Dermoscopic structures and patterns used in melanoma detection.

Melanoma is the leading cause of skin cancer-related deaths. Yet, early detection remains the most cost-effective means of preventing death from melanoma. Early detection can be achieved by a physician and/or the patient (also known as a self-skin exam). Skin exams performed by physicians are further enhanced using dermoscopy. Dermoscopy is a non-invasive technique that allows for the visualization of subsurface structures that are otherwise not visible to the naked eye. Evidence demonstrates that dermoscopy improves the diagnostic accuracy for skin cancer, including melanoma; it decreases the number of unnecessary skin biopsies of benign lesions and improves the benign-to-malignant biopsy ratio. Yet, these improvements are contingent on acquiring dermoscopy training. Dermoscopy is used by clinicians who evaluate skin lesions and perform skin cancer screenings. In general, under dermoscopy nevi tend to appear as organized lesions, with one or two structures and colors, and no melanoma-specific structures. In contrast, melanomas tend to manifest a disorganized pattern, with more than two colors and, usually, at least one melanoma-specific structure. This review is intended to familiarize the reader with the dermoscopic structures and patterns used in melanoma detection.

Bridges and Mechanisms: Integrating Systems Science Thinking into Implementation Research.

We present a detailed argument for how to integrate, or bridge, systems science thinking and methods with implementation science. We start by showing how fundamental systems science principles of structure, dynamics, information, and utility are relevant for implementation science. Then we examine the need for implementation science to develop and apply richer theories of complex systems. This can be accomplished by emphasizing a causal mechanisms approach. Identifying causal mechanisms focuses on the "cogs and gears" of public health, clinical, and organizational interventions. A mechanisms approach focuses on how a specific strategy will produce the implementation outcome. We show how connecting systems science to implementation science opens new opportunities for examining and addressing social determinants of health and conducting equitable and ethical implementation research. Finally, we present case studies illustrating successful applications of systems science within implementation science in community health policy, tobacco control, health care access, and breast cancer screening.

Dermoscopy in Selected Latin American Countries: A Preliminary Look into Current Trends and Future Opportunities Among Dermatology Residency Programs.

INTRODUCTION: Skin cancer remains a global public health burden. Dermoscopy is a useful technique that aids in early detection and increases diagnostic accuracy with adequate training. However, dermoscopy is not uniformly taught to residents worldwide. Dermoscopy training in Latin American dermatology residency programs has not been explored. OBJECTIVES: To assess current dermoscopy training among dermatology residency programs in Latin America (eg training modalities, preferred/most effective modalities per residents, diseases/pathologies taught). METHODS: Cross-sectional survey distributed via e-mail between March and May 2021. Chief residents from Argentina, Brazil, Colombia, Costa Rica, Chile, Ecuador, Guatemala, Mexico, Panama, and Uruguay were invited to participate. RESULTS: 81 chief residents completed the questionnaire (81/126, 64.2%). Seventy-two percent of programs had an established dermoscopy curriculum, with dedicated hours of training varying greatly by program. Institutions commonly utilized sessions with "unknown" dermoscopy images and direct teaching by experts in the clinical setting as supplements to lectures, also described by residents as most effective. The most commonly taught methods included pattern analysis (74.1%), the two-step algorithm (61.7%), and the ABCD rule (59.3%). Almost all respondents reported desiring additional training during residency and believe that dermoscopy training should be a requirement to graduate from residency. CONCLUSIONS: This study highlights a preliminary look into current landscape in dermoscopy training among selected Latin American dermatology residency programs, demonstrating room for improvement and standardization in dermoscopic education and training. Our results serve as a baseline reference and provide valuable information to guide future educational initiatives incorporating successful teaching strategies (eg. spaced education/repetition, flipped classroom model) used in dermatology and other fields.

Body mass index rebound and pubertal timing in girls with and without a family history of breast cancer: the LEGACY girls study.

