Publications by authors named "Nadine Haddad"

19 Publications

  • Page 1 of 1

Epidemiology of severe cases of influenza and other acute respiratory infections in the Eastern Mediterranean Region, July 2016 to June 2018.

J Infect Public Health 2020 Mar 4;13(3):423-429. Epub 2019 Jul 4.

Infectious Hazard Management Unit, Department of Health Emergencies, World Health Organization, Regional Office for the Eastern Mediterranean, Cairo, Egypt.

Background: Influenza surveillance systems in the Eastern Mediterranean Region have been strengthened in the past few years and 16 of the 19 countries in the Region with functional influenza surveillance systems report their influenza data to the EMFLU Network. This study aimed to investigate the epidemiology of circulating influenza viruses, causing SARI, and reported to the EMFLU during July 2016 to June 2018.

Methods: Data included in this study were collected by 15 countries of the Region from 110 SARI sentinel surveillance sites over two influenza seasons.

Results: A total of 40,917 cases of SARI were included in the study. Most cases [20,551 (50.2%)] were less than 5years of age. Influenza virus was detected in 3995 patients, 2849 (11.8%) were influenza A and 1146 (4.8%) were influenza B. Influenza A(H1N1)pdm09 was the predominant circulating subtype with 1666 cases (58.5%). Other than influenza, respiratory syncytial virus was the most common respiratory infection circulating, with 277 cases (35.9%).

Conclusion: Influenza viruses cause a high number of severe respiratory infections in EMR. It is crucial for the countries to continue improving their influenza surveillance capacity in order detect any unusual influenza activity or new strain that may cause a pandemic.
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http://dx.doi.org/10.1016/j.jiph.2019.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102678PMC
March 2020

Peripheral precocious puberty including congenital adrenal hyperplasia: causes, consequences, management and outcomes.

Best Pract Res Clin Endocrinol Metab 2019 06 13;33(3):101273. Epub 2019 Apr 13.

Riley Hospital for Children, 705 Barnhill Dr, Rm 5960, Indianapolis, IN 46202, USA. Electronic address:

Peripheral precocious puberty results from peripheral production of sex steroids independent of activation of the hypothalamic-pituitary gonadal axis. It is much less common than central precocious puberty. Causes are variable and can be congenital or acquired. In this review, we will discuss the diagnosis and management of the most common etiologies including congenital adrenal hyperplasia, McCune Albright syndrome, familial male-limited precocious puberty, and adrenal and gonadal tumors.
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http://dx.doi.org/10.1016/j.beem.2019.04.007DOI Listing
June 2019

An ovulating follicle presenting as a testicular mass in a teenage patient with ovotesticular DSD.

Urol Case Rep 2018 May 31;18:26-28. Epub 2018 Jan 31.

Department of Urology, Section of Pediatric Urology, Riley Hospital for Children at IU Health, 702 Barnhill Drive, Suite 4230, Indianapolis, IN, 46202, USA.

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http://dx.doi.org/10.1016/j.eucr.2018.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910528PMC
May 2018

Lebanon's experience in surveillance of communicable diseases during a mass gathering: Sixth Francophone Games, 2009.

East Mediterr Health J 2017 Mar 30;23(2):119-125. Epub 2017 Mar 30.

Ministry of Public Health, Beirut, Lebanon.

In 2009, Lebanon hosted the 6th Francophone Games. Pandemic A(H1N1)2009 virus presented significant health threat at the time. A surveillance strategy was implemented for the timely detection and management of epidemiological events and outbreaks, in particular for A(H1N1)2009 virus cases. Data were collected and managed daily and feedback was generated through daily bulletins. A total of 299 medical consultations were reported, 29% of which related to infectious diseases. There were 10 cases reported as acute respiratory infections; all tested negative for A(H1N1)2009 virus within 24 hours. Twenty-three cases of gastroenteritis were reported, for which 11 stool cultures were negative. While pandemic A(H1N1)2009 did not interfere with the Games, it was essential to strengthen surveillance and to have timely epidemiological information. This was achieved through preparedness, a multi-disciplinary approach, timely management and coordination.
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March 2017

INCIDENCE OF CENTRAL DIABETES INSIPIDUS IN CHILDREN PRESENTING WITH POLYDIPSIA AND POLYURIA.

