Life Sciences Commons^™

Serum Dioxins And Polychlorinated Biphenyls Are Associated With Growth Among Russian Boys, Jane Burns, Paige Williams, Oleg Sergeyev, Susan Korrick, Mary Lee, Boris Revich, Larisa Altshul, Julie Del Prato, Olivier Humblet, Donald Patterson, Wayman Turner, Larry Needham, Mikhail Starovoytov, Russ Hauser

Mary M. Lee

OBJECTIVE: We evaluated the associations of serum dioxins and polychlorinated biphenyls (PCBs) with longitudinally assessed growth measurements among peripubertal Russian boys.

METHODS: A total of 499 boys from Chapaevsk, Russia, aged 8 to 9 years were enrolled in the study from 2003 to 2005 and were followed prospectively for 3 years. Blood samples were collected and physical examinations were conducted at entry and repeated at annual study visits. Multivariate mixed-effects regression models for repeated measures were used to examine the associations of serum dioxins and PCBs with longitudinal measurements of BMI, height, and height velocity.

RESULTS: Serum dioxin (total 2005 …

Measurement Of Mullerian Inhibiting Substance Facilitates Management Of Boys With Microphallus And Cryptorchidism, Madhusmita Misra, David Maclaughlin, Patricia Donahoe, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) is a gonadal hormone expressed in a sexually dimorphic pattern. In males, serum MIS reflects Sertoli cell function and provides an estimate of seminiferous tubular integrity. We examined the role of MIS determination in the evaluation of boys with microphallus (n = 62) and/or cryptorchidism (n = 156). MIS was normal in 69.2% of boys with isolated microphallus compared with 38.1% of boys with microphallus and coexisting cryptorchidism (P < 0.05). In the cryptorchid group, MIS was normal in 46.8%, low in 24.4%, and absent in 28.8%. Normal values for age were associated with testicular tissue, whereas …

Augmented Growth Hormone (Gh) Secretory Burst Frequency And Amplitude Mediate Enhanced Gh Secretion During A Two-Day Fast In Normal Men, Mark Hartman, Johannes Veldhuis, Michael Johnson, Mary Lee, K. Alberti, Eugene Samojlik, Michael Thorner

Mary M. Lee

Serum GH concentrations are increased in fasted or malnourished human subjects. We investigated the dynamic mechanisms underlying this phenomenon in nine normal men by analyzing serum GH concentrations measured in blood obtained at 5-min intervals over 24 h on a control (fed) day and on the second day of a fast with a multiple-parameter deconvolution method to simultaneously resolve endogenous GH secretory and clearance rates. Two days of fasting induced a 5-fold increase in the 24-h endogenous GH production rate [78 +/- 12 vs. 371 +/- 57 micrograms/Lv (Lv, liter of distribution volume) or 0.24 +/- 0.038 vs. 1.1 +/- …

Transient Hyperthyroidism In An Adolescent With Hydatidiform Mole, Madhusmita Misra, Lynne Levitsky, Mary Lee

Mary M. Lee

No abstract provided.

Mullerian Inhibiting Substance In Humans: Normal Levels From Infancy To Adulthood, Mary Lee, Patricia Donahoe, Tomonobu Hasegawa, Bernard Silverman, Gretchen Crist, Sharon Best, Yukihiro Hasegawa, Richard Noto, David Schoenfeld, David Maclaughlin

Mary M. Lee

Mullerian-inhibiting substance (MIS) is a gonadal hormone synthesized by Sertoli cells of the testis and granulosa cells of the ovary. To facilitate the use of MIS for the evaluation of intersex disorders and as a tumor marker in women with MIS-expressing ovarian tumors, we measured MIS in 600 serum samples from males and females. These data show that mean MIS values for males rise rapidly during the first year of life and are highest during late infancy, then gradually decline until puberty. In contrast, MIS values in females are lowest at birth and exhibit a minimal increase throughout the prepubertal …

Serum Concentrations Of Organochlorine Pesticides And Growth Among Russian Boys, Jane Burns, Paige Williams, Oleg Sergeyev, Susan Korrick, Mary Lee, Boris Revich, Larisa Altshul, Julie Del Prato, Olivier Humblet, Donald Patterson, Wayman Turner, Mikhail Starovoytov, Russ Hauser

