Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity.

OBJECTIVE: To determine whether insulin-sensitizing drugs would improve ovulation and T levels in women with polycystic ovary syndrome (PCOS), without clinical or biochemical criteria indicating insulin resistance and whether the combination of two distinct insulin-sensitizing drugs would be of any benefit over either drug alone. DESIGN: Randomized controlled double-blind trial. SETTING: A referral center in Caracas, Venezuela. PATIENT(S): One hundred twenty-eight nonobese PCOS women with normal indices of insulin sensitivity-that is, normal glucose tolerance, fasting insulin, peak insulin during an oral glucose tolerance test (OGTT), and fasting glucose-to-insulin ratio. Twenty-eight women were lost to follow-up initially and did not receive any intervention. INTERVENTION(S): One hundred women received twice daily one of the following for 6 months: metformin (850 mg), rosiglitazone (4 mg), combination of both drugs, or at least one placebo. MAIN OUTCOME MEASURE(S): Frequencies of ovulation and serum free T after 6 months. RESULT(S): Frequencies of ovulation were higher after treatment with an insulin-sensitizing drug (ovulations per subject in 6 months: metformin, 3.3; rosiglitazone, 2.4; and combination, 3.4) than with placebo (0.4). Ovulatory frequencies increased significantly more with metformin than rosiglitazone, and the combination was not more potent. After treatment, serum free-T levels were comparable among all active treatment groups (metformin: 2.34 pg/mL, rosiglitazone: 3.06 pg/mL, and combination: 2.39 pg/mL) and were significantly lower than in the placebo group (7.26 pg/mL). Compared with placebo, fasting insulin levels, area under the insulin curve during OGTT, the homeostatic model assessment of insulin sensitivity, and OGTT-derived insulin sensitivity index improved significantly after metformin or combination therapies but not after rosiglitazone. CONCLUSION(S): These findings suggest that insulin-sensitizing drugs increase ovulatory frequency and ameliorate hyperandrogenemia, even in nonobese women with PCOS who appear to have normal insulin sensitivity.

Accelerated versus slowly progressive forms of puberty in girls with precocious and early puberty. Gonadotropin suppressive effect and final height obtained with two different analogs.

OBJECTIVES: To distinguish which children with precocious puberty (PP) and early puberty (EP) should be treated and which followed without therapy. To determine the effect of GnRH analog treatment on the final height of treated patients and compare the effect of two different analogs on gonadotropin suppression and final height. STUDY DESIGN: Sixteen females with PP or EP with a mean chronological age (CA) of 8.8 +/- 1.4 years and a mean bone age (BA) of 10.8 +/- 1.3 years were treated for a mean of 2.7 +/- 1.0 years with a GnRH analog (triptorelin or leuprolide acetate; group A), while 21 girls with a mean CA of 8.5 +/- 1.0 years, a mean BA of 9.7 +/- 1.4 years and a predicted adult height of >155 cm were followed without therapy (group B). Criteria for treatment were one of: a. predicted adult height (PAH) of <155 cm initially or at any time during follow up; b. PAH over 155 cm with a dramatic decrease in PAH over a 6-month follow-up period; c. advanced and rapidly progressing breast development for age (Tanner 3 before the age of 9 years). RESULTS: GnRHa therapy suppressed gonadotropins in group A, while gonadotropins increased gradually in group B. Height velocity (HV) decreased in group A, while it remained accelerated in group B; BA increased a mean of 1.7 +/- 0.5 years in group A and 3.2 +/- 0.3 years in group B. This resulted in a height increase in group A from a baseline PAH of 153.7 +/- 1.2 cm to a final height (FH) of 160.9 +/- 4.0 cm (p <0.001), clearly above their target height (TH) of 157.7 +/- 4.2 cm. The height of group B children did not change over time (164.1 +/- 4.1 cm before therapy and 166.0 +/- 6.0 cm at FH), both above their TH. The mean leuprolide acetate dose utilized in this study decreased during treatment, while both the initial and final triptorelin dose remained unchanged. Adequate gonadotropin suppression (peak level of LH and FSH of <2 IU/l after i.v. GnRH stimulation) was noted with both leuprolide acetate and triptorelin, although LH suppression was slightly more pronounced with triptorelin. BA advanced 1.8 +/- 0.4 years during leuprolide acetate treatment and 1.5 +/- 0.3 years with triptorelin, so that FH increased a mean of 5.5 +/- 1.3 cm with leuprolide acetate and 8.7 +/- 2.2 cm with triptorelin. CONCLUSIONS: PAH of <155 cm before or during therapy, PAH of >155 cm with a dramatic decrease in predicted height over a 6-month follow-up period and/or advanced and rapidly progressing breast development in girls with PP or EP were useful parameters in deciding which patients to treat. GnRHa therapy suppressed gonadotropins, HV and bone maturation in children with an accelerated form of PP or EP, resulting in a significant height increase. Final height remained stable over time in untreated patients. Adequate gonadotropin suppression was noted with both analogs, although with the doses of analog used in our study, LH and BA suppression were more pronounced with triptorelin, resulting in a larger height gain.