BACKGROUND: Heavier body mass index (BMI) is the most established predictor of earlier age at puberty. However, it is unknown whether the timing of the childhood switch to heavier BMI (age at BMI rebound) also matters for puberty. METHODS: In the LEGACY Girls Study (n = 1040), a longitudinal cohort enriched with girls with a family history of breast cancer, we collected paediatric growth chart data from 852 girls and assessed pubertal development every 6 months. Using constrained splines, we interpolated individual growth curves and then predicted BMI at ages 2, 4, 6, 8 and 9 years for 591 girls. We defined age at BMI rebound as the age at the lowest BMI between ages 2 and 8 years and assessed its association with onset of thelarche, pubarche and menarche using Weibull survival models. RESULTS: The median age at BMI rebound was 5.3 years (interquartile range: 3.6-6.7 years). A 1-year increase in age at BMI rebound was associated with delayed thelarche (HR = 0.90; 95% CI = 0.83-0.97) and menarche (HR = 0.86; 95% CI = 0.79-0.94). The magnitude of these associations remained after adjusting for weight between birth and 2 years, was stronger after adjusting for BMI at age 9, and was stronger in a subset of girls with clinically assessed breast development. CONCLUSIONS: Earlier BMI rebound is associated with earlier pubertal timing. Our observation that BMI rebound may be a driver of pubertal timing in girls with and without a family history of breast cancer provides insight into how growth and pubertal timing are associated with breast cancer risk.

La salud mental de los trabajadores de salud en Guatemala durante la pandemia de COVID-19: resultados de base del estudio de cohortes HÉROES / Mental health of Guatemalan health care workers during the COVID-19 pandemic: baseline findings from the HEROES cohort study / Saúde mental dos trabalhadores da saúde guatemaltecos durante a pandemia de COVID-19: constatações basais do estudo da coorte HEROES

RESUMEN Objetivos. Evaluar la prevalencia de base de los trastornos de salud mental y exposiciones conexas en una cohorte de trabajadores de salud de Guatemala. Métodos Se analizó la información de base del estudio HÉROES (por COVID-19 HEalth caRe wOrkeRs Study, sobre los trabajadores de salud durante la pandemia) en Guatemala, realizado en línea en el 2020. Las variables de resultado fueron malestar psicológico y síntomas depresivos. Las exposiciones incluyeron experiencias con la COVID-19, características sociodemográficas y características del trabajo. En los análisis se utilizaron modelos de regresión de Poisson brutos y ajustados. Resultados. De los 1801 trabajadores de salud que aceptaron participar, 1522 (84,5%) completaron el cuestionario; 1014 (66,8%) eran mujeres. De los participantes, 59,1% (intervalo de confianza de 95% [IC 95%] = 56,6-61,5) tuvo un tamizaje positivo para malestar psicológico y 23% (IC 95% = 20,9-25,2) para síntomas depresivos de moderados a graves. Las experiencias con la pandemia de COVID-19, las características sociodemográficas y las características del trabajo se correlacionaron con las variables de resultado del estudio. Los participantes que estaban preocupados por el contagio de la COVID-19 tuvieron un mayor riesgo de malestar psicológico (riesgo relativo [RR] = 1,47; IC 95% = 1,30-1,66) y síntomas depresivos (RR = 1,51; IC 95% = 1,17-1,96). Asimismo, los participantes más jóvenes presentaban un riesgo alto de malestar psicológico (RR = 1,80; IC 95% = 1,24-2,63) y síntomas depresivos (razón de posibilidades [OR] = 4,58; IC 95% = 1,51-13,87). Conclusiones. Las afecciones de salud mental tienen una prevalencia sumamente alta en los trabajadores de salud de Guatemala.

ABSTRACT Objectives. To assess the baseline prevalence of mental health conditions and associated exposures in a cohort of health care workers (HCWs) in Guatemala. Methods. We analyzed baseline information from the 2020 Web-based COVID-19 Health Care Workers Study (HEROES)-Guatemala. Outcomes included mental distress and depressive symptoms. Exposures included COVID-19 experiences, sociodemographic characteristics, and job characteristics. We used crude and adjusted Poisson regression models in our analyses. Results. Of the 1801 HCWs who accepted to participate, 1522 (84.5%) completed the questionnaire; 1014 (66.8%) were women. Among the participants, 59.1% (95% confidence interval [CI] = 56.6, 61.5) screened positive for mental distress and 23% (95% CI = 20.9, 25.2) for moderate to severe depressive symptoms. COVID-19 experiences, sociodemographic characteristics, and job characteristics were associated with the study outcomes. Participants who were worried about COVID-19 infection were at higher risk of mental distress (relative risk [RR] = 1.47; 95% CI = 1.30, 1.66) and depressive symptoms (RR = 1.51; 95% CI = 1.17, 1.96). Similarly, the youngest participants were at elevated risk of mental distress (RR = 1.80; 95% CI = 1.24, 2.63) and depressive symptoms (OR = 4.58; 95% CI = 1.51, 13.87). Conclusions. Mental health conditions are highly prevalent among Guatemalan.

