43 results on '"Bakalov VK"'
Search Results
2. Low- versus high-baseline epinephrine output shapes opposite innate cytokine profiles: presence of Lewis- and Fischer-like neurohormonal immune phenotypes in humans?
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ELENKOV IJ, KVETNANSKY R, HASHIRAMOTO A, BAKALOV VK, LINK AA, ZACHMAN K, CRANE M, JEZOVA D, ROVENSKY J, DIMITROV MA, GOLD PW, FLEISHER T, CHROUSOS GP, WILDER RL, J. I.M.M.U.N.O.L. AUG, BONINI, Sergio, Elenkov, Ij, Kvetnansky, R, Hashiramoto, A, Bakalov, Vk, Link, Aa, Zachman, K, Crane, M, Jezova, D, Rovensky, J, Dimitrov, Ma, Gold, Pw, Bonini, Sergio, Fleisher, T, Chrousos, Gp, Wilder, Rl, and Aug, J. I. M. M. U. N. O. L.
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- 2008
3. Analysis of auditory phenotype and karyotype in 200 females with Turner syndrome.
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King KA, Makishima T, Zalewski CK, Bakalov VK, Griffith AJ, Bondy CA, and Brewer CC
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- 2007
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4. Uterine development in Turner syndrome.
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Bakalov VK, Shawker T, Ceniceros I, Bondy CA, Bakalov, Vladimir K, Shawker, Thomas, Ceniceros, Irene, and Bondy, Carolyn A
- Abstract
Objective: To evaluate uterine development of women with Turner syndrome (TS) receiving conventional medical care.Study Design: In a cross-sectional study we used ultrasonography for uterine evaluation in 86 women with TS 18 to 45 years of age participating in an intramural NIH study, and who had abnormal karyotypes in >70% of white blood cells. Outcomes were uterine dimensions and shape. Information on hormone treatment was obtained by personal interview.Results: Twenty-five percent had a mature in size and shape uterus, and 31% had an immature uterus, with the remainder in a transitional category. Twenty percent of all participants were not taking hormone replacement therapy (HRT) in the preceding year. The majority on treatment were taking conjugated estrogens (CE) or oral contraceptives (OC). Factors associated with uterine maturity were history of spontaneous puberty and duration and type of HRT, with estradiol-based treatment being the most effective. The age at starting HRT was not a critical factor.Conclusions: Women with TS may develop a normal uterus even at a late start of HRT given adequate duration of treatment and regardless of karyotype. [ABSTRACT FROM AUTHOR]- Published
- 2007
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5. Effects of ovarian failure and X-chromosome deletion on body composition and insulin sensitivity in young women.
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Corrigan EC, Nelson LM, Bakalov VK, Yanovski JA, Vanderhoof VH, Yanoff LB, Bondy CA, Corrigan, Emily C, Nelson, Lawrence M, Bakalov, Vladimir K, Yanovski, Jack A, Vanderhoof, Vien H, Yanoff, Lisa B, and Bondy, Carolyn A
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- 2006
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6. Prolongation of the cardiac QTc interval in Turner syndrome.
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Bondy CA, Van PL, Bakalov VK, Sachdev V, Malone CA, Ho VB, Rosing DR, Bondy, Carolyn A, Van, Phillip L, Bakalov, Vladimir K, Sachdev, Vandana, Malone, Carol A, Ho, Vincent B, and Rosing, Douglas R
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- 2006
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7. Major vascular anomalies in Turner syndrome: prevalence and magnetic resonance angiographic features.
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Ho VB, Bakalov VK, Cooley M, Van PL, Hood MN, Burklow TR, and Bondy CA
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- 2004
8. Genetic vs hormonal factors in lipid metabolism in women.
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Taylor HS, Bondy CA, Bakalov VK, and Taylor, Hugh S
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- 2004
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9. Prolonged rate-corrected QT interval and other electrocardiogram abnormalities in girls with Turner syndrome.
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Bondy CA, Ceniceros I, Van PL, Bakalov VK, and Rosing DR
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- 2006
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10. Declining estrogen in young women with turner syndrome.
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Bondy CA, Ceniceros I, Lange E, and Bakalov VK
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- 2006
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11. X chromosome parental origin and aortic stiffness in turner syndrome.
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Abd-Elmoniem KZ, Bakalov VK, Matta JR, Muldoon N, Hanover JA, Bondy CA, and Gharib AM
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- Adult, Cross-Sectional Studies, Female, Humans, Middle Aged, Vascular Stiffness genetics, Vascular Stiffness physiology, Chromosomes, Human, X genetics, Turner Syndrome genetics, Turner Syndrome physiopathology
- Abstract
Introduction: Aortic abnormalities contribute to increased morbidity and mortality of women with Turner syndrome (TS). Impaired aortic stiffness may prove to have clinical prognostic value in TS as is the case in other diseases such as Marfan syndrome, diabetes and hypertension. Additionally, the parental origin of the X chromosome in TS may influence aortic stiffness., Objective: To assess the relation between X chromosome parental origin and aortic stiffness in TS patients., Methods: Twenty-four subjects with TS participated in this cross-sectional study at a tertiary care centre. The parental origin of the X chromosome was determined. Cardiac-gated multidetector computerized tomography (MDCT) was performed and distensibility of the ascending aorta (AA), a measure of aortic stiffness, was calculated., Results: Fourteen women were Xm (maternal origin) and 10 were Xp (paternal origin) for their inheritance of the single X chromosome. Age, body size, blood pressure and AA areas were similar in the two groups. However, the calculated AA distensibility was significantly lower in the Xm group (2·8 ± 1·1 mm/Hg) than in the Xp group (4·1 ± 1·5 mm/Hg); P < 0·05. Conclusion This study demonstrates that TS subjects that inherit their single X chromosome from their mother (Xm) have a significantly stiffer aorta compared with the TS with a paternally originating X chromosome (Xp), consistent with a potentially greater risk for cardiovascular complications. These findings suggest that parental chromosomal analysis and aortic stiffness measurements would be useful for the risk assessment and clinical management of TS patients., (Published 2014. This article is a U.S. Government work and is in the public domain in the USA.)
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- 2014
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12. Bicuspid aortic valve and aortic coarctation are linked to deletion of the X chromosome short arm in Turner syndrome.
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Bondy C, Bakalov VK, Cheng C, Olivieri L, Rosing DR, and Arai AE
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- Bicuspid Aortic Valve Disease, Chromosome Breakpoints, Chromosomes, Human, Pair 14, Female, Heart Defects, Congenital diagnosis, Heart Defects, Congenital epidemiology, Heart Defects, Congenital etiology, Humans, Karyotype, Phenotype, Prevalence, Pulmonary Veins abnormalities, Translocation, Genetic, Turner Syndrome complications, Aortic Coarctation etiology, Aortic Valve abnormalities, Chromosome Deletion, Chromosomes, Human, X, Heart Valve Diseases etiology, Turner Syndrome genetics, Turner Syndrome pathology
- Abstract
Background: Congenital heart disease (CHD) is a cardinal feature of X chromosome monosomy, or Turner syndrome (TS). Haploinsufficiency for gene(s) located on Xp have been implicated in the short stature characteristic of the syndrome, but the chromosomal region related to the CHD phenotype has not been established., Design: We used cardiac MRI to diagnose cardiovascular abnormalities in four non-mosaic karyotype groups based on 50-metaphase analyses: 45,X (n=152); 46,X,del(Xp) (n=15); 46,X,del(Xq) (n=4); and 46,X,i(Xq) (n=14) from peripheral blood cells., Results: Bicuspid aortic valves (BAV) were found in 52/152 (34%) 45,X study subjects and aortic coarctation (COA) in 19/152 (12.5%). Isolated anomalous pulmonary veins (APV) were detected in 15/152 (10%) for the 45,X study group, and this defect was not correlated with the presence of BAV or COA. BAVs were present in 28.6% of subjects with Xp deletions and COA in 6.7%. APV were not found in subjects with Xp deletions. The most distal break associated with the BAV/COA trait was at cytologic band Xp11.4 and ChrX:41,500 000. One of 14 subjects (7%) with the 46,X,i(Xq) karyotype had a BAV and no cases of COA or APV were found in this group. No cardiovascular defects were found among four patients with Xq deletions., Conclusions: The high prevalence of BAV and COA in subjects missing only the X chromosome short arm indicates that haploinsufficiency for Xp genes contributes to abnormal aortic valve and aortic arch development in TS.