Endocr Pract 2016 Dec 19;22(12):1383-1386. Epub 2016 Aug 19.

Objective: Polydipsia and polyuria are common reasons for referral to the Pediatric Endocrine clinic. In the absence of hyperglycemia, diabetes insipidus (DI) should be considered. The objectives of the study were to determine the prevalence of central DI (CDI) in a group of children presenting for evaluation of polydipsia and polyuria, and to determine if predictive features were present in patients in whom the diagnosis of DI was made.

Methods: The study was a retrospective chart review of children presenting to the endocrine clinic with complaints of polydipsia and polyuria over a 5-year period.

Results: The charts of 41 patients (mean age 4.9 ± 3.7 years, 28 males) were reviewed. CDI was diagnosed in 8 (20%) children based on abnormal water deprivation test (WDT) results. All but one patient had abnormal magnetic resonance imaging (MRI) findings, the most common being pituitary stalk thickening. Children with DI were older (7.86 ± 4.40 vs. 4.18 ± 3.20 years, P = .01) and had a higher propensity for cold beverages intake and unusual water-seeking behaviors compared to those without DI. Baseline WDT also revealed higher serum sodium (Na) and osmolality.

Conclusion: The incidence of CDI in children presenting with polydipsia and polyuria is low. Factors associated with higher likelihood of pathology include older age, propensity for cold beverage intake, and higher baseline serum Na and osmolality on a WDT.

Abbreviations: BMI = body mass index CDI = central diabetes insipidus DI = diabetes insipidus Na = sodium WDT = water deprivation test.
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http://dx.doi.org/10.4158/EP161333.ORDOI Listing
December 2016

Varicocele: a dilemma in adolescent males.

Pediatr Endocrinol Rev 2014 Feb;11 Suppl 2:274-83

Varicoceles are the most common cause of infertility in men. Despite the high prevalence of varicoceles, only a small percentage of men with varicoceles have subfertility or infertility. In adolescents, the prevalence of varicoceles increases dramatically during puberty to reach adult prevalence rates. The development of varicoceles during puberty can impair testicular growth and function. Data on hormonal and semen parameters in adolescents with varicoceles are limited, making it harder to determine which varicoceles are associated with infertility and which may benefit from surgery. The main indications for varicocelectomy in adolescents with varicoceles include a volume differential between unaffected and affected testes or abnormality in semen analysis.
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February 2014

Hyperinsulinemia promotes metastasis to the lung in a mouse model of Her2-mediated breast cancer.

Endocr Relat Cancer 2013 Jun 21;20(3):391-401. Epub 2013 May 21.

Division of Endocrinology, Diabetes and Bone Diseases, The Samuel Bronfman Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.

The Her2 oncogene is expressed in ∼25% of human breast cancers and is associated with metastatic progression and poor outcome. Epidemiological studies report that breast cancer incidence and mortality rates are higher in women with type 2 diabetes. Here, we use a mouse model of Her2-mediated breast cancer on a background of hyperinsulinemia to determine how elevated circulating insulin levels affect Her2-mediated primary tumor growth and lung metastasis. Hyperinsulinemic (MKR(+/+)) mice were crossed with doxycycline-inducible Neu-NT (MTB/TAN) mice to produce the MTB/TAN/MKR(+/+) mouse model. Both MTB/TAN and MTB/TAN/MKR(+/+) mice were administered doxycycline in drinking water to induce Neu-NT mammary tumor formation. In tumor tissues removed at 2, 4, and 6 weeks of Neu-NT overexpression, we observed increased tumor mass and higher phosphorylation of the insulin receptor/IGF1 receptor, suggesting that activation of these receptors in conditions of hyperinsulinemia could contribute to the increased growth of mammary tumors. After 12 weeks on doxycycline, although no further increase in tumor weight was observed in MTB/TAN/MKR(+/+) compared with MTB/TAN mice, the number of lung metastases was significantly higher in MTB/TAN/MKR(+/+) mice compared with controls (MTB/TAN/MKR(+/+) 16.41±4.18 vs MTB/TAN 5.36±2.72). In tumors at the 6-week time point, we observed an increase in vimentin, a cytoskeletal protein and marker of mesenchymal cells, associated with epithelial-to-mesenchymal transition and cancer-associated fibroblasts. We conclude that hyperinsulinemia in MTB/TAN/MKR(+/+) mice resulted in larger primary tumors, with more mesenchymal cells and therefore more aggressive tumors with more numerous pulmonary metastases.
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http://dx.doi.org/10.1530/ERC-12-0333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4093836PMC
June 2013