RESUMO Objetivos. Avaliar a prevalência basal de condições de saúde mental e exposições associadas em uma coorte de trabalhadores da saúde (TS) na Guatemala. Métodos. Analisamos as informações da linha de base do estudo on-line sobre trabalhadores da saúde e a COVID-19 (HEROES), realizado em 2020 na Guatemala. Os desfechos incluíram angústia debilitante e sintomas de depressão. As exposições incluíram experiências com a COVID-19, características sociodemográficas e características do trabalho. Usamos em nossas análises modelos de regressão bruta e ajustada de Poisson. Resultados. Dos 1801 TS que concordaram em participar, 1522 (84,5%) preencheram o questionário, sendo que 1014 (66,8%) eram mulheres. Dentre esses participantes, 59,1% (intervalo de confiança [IC] de 95%=56,6; 61,5) apresentaram resultado positivo na triagem de angústia debilitante e 23% (IC 95%=20,9, 25,2) apresentaram resultado positivo para sintomas de depressão moderados a graves. Experiências com COVID-19, e características sociodemográficas e de trabalho apresentaram associação com os resultados do estudo. Os participantes que estavam preocupados com infecção por COVID-19 apresentaram maior risco de angústia debilitante (risco relativo [RR]=1,47; IC95%=1,30; 1,66) e sintomas de depressão (RR=1,51; IC 95% =1,17; 1,96). Da mesma maneira, os participantes mais jovens apresentaram alto risco de apresentarem angústia debilitante (RR=1,80; IC 95%=1,24; 2,63) e sintomas de depressão (OR=4,58; IC 95%=1,51; 13,87). Conclusões. Condições de saúde mental são altamente prevalentes entre os guatemaltecos.

Prevalencia de embarazo en adolescentes, Yopal-Casanare, Colombia, 2013-2014 / Prevalence of teenage pregnancy in Ybpal-Casanare, Colombia, 2013-2014

RESUMEN Objetivo: Establecer la prevalencia de embarazo en mujeres adolescentes desde los registros de nacidos vivos del municipio de Yopal entre 2013-2014. Materiales y métodos: Estudio descriptivo transversal desde la base de datos del módulo de nacidos vivos del Registro Único de Afiliados del Departamento Nacional de Estadística (DANE), suministrado por la Secretaría de Salud de Yopal. Se incluyeron registros completos de toda gestante menor de 19 años. Se estudiaron sus características sociodemográficas, antecedentes de la gestación y características específicas del nacimiento. Análisis mediante estadística descriptiva. Resultados: El 21,9 % (1.286/5.848) de registros correspondieron a gestantes adolescentes entre 1019 años, con edad promedio 17,4 ± 1,47 años; edad promedio del padre 23,9 ± 5,66 años; mediana de embarazos = 1 (rango = 1-4); más de cuatro controles prenatales 707 (55,0 %); primigestantes 1.033 (80,3 %); periodo intergenésico menor de dos años 54 (25,7 %); parto espontáneo 894 (69,5 %) y cesárea 392 (30,5 %); presentaron bajo peso al nacer 54 (4,2 %) neonatos. Conclusión: La prevalencia del embarazo en adolescentes en Yopal fue superior a la nacional, de 19,5 %; las gestantes adolescentes del área rural acceden menos a los controles prenatales. Estos datos conllevan revisar y fortalecer las estrategias municipales de prevención de este evento.

ABSTRACT Objective: To determine the prevalence of teenage pregnancy on the basis of live birth records in the Municipality of Yopal between 2013-2014. Materials and methods: Descriptive cross-sectional study conducted on the basis of the live birth module database contained in the Single Registry of the National Statistics Department (DANE), made available by the Health Secretariat of Yopal. Full records of all pregnant women under 19 were included. Sociodemographic characteristics, pregnancy history and specific characteristics of the birth were studied. Descriptive statistical analysis was done. Results: Of the records, 21.9 %(1,286/5,848) were pregnant teens between 10-19 years, with a mean age of 17.4 ± 1.47 years; mean age of the fathers was 23.9 ± 5.66 years; pregnancy median = 1 (range = 1-4); more than four prenatal visits 707 (55.0 %); primigravidae 1,033 (80.3 %); inter-pregnancy period of less than two years 54 (25.7 %); spontaneous delivery 894 (69.5 %) and cesarean section 392 (30,5 %); low birth weight, 54 (4.2 %) neonates. Conclusion: The prevalence of pregnancy among adolescents in Yopal was higher than the national prevalence, at 19.5 %; pregnant adolescents who come from the rural areas have access to a smaller number of prenatal visits. These data point to the need of revisiting and strengthening municipal strategies for the prevention of teenage pregnancy.