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- 2013
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13. Parity and aortic dimensions in healthy women.
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Gutin LS, Merz AE, Bakalov VK, Gharib AM, and Bondy CA
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- Adult, Aorta anatomy & histology, Aorta, Thoracic anatomy & histology, Cross-Sectional Studies, Female, Humans, Middle Aged, Pregnancy, Aorta physiology, Aorta, Thoracic physiology, Parity physiology
- Published
- 2013
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14. High levels of education and employment among women with Turner syndrome.
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Gould HN, Bakalov VK, Tankersley C, and Bondy CA
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- Adult, Aged, Cross-Sectional Studies, Educational Status, Employment, Female, Humans, Middle Aged, United States, Turner Syndrome epidemiology
- Abstract
Background: Turner Syndrome (TS) is due to X chromosome monosomy and affects ~1 per 2500 females at birth. The major features are short stature and primary ovarian failure. Short stature and monosomy for a maternal X chromosome have been implicated in impaired functionality in adult life; however, data on adult outcomes in TS are limited. In this study we evaluated the influence of adult height and parental origin of the single X chromosome on education, employment, and marital outcomes among women with TS., Methods: This was a cross-sectional study of 240 women (25-67 years old) with TS participating in an intramural National Institutes of Health (NIH) study. Parental origin of the single X chromosome was determined by genotyping proband and parental genomic DNA. Information on education, employment, and family status was self reported. Normative data was obtained from the U.S. Bureaus of Census and Labor and Statistics., Results: Seventy percent of the TS group had a baccalaureate degree or higher, compared with 30% of U.S. women (p<0.0001). Eighty percent of the TS group was employed compared with 70% of the U.S. female population. Approximately 50% of the TS group had ever married, compared with 78% of the general female population (p<0.0001). Height and parental origin of the single normal X chromosome had no association with education, employment, or marital status., Conclusion: Women with TS currently achieve education and employment levels higher than the female U.S. population but are less likely to marry. Neither adult height nor parental origin of the single X chromosome influenced outcomes in education, employment, or marriage.
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- 2013
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15. Perturbation of the transforming growth factor β system in Turner syndrome.
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Zhou J, Arepalli S, Cheng CM, Bakalov VK, and Bondy CA
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- Adult, Antigens, CD blood, Endoglin, Enzyme-Linked Immunosorbent Assay, Female, Humans, Receptors, Cell Surface blood, Transforming Growth Factor beta1 blood, Transforming Growth Factor beta2 blood, Turner Syndrome blood
- Abstract
Objective: To measure components of the circulating transforming growth factor β (TGFβ) system in patients with Turner syndrome (TS) compared to relevant controls and to ascertain correlation with endocrine and cardiovascular parameters., Methods: TGFβ1, TGFβ2 and endoglin (a vascular TGF receptor component) were measured using enzyme-linked immunoassays in the sera of 40 subjects with TS and 40 healthy volunteer women. The cardiovascular phenotype in TS subjects was extensively characterized by cardiac magnetic resonance (MR) and echo., Results: TGFβ1 levels were about 3-fold higher in TS while TGFβ2 levels were about 3.5-fold higher in controls (P<0.000 1 for both). Soluble endoglin levels were 25% higher in TS (P<0.000 1). Variation in TGFβ system components was not explained by age, blood pressure, platelet count, thyroid function, body proportions or cardiovascular phenotype., Conclusion: There is profound perturbation of the TGFβ system evident in the circulation of individuals with TS.
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- 2012
16. N-terminal pro-brain natriuretic peptide levels and aortic diameters.
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Gutin LS, Bakalov VK, Rosing DR, Arai AE, Gharib AM, and Bondy CA
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- Adolescent, Adult, Aged, Case-Control Studies, Cohort Studies, Female, Humans, Magnetic Resonance Imaging, Middle Aged, Turner Syndrome pathology, Young Adult, Aorta pathology, Natriuretic Peptide, Brain blood, Peptide Fragments blood, Turner Syndrome blood
- Abstract
Background: Women with X-chromosome monosomy or Turner syndrome (TS) are at increased risk for aortic dilation and dissection. To better understand the pathology and develop tools to monitor the risk of aortic disease, we investigated N-terminal pro-brain natriuretic peptide (BNP) (NT-proBNP) levels in women with TS and healthy female controls., Methods: We evaluated NT-proBNP levels in women with karyotype-proven TS and healthy female volunteers in relation to ascending aortic diameter and descending aortic diameter measured by cardiovascular magnetic resonance imaging., Results: The NT-proBNP levels were strongly and positively correlated with ascending aortic diameter and descending aortic diameter in both cohorts. The TS group (n = 114, age 37.4 ± 12 yr) had greater body surface area-indexed aortic diameters and higher NT-proBNP levels than the control group (n = 27, age 46.4 ± 11 years): 88.3 ± 62.7 versus 53.5 ± 35 pg/mL, P = .0003. Within the TS group, NT-proBNP levels were higher in those with dilated ascending aorta (n = 42, 112.4 ± 75.7 pg/mL) compared with those with normal aortic dimensions (n = 72, 74.2 ± 49 pg/mL, P = .0014). Abnormally high NT-pro BNP levels were seen in 3 of 4 TS women who presented with previously undetected aortic aneurysm and/or dissection., Conclusions: The NT-proBNP levels are positively associated with aortic diameters in women with and without TS, suggesting a role for BNP in arterial wall homeostasis. Further study is necessary to determine whether NT-proBNP measurement may be used to monitor aortic diameter and/or detect aortic pathology in individuals at risk for aortic disease., (Published by Mosby, Inc.)
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- 2012
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17. Autoimmune disorders in women with turner syndrome and women with karyotypically normal primary ovarian insufficiency.
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Bakalov VK, Gutin L, Cheng CM, Zhou J, Sheth P, Shah K, Arepalli S, Vanderhoof V, Nelson LM, and Bondy CA
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- Adolescent, Adult, Aged, Cytokines immunology, Cytokines metabolism, Estrogens immunology, Estrogens metabolism, Female, Hashimoto Disease epidemiology, Hashimoto Disease etiology, Humans, Inflammatory Bowel Diseases epidemiology, Inflammatory Bowel Diseases etiology, Middle Aged, Pregnancy, Prevalence, Primary Ovarian Insufficiency genetics, Primary Ovarian Insufficiency immunology, Risk Factors, Smoking, Turner Syndrome genetics, Turner Syndrome immunology, Young Adult, Autoimmune Diseases epidemiology, Autoimmune Diseases etiology, Primary Ovarian Insufficiency complications, Turner Syndrome complications
- Abstract
The higher prevalence of autoimmune diseases in women compared to men could be due to effects of ovarian hormones, pregnancy and/or the presence of a second X chromosome. To elucidate the role of these factors, we investigated the prevalence and spectrum of autoimmune diagnoses in women with primary ovarian insufficiency associated with X chromosome monosomy (Turner syndrome, TS, n = 244) and women with karyotypically normal (46,XX) primary ovarian insufficiency (POI, n = 457) in a prospective study, conducted at the National Institutes of Health. We compared the study group prevalence to normative data for the U.S. population of women. Chronic lymphocytic (Hashimoto's) thyroiditis (HT) occurred in 37% of women with TS vs. 15% with POI (P < 0.0001); HT prevalence in both ovarian insufficiency groups significantly exceeded that in U.S. population of women (5.8%). Inflammatory bowel (IBD, 4%) and celiac disease (CD, 2.7%) were significantly increased in TS, but not in POI. No other autoimmune diagnosis, including Graves' disease or Type 1 diabetes appears to be significantly increased in either group. Women with TS had higher pro-inflammatory IL6 and TGF β1 levels (p < 0.0001 for both), and lower anti-inflammatory IL10 and TGF β2 levels (p < 0.005 for both) compared to POI and to normal volunteers. Lifetime estrogen exposure and parity were significantly lower in TS compared to POI, which were in turn lower than the general population of women. The finding that lymphocytic thyroiditis is greatly increased in both women with TS and POI suggests that factors associated with ovarian insufficiency per se promote this form of autoimmunity. The absence of a normal second X-chromosome further contributes to increased autoimmunity in TS., (Published by Elsevier Ltd.)