Mary M. Lee

BACKGROUND: Limited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth. OBJECTIVE: We evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels. METHODS: A cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and …

Mullerian Inhibiting Substance In The Diagnosis And Management Of Intersex And Gonadal Abnormalities, Michael Gustafson, Mary Lee, Lara Asmundson, David Maclaughlin, Patricia Donahoe

Mary M. Lee

Mullerian inhibiting substance (MIS), a gonadal hormone important in sexual differentiation, is high (10 to 70 ng/mL) in human male serum postnatally for several years before declining during the peripubertal period, but is undetectable in female serum until the onset of puberty. The sexually dimorphic secretion of MIS suggested possibilities for its use in several clinical settings. Thirty-one patients with intersex and gonadal anomalies from 17 institutions were therefore evaluated between 1989 and 1992 with an MIS enzyme-linked immunosorbent assay (ELISA). Serum MIS levels correlated with the presence of testicular tissue in two patients with suspected anorchia, five patients with …

Campylobacter Meningitis In Childhood, Mary Lee, Robert Welliver, Leonard La Scolea

Mary M. Lee

No abstract provided.

Predictors Of Serum Dioxin, Furan, And Pcb Concentrations Among Women From Chapaevsk, Russia, Olivier Humblet, Paige Williams, Susan Korrick, Oleg Sergeyev, Claude Emond, Linda Birnbaum, Jane Burns, Larisa Altshul, Donald Patterson, Wayman Turner, Mary Lee, Boris Revich, Russ Hauser

Mary M. Lee

Dioxins, furans, and polychlorinated biphenyls (PCBs) are persistent and bioaccumulative toxic chemicals that are ubiquitous in the environment. We assessed predictors of their serum concentrations among women living in a Russian town contaminated by past industrial activity. Blood samples from 446 mothers aged 23-52 years were collected between 2003-2005 as part of the Russian Children's Study. Serum dioxin, furan, and PCB concentrations were quantified using high-resolution gas chromatography-mass spectrometry. Potential determinants of exposure were collected through interviews. Multivariate linear regression models were used to identify predictors of serum concentrations and toxic equivalencies (TEQs). The median total PCB concentrations and total …

Mentoring Fathers Of Children Newly Diagnosed With T1dm, Susan Sullivan-Bolyai, Carol Bova, Mary Lee, Philip Gruppuso

Mary M. Lee

PURPOSE: To pilot test a social support intervention for fathers of children (T1DM).

DESIGN AND METHODS: The pilot study was part of a larger randomized, controlled clinical trial. Father participants (28 fathers of children newly diagnosed) were recruited from two pediatric diabetes centers. For 12 months fathers (n = 19) and their spouses in the experimental arm received social support (home visits and phone calls). Control group fathers (n = 9) and their spouses received the phone number of an experienced parent (but not formally educated to provide social support) to call as needed.

RESULTS: Fathers in the intervention group …

Key Factors In The Regulation Of Fetal And Postnatal Leydig Cell Development, Xiufeng Wu, Shengqin Wan, Mary Lee

Mary M. Lee

The primary function of testicular Leydig cells is the production of androgens to promote sexual differentiation in the fetus, secondary sexual maturation at puberty, and spermatogenesis in the adult. The fetal and postnatal (adult) populations of Leydig cells differ morphologically and have distinct profiles of gene expression. As postnatal Leydig cells differentiate, they transition through three discrete maturational stages characterized by decreasing proliferative rate and increasing testosterone biosynthetic capacity. In this review, we discuss the development of both fetal and postnatal Leydig cells and review the regulation of this process by some of the key hormones and growth factors.