Expression of recombinant SnRK1 in E. coli. Characterization of adenine nucleotide binding to the SnRK1.1/AKINßγ-ß3 complex.

The SnRK1 complexes in plants belong to the family of AMPK/SNF1 kinases, which have been associated with the control of energy balance, in addition to being involved in the regulation of other aspects of plant growth and development. Analysis of complex formation indicates that increased activity is achieved when the catalytic subunit is phosphorylated and bound to regulatory subunits. SnRK1.1 subunit activity is higher than that of SnRK1.2, which also exhibits reduced activation due to the regulatory subunits. The catalytic phosphomimetic subunits (T175/176D) do not exhibit high activity levels, which indicate that the amino acid change does not produce the same effect as phosphorylation. Based on the mammalian AMPK X-ray structure, the plant SnRK1.1/AKINßγ-ß3 was modeled by homology modeling and Molecular Dynamics simulations (MD). The model predicted an intimate and extensive contact between a hydrophobic region of AKINßγ and the ß3 subunit. While the AKINßγ prediction retains the 4 CBS domain organization of the mammalian enzyme, significant differences are found in the putative nucleotide binding pockets. Docking and MD studies identified two sites between CBS 3 and 4 which may bind adenine nucleotides, but only one appears to be functional, as judging from the predicted binding energies. The recombinant AKINßγ-ßs complexes were found to bind adenine nucleotides with dissociation constant (Kd) in the range of the AMP low affinity site in AMPK. The saturation binding data was consistent with a one-site model, in agreement with the in silico calculations. As has been suggested previously, the effect of AMP was found to slow down dephosphorylation but did not influence activity.

GIST apendicular / Appendicular GIST

El tumor del estroma gastrointestinal (Gastrointestinal Stromal Tumor, GIST), localizado en el apéndice, constituye una entidad poco frecuente. Su cuadro clínico e imaginológico es indistinguible de una apendicitis aguda, por lo que su diagnóstico definitivo está dado por el estudio histopatológico e inmunohistoquímico. El tratamiento estándar es la apendicectomía. El propósito de este artículo es la presentación de un caso clínico y la revisión de la literatura.

The gastrointestinal stromal tumor (GIST) located in the appendix is a rare entity. It is clinical indistinguishable from acute appendicitis, so definitive diagnosis is given by the histopathological and immunohistochemical studies. The standard treatment is appendectomy. The purpose of this article is presenting a case study and review of the literature.

Leuprolide acetate-stimulated androgen response during female puberty.

BACKGROUND: A physiological increase in androgen levels occurs during adolescence. Measuring androgen concentrations is the best method to distinguish normal evolution processes from hyperandrogenic disorders. HYPOTHESIS: The increase in circulating androgens during puberty is inversely associated with insulin sensitivity in normal weight girls. OBJECTIVE: To assess circulating levels of ovarian androgens and anti-Müllerian hormone (AMH) at baseline and after GnRH analogue (GnRH-a) stimulation in normal pubertal girls across different Tanner stages. We also studied the association between this response and insulin sensitivity. DESIGN: Prospective study of healthy girls (6-12 years) from the local community (n = 63). METHODS: Tanner I (n = 23) subjects were assessed cross-sectionally, and Tanner II girls (n = 40) were evaluated every 6 months until they reached Tanner V. Early morning dehydroepiandrosterone sulphate (DHEA-S), AMH, sex hormone-binding globulin (SHBG), androstenedione, glucose and insulin levels were measured. A GnRH-a test (500 µg/m(2) ; sc) and oral glucose intolerance test (OGTT) were performed. Differences throughout puberty were evaluated. RESULTS: Basal and/or stimulated Testosterone DHEA-S and 17-hydroxyprogesterone (17OHP) were inversely associated with insulin sensitivity (WIBSI) from the beginning of puberty, whereas androstenedione was directly associated with gonadotrophins. AMH was inversely associated with basal and stimulated gonadotrophins and directly with insulin area under the curve (AUC) only in the early stages of puberty. 17OHP and testosterone responsiveness increased significantly during puberty in all subjects, whereas testosterone levels changed less consistently. This pattern of ovarian-steroidogenic response was most evident during mid- and late puberty. Moreover, during late puberty only, basal 17OHP, testosterone and DHEA-S were positively associated with gonadotrophins. CONCLUSION: In normal nonobese girls born appropriate for gestational age, androgen synthesis was associated with insulin sensitivity in early puberty and with LH only in late puberty.