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- 2012
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18. Trends in GH use in a Turner syndrome natural history study.
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Gutin L, Collier S, Bakalov VK, and Bondy C
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- Abdominal Fat, Adolescent, Adult, Child, Female, Humans, Retrospective Studies, Body Height drug effects, Drug Therapy trends, Growth Hormone therapeutic use, Turner Syndrome drug therapy
- Abstract
The present observations are derived from 273 girls and women aged 7-40 years participating in the National Institutes of Health natural history study of Turner syndrome (TS) in the interval 2001-2011. There was a higher percentage of GH use among individuals in the pediatric age group (7-17, n = 118, 83%) compared to young adult women with prior GH use (18-40, n = 155, 61%). The major factor in this divergence seems to be a trend toward earlier diagnosis of TS in the younger age group. We find a striking association between history of GH use and lower total body and abdominal fat mass in young adults with TS approximately one decade after discontinuation of GH treatment. The interpretation of this observation is limited by the fact that our study subjects were not randomly assigned to GH treatment. There may be a bias involving poor health care, childhood obesity, delayed diagnosis, absent GH treatment and persistent adult obesity. Further studies on the socioeconomic factors implicated in patterns of GH use and non-use for girls with TS are needed to illuminate this important issue.
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- 2012
19. Otolaryngologic markers for the early diagnosis of Turner syndrome.
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Makishima T, King K, Brewer CC, Zalewski CK, Butman J, Bakalov VK, Bondy C, and Griffith AJ
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- Adolescent, Adult, Child, Early Diagnosis, Female, Humans, Middle Aged, Mouth Diseases congenital, Palate abnormalities, Prospective Studies, Turner Syndrome complications, Turner Syndrome genetics, Young Adult, Hearing Loss genetics, Mouth Diseases genetics, Otitis Media genetics, Turner Syndrome diagnosis
- Abstract
Objective: To identify and characterize otolaryngologic markers for the early diagnosis of Turner syndrome (TS)., Study Design: Prospective cohort survey., Setting: Clinical Center of the National Institutes of Health (NIH)., Patients: Ninety-one females, 7-61 years old (average=28.7 y), enrolled in a multidisciplinary study of karyotype-phenotype correlations in TS., Main Outcome Measures: Age at diagnosis, X chromosome karyotype, history of chronic or recurrent otitis media (OM), sensorineural hearing loss (SNHL), palate dysmorphism, pinna deformity, pterygium colli, low posterior hairline, low-set ears, and micrognathia., Results: Sixty-nine (76%) patients had a history of chronic or recurrent OM, 62 (68%) had a dysmorphic palate, 57 (63%) had SNHL, and 90 (99%) had one or more of these findings. 83 (91%; average age at diagnosis=9.4 y) had one or more external craniofacial signs: pinna abnormalities, pterygium colli, low-set ears, micrognathia or a low posterior hairline. Eight patients (average age at diagnosis=13.2 y) had no external craniofacial signs, although seven (88%) of these eight patients had a history of chronic or recurrent OM, dysmorphic palate or SNHL. The age at diagnosis was not significantly different between groups with or without external craniofacial signs (P=0.126)., Conclusions: PATIENTS with mild or incompletely penetrant TS phenotypes often present with otitis media, hearing loss, or both before the diagnosis of TS is established. Palatal dysmorphism, including ogival morphology, is another otolaryngologic marker for TS. Prompt recognition of these manifestations of TS could hasten its diagnosis and appropriate medical care.
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- 2009
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20. X-chromosome gene dosage and the risk of diabetes in Turner syndrome.
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Bakalov VK, Cheng C, Zhou J, and Bondy CA
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- Adult, Aged, Autoimmunity, Diabetes Mellitus epidemiology, Female, Gene Expression Profiling, Glucose metabolism, Glucose Intolerance epidemiology, Humans, Middle Aged, Prevalence, Risk, Turner Syndrome complications, Turner Syndrome metabolism, Diabetes Mellitus etiology, Gene Dosage, Genes, X-Linked, Turner Syndrome genetics
- Abstract
Background: Turner syndrome (TS) is caused by the absence or fragmentation of the second sex chromosome. An increased risk of diabetes mellitus (DM) has consistently been noted, but the specific phenotype and genetic etiology of this trait are unknown., Methods: In a prospective study, we examined the prevalence of DM in adult participants in an intramural National Institutes of Health (NIH) TS study. Results were analyzed with respect to karyotype, age, body mass index (BMI), and autoimmune indices. Insulin sensitivity and secretion were compared in age- and BMI-matched euglycemic women with TS and healthy female controls. We compared gene expression profiles in lymphocytes from differentially affected TS groups., Results: Type 2 DM was present in 56 of 224 (25%) of the women with TS; type 1 DM was found in only one woman (<0.5%). DM was more prevalent among women with an isoXq chromosome compared to X monosomy (40.0 vs. 17.3%; P = 0.004). Euglycemic women with TS (n = 72; age, 33 +/- 12 yr; BMI, 23 +/- 3 kg/m(2)) had significantly higher glycemic and lower insulin responses to OGTT, with insulin sensitivity similar to controls. Gene expression profiles comparing 46,X,i(X)q vs. 45,X groups showed a significant increase in Xq transcripts and in potentially diabetogenic autosomal transcripts in the isoXq group., Conclusion: Type 2 DM associated with deficient insulin release is significantly increased among women with monosomy for the X-chromosome but is increased even more among women with monosomy for Xp coupled with trisomy for Xq. These data suggest that haploinsufficiency for unknown Xp genes increases risk for DM and that excess dosage of Xq genes compounds the risk.
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- 2009
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21. Reduced abdominal adiposity and improved glucose tolerance in growth hormone-treated girls with Turner syndrome.