Reduced serum glycodelin and insulin-like growth factor-binding protein-1 in women with polycystic ovary syndrome during first trimester of pregnancy.

The polycystic ovary syndrome (PCOS) is associated with an increased rate of early pregnancy loss (EPL). Hyperinsulinemia is an independent risk factor for EPL and has been found to decrease levels of glycodelin and IGF binding protein-1 (IGFBP-1), two major endometrial proteins. We hypothesized that serum glycodelin IGFBP-1 concentrations would be reduced in women with PCOS during the first trimester of pregnancy. Fasting serum insulin, glycodelin, and IGFBP-1 were measured, and oral glucose tolerance tests were performed in 72 women with PCOS and 62 normal women. Each woman was seen once and assigned to one of three gestational groups: wk 3-5, 6-8, and 9-11. The insulin sensitivity index during oral glucose tolerance test was lower in women with PCOS compared with normal women throughout the first trimester (P < 0.0001). Both serum glycodelin and IGFBP-1 were markedly lower in women with PCOS (for glycodelin: wk 3-5, P < 0.0001; wk 6-8, P = 0.03; wk 9-11, P = 0.19; and for IGFBP-1: wk 3-5 and 6-8, P < 0.0001; wk 9-11, P = 0.0003). Comparing women with PCOS who experienced EPL with those who did not, serum glycodelin was significantly lower during wk 3-8 (P < 0.02) and serum IGFBP-1 during wk 9-11 (P = 0.003). During the first trimester, serum glycodelin and IGFBP-1 concentrations are markedly decreased in PCOS, implicating endometrial epithelial and stromal dysfunction during periimplantation and early pregnancy as a possible mechanism for EPL in PCOS. These decreases are likely to be secondary to hyperinsulinemia and reduced insulin sensitivity.

Is insulin-like growth factor-1 monitoring useful in assessing the response to growth hormone of growth hormone-deficient children?

OBJECTIVE: To assess the relationship between insulin-like growth factor-1 (IGF-1), the growth hormone (GH) dose utilized to treat GH-deficient children and the changes noticed in height-standard deviation score (H-SDS) and height velocity (HV). STUDY DESIGN: We studied 24 prepubertal GH-deficient patients with a mean age of 10.5 +/- 1.8 years and a mean bone age (BA) of 8.4 +/- 2.1 years. H-SDS for chronologic age (CA) and BA before therapy were -2.6 +/- 0.8 and -1.2 +/- 0.8, whereas height velocity (HV)-SDS was -1.1 +/- 1.5. Serum IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) levels were measured before, after 6 and 12 months of GH, and correlated with the GH dose used. Based on the increment of IGF-1 used during treatment, patients were divided into 2 groups: G1 (>1 SDS) and G2 (<1 SDS). HV-SDS and interval height increases were analyzed. RESULTS: HV-SDS, as well as H-SDS for CA and BA during the first year of treatment, were significantly greater than before therapy. IGF-1 SDS increased significantly during the first 6 months of therapy (P <.0003), but increased no further at 12 months despite the use of a higher GH dose (0.1 vs 0.14 IU/kg/day), whereas IGFBP-3 SDS increased at both 6 and 12 months. There was no correlation between the GH dose used and IGF-1 and IGFBP-3 levels. When patients were divided according to their IGF-1 increment during therapy, a significant increase in H-SDS for BA and in HV-SDS was noted only in group 2. CONCLUSIONS: The increment in IGF-1 SDS during therapy did not correlate with the interval height increase. IGF-1 measurement may be helpful in monitoring compliance and safety, but seems to be less useful in adjusting the GH dose needed to treat prepubertal GH-deficient children.

