A Pilot Study: Cardiac Parameters in Children Receiving New-Generation Antidepressants.

OBJECTIVE: Because of concerns about potential associations between high doses of citalopram and QTc prolongation in adults, this study examined whether such associations are operant in children. We hypothesized that therapeutic doses of nontricyclic antidepressant medications (non-TCAs) prescribed to children would be cardiovascularly safe. STUDY DESIGN: The sample consisted of 49 psychiatrically referred children and adolescents 6 to 17 years old of both sexes treated with a non-TCA (citalopram, escitalopram, fluoxetine, paroxetine, sertraline, bupropion, duloxetine, venlafaxine, mirtazapine). To standardize the doses of different antidepressants, we converted doses of individual medicines into "citalopram equivalent doses" (CEDs) based on dosing recommendation for individual antidepressants. Correlation analysis was carried out to compare the continuous and weight-based CED to variables of interest. A QTc grouping was defined as normal, borderline, or abnormal, and CED was compared across QTc groupings using linear regression. An antidepressant dosage group was defined as low or high dose, and a t test compared variables of interest across dosage groups. RESULTS: No significant associations were found between total or weight-corrected CEDs of any antidepressant examined and QTc or any other electrocardiogram or blood pressure parameters. In patients taking citalopram or escitalopram, a significant correlation was found between PR interval and total daily dose, which disappeared when weight-based doses were used or when corrected by age. CONCLUSIONS: Although limited by a relatively small sample size, these results suggest that therapeutic doses of non-TCA antidepressants when used in children do not seem to be associated with prolonged QTc interval or other adverse cardiovascular effects.

Thoracic aortic disease in two patients with juvenile polyposis syndrome and SMAD4 mutations.

Dilation or aneurysm of the ascending aorta can progress to acute aortic dissection (Thoracic Aortic Aneurysms and Aortic Dissections, TAAD). Mutations in genes encoding TGF-ß-related proteins (TGFBR1, TGFBR2, FBN1, and SMAD3) cause syndromic and inherited TAAD. SMAD4 mutations are associated with juvenile polyposis syndrome (JPS) and a combined JPS-hereditary hemorrhagic telangiectasia (HHT) known as JPS-HHT. A family with JPS-HHT was reported to have aortic root dilation and mitral valve abnormalities. We report on two patients with JPS-HHT with SMAD4 mutations associated with thoracic aortic disease. The first patient, an 11-year-old boy without Marfan syndrome features, had JPS and an apparently de novo SMAD4 mutation (c.1340_1367dup28). Echocardiography showed mild dilation of the aortic annulus and aortic root, and mild dilation of the sinotubular junction and ascending aorta. Computed tomography confirmed aortic dilation and showed small pulmonary arteriovenous malformations (PAVM). The second patient, a 34-year-old woman with colonic polyposis, HHT, and features of Marfan syndrome, had a SMAD4 mutation (c.1245_1248delCAGA). Echocardiography showed mild aortic root dilation. She also had PAVM and hepatic focal nodular hyperplasia. Her family history was significant for polyposis, HHT, thoracic aortic aneurysm, and dissection and skeletal features of Marfan syndrome in her father. These two cases confirm the association of thoracic aortic disease with JPS-HHT resulting from SMAD4 mutations. We propose that the thoracic aorta should be screened in patients with SMAD4 mutations to prevent untimely death from dissection. This report also confirms that SMAD4 mutations predispose to TAAD.

Antimicrobial resistance and virulence profiles of Enterobacterales isolated from two-finger and three-finger sloths (Choloepus hoffmanni and Bradypus variegatus) of Costa Rica.