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Wooten N, Bakalov VK, Hill S, and Bondy CA
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- Abdominal Fat pathology, Adolescent, Adult, Child, Female, Follow-Up Studies, Glucose Intolerance drug therapy, Glucose Tolerance Test, Human Growth Hormone pharmacology, Humans, Insulin Resistance, Puberty drug effects, Retrospective Studies, Turner Syndrome pathology, Abdominal Fat drug effects, Adiposity drug effects, Blood Glucose metabolism, Human Growth Hormone therapeutic use, Turner Syndrome drug therapy
- Abstract
Background: Individuals with Turner syndrome (TS) are at increased risk for impaired glucose tolerance and diabetes mellitus. It is unknown whether pharmacological GH treatment commonly used to treat short stature in TS alters this risk., Objective: Our objective was to compare adiposity and glucose tolerance in GH-treated vs. untreated girls with TS., Methods: In a cross sectional study, GH-treated girls with TS (n = 76; age 13.6 +/- 3.7 yr) were compared to girls with TS that never received GH (n = 26; age 13.8 +/- 3.5 yr). Protocol studies took place in the NIH Clinical Research Center from 2001-2006 and included oral glucose tolerance tests, body composition analysis by dual-energy x-ray absorptiometry, and abdominal fat quantification by magnetic resonance imaging. GH was not given during testing., Results: Total body fat (35 +/- 8 vs. 28 +/- 8%, P < 0.0001), sc abdominal fat (183 vs. 100 ml, P = 0.001), and intraabdominal fat (50 vs. 33 ml, P < 0.0001) were significantly greater in untreated girls. Fasting glucose and insulin were similar, but the response to oral glucose was significantly impaired in the untreated group (28 vs. 7% with impaired glucose tolerance, P = 0.006). A specific excess of visceral fat and insulin resistance was apparent only in postpubertal girls that had never received GH. GH-treated girls demonstrated lower adiposity compared with untreated girls for an average of 2 yr after discontinuation of GH., Conclusions: Abdominal adiposity is significantly lower and glucose tolerance significantly better in GH-treated vs. untreated girls with TS, suggesting that beneficial effects upon body composition and regional fat deposition outweigh transient insulin antagonism associated with GH administration.
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- 2008
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22. Fracture risk and bone mineral density in Turner syndrome.
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Bakalov VK and Bondy CA
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- Fractures, Bone drug therapy, Fractures, Bone etiology, Hormone Replacement Therapy, Humans, Risk Factors, Turner Syndrome complications, Turner Syndrome drug therapy, Bone Density, Fractures, Bone metabolism, Turner Syndrome metabolism
- Abstract
Bone health is a major lifelong concern in caring for women and girls with Turner syndrome (TS). There is an approximately 25% increase in fracture risk most of which is related to medium or high impact trauma. The long bones, especially of the forearm are predominantly affected. This fact may be due to a selective cortical bone deficiency in TS which is unrelated to hypogonadism. In addition, lack of adequate estrogen replacement can lead to trabecular bone deficiency and increase in vertebral compression fractures after age 45. Evaluation of bone density by dual X-ray absorptiometry (DEXA) is important, however, it should be used judiciously in TS in view of its inherent tendency to underestimate the bone density of people with short stature. Bone size-independent methods, such as QCT or volumetric transformation of DEXA data should be used in individuals shorter than 150 cm. Achieving optimal bone density is of critical importance for fracture prevention in TS, and should be pursued by timely introduction of hormone replacement therapy, adequate dose of estrogens during the young adult life, optimal calcium and vitamin D intake and regular physical exercise. In addition, other measures to prevent fall and trauma should be considered, including optimizing hearing and vision, avoiding contact sports and exercise to improve coordination.
- Published
- 2008
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23. Growth hormone treatment and left ventricular dimensions in Turner syndrome.
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Matura LA, Sachdev V, Bakalov VK, Rosing DR, and Bondy CA
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- Adolescent, Adult, Body Surface Area, Child, Cross-Sectional Studies, Echocardiography, Doppler, Female, Heart Ventricles diagnostic imaging, Human Growth Hormone therapeutic use, Humans, Regression Analysis, Turner Syndrome physiopathology, Growth Hormone therapeutic use, Heart drug effects, Heart Ventricles drug effects, Human Growth Hormone pharmacology, Turner Syndrome diagnostic imaging, Turner Syndrome drug therapy
- Abstract
Objective: To determine whether cardiac dimensions were different in girls with Turner syndrome (TS) who received growth hormone (GH) compared with those who did not receive GH., Study Design: This retrospective, cross-sectional study analyzed echocardiograms in 86 females with TS divided into GH-treated (n = 67) and untreated (n = 19) groups. The subjects all participated in the National Institutes of Health protocol between 2001 and 2006., Results: The average age was 16.2 years (range, 10 to 25 years), and average duration of GH treatment was 4.4 years (range, 1 to 14 years). The GH-treated group was taller by approximately 7 cm (P = .004), but cardiac dimensions normalized to body surface area (BSA), including septal and posterior wall thickness and left ventricular (LV) mass and internal diameters, did not differ significantly between the 2 groups. The fractional shortening index was similar in the 2 groups. Multiple regression analyses indicated that BSA, but not duration of GH treatment, predicted LV dimensions in girls with TS., Conclusions: GH treatment of girls with TS increases stature but does not disproportionately affect cardiac dimensions.
- Published
- 2007
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24. The physical phenotype of girls and women with Turner syndrome is not X-imprinted.
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Bondy CA, Matura LA, Wooten N, Troendle J, Zinn AR, and Bakalov VK
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- Adolescent, Adult, Aged, Body Height genetics, Child, Female, Humans, Middle Aged, Phenotype, Chromosomes, Human, X, Genomic Imprinting, Turner Syndrome genetics
- Abstract
Certain behavioral and metabolic aspects of Turner syndrome (TS) are attributed to X-chromosome genomic imprinting. To investigate the possible contribution of imprinting to the physical features of the TS phenotype in live-born individuals, we genotyped the single normal X-chromosome in subjects with TS who all underwent a comprehensive evaluation as part of the NIH genotype-phenotype protocol. All had physical examinations, auxological measurements and imaging of the renal and cardiovascular systems. Absolute height and height as a percent of predicted height was the same in X(M) (n = 56) and X(P) (n = 23) subjects that had reached final height and were not growth hormone treated. Interestingly, adult height was significantly correlated with maternal but not paternal heights in both X(M) and X(P) groups. Neck webbing was found in 35% of the X(M) (n = 133) and 22% of the X(P) (n = 50) groups (P = 0.11). Renal anomalies were present in 24% of X(M) and 25% of X(P) groups (P = 0.9). Bicuspid aortic valve was found in 26% of X(M) and 24% of X(P) groups (P = 0.83), and any cardiovascular anomaly (abnormal aortic valve, aortic coarctation, elongated transverse aortic arch, anomalous pulmonary venous connection, left superior vena cava) affected 55% of X(M) and 52% of X(P) groups. Thus, we found no evidence for X-linked genomic imprinting effects on stature or lymphatic, renal or cardiovascular development in TS. Our sample size was sufficient to exclude such effects within 95% confidence limits. We did demonstrate a selective maternal effect on final stature that was independent of X-chromosome origin, suggesting potential autosomal imprinting effects on growth revealed by X monosomy.
- Published
- 2007
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25. Deficient medical care for adults with the Turner syndrome.
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Bondy C, Bakalov VK, Lange ED, and Ceniceros I
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- Adolescent, Adult, Audiometry statistics & numerical data, Cross-Sectional Studies, Echocardiography statistics & numerical data, Female, Humans, Kidney diagnostic imaging, Middle Aged, Retrospective Studies, Quality of Health Care, Turner Syndrome complications, Turner Syndrome diagnosis
- Published
- 2006
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26. The effects of growth hormone treatment on bone mineral density and body composition in girls with turner syndrome.