El estado de salud de las mujeres latinoamericanas y su relación con la desigualdad de género / The health status of Latin American women and its relation with gender inequality

Existen diferencias en las manifestaciones clínicas de la insuficiencia cardíaca entre los géneros, hay una mayor proporción de mujeres con insuficiencia cardíaca de etiología hipertensiva y una menor frecuencia de cardiopatía isquémica; la diabetes es un factor de riesgo de insuficiencia cardíaca en las mujeres pos menopáusicas. Estas diferencias se explican por factores hormonales, de esta manera, con la edad, la masa del ventrículo izquierdo se incrementa en las mujeres, quienes presentan hipertrofia concéntrica, en tanto que disminuye en los hombres generando hipertrofia excéntrica. Esta diferencia favorece que la presentación de la enfermedad tenga lugar tardíamente en las mujeres, explicada por la menopausia, ya que los estrógenos reducen la masa ventricular izquierda, disminuyen la fibrosis, los niveles de renina y mejoran la vasodilatación. La insuficiencia cardíaca con función ventricular izquierda conservada es la presentación clínica más frecuente, sin embargo, las manifestaciones de la enfermedad se descubren tardíamente, y se estudian con menor frecuencia; además, se ha demostrado que las mujeres tienen una peor calidad de vida, peor estado funcional y más síntomas psicológicos que los hombres. Hasta la fecha no se conocen estudios en Latinoamérica que hayan evaluado la prevalencia, la presentación clínica, la etiología ni el pronóstico de las mujeres con insuficiencia cardíaca y por esta razón es primordial iniciar un registro que permita conocer el estado de la salud cardiovascular de las mujeres latinoamericanas y avanzar en la reducción de las inequidades...

Hormonal profile and androgen receptor study in prepubertal girls with hypertrichosis.

BACKGROUND: Prepubertal hypertrichosis is a reportedly benign condition characterized by an excessive growth of vellous hair in non-androgen dependent areas of the body compared to the amount usually present in normal subjects of the same age, race and sex. Although this condition is usually considered idiopathic and regarded as benign, it may be very disturbing cosmetically, causing significant patient and parental anxiety. METHOD: We performed a hormonal and androgen receptor study in 42 prepubertal girls with hypertrichosis and 29 control girls from 2 to 8 years of age. Both groups underwent a determination of basal LH, FSH, 17OH progesterone, androstenedione, testosterone, estradiol and SHBG, abdominal ultrasound to assess ovarian morphology, and the number of androgen receptor CAG/GGC repeats in DNA obtained from peripheral leukocytes. RESULTS: The hypertrichosis score was higher in the cases compared to controls. Serum gonadotropins and sex steroids were similar in both groups, but SHBG was significantly lower in the girls with hypertrichosis (71.1 ± 2.9 vs 81.9 ± 3.0 nmol/L, p < 0.02). The distribution of shorter, larger and total alleles was not statistically different between cases and controls. The combined analysis of CAG/GGC, however, showed a significantly higher prevalence of the most androgen-sensitive haplotypes (1-2: <22CAG + 17/17GGC- < 14CAG + 17/18GGC) in girls with hypertrichosis compared to controls. CONCLUSIONS: We conclude that girls with hypertrychosis exhibit AR(s) with enhanced sensitivity, which may facilitate the growth of their body hair.

Diferencias de género en el tratamiento de la falla cardíaca / Gender differences in the treatment of heart failure

INTRODUCCIÓN: la falla cardíaca representa un problema creciente de salud con una alta prevalencia en el sexo femenino; sin embargo, no se han reportado estudios en población de mujeres latinoamericanas que permitan identificar si existen diferencias de género tanto en la presentación clínica como en el tratamiento de esta patología. OBJETIVO: evaluar si existen diferencias tanto en las características clínicas y epidemiológicas como en el manejo farmacológico en función del género, en una serie de pacientes con falla cardíaca atendidos en un centro de referencia cardiovascular en Colombia. METODOLOGÍA: estudio observacional, descriptivo, que evaluó a todos los pacientes hospitalizados por síndrome de falla cardiaca como diagnóstico principal durante julio de 2009 y julio de 2010 en un centro de referencia cardiovascular colombiano. RESULTADOS: se incluyeron 204 pacientes, 36,7% de sexo femenino, cuya edad promedio fue mayor en las mujeres; la fracción de eyección promedio fue similar. Las mujeres tenían falla renal con mayor frecuencia. Se encontró menor uso de betabloqueadores, así como de implante de cardiodesfibrilador. CONCLUSIÓN: para la población estudiada se encontró que existen diferencias entre ambos sexos tanto en las variables demográficas como clínicas. A pesar de presentar mayores comorbilidades, las mujeres con falla cardiaca reciben con menor frecuencia terapias como los betabloqueadores y el cardiodesfibrilador implantable que han demostrado disminuir la mortalidad. Es necesario ampliar el conocimiento de las diferencias de género mediante la creación de un registro multicéntrico latinoamericano que permita incidir en la toma de decisiones clínicas propias para la región.