Hypothalamic obesity syndrome: rare presentation of CNS+ B-cell lymphoblastic lymphoma.

Pediatr Blood Cancer 2012 Nov 27;59(5):930-3. Epub 2011 Dec 27.

Section of Pediatric Hematology/Oncology, Riley Hospital for Children, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Hypothalamic obesity syndrome can affect brain tumor patients following surgical intervention and irradiation. This syndrome is rare at diagnosis in childhood cancer, but has been reported with relapse of acute lymphoblastic leukemia. Here we present a case of hypothalamic obesity syndrome as the primary presentation of a toddler found to have CNS+ B-cell lymphoblastic lymphoma. Cytogenetic studies on diagnostic cerebrospinal fluid revealed MLL gene rearrangement (11q23). Hyperphagia and obesity dramatically improved following induction and consolidation chemotherapy. We describe a novel presentation of hypothalamic obesity syndrome in CNS B-cell lymphoblastic lymphoma, responsive to chemotherapy.
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http://dx.doi.org/10.1002/pbc.24058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020003PMC
November 2012

A phase II study of lipoplatin (liposomal cisplatin)/vinorelbine combination in HER-2/neu-negative metastatic breast cancer.

Clin Breast Cancer 2011 Dec 10;11(6):384-9. Epub 2011 Oct 10.

Hammoud Hospital University Medical Center, Saida, Lebanon.

Unlabelled: We assessed the efficacy and safety of a liposomal cisplatin (lipoplatin) and vinorelbine combination in metastatic breast cancer (MBC). Thirty-five patients were treated. The objective response rate was 53.1% and the median survival time was 22 months. Grade 3/4 neutropenia was observed in 44% of cycles, and febrile neutropenia was seen in 4 patients (11.4%). No grade 3/4 nephrotoxicity or neuropathy was noted. This combination is effective and well tolerated in patients with MBC and it warrants investigation as first-line treatment.

Background: Liposomal cisplatin (lipoplatin) has a mechanism of action similar to that of cisplatin, with reduced toxicities and enhanced or similar efficacy. We wanted to assess the efficacy and safety of a lipoplatin/vinorelbine combination in a phase II clinical trial in metastatic breast cancer (MBC).

Methods: Thirty-five patients with HER-2/neu-negative (HER-2/neu(-)) MBC were enrolled. Lipoplatin 120 mg/m(2) (days 1, 8, and 15) and vinorelbine 30 mg/m(2) (days 1 and 8) were administered in a 21-day cycle.

Results: Thirty-five patients were included in the intent-to-treat (ITT) analysis; 32 patients were evaluable for response. The objective response rate was 53.1%. Complete response (CR) was achieved in 3 patients (9.4%), partial response (PR) was seen in 14 patients (43.8%), stable disease (SD) was obtained in 12 patients (37.5%), and progressive disease (PD) was seen in 3 patients (9.4%). Median time to disease progression was 8 months (range 6-10 months). After a median follow-up of 15.5 months, 18 patients were still alive; the median survival time was 22 months (95% confidence interval [CI], 14-30). A total of 174 cycles were administered. Neutropenia was the most frequent hematologic toxicity, with grade 3/4 neutropenia observed in 44% of cycles. Febrile neutropenia was observed in 4 patients (11.4%). No grade 3/4 nephrotoxicity or neuropathy was noted. Grade 1/2 nephrotoxicity occurred in 8 patients (22.9%) and grade 3 vomiting was seen in 3 patients (8.6%).