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Ari M, Bakalov VK, Hill S, and Bondy CA
- Subjects
- Adipose Tissue drug effects, Adolescent, Body Height drug effects, Bone Development drug effects, Bone and Bones diagnostic imaging, Bone and Bones drug effects, Child, Cross-Sectional Studies, Female, Humans, Muscles drug effects, Radiography, Body Composition drug effects, Bone Density drug effects, Human Growth Hormone pharmacology, Human Growth Hormone therapeutic use, Turner Syndrome drug therapy
- Abstract
Background: Many girls with Turner syndrome (TS) are treated with GH to increase adult height. In addition to promoting longitudinal bone growth, GH has effects on bone and body composition., Objective: The objective was to determine how GH treatment affects bone mineral density (BMD) and body composition in girls with TS., Method: In a cross-sectional study, we compared measures of body composition and BMD by dual energy x-ray absorptiometry, and phalangeal cortical thickness by hand radiography in 28 girls with TS who had never received GH and 39 girls who were treated with GH for at least 1 yr. All girls were participants in a National Institutes of Health (NIH) Clinical Research Center (CRC) protocol between 2001 and 2006., Results: The two groups were similar in age (12.3 yr, sd 2.9), bone age (11.5 yr, sd 2.6), and weight (42.8 kg, sd 16.6); but the GH-treated group was taller (134 vs. 137 cm, P = 0.001). The average duration of GH treatment was 4.2 (sd 3.2) yr (range 1-14 yr). After adjustment for size and bone age, there were no significant differences in BMD at L1-L4, 1/3 radius or cortical bone thickness measured at the second metacarpal. However, lean body mass percent was higher (P < 0.001), whereas body fat percent was lower (P < 0.001) in the GH-treated group. These effects were independent of estrogen exposure and were still apparent in girls that had finished GH treatment at least 1 yr previously., Conclusions: Although GH treatment has little effect on cortical or trabecular BMD in girls with TS, it is associated with increased lean body mass and reduced adiposity.
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- 2006
- Full Text
- View/download PDF
27. Testosterone deficiency in young women with 46,XX spontaneous premature ovarian failure.
- Author
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Kalantaridou SN, Calis KA, Vanderhoof VH, Bakalov VK, Corrigan EC, Troendle JF, and Nelson LM
- Subjects
- Cross-Sectional Studies, Female, Humans, Testosterone genetics, Chromosomes, Human, X genetics, Gonadal Dysgenesis, Mixed genetics, Gonadal Dysgenesis, Mixed metabolism, Primary Ovarian Insufficiency genetics, Primary Ovarian Insufficiency metabolism, Testosterone blood, Testosterone deficiency
- Abstract
Objective: To determine whether women with 46,XX spontaneous premature ovarian failure have lower serum free-T levels than do control women., Design: Cross-sectional., Setting: National Institutes of Health Clinical Research Center., Patient(s): Women with 46,XX spontaneous premature ovarian failure (n = 130)., Intervention(s): Evaluation while off any estrogen therapy and then again after receiving a standardized hormone regimen. Regularly menstruating control women (n = 65) were sampled during the midfollicular phase., Main Outcome Measure(s): Serum total T by RIA after extraction and column chromatography, free T by equilibrium dialysis, and sex hormone-binding globulin by immunoradiometric assay., Result(s): While off estrogen therapy patients had a median serum free-T concentration that was statistically significantly lower than controls (2.2 vs. 3.3 pg/mL). This dropped significantly lower to 1.9 pg/mL while the patients were on physiologic transdermal E(2) therapy. This is despite the fact that sex hormone-binding globulin levels did not change. While on E(2) therapy, 13% of women (95% confidence interval, 7.9%-20.3%) had serum free-T levels below the lower limit of normal (<1.1 pg/mL)., Conclusion(s): As a group, young women with 46,XX spontaneous premature ovarian failure have reduced circulating free-T levels, both during an interval off of estrogen therapy and while on physiologic transdermal E(2) therapy.
- Published
- 2006
- Full Text
- View/download PDF
28. Monosomy for the X-chromosome is associated with an atherogenic lipid profile.
- Author
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Van PL, Bakalov VK, and Bondy CA
- Subjects
- Cholesterol blood, Cholesterol, HDL blood, Cholesterol, LDL blood, Female, Humans, Particle Size, Primary Ovarian Insufficiency blood, Primary Ovarian Insufficiency genetics, Triglycerides blood, Turner Syndrome blood, Turner Syndrome genetics, Atherosclerosis blood, Atherosclerosis genetics, Chromosomes, Human, X genetics, Lipids blood, Monosomy genetics
- Abstract
Context and Objective: Men typically have a more atherogenic lipid profile than women characterized by higher low-density lipoprotein (LDL) cholesterol and triglyceride levels and reduced lipid particle size, contributing to a greater risk for coronary disease. To determine whether X-chromosomal gene dosage affects lipid metabolism independent of sex steroid effects, we compared lipid profiles in age- and body mass-matched young women with ovarian failure, differing only in X-chromosome dosage., Design, Setting, and Patients: Women with premature ovarian failure associated with monosomy X or Turner syndrome (TS, n = 118) were compared with women with 46,XX premature ovarian failure (n = 51) in an in-patient clinical research center unit at the National Institutes of Health. These women were normally on estrogen replacement treatment but discontinued the estrogen 2 wk before study., Major Outcomes: Fasting lipid levels and nuclear magnetic resonance lipid particle profiles in the two study groups were the major outcomes., Results: Average age and body mass were similar in the two groups of women, but LDL cholesterol (P = 0.001) and triglyceride levels (P = 0.0005) were higher in the TS group. Also among women with TS, average LDL particle size was reduced (P < 0.0001) and LDL particle concentration increased, with a 2-fold increase in the smallest particle categories (P < 0.0001). Whereas total high-density lipoprotein cholesterol levels were similar, high-density lipoprotein particle size was significantly smaller in women with TS, compared with women with premature ovarian failure (P < 0.0001)., Conclusions: Women with 45,X with ovarian failure exhibit a distinctly more atherogenic lipid profile than 46,XX women with ovarian failure, suggesting that the second X-chromosome contributes to a more salutary lipid profile in normal women, independent of sex steroid effects.
- Published
- 2006
- Full Text
- View/download PDF
29. Investigation of cardiac status and bone mineral density in Turner syndrome.
- Author
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Bondy CA and Bakalov VK
- Subjects
- Female, Heart diagnostic imaging, Humans, Osteoporosis diagnosis, Radiography, Bone Density, Heart Diseases diagnosis, Turner Syndrome physiopathology
- Abstract
This review highlights recent developments in the detection and management of congenital heart disease and osteoporosis in patients with monosomy X, or Turner syndrome (TS). Magnetic resonance angiography (MRA) using gadolinium as a contrast agent demonstrates a higher prevalence and greater diversity of congenital cardiovascular defects than previously recognized in TS. Almost 50% of girls and women with TS have marked tortuosity or ectasia of the aortic arch, suggesting that these individuals may be at greater risk for aneurysm formation or dissection and therefore require closer monitoring. MRA also reveals that major venous anomalies are common in TS, with partial anomalous pulmonary venous return and persistent left superior vena cava each found in about 13% of patients. MR imaging even without contrast is a valuable complement to routine cardiac ultrasound in detecting abnormalities of the aortic valve. Abnormal electrocardiographic findings, including prolongation of the QTc interval, have recently been documented in many individuals with TS. Conduction and repolarization abnormalities have not been associated with congenital anatomic defects and are as common in young girls as adults. The clinical significance of these electrophysiological findings is unknown at present, but attention to the ECG in TS is important, particularly in monitoring the QTc when prescribing drugs associated with QT prolongation. Patients with TS are at high risk for osteoporosis as a result of premature ovarian failure and intrinsic bone abnormalities specific to the syndrome. Low cortical bone mineral density (BMD) is apparent in prepubertal girls, and it remains low in adults, independent of estrogen treatment and other hormonal factors. The low mineralization of cortical bone in TS may be associated with a small increased fracture risk, but no treatments are known to increase cortical bone mineral content in TS. Trabecular BMD is normal in TS women who have received continuous estrogen treatment from their mid-teens, although areal densitometry scores may be misleadingly low in very small patients. However, young women with ovarian failure who have not received estrogen treatment for extended periods of time are at high risk for osteoporosis of trabecular bone of the spine, with associated compression fractures and height loss. Therefore, judicious management of estrogen therapy to prevent osteoporosis while minimizing estrogen-associated adverse events is a challenging aspect of care for girls and women with TS.