Consensus Statement On The Use Of Gonadotropin-Releasing Hormone Analogs In Children, Jean-Claude Carel, Erica Eugster, Alan Rogol, Lucia Ghizzoni, Mark Palmert, Mary Lee

Mary M. Lee

OBJECTIVE: Gonadotropin-releasing hormone analogs revolutionized the treatment of central precocious puberty. However, questions remain regarding their optimal use in central precocious puberty and other conditions. The Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology convened a consensus conference to review the clinical use of gonadotropin-releasing hormone analogs in children and adolescents. PARTICIPANTS: When selecting the 30 participants, consideration was given to equal representation from North America (United States and Canada) and Europe, an equal male/female ratio, and a balanced spectrum of professional seniority and expertise. EVIDENCE: Preference was given to articles written in English with long-term …

The Role Of Mullerian Inhibiting Substance In The Evaluation Of Phenotypic Female Patients With Mild Degrees Of Virilization, Madhusmita Misra, David Maclaughlin, Patricia Donahoe, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) is a sexually dimorphic gonadal hormone with proven efficacy in the evaluation of boys with cryptorchidism and children with intersex conditions. We examined the role of MIS determination in the evaluation of 65 phenotypic females with mild virilization. Among the 28 subjects with MIS values elevated above the normal female range, all had abnormal gonadal tissue: ovotestes in 11, testes in 7, dysgenetic gonads in 7, and MIS-secreting ovarian tumors in 3. Among the 37 children with serum MIS in the normal female range, 19 had detectable MIS and 18 had unmeasurable MIS. In the former …

The Influence Of Endocrine Disruptors On Pubertal Timing, Elka Jacobson-Dickman, Mary Lee

Mary M. Lee

PURPOSE OF REVIEW: Overview of the effects of endocrine disruptors on pubertal timing. RECENT FINDINGS: Epidemiologic studies in humans support animal data demonstrating that exposures to endocrine-disrupting compounds have pronounced effects on pubertal timing and that the timing of endocrine-disrupting compound exposure and the specific agent causes different outcomes. Recent studies confirm subtle effects of lead, dioxins, and phytoestrogens on delaying onset of puberty and demonstrate an association of phthalates and polychlorinated biphenyls with earlier breast development and menarche, respectively. These studies, however, are complicated by mixed exposures of compounds which individually may have opposing actions on the reproductive axis. …

Alterations In The Pulsatile Mode Of Growth Hormone Release In Men And Women With Insulin-Dependent Diabetes Mellitus, Christopher Asplin, Amilton Faria, Elizabeth Carlsen, Veronica Vaccaro, Richard Barr, Ali Iranmanesh, Mary Lee, Johannes Veldhuis, William Evans

Mary M. Lee

The mechanisms responsible for the elevated levels of circulating GH observed in diabetes mellitus (DM) remain incompletely defined. To assess the episodic fluctuations in serum GH as a reflection of hypothalamic-pituitary activity, we accumulated GH concentration-time series in a total of 48 adult men and women with and without insulin-dependent DM by obtaining serum samples at 10-min intervals over 24 h. Significant pulses of GH release were subsequently identified and characterized by an objective, statistically based pulse detection algorithm (Cluster) and fixed circadian (24-h) periodicities of secretory activity, resolved using Fourier expansion timeseries analysis. Compared to those in age-matched controls, …

Hypothyroidism In Down Syndrome: Screening Guidelines And Testing Methodology, Olga Hardy, Gordon Worley, Mary Lee, Shu Chaing, Joanne Mackey, Blythe Crissman, Priya Kishnani

Mary M. Lee

No abstract provided.

Mullerian Inhibiting Substance As A Marker For Ovarian Sex-Cord Tumor, Michael Gustafson, Mary Lee, Robert Scully, Ashby Moncure, Toshio Hirakawa, Annekathryn Goodman, Howard Muntz, Patricia Donahoe, David Maclaughlin, Arlan Fuller

Mary M. Lee

No abstract provided.