INTRODUCTION: heart failure is a growing health problem with a high prevalence in females; however, there are no studies reporting if there are gender differences in both the clinical presentation and treatment of this pathology in Latin-American women. OBJECTIVE: to assess whether there are differences in both clinical and epidemiological characteristics and pharmacological management in terms of gender, in a series of patients with heart failure treated at a cardiovascular referral center in Colombia. METHODS: observational descriptive study, which evaluated all patients hospitalized for heart failure syndrome as the primary diagnosis between July 2009 and July 2010 in a Colombian cardiovascular referral center. RESULTS: 204 patients were included, 36.7% were females. Mean age was higher in women; the mean ejection fraction was similar in both groups. Women had more frequently renal failure. Lower use of beta blockers, as well as of cardiac defibrillator implant was found in women. CONCLUSION: in this study population we found that there are gender differences in both demographic and clinical variables. Despite presenting more comorbidities, women with heart failure less frequently receive the therapies that have shown to reduce mortality such as beta blockers and implantable cardioverter defibrillator. It is necessary to expand our knowledge of gender differences through the creation of a Latin American multicenter registry that effectively enable to influence the clinical decision making proper for the region.

Ovarian function in adolescents with McCune-Albright syndrome.

OBJECTIVE: To evaluate ovarian function, especially ovulation rate, in adolescents with McCune-Albright syndrome (MAS) and a history of peripheral precocious puberty. DESIGN: Prospective cross-sectional study. SETTING: Academic center. PATIENT(S): A total of eight adolescents with MAS were compared with 15 healthy adolescents matched by age, Tanner stage and body mass index. INTERVENTION(S): We determined basal gonadotropins, sex steroids, sex hormone binding globulin, anti-Müllerian hormone, glucose and insulin. A leuprolide acetate test was performed to measure luteinizing hormone (LH) and follicle stimulating hormone (FSH) (at 0 and 3 h), and 17B-estradiol, testosterone and 17-OH-progesterone (at 0 and 24 h). Salivary progesterone levels were used to assess ovulation during the 13th, 18th, 23rd and 28th days of each menstrual cycle for three to five consecutive cycles, and one pelvic ultrasound was performed during the follicular phase. MAIN OUTCOME MEASURE(S): Ovulation rate in adolescents with MAS. RESULT(S): The proportion of ovulatory cycles was 52.6% in controls compared with 35.7% in patients with MAS. CONCLUSION(S): The adolescent girls with MAS appear to have a lower ovulatory rate compared with controls.

Effects of the IGF-I/IGFBP-3 complex on GH and ghrelin nocturnal concentrations in low birth weight children.

OBJECTIVE: There is limited information regarding the effects of IGF-I and/or IGFBP-3 on circulating ghrelin concentrations. To determine the effects of IGF-I on GH and ghrelin concentrations, we examined the GH and ghrelin nocturnal profiles before and after the administration of the IGF-I/-IGFBP-3 complex (Iplex) to low birth weight children. DESIGN: The children were studied on two separate occasions, the first under basal conditions, and the second time after the sc administration of 1 mg/kg of Iplex at 2100 h. Blood samples for determination of GH and ghrelin were obtained every 20 min between 2300 h and 0700 h, while the children were sleeping. In each patient, we calculated the mean GH and ghrelin area under the curve (GH AUC and GHR AUC), both under basal conditions and after the administration of the IGF-I/IGFBP-3 complex. SETTING: The study was performed at a University Research Centre located at a General Hospital in Santiago, Chile. PATIENTS: Twenty prepubertal children (11 boys and 9 girls), born after a full-term pregnancy with a birth weight below 2.8 kg were studied at a mean +/- SEM age of 7.3 +/- 0.5 years (range 4-11 years). Their mean height was -1.8 +/- 0.3 standard deviation score (SDS) and their mean BMI was 0.1 +/- 0.2 SDS at the time of the study. MAIN OUTCOME AND RESULTS: Mean nocturnal GH AUC exhibited a significant decrease (2903 +/- 185 vs 1860 +/- 122 ng/ml min, P < 0.01), whereas mean GHR AUC showed a significant increase after administration of the IGF-I/IGFBP-3 complex (68 +/- 16 vs 288 +/- 36 ng/ml min, P < 0.01). CONCLUSIONS: These findings indicate that the IGF-I/IGFBP-3 complex appears to have opposite effects on circulating GH and ghrelin concentrations in low birth weight children, suggesting that, in addition to its known negative feed-back effect on GH, IGF-I and/or IGFBP-3 may have a positive feed-back effect on ghrelin.