- Published
- 2006
- Full Text
- View/download PDF
30. Declining estrogen use in young women with Turner syndrome.
- Author
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Bondy CA, Ceniceros I, Lange E, and Bakalov VK
- Subjects
- Adolescent, Adult, Female, Humans, Middle Aged, Patient Education as Topic, Retrospective Studies, Risk Factors, Estrogens pharmacology, Treatment Refusal, Turner Syndrome drug therapy
- Published
- 2006
- Full Text
- View/download PDF
31. Growth hormone treatment and aortic dimensions in Turner syndrome.
- Author
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Bondy CA, Van PL, Bakalov VK, and Ho VB
- Subjects
- Adolescent, Body Height drug effects, Child, Child, Preschool, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Imaging, Mitral Valve anatomy & histology, Retrospective Studies, Aorta anatomy & histology, Aorta, Thoracic anatomy & histology, Growth Hormone therapeutic use, Turner Syndrome drug therapy, Turner Syndrome pathology
- Abstract
Background: In recent years many girls with Turner syndrome (TS) have been treated with supraphysiological doses of GH to increase adult height. In addition to promoting statural growth, GH may have direct effects on the cardiovascular system., Objective: We sought to determine whether GH treatment affects aortic diameter in girls with TS because there is an increased risk for aortic dilation and dissection in this syndrome., Methods: In a retrospective, cross-sectional study, we compared ascending and descending aortic diameters measured by magnetic resonance imaging in GH-treated (n = 53) vs. untreated (n = 48) patients with TS participating in a National Institutes of Health protocol between 2001 and 2004., Results: The average duration of GH treatment was 4.7 with se 0.4 yr (range 2-11 yr). The two groups were similar in age and weight, but GH-treated subjects were on average 8 cm taller (P = 0.002). The diameter of the ascending aorta was increased by 7.3% and descending aorta by 8.9% in the GH-treated group. However, after correction for age, height, weight, and presence of bicuspid aortic valve and coarctation, using a multiple regression, neither history of GH treatment nor the length of GH treatment had an effect on the aortic diameter. Weight (P = 0.02), height (P = 0.001), and presence of bicuspid aortic valve (P = 0.0001) were associated with larger ascending aortic diameter, whereas age (P = 0.008), height (P = 0.02), and history of coarctation (P = 0.006) were associated with larger descending aortic diameter., Conclusions: GH treatment of girls with TS does not seem to affect ascending or descending aortic diameter above the increase related to the larger body size.
- Published
- 2006
- Full Text
- View/download PDF
32. Maternal X chromosome, visceral adiposity, and lipid profile.
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Van PL, Bakalov VK, Zinn AR, and Bondy CA
- Subjects
- Adiposity physiology, Adult, Cardiovascular Diseases epidemiology, Female, Gene Expression, Gene Silencing, Genes, X-Linked, Humans, Turner Syndrome genetics, Turner Syndrome physiopathology, X Chromosome Inactivation, Adiposity genetics, Chromosomes, Human, X, Lipids blood
- Published
- 2006
- Full Text
- View/download PDF
33. Autoimmune oophoritis as a mechanism of follicular dysfunction in women with 46,XX spontaneous premature ovarian failure.
- Author
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Bakalov VK, Anasti JN, Calis KA, Vanderhoof VH, Premkumar A, Chen S, Furmaniak J, Smith BR, Merino MJ, and Nelson LM
- Subjects
- Adolescent, Adult, Autoimmune Diseases blood, Autoimmune Diseases pathology, Chromosome Aberrations, Chromosome Disorders blood, Chromosome Disorders genetics, Chromosome Disorders pathology, Confidence Intervals, Female, Humans, Oophoritis blood, Oophoritis pathology, Ovarian Follicle metabolism, Primary Ovarian Insufficiency blood, Primary Ovarian Insufficiency pathology, Prospective Studies, Autoimmune Diseases genetics, Chromosomes, Human, X genetics, Oophoritis genetics, Ovarian Follicle pathology, Primary Ovarian Insufficiency genetics
- Abstract
Objective: To assess the association between serum adrenal cortex autoantibodies and histologically confirmed autoimmune lymphocytic oophoritis., Design: Controlled, prospective., Setting: Tertiary research center., Patient(s): Two hundred sixty-six women with 46,XX spontaneous premature ovarian failure., Intervention(s): Ovarian biopsy in 10 women., Main Outcome Measure(s): Serum adrenal cortex autoantibodies assessed by indirect immunofluorescence and autoimmune oophoritis assessed by immunohistochemical lymphocyte markers., Result(s): We obtained a histologic diagnosis of autoimmune oophoritis in four women who tested positive for adrenal cortex autoantibodies and excluded this diagnosis in ovarian biopsies from six women who tested negative for adrenal cortex autoantibodies (4/4 vs. 0/6). Women with histologically confirmed autoimmune oophoritis had a greater total ovarian volume as assessed by transvaginal sonography (11.4 +/- 5.6 mL vs. 1.5 +/- 0.4 mL) (mean +/- SEM). They were also more likely to have subclinical adrenal insufficiency and clinical signs of androgen deficiency (3/4 vs. 0/6). Overall, 10/266 women tested positive for adrenal cortex autoantibodies (3.8%, 95% confidence interval: 1.8%-6.5%)., Conclusion(s): In women who present with 46,XX spontaneous premature ovarian failure as their primary concern there is a clear association between serum adrenal cortex autoantibodies and the presence of histologically confirmed autoimmune oophoritis.
- Published
- 2005
- Full Text
- View/download PDF
34. Association between fetal lymphedema and congenital cardiovascular defects in Turner syndrome.
- Author
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Loscalzo ML, Van PL, Ho VB, Bakalov VK, Rosing DR, Malone CA, Dietz HC, and Bondy CA
- Subjects
- Adult, Female, Genotype, Humans, Kidney abnormalities, Linear Models, Phenotype, Prospective Studies, Turner Syndrome genetics, Aortic Coarctation complications, Aortic Valve abnormalities, Fetal Diseases, Lymphedema complications, Turner Syndrome complications
- Abstract
Objectives: Turner syndrome (TS) is associated with congenital cardiovascular defects (CCVDs), most commonly bicuspid aortic valve (BAV) and aortic coarctation (COARC), congenital renal anomalies, and fetal lymphedema. It has been theorized that compressive or obstructive effects of fetal lymphedema may actually cause cardiovascular and renal dysmorphogenesis in TS. The objective of this study was to determine whether there is a specific association between a history of fetal lymphedema and CCVDs in monosomy X, or TS, independent of karyotype or general severity of the phenotype., Methods: This was a prospective study of 134 girls and women who have TS (mean age: 30 years) and were clinically evaluated for evidence of fetal lymphedema, classified as central (signified by the presence of neck webbing) or peripheral (current or perinatal, or dysplastic fingernails). The presence of BAV and/or COARC was detected by magnetic resonance imaging combined with echocardiography, and renal anomalies were determined by ultrasound., Results: There is a strong association between developmental central lymphedema, signified by neck webbing, and the presence of BAV (chi2 = 10) and COARC (chi2 = 8). The association between webbed neck and CCVDs was independent of karyotype. There was, in contrast, no significant association between renal anomalies and webbed neck or CCVDs., Conclusions: The strong, statistically significant association between neck webbing and the presence of BAV and COARC in TS suggests a pathogenetic connection between fetal lymphatic obstruction and defective aortic development. The presence of neck webbing in TS should alert the clinician to the possibility of congenital cardiovascular defects.