Effects of metformin on early pregnancy loss in the polycystic ovary syndrome.

Polycystic ovary syndrome is the most common form of female infertility in the United States. In addition to poor conception rates, pregnancy loss rates are high (30-50%) during the first trimester. We hypothesized that hyperinsulinemic insulin resistance contributes to early pregnancy loss in the syndrome, and that decreasing hyperinsulinemic insulin resistance with metformin during pregnancy would reduce the rate of early pregnancy loss. We conducted a retrospective study of all women with polycystic ovary syndrome who were seen in an academic endocrinology clinic within the past 4.5 yr and who became pregnant during that time. Sixty-five women received metformin during pregnancy (metformin group) and 31women did not (control group). The early pregnancy loss rate in the metformin group was 8.8% (6 of 68 pregnancies), as compared with 41.9% (13 of 31 pregnancies) in the control group (P < 0.001). In the subset of women in each group with a prior history of miscarriage, the early pregnancy loss rate was 11.1% (4 of 36 pregnancies) in the metformin group, as compared with 58.3% (7 of 12 pregnancies) in the control group (P = 0.002). Metformin administration during pregnancy reduces first-trimester pregnancy loss in women with the polycystic ovary syndrome.

Enfermedades tropicales en niños: una evaluación hospitalaria / Tropical disease in children: a hospital evaluation

Las enfermedades tropicales son muy frecuentes en los niños de los países subdesarrollados. Venezuela, ubicada en estos países, tiene a su población infantil expuesta a estas enfermedades, las cuales ameritan evaluaciones y actualizaciones constantes. En un estudio prospectivo de enfermedades tropicales, efectuado en el Hospital Universitario de Caracas, se incluyeron 341 niños con diagnóstico de certeza de estas enfermedades. Cuyo propósito fue, el de obtener información sobre la atención hospitalaria y la justificación de las hospitalizaciones. Se identificaron 45 niños con paludismo, 163 con leishmaniasis, 7 con amibiasis, 98 con dengue, 15 con emponzoñamiento ofídico, 3 con emponzoñamiento escorpiónico, 6 con cisticercosis y 4 con diarrea bacterianas. Procedían de 17 entidades federales del país. Enero fue el mes con el mayor porcentaje de ingresos (14,9 por ciento). Durante la estación seca ingresó el 57 por ciento de los pacientes. Todos evolucionaron satisfactoriamente. La estancia hospitalaria fue de 4.378 días y el promedio de hospitalización de 12,8 días. Los pacientes le costaron al hospital, al precio de un día 1 cama del 30 de junio de 1998; Bs. 47.740.000 ($ 86.486). Como conclusión se infirió que, el costo monetario de los pacientes, estuvo muy influenciado por los largos períodos de estancia hospitalaria. Este costo pudo disminuirse si, se hubiese tenido un criterio más adecuado de las justificaciones y pertinencias de las hospitalizaciones

Evaluación bacteriológica de hemocultivos en niños / Bacteriologic evaluation of hemocultives in childrens

Con el propósito de describir y analizar los aislamientos bacterilógicos de los hemocultivos procedentes de niños hospitalizados, procesados en la Sección de Bacteriología del Hospital Universitario de Caracas, se efectuó un estudio de vigilancia bacteriológica durante 17 meses. Se identificaron 144 niños con aislamientos microbiológicos en sus hemocultivos, 57 por ciento del sexo masculino y 43 por ciento del femenino. Terapia Intensiva Neonatal fue el servicio con mayor número de pacientes con hemocultivos positivos, seguido del servicio de Pediatría Médica. Serratia marcescens(22 por ciento) fue la bacteria con mayor número de aislamientos, seguida por Klebsiella Pneumoniae (15 por ciento) y de Staphylococcus aureus (12 por ciento). Las bacterias Gram negativas predominaron sobre las bacterias Gram positivas. Las primeras presentaron severos problemas en la sensibilidad a los antimicrobianos, particularmente para aminoglucósidos y cefalosporinas de tercera generación. Las bacterias Gram positivas no presentaron grandes problemas en la sensibilidad a los antimicrobianos. El hemocultivo continúa siendo el mejor procedimiento para el diagnóstico de infecciones severas en los niños