Conclusions: The results of this trial reveal that vinorelbine/lipoplatin is effective in treating patients with MBC. This regimen is well tolerated with no grade 3/4 nephrotoxicity or neuropathy. The investigation of this regimen as first-line treatment in MBC is warranted.
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http://dx.doi.org/10.1016/j.clbc.2011.08.005DOI Listing
December 2011

Age-dependent retinal iron accumulation and degeneration in hepcidin knockout mice.

Invest Ophthalmol Vis Sci 2011 Jan 5;52(1):109-18. Epub 2011 Jan 5.

University of Pennsylvania, Philadelphia, PA, USA.

Purpose: Iron dysregulation can cause retinal disease, yet retinal iron regulatory mechanisms are incompletely understood. The peptide hormone hepcidin (Hepc) limits iron uptake from the intestine by triggering degradation of the iron transporter ferroportin (Fpn). Given that Hepc is expressed in the retina and Fpn is expressed in cells constituting the blood-retinal barrier, the authors tested whether the retina may produce Hepc to limit retinal iron import.

Methods: Retinas of Hepc(-/-) mice were analyzed by histology, autofluorescence spectral analysis, atomic absorption spectrophotometry, Perls' iron stain, and immunofluorescence to assess iron-handling proteins. Retinal Hepc mRNA was evaluated through qPCR after intravitreal iron injection. Mechanisms of retinal Hepc upregulation were tested by Western blot analysis. A retinal capillary endothelial cell culture system was used to assess the effect of exogenous Hepc on Fpn.

Results: Hepc(-/-) mice experienced age-dependent increases in retinal iron followed by retinal degeneration with autofluorescent RPE, photoreceptor death, and subretinal neovascularization. Hepc(-/-) mice had increased Fpn immunoreactivity in vascular endothelial cells. Conversely, in cultured retinal capillary endothelial cells, exogenous Hepc decreased both Fpn levels and iron transport. The retina can sense increased iron levels, upregulating Hepc after phosphorylation of extracellular signal regulated kinases.

Conclusions: These findings indicate that Hepc is essential for retinal iron regulation. In the absence of Hepc, retinal degeneration occurs. Increases in Hepc mRNA levels after intravitreal iron injection combined with Hepc-mediated decreases in iron export from cultured retinal capillary endothelial cells suggest that the retina may use Hepc for its tissue-specific iron regulation.
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http://dx.doi.org/10.1167/iovs.10-6113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053271PMC
January 2011

Budd-Chiari syndrome and heparin-induced thrombocytopenia in polycythemia vera: successful treatment with repeated TIPS and interferon alpha.

J Cancer Res Ther 2009 Oct-Dec;5(4):305-8

Department of Oncology, Rizk Hospital, Beirut, Lebanon.

Polycythemia vera (PV) is a common cause of Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT). The postpartum period is a precipitating cofactor. An additional heparin-induced thrombocytopenia/thrombosis (HIT/T) leads to a life-threatening condition in which transjugular intrahepatic portosystemic shunting (TIPS) seems to be the only life-saving procedure. We describe the case of a subacute BCS and PVT in the late postpartum period. The diagnosis was established using CT scan, MRI, and Doppler ultrasonography of abdominal vessels and the laboratory findings were compatible with PV. After a successful creation of TIPS, a HIT/T worsened the hemorrhagic and thrombotic picture. TIPS procedure was successfully repeated and heparin was replaced with Fondaparinux and then vitamin K antagonist. The treatment with interferon alpha-2A, started after the normalization of liver functions, resulted in a complete remission within 6 months. The JAK2 V617F mutation clone remained undetectable after 2 years' follow-up.
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http://dx.doi.org/10.4103/0973-1482.59917DOI Listing
May 2010

Ceruloplasmin/hephaestin knockout mice model morphologic and molecular features of AMD.