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- 2005
- Full Text
- View/download PDF
35. Screening for known mutations in EIF2B genes in a large panel of patients with premature ovarian failure.
- Author
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Fogli A, Gauthier-Barichard F, Schiffmann R, Vanderhoof VH, Bakalov VK, Nelson LM, and Boespflug-Tanguy O
- Abstract
BACKGROUND: Premature Ovarian Failure (POF), defined as the development of hypergonadotropic amenorrhea before the age of 40 years, occurs in about 1% of all women. Other than karyotype abnormalities, very few genes are known to be associated with this ovarian dysfunction. Recently, in seven patients who presented with POF and white matter abnormalities on MRI (ovarioleukodystrophy) eight mutationswere found in EIF2B2, 4 and 5. METHODS: To further test the involvement of known mutations of EIF2B genes in POF, we screened 93 patients with POF who did not have identified leukodystrophy or neurological symptoms. We evaluated these eight mutations and two additional mutations that had been found in patients with milder forms of eIF2B-related disorders. We used restriction enzymes and direct sequencing. RESULTS: None of the known mutations in EIF2B genes, either homozygous or heterozygous, were identified in our 93 patients with pure 46,XX POF. The upper 95 % confidence limit of the proportion 0/93 is 3.2%. CONCLUSIONS: We conclude that eIF2B mutations, already described in cases of POF associated with white matter abnormalities, are an uncommon cause of pure spontaneous premature ovarian failure.
- Published
- 2004
- Full Text
- View/download PDF
36. Growth hormone therapy and bone mineral density in Turner syndrome.
- Author
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Bakalov VK, Van PL, Baron J, Reynolds JC, and Bondy CA
- Subjects
- Adolescent, Adult, Bone Diseases etiology, Case-Control Studies, Child, Cross-Sectional Studies, Female, Femur Neck, Growth Disorders etiology, Hip Joint, Humans, Lumbar Vertebrae, Bone Density drug effects, Bone Diseases drug therapy, Growth Disorders drug therapy, Human Growth Hormone therapeutic use, Turner Syndrome complications
- Abstract
In a previous report, preliminary data showed a significant reduction in cortical bone mineral density (BMD) in women with Turner syndrome that had been treated with GH compared with women with Turner syndrome that had not been treated. To clarify this point, we have investigated the effects of GH treatment at multiple sites in this case-control, cross-sectional study. There were 23 women per group, who were similar in age, height, body mass index, estrogen use, and ethnic makeup. Median age (range) at start and duration of GH treatment was 9 (3-17) and 5 (2-9) yr, respectively. GH-treated women had a slightly greater ( approximately 8%, P = 0.03) width of the radial shaft, but otherwise there were no significant differences between groups in bone dimensions or BMD at the distal radius, lumbar spine, or femoral neck. Furthermore, regression analysis in a linear model including independent variables of age, age at diagnosis, body mass index, presence of spontaneous puberty, and GH use confirmed that GH use did not contribute to variation in BMD.
- Published
- 2004
- Full Text
- View/download PDF
37. Impaired insulin secretion in the Turner metabolic syndrome.
- Author
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Bakalov VK, Cooley MM, Quon MJ, Luo ML, Yanovski JA, Nelson LM, Sullivan G, and Bondy CA
- Subjects
- Adult, Area Under Curve, Blood Glucose analysis, Case-Control Studies, Female, Glucose, Glucose Tolerance Test methods, Humans, Insulin blood, Insulin Secretion, Primary Ovarian Insufficiency diagnosis, Primary Ovarian Insufficiency metabolism, Turner Syndrome diagnosis, Insulin metabolism, Turner Syndrome metabolism
- Abstract
An increased prevalence of impaired glucose homeostasis (IGH) and diabetes mellitus is reported in monosomy X, or Turner syndrome (TS). To determine whether IGH is an intrinsic feature of this syndrome, independent of obesity or hypogonadism, we compared results of a standard oral glucose challenge in age- and body mass index-matched women with TS and with karyotypically normal premature ovarian failure (POF). Fasting glucose levels were normal in both groups, but glucose values after oral glucose challenge were higher in TS [2-h glucose, 135 +/- 36 mg/dl (7.5 +/- 2.0 mmol/liter) in TS and 97 +/- 18 mg/dl (5.4 +/- 1.0 mmol/liter) in POF; P < 0.0001]. Glucose-stimulated insulin secretion was lower in TS; e.g. the initial insulin response (DeltaI/DeltaG(30)) was decreased by 60% compared with POF (P < 0.0001). We also compared responses to a standard iv glucose tolerance test in women with TS and in age- and body mass index-matched normal women and found that the insulin area under the curve was 50% lower in women with TS (P = 0.003). Insulin sensitivity measured by the quantitative insulin sensitivity check index was higher in women with TS compared with both control groups. Thus, IGH is not secondary to obesity or hypogonadism in TS, but it is a distinct entity characterized by decreased insulin secretion, suggesting that haploinsufficiency for X-chromosome gene(s) impairs beta-cell function and predisposes to diabetes mellitus in TS.
- Published
- 2004
- Full Text
- View/download PDF
38. The prevalence of diabetes mellitus in the parents of women with Turner's syndrome.
- Author
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Bakalov VK, Cooley MM, Troendle J, and Bondy CA
- Subjects
- Adolescent, Adult, Case-Control Studies, Child, Female, Humans, Male, Middle Aged, Prevalence, Risk, Diabetes Mellitus epidemiology, Parents, Turner Syndrome
- Published
- 2004
- Full Text
- View/download PDF
39. Selective reduction in cortical bone mineral density in turner syndrome independent of ovarian hormone deficiency.
- Author
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Bakalov VK, Axelrod L, Baron J, Hanton L, Nelson LM, Reynolds JC, Hill S, Troendle J, and Bondy CA
- Subjects
- Absorptiometry, Photon, Adult, Female, Humans, Primary Ovarian Insufficiency metabolism, Bone Density, Estrogens deficiency, Radius metabolism, Turner Syndrome metabolism
- Abstract
Women with Turner syndrome (TS) are at risk for osteoporosis from ovarian failure and possibly from haploinsufficiency for bone-related X-chromosome genes. To establish whether cortical or trabecular bone is predominantly affected, and to control for the ovarian failure, we studied forearm bone mineral density (BMD) in 41 women with TS ages 18-45 yr and in 35 age-matched women with karyotypically normal premature ovarian failure (POF). We measured BMD at the 1/3 distal radius (D-Rad(1/3); predominantly cortical bone) and at the ultradistal radius (UD-Rad; predominantly trabecular bone) by dual x-ray absorptiometry. Women with TS had lower cortical BMD compared with POF (D-Rad(1/3) Z-score = -1.5 +/- 0.8 for TS and 0.08 +/- 0.7 for POF; P < 0.0001). In contrast, the primarily trabecular UD-Rad BMD was normal in TS and not significantly different from POF (Z-score = -0.62 +/- 1.1 for TS and -0.34 +/- 1.0 for POF; P = 0.26). The difference in cortical BMD remained after adjustment for height, age of puberty, lifetime estrogen exposure, and serum 25-hydroxyvitamin D (P = 0.0013). Cortical BMD was independent of serum IGF-I and -II, PTH, and testosterone in TS. We conclude that there is a selective deficiency in forearm cortical bone in TS that appears independent of ovarian hormone exposure and is probably related to X-chromosome gene(s) haploinsufficiency.
- Published
- 2003
- Full Text
- View/download PDF
40. Mechanisms of follicular dysfunction in 46,XX spontaneous premature ovarian failure.
- Author
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Nelson LM and Bakalov VK
- Subjects
- Adult, Animals, Female, Humans, Infertility, Female pathology, Infertility, Female physiopathology, Ovarian Follicle pathology, Ovary pathology, Primary Ovarian Insufficiency pathology, Primary Ovarian Insufficiency therapy, Prognosis, Ovarian Follicle physiopathology, Primary Ovarian Insufficiency genetics, Primary Ovarian Insufficiency physiopathology
- Abstract
Approximately one half of young women who have 46,XX spontaneous premature ovarian failure have ovarian follicles remaining in the ovary. These follicles function intermittently and unpredictably, and pregnancies can occur in these women without intervention, even many years after the diagnosis. Clearly, the term "premature menopause" is an inaccurate term for this condition. At present, there are no proven therapies that will improve follicular function for these women. Inappropriate luteinization related to low follicle number seems to be a major mechanism of follicular dysfunction. Autoimmune oophoritis, although apparently an uncommon cause of follicular dysfunction in these women, nonetheless presents the opportunity to develop an effective therapy to restore fertility. Young women with 46,XX spontaneous premature ovarian failure benefit from the care of a sensitive clinician, one who is willing to spend a little more time informing them about the diagnosis and referring them to other sources of information. With appropriate medical management and emotional support provided by a sensitive clinician, most young women with 46,XX spontaneous premature ovarian failure will lead happy, healthy, and fulfilling lives.