Diagnostic criteria for polycystic ovary syndrome and ovarian morphology in women with type 1 diabetes mellitus.

CONTEXT: The criteria for diagnosis of polycystic ovary syndrome (PCOS) have been modified and now include polycystic ovary morphology (PCOM). OBJECTIVE: The purpose of this study was to determine the frequency of PCOS and PCOM in women with type 1 diabetes mellitus (DM1). DESIGN: We evaluated the clinical, hormonal, and ultrasonographic characteristics in women with DM1 and compared them with a carefully matched group of normal women in a cross-sectional study. SETTING: The study was conducted at an academic research institute located within a general hospital. PATIENTS: All the women with DM1 attending our hospital who had experienced menarche at least 2.5 yr earlier were invited to participate and were compared with healthy women with regular menses and without a history of hyperandrogenism [controls (C)]. RESULTS: Hirsutism was present in 28.6 and 0.0% of DM1 and C, respectively (P < 0.001). Biochemical hyperandrogenism was present in 23.8 and 7.9% of DM1 and C, respectively. DM1 women had higher levels of testosterone and androstenedione and larger ovarian volume and follicle number by ovary than C. PCOM was present in 54.8% of DM1 and 13.2% of C (P < 0.001). Oligomenorrhea was present in 19% of women with DM1. The frequency of PCOS was 40.5 and 2.6% in DM1 and C, respectively (relative risk, 15.4; 95% confidence interval, 2.2-110.2; P < 0.0001). The proportion of women using intensive insulin treatment was higher in those with PCOM/PCOS (P < 0.05). Intensive treatment was a significant factor over having PCOM/PCOS (P < 0.05). CONCLUSIONS: A high frequency of hyperandrogenism, PCOM, and PCOS is observed in DM1, which appears to be associated with intensive insulin treatment.

Activating GNAS1 gene mutations in patients with premature thelarche.

OBJECTIVE: To identify GNAS1 gene mutations in girls with exaggerated and/or chronic fluctuating thelarche for at least 1-year duration with no other signs of precocious puberty, skeletal dysplasia, or typical skin lesions of McCune-Albright syndrome. STUDY DESIGN: We studied the GNAS1 gene mutation by allele-specific polymerase chain reaction and enzymatic digestion in leukocyte DNA in 23 girls previously described. RESULTS: Fluctuating thelarche was present in 14 girls and exaggerated thelarche was observed in 9. Molecular study revealed that 6 girls had a substitution of arginine by histidine in codon 201 (R201H [+]). Three R201H (+) girls reached their menarche at a mean chronologic age of 10.8 years and 9 of the R201H (-) girls at a mean age of 11 years. CONCLUSIONS: Activating mutations of GNAS1 gene may be observed in some girls with chronic fluctuating and/or exaggerated thelarche, without other classic signs of McCune-Albright syndrome.

Changes in appetite and body weight in response to long-term oral administration of the ghrelin agonist GHRP-2 in growth hormone deficient children.

GHRP-2 (GPA-748, Wyeth-Ayerst) is an orally active peptide growth hormone (GH) secretagogue which acts through a G-protein coupled receptor for which the natural ligand--an acylated 28 amino acid peptide, ghrelin--was recently isolated. Ghrelin and its analogs have potent GH-releasing activities, but in animal studies ghrelin also causes weight gain. As part of a study examining the effect of GHRP-2 on GH secretory dynamics and growth, we evaluated its effects on appetite and body weight. Ten prepubertal children with GH deficiency (growth velocity < or = 4 cm/year in association with a GH response to two provocative stimuli < 10 ng/ml) were included in the study. At the beginning of the study their age was 10.4 +/- 2 years (mean +/- SD), with a height of -3.8 +/- 0.1 SDS. Body mass index (BMI) was 17.9 +/- 3.6 kg/m2, and the BMI Z score 0.21 +/- 1.51 SDS. GHRP-2 was administered orally at a dose of 900 microg/kg b.i.d. for 12 months. Seven out of ten patients reported a significant increase in appetite during the first 6 months of the study. There was a tendency for the BMI SDS to increase during the study, but this increase did not reach statistical significance (0.21 +/- 1.5 vs 0.25 +/- 1.5 SDS). These results suggest that at a dose of 900 microg/kg b.i.d., GHRP-2 appears to have a transient stimulatory effect on appetite, but does not have a chronic clinically significant effect on BMI in children with GH deficiency.