Mis/Amh In The Assessment Of Cryptorchidism And Intersex Conditions, Mary Lee, Madhusmita Misra, Patricia Donahoe, David Maclaughlin

Mary M. Lee

Mullerian inhibiting substance (MIS), also known as anti-Mullerian hormone (AMH), causes Mullerian duct involution during male sexual differentiation and also has a postnatal regulatory role in the gonads. Serum MIS/AMH has a gonad specific pattern of expression and its concentrations are sexually dimorphic in children; hence measurement of serum MIS/AMH helps in the evaluation of children with gonadal disorders. In boys with cryptorchidism (non-palpable gonads), serum MIS/AMH correlates with testicular tissue. A measurable value is predictive of undescended testes while an undetectable value is highly suggestive of anorchia. In minimally virilized phenotypic females, MIS/AMH helps differentiate between gonadal and non-gonadal …

Insulin Pump Therapy In Toddlers And Preschool Children With Type 1 Diabetes Mellitus, Jean Litton, Alan Rice, Nancy Friedman, Jon Oden, Mary Lee, Michael Freemark

Mary M. Lee

OBJECTIVE: To test whether glycemic control in young children could be achieved more effectively and safely by using continuous insulin infusions administered by insulin pumps.

STUDY DESIGN: We analyzed the effects of pump therapy in nine toddlers in whom type 1 diabetes developed between the ages of 10 and 40 months. After a mean of 13.7 months of therapy with multiple daily injections, patients were treated with insulin pumps for periods ranging from 7 to 19 months (mean, 12.7 months).

RESULTS: Before initiation of pump therapy, HbA1c levels averaged 9.5% +/- 0.4%, and patients had a mean of 0.52 episodes …

Mullerian Inhibiting Substance Inhibits Testosterone Synthesis In Adult Rats, V. Sriraman, E. Niu, J. Matias, Patricia Donahoe, David Maclaughlin, Matthew Hardy, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) is a gonadal hormone that causes regression of the Mullerian ducts during male sexual differentiation. Postnatally, MIS inhibits the proliferation and differentiation of immature Leydig cells, and transgenic mice that overexpress MIS have decreased serum testosterone concentrations. To elucidate the effects of MIS on androgen regulation in the postnatal testis, we examined testosterone synthesis in adult Sprague-Dawley rats following intratesticular and intraperitoneal injections of MIS. Intratesticular MIS injection achieved high local concentrations of MIS (574.0 +/- 60.0 ng/mL) at 4 hours, with a corresponding decline in serum testosterone concentrations to 0.7 +/- 0.1 ng/mL, compared to …

Triploid Mosaicism In A 45,X/69,Xxy Infant, Denise Quigley, Marie Mcdonald, Vidya Krishnamuthy, Priya Kishnani, Mary Lee, Andrea Haqq, Barbara Goodman

Mary M. Lee

We report on an infant referred for chromosome analysis during the neonatal period due to ambiguous genitalia. The genitalia appeared male with bilaterally palpable testes, penoscrotal hypospadias, chordee, and a bifid scrotum. Chromosome analysis and interphase FISH analysis of lymphocytes showed a 45,X karyotype and no evidence for SRY in 200 nuclei examined, respectively. Subsequent chromosome analysis of fibroblasts revealed a 69,XXY karyotype. Molecular studies were carried out to determine the etiology of the chromosome findings. Results indicated that the two cell lines are mosaic rather than chimeric and that the triploidy resulted from delayed dispermy rather than delayed polar …

Infant Formula, Autoimmune Triggers, And Type 1 Diabetes, David Harlan, Mary Lee

Mary M. Lee

No abstract provided.

Isolation Of The Rat Gene For Mullerian Inhibiting Substance, Christopher Haqq, Mary Lee, Richard Tizard, Mark Wysk, Janice Demarinis, Patricia Donahoe, Richard Cate

Mary M. Lee

Mullerian inhibiting substance (MIS), a testicular glycoprotein also known as anti-Mullerian hormone, plays a key role in male sexual development by causing regression of the Mullerian duct, the anlagen of the uterus, the Fallopian tubes, and part of the vagina. MIS is also expressed in the postnatal ovary, but its precise function is still not known. We report here the complete nucleotide sequence of the rat MIS gene. Rat MIS is encoded in five exons and is synthesized as a precursor of 553 amino acids, containing a 24-amino-acid leader. Based on homology with human MIS, we predict that the rat …

Diagnostic Utility Of Mullerian Inhibiting Substance Determination In Patients With Primary And Recurrent Granulosa Cell Tumors, Andrew Lane, Mary Lee, Arlan Fuller, David Kehas, Patricia Donahoe, David Maclaughlin