Invest Ophthalmol Vis Sci 2008 Jun 7;49(6):2728-36. Epub 2008 Mar 7.

FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Purpose: Iron is an essential element in human metabolism but also is a potent generator of oxidative damage with levels that increase with age. Several studies suggest that iron accumulation may be a factor in age-related macular degeneration (AMD). In prior studies, both iron overload and features of AMD were identified in mice deficient in the ferroxidase ceruloplasmin (Cp) and its homologue hephaestin (Heph) (double knockout, DKO). In this study, the location and timing of iron accumulation, the rate and reproducibility of retinal degeneration, and the roles of oxidative stress and complement activation were determined.

Methods: Morphologic analysis and histochemical iron detection by Perls' staining was performed on retina sections from DKO and control mice. Immunofluorescence and immunohistochemistry were performed with antibodies detecting activated complement factor C3, transferrin receptor, L-ferritin, and macrophages. Tissue iron levels were measured by atomic absorption spectrophotometry. Isoprostane F2alpha-VI, a specific marker of oxidative stress, was quantified in the tissue by gas chromatography/mass spectrometry.

Results: DKOs exhibited highly reproducible age-dependent iron overload, which plateaued at 6 months of age, with subsequent progressive retinal degeneration continuing to at least 12 months. The degeneration shared some features of AMD, including RPE hypertrophy and hyperplasia, photoreceptor degeneration, subretinal neovascularization, RPE lipofuscin accumulation, oxidative stress, and complement activation.

Conclusions: DKOs have age-dependent iron accumulation followed by retinal degeneration modeling some of the morphologic and molecular features of AMD. Therefore, these mice are a good platform on which to test therapeutic agents for AMD, such as antioxidants, iron chelators, and antiangiogenic agents.
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http://dx.doi.org/10.1167/iovs.07-1472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569891PMC
June 2008

Three novel missense mutations within the LHX4 gene are associated with variable pituitary hormone deficiencies.

J Clin Endocrinol Metab 2008 Mar 11;93(3):1062-71. Epub 2007 Dec 11.

University Children's Hospital, Leipzig, Germany.

Context: The LHX4 LIM-homeodomain transcription factor has essential roles in pituitary gland and nervous system development. Heterozygous mutations in LHX4 are associated with combined pituitary hormone deficiency.

Objectives: Our objectives were to determine the nature and frequency of LHX4 mutations in patients with pituitary hormone deficiency and to examine the functional outcomes of observed mutations.

Design: The LHX4 gene sequence was determined from patient DNA. The biochemical and gene regulatory properties of aberrant LHX4 proteins were characterized using structural predictions, pituitary gene transcription assays, and DNA binding experiments.

Patients: A total of 253 patients from 245 pedigrees with GH deficiency and deficiency of at least one additional pituitary hormone was included in the study.

Results: In five patients, three types of heterozygous missense mutations in LHX4 that result in substitution of conserved amino acids were identified. One substitution is between the LIM domains (R84C); the others are in the homeodomain (L190R; A210P). The patients have GH deficiency; some also display reductions in TSH, LH, FSH, or ACTH, and aberrant pituitary morphology. Structural models predict that the aberrant L190R and A210P LHX4 proteins would have impaired DNA binding and gene activation properties. Consistent with these models, EMSAs and transfection experiments using pituitary gene promoters demonstrate that whereas the R84C form has reduced activity, the L190R and A210P proteins are inactive.

Conclusions: LHX4 mutations are a relatively rare cause of combined pituitary hormone deficiency. This report extends the range of phenotypes associated with LHX4 gene mutations and describes three novel exonic mutations in the gene.
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http://dx.doi.org/10.1210/jc.2007-1525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2266965PMC
March 2008

An update on the treatment of precocious puberty in McCune-Albright syndrome and testotoxicosis.