- Published
- 2003
- Full Text
- View/download PDF
41. Bone mineral density and fractures in Turner syndrome.
- Author
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Bakalov VK, Chen ML, Baron J, Hanton LB, Reynolds JC, Stratakis CA, Axelrod LE, and Bondy CA
- Subjects
- Absorptiometry, Photon, Adult, Body Height, Body Mass Index, Body Surface Area, Body Weight, Bone Density drug effects, Estrogens therapeutic use, Female, Femoral Neck Fractures diagnosis, Femoral Neck Fractures drug therapy, Femur Neck drug effects, Femur Neck injuries, Femur Neck physiopathology, Hormone Replacement Therapy, Humans, Lumbar Vertebrae drug effects, Lumbar Vertebrae physiopathology, Middle Aged, Osteoporosis diagnosis, Osteoporosis drug therapy, Osteoporosis physiopathology, Patient Compliance, Predictive Value of Tests, Prevalence, Spinal Fractures diagnosis, Spinal Fractures drug therapy, Treatment Outcome, Turner Syndrome diagnosis, Turner Syndrome drug therapy, Women's Health, Bone Density physiology, Femoral Neck Fractures physiopathology, Lumbar Vertebrae injuries, Spinal Fractures physiopathology, Turner Syndrome physiopathology
- Abstract
Purpose: To determine whether women with Turner syndrome who were treated with estrogen were more likely to have osteoporosis and fractures., Methods: Areal bone density at the lumbar spine and femoral neck was measured in 40 adult women with Turner syndrome and 43 age-matched healthy women using dual-energy X-ray absorptiometry. Histories of estrogen treatment and fractures were obtained by structured personal interviews., Results: Mean (+/- SD) areal bone density was significantly lower at the lumbar spine (0.87 +/- 0.11 g/cm(2) vs. 0.98 +/- 0.10 g/cm(2), P <0.001) and femoral neck (0.68 +/- 0.07 g/ cm(2) vs. 0.83 +/- 0.08 g/cm(2), P <0.001) in women with Turner syndrome than in controls. The diagnostic criterion for osteoporosis (T-score <-2.5) was met by 8 women with Turner syndrome (20%) with scores at the lumbar spine and by 3 (8%) with scores at the femoral neck. All women diagnosed with osteoporosis were less than 150 cm in height. Areal bone density correlated significantly with height (lumbar spine: R(2) = 0.3, P <0.001; femoral neck: R(2) = 0.4, P <0.001). Adjustments for skeletal size reduced the differences between the groups as well as the number of women diagnosed with osteoporosis (e.g., from 8 to 2 women based on lumbar spine scores). The prevalence and type of fractures were similar in the two groups., Conclusions: The prevalence of osteoporosis and bone fractures is not increased significantly in women with Turner syndrome who are treated with standard estrogen therapy. Women less than 150 cm in height are likely to be misdiagnosed with osteoporosis when areal bone density is measured, unless adjustments for body size are made.
- Published
- 2003
- Full Text
- View/download PDF
42. Adrenal antibodies detect asymptomatic auto-immune adrenal insufficiency in young women with spontaneous premature ovarian failure.
- Author
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Bakalov VK, Vanderhoof VH, Bondy CA, and Nelson LM
- Subjects
- Adrenal Insufficiency blood, Adrenal Insufficiency immunology, Adrenocorticotropic Hormone, Adult, Autoimmune Diseases blood, Autoimmune Diseases immunology, Cross-Sectional Studies, Female, Fluorescent Antibody Technique, Indirect, Humans, Hydrocortisone blood, Polyendocrinopathies, Autoimmune diagnosis, Adrenal Glands immunology, Adrenal Insufficiency diagnosis, Adrenal Insufficiency etiology, Autoantibodies analysis, Autoimmune Diseases diagnosis, Autoimmune Diseases etiology, Primary Ovarian Insufficiency complications
- Abstract
Background: Auto-immune adrenal insufficiency is a potentially fatal disorder. Young women with spontaneous premature ovarian failure (POF) are at increased risk of developing this condition., Methods: We further characterized auto-immune adrenal insufficiency in this population by conducting an in-depth cross-sectional evaluation of adrenal function in a series of 123 women., Results: We uncovered a new diagnosis of adrenal insufficiency in four women [3.2%, 95% confidence interval (CI) 0.2-6.4%]. All four tested positive for adrenal antibodies as detected by a clinically available indirect immunofluorescence assay. A positive adrenal antibody test was highly associated with adrenal insufficiency while a negative test was associated with normal adrenal function in all cases (P < 0.001). Adrenal antibodies increased the pretest probability of adrenal insufficiency from 3.2 to 67%. As a screening method the cortisol response during a standard adrenocorticotrophic hormone (ACTH) stimulation test gave two false positive results (1.7%, upper 95% confidence limit 5.0%)., Conclusions: Our findings suggest that measuring adrenal antibodies would be an effective screening method by which to detect auto-immune adrenal insufficiency in young women with spontaneous POF. The standard ACTH stimulation test should be reserved to confirm adrenal insufficiency in women with adrenal antibodies, or those with signs and symptoms of adrenal insufficiency.
- Published
- 2002
- Full Text
- View/download PDF
43. IL-12, TNF-alpha, and hormonal changes during late pregnancy and early postpartum: implications for autoimmune disease activity during these times.
- Author
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Elenkov IJ, Wilder RL, Bakalov VK, Link AA, Dimitrov MA, Fisher S, Crane M, Kanik KS, and Chrousos GP
- Subjects
- Adult, Blood Cell Count, Calcifediol blood, Estradiol blood, Female, Humans, Hydrocortisone urine, Pregnancy Trimester, Third, Progesterone blood, Autoimmune Diseases etiology, Interleukin-12 biosynthesis, Postpartum Period metabolism, Pregnancy immunology, Pregnancy metabolism, Pregnancy Complications etiology, Puerperal Disorders etiology, Tumor Necrosis Factor-alpha biosynthesis
- Abstract
Clinical observations indicate that some autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, frequently remit during pregnancy but exacerbate, or have their onset, in the postpartum period. The immune basis for these phenomena is poorly understood. Recently, excessive production of IL-12 and TNF-alpha was causally linked to rheumatoid arthritis and multiple sclerosis. We studied 18 women with normal pregnancies in their third trimester and during the early postpartum period. We report that during the third trimester pregnancy, ex vivo monocytic IL-12 production was about 3-fold and TNF-alpha production was approximately 40% lower than postpartum values. At the same time, urinary cortisol and norepinephrine excretion and serum levels of 1,25-dihydroxyvitamin were 2- to 3-fold higher than postpartum values. As shown previously, these hormones can directly suppress IL-12 and TNF-alpha production by monocytes/macrophages in vitro. We suggest that a cortisol-, norepinephrine-, and 1,25-dihydroxyvitamin-induced inhibition and subsequent rebound of IL-12 and TNF-alpha production may represent a major mechanism by which pregnancy and postpartum alter the course of or susceptibility to various autoimmune disorders.
- Published
- 2001
- Full Text
- View/download PDF
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