. RESULTS: aBMD was lower in girls with AN vs controls at the lumbar spine and hip but not at the distal radius. Girls with AN had lower total (P < .0001) and trabecular volumetric BMD (P = .02) and higher cortical porosity (P = .03) and trabecular separation (P = .04). Despite comparable total cross-sectional area, trabecular area was higher in girls with AN (P = .04), and cortical area and thickness were lower (P = .002 and .02, respectively). FEA-estimated failure load was lower in girls with AN (P = .004), even after controlling for distal radius aBMD. CONCLUSIONS: Both cortical and trabecular microarchitecture are altered in adolescent girls with AN. FEA-estimated failure load is decreased, indicative of reduced bone strength. The finding of reduced cortical bone area in girls with AN is consistent with impaired cortical bone formation at the endosteum as a mechanism underlying these findings.