J Pediatr Endocrinol Metab 2007 Jun;20(6):653-61

Department of Pediatrics, Section of Endocrinology and Diabetology, Indiana University School of Medicine, Indianapolis, IN, USA.

McCune-Albright syndrome and testotoxicosis are rare forms of peripheral precocious puberty. Our understanding of the pathophysiology and mechanism of these diseases has significantly increased following identification of their underlying molecular etiology. However, their treatment remains challenging. We provide a review of the various treatment modalities used in both conditions with an update on recent trials using novel and promising pharmacological agents.
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http://dx.doi.org/10.1515/jpem.2007.20.6.653DOI Listing
June 2007

Hypopituitarism and neurodevelopmental abnormalities in relation to central nervous system structural defects in children with optic nerve hypoplasia.

J Pediatr Endocrinol Metab 2005 Sep;18(9):853-8

Department of Pediatrics, Section of Endocrinology and Diabetology, Indiana University School of Medicine, Indianapolis, IN, USA.

Objective: Optic nerve hypoplasia (ONH) is a heterogeneous disease with variable findings of pituitary insufficiency, CNS and neurodevelopmental abnormalities. We characterized the spectrum of endocrinopathy in a cohort of children with ONH and attempted to correlate the presence of different midline CNS findings with the degree of hypopituitarism. The correlation of variable CNS abnormalities with the presence of a seizure disorder and neurodevelopmental delay was also examined.

Methods: Charts of 56 patients with ONH referred to our endocrine clinics between 1990 and 2000 were reviewed. Neurodevelopmental assessment was based on questionnaires sent to families during the study period.

Results: Forty-six patients (82%) had hypopituitarism, with growth hormone deficiency being the most common endocrinopathy. All patients with diabetes insipidus, hypocortisolism, and hypogonadotropin hypogonadism also had combined pituitary hormone deficiency. Evolving pituitary hormone deficiency was observed in two of 37 patients diagnosed with hypopituitarism in the first 3 years of life. No single midline CNS finding correlated with the presence of hypopituitarism or a seizure disorder. However, hydrocephalus or a seizure disorder was more commonly seen in patients with developmental delay.

Conclusion: ONH is a heterogeneous disorder with possible multifactorial etiologies. All patients with this diagnosis deserve a comprehensive endocrine and neurodevelopmental evaluation.
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http://dx.doi.org/10.1515/jpem.2005.18.9.853DOI Listing
September 2005

Infancy-onset cystic fibrosis-related diabetes.

Diabetes Care 2005 Oct;28(10):2593-4

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http://dx.doi.org/10.2337/diacare.28.10.2593DOI Listing
October 2005

Pancreatic enzyme elevations in children with diabetic ketoacidosis.

J Pediatr 2004 Jul;145(1):122-4

Department of Pediatrics, Section of Endocrinology and Diabetology, Indiana University School of Medicine, Indianapolis, 46202, USA.

The incidence of pancreatic enzyme elevations in children with diabetic ketoacidosis (DKA) compared with children with newly diagnosed diabetes without DKA was assessed in a prospective study. Pancreatic enzyme elevations, particularly hyperlipasemia, are common but not associated with significant symptomatology. Acute pancreatitis was diagnosed in 2% of children with DKA.
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http://dx.doi.org/10.1016/j.jpeds.2004.03.050DOI Listing
July 2004

Turner syndrome (45x) with clitoromegaly.

J Urol 2003 Oct;170(4 Pt 1):1355-6

Department of Pediatrics, Section of Endocrinology and Diabetology, Indiana University School of Medicine, Indianapolis, USA.

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http://dx.doi.org/10.1097/01.ju.0000085983.81063.3fDOI Listing
October 2003

Seminoma and a gonadoblastoma in an infant with mixed gonadal dysgenesis.

J Pediatr 2003 Jul;143(1):136

Department of Pediatrics, Indiana University School of Medicine, Indianapolis, USA.

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http://dx.doi.org/10.1016/S0022-3476(03)00132-XDOI Listing
July 2003