Fasting and post-glucose ghrelin levels in SGA infants: relationships with size and weight gain at one year of age.

Wide ranges in postnatal weight gain are seen in infants born small for gestational age (SGA); most show some catch-up growth and this may be driven by increased appetite. Ghrelin, the natural ligand of the GH secretagogue receptor, has potent orexigenic effects. In adults circulating ghrelin levels are increased in anorexia, decreased in obesity and show post prandial suppression. The aim of the present study was to test the hypothesis that rate of weight gain over the first year in SGA infants may relate to variable suppression of circulating ghrelin levels. Serum ghrelin levels were measured in 1 y old infants born SGA (n = 85) and in control infants born adequate for gestatitional age (AGA) (n = 22) fasting and 10 minutes after intravenous (iv) glucose (0.5 g/Kg of 25% dextrose). Sex- and gestational age-adjusted SD scores (SDS) for body weight were calculated at birth and at 1 y, and delta weight SDS between 0-1 y was calculated as an index of postnatal weight gain. In both SGA and AGA groups, ghrelin levels reduced from fasting (mean +/- SE: 104.4 +/- 6.4 fmol/ml) to 10 minutes post-iv glucose (82.7 +/- 5.3, p < 0.005). There were no differences in ghrelin levels between SGA and AGA infants (fasting or post-iv glucose). However, in SGA infants ghrelin levels post-glucose, but not fasting, were psitively related to current length (r = 0.28, p < 0.05), weight (r = 0.23, p < 0.05) and to change in weight SDS 0-1 y (r = 0.22, p < 0.05). SGA infants who showed poor catch-up growth showed a larger decline in ghrelin concentrations post-iv glucose. In conclusion, circulating ghrelin levels rapidly decreased after iv glucose. Higher ghrelin levels or lower reductions in circulating levels following iv glucose were seen in SGA infants who showed greater infancy weight gain, suggesting that sustained orexigenic drive could contribute to postnatal catch-up growth.

Effects of treatment with GH alone or in combination with LHRH analog on bone mineral density in pubertal GH-deficient patients.

The aim of the present study was to assess the impact of treatment with GH with or without LHRH analog (LHRH-A) on bone mineralization of GH-deficient adolescents. We studied 17 pubertal, treatment-naive, GH-deficient patients (10 girls and 7 boys) in a prospective, randomized trial. Mean chronological age and mean bone age were 14.1 +/- 0.4 and 11.3 +/- 0.3 yr, respectively, at the beginning of the study. Treatment with GH + LHRH-A (n = 7) or GH alone (n = 10) started simultaneously. Nutropin was administered at a dose of 0.1 U/kg per day sc until patients reached near final height (NFH), defined as a bone age of 14 yr in girls and 16 yr in boys. Mean time of GH therapy in the patients treated with GH+LHRH-A was 4.8 +/- 0.5 yr and in the patients treated with GH alone 2.9 +/- 0.7 yr. Lupron was administered at a dose of 300 microg/kg every 28 d im for 3 yr. Bone mineral density (BMD) was assessed yearly by dual-energy x-ray absorptiometry at the lumbar spine (L2-L4) and femoral neck at the beginning of the study, after 3 yr of hormonal therapy, and at NFH. Statistical analysis was performed by t test and ANOVA. We observed a significant increase in lumbar and femoral bone mineral content, BMD, SD score, and bone mineral apparent density, compared with baseline in both groups of patients, regardless of whether they were treated with GH alone or in combination with LHRH-A. The patients treated with GH + LHRH-A had a significantly lower bone mineral content after 3 yr of therapy. This difference, however, did not persist after both groups of patients reached NFH. These results indicate that delaying puberty with LHRH-A in GH-deficient patients treated with GH diminishes transient bone mineralization but does not appear to have a permanent impact on BMD.