Mary M. Lee

OBJECTIVES: In this study we evaluated changes in serum Mullerian inhibiting substance (MIS) concentration in a large number of patients with granulosa cell tumors (GCT) to determine whether MIS is elevated at the time of presentation and whether MIS is an index of successful surgical resection and management of recurrences. METHODS: We retrospectively reviewed MIS levels from 17 subjects prior to tumor resection and studied serial MIS samples from 56 subjects following initial tumor resection. Clinical follow-up information was available for 36 of those with postoperative MIS values. Serum MIS was measured by an ELISA. MIS values were compared to …

Blood Lead Levels And Delayed Onset Of Puberty In A Longitudinal Study Of Russian Boys, Paige Williams, Oleg Sergeyev, Mary Lee, Susan Korrick, Jane Burns, Olivier Humblet, Julie Del Prato, Boris Revich, Russ Hauser

Mary M. Lee

OBJECTIVE: We evaluated the association of blood lead levels (BLLs) with pubertal onset in a longitudinal cohort of Russian boys.

METHODS: A total of 489 Russian boys were enrolled in 2003-2005, at 8 to 9 years of age, and were monitored annually through May 2008. Cox proportional-hazards models were used to evaluate the association of BLLs at enrollment with time to pubertal onset during follow-up monitoring.

RESULTS: A total of 481 boys had BLLs, with a median of 3 microg/dL and 28% with values of > or =5 microg/dL. The proportion of pubertal boys increased with age, from 12% at age …

Serum Adrenal Steroid Concentrations In Premature Infants, Mary Lee, Lakshmy Rajagopalan, Gregory Berg, Thomas Moshang

Mary M. Lee

To evaluate serum adrenal steroid concentrations in preterm infants, 17-hydroxyprogesterone (17-OHP), 17-hydroxypregnenolone, 11-deoxycortisol, cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione, 18-hydroxycorticosterone, and aldosterone values were determined in 9 sick and 13 healthy premature infants. Serum steroid concentrations were compared to previously reported data from healthy full-term infants. 17-OHP, 11-deoxycortisol, and aldosterone values were higher in sick preterm infants than in healthy preterm infants. Compared to healthy full-term infants, the premature infants-had significantly higher 17-hydroxypregnenolone, 17-OHP, and DHEA sulfate concentrations. Cortisol values were not different between the sick and healthy preterm infants and were similar to full-term values. Aldosterone values were also …

Clinical Management Of Intersex Abnormalities, Patricia Donahoe, David Powell, Mary Lee

Mary M. Lee

No abstract provided.

Clinical Practice. Idiopathic Short Stature, Mary Lee

Mary M. Lee

No abstract provided.

Physical Growth And Sexual Maturation Of Boys In Chapaevsk, Russia, Mary Lee, Oleg Sergeyev, Paige Williams, Susan Korrick, Vladimir Zeilert, Boris Revich, Russ Hauser

Mary M. Lee

We characterized physical growth and sexual maturation in 2,579 boys, ages 10 through 16.99 years, residing in Chapaevsk, Russia in order to establish region-specific reference data. Age-specific norms were established for height, weight, and BMI, and compared to US reference data by z-score analysis, while mean heights and weights by age were compared to published national Russian data. Compared to US boys, height was slightly lower (overall z-score -0.18) at all ages except the oldest (16-16.99 yr), while weight and BMI were moderately lower (overall z-score -0.52 and -0.61, respectively). Chapaevsk boys were significantly taller (1.15 cm) and thinner (-1.28 …

Guidelines For The Use Of Growth Hormone In Children With Short Stature., Mary Lee

Mary M. Lee

On the basis of the information currently available, the only conditions in which GH therapy appears to be safe and effective in increasing adult height are GH deficiency and, likely, Turner syndrome. Therapy with GH also increases the growth velocity of children with CRI and may increase adult height, but no long-term data are available. Encouraging short-term results have been reported in patients with a few other conditions, such as patients with glucocorticoid-induced growth failure, renal transplantation, and Prader-Willi syndrome, but the data are limited and no long-term studies have been reported; in many other conditions the data are either …