Background: Wildlife has been recently recognized as an environmental reservoir for antimicrobial resistance (AMR). However, less information on this topic is available in animals released back into the wild after rehabilitation in wildlife facilities, compared with studies performed exclusively in captive or free-ranging wildlife. This study aimed to evaluate the potential influence of captivity and/or treatment while in captivity of wild sloths on the AMR and virulence profiles of sloths' Enterobacterales. Methods: Oral and rectal swab samples were collected from 39 two-finger (Choloepus hoffmanni) and three-finger sloths (Bradypus variegatus) of Costa Rica (n = 78) and analyzed using conventional bacteriological techniques. A generalized linear mixed model was applied to estimate the isolates' multiple antimicrobial resistance and virulence indices as a function of animal status. Results: A considerable level of resistance was detected, especially for Citrobacter youngae and Escherichia coli, with 17.5% of isolates classified as multidrug-resistant. Virulence indices of isolates from rehabilitated sloths were significantly higher than the ones from sloths being hand-reared for shorter periods. Conclusions: To our knowledge, this is the first description of sloths' antimicrobial resistant Enterobacterales, suggesting that sloths' rehabilitation and consequent exposure to humans, may promote the selection of bacteria with higher virulence. Ultimately, these bacteria may represent a threat to human and animal health due to their zoonotic potential and AMR and virulence profiles.

Antiandrogenic and apoptotic effects of RU-486 on animal prostate.

Mifepristone (RU-486) is a potent antagonist of steroid hormone receptors such as glucocoticoid and progesterone receptors. This compound also is a very strong inducer of the interaction between androgen receptors and corepressors NCoR and SMRT and therefore could be used as selective receptor modulator. In this study we determined the relative binding affinity of RU-486 to androgen receptors (AR) obtained from rat prostate cytosol as well as the in vivo effect of different doses of RU-486 on the prostate weight of hamsters treated with dihydrotestosterone and/or RU-486. We determined also the prostate cell death (apoptosis) in hamster treated with, dihydrotestosterone (DHT) and/or RU-486. The results of this study indicated that the relative binding affinity of RU-486 for AR is 4.3%. The data from the in vivo experiments also showed that RU-486 inhibited the prostate weight significantly in the highest doses thus indicating the antagonistic action of this compound on hamster prostate. The immunohistochemistry analysis showed that after 1 month of castration, the hamster prostate was atrophic. Treatment with DHT produced epithelial cell activity (measured by the increase in the prostate weight) and very low rate of apoptosis. When DHT was administered together with RU-486 (10 mg/kg) no change was observed. On the other hand, DHT plus higher doses of RU-486 (40, 80 mg/kg) resulted in an increase of apoptosis in stromal and secretory epithelial cells. In addition to the increase of the prostate cell apoptosis produced by the treatment with high dose of RU-486, other factors could contribute to the decrease of the prostate weight observed. Another possibility could be a reduction in the ductal fluid due to poor epithelial cell secretory activity more than apoptosis itself. Furthermore, in this experiment, RU-486 could have inhibited the growth of the prostate gland produced by DHT in a greater extent than the induction of atrophy and cell death. This fact could depend on the doses used, due to the low affinity of this compound for the androgen receptors.

Factores biológicos relacionados con la masa ósea en hombres de edad mediana / Biological Factors Associated to Bone Mass in Middle-Aged Men

RESUMEN Introducción: La osteoporosis masculina es una enfermedad clínica heterogénea y subdiagnosticada, con múltiples factores de riesgo. Requiere un proceso de diagnóstico en ocasiones más complejo que en las mujeres. Objetivo: Identificar factores biológicos relacionados con la masa ósea en hombres de edad mediana. Métodos: Se realizó estudio descriptivo, transversal, en 43 hombres de edad mediana (40-59 años) entre abril de 2017 y mayo de 2018, que fueron atendidos en el Policlínico Universitario Vedado. Se estudiaron los antecedentes patológicos familiares (APF) de osteoporosis masculina o fracturas por fragilidad, índice de masa corporal (IMC), circunferencia de la cintura (CC), presión arterial (PA), glucemia, colesterol, triglicéridos, creatinina, hormona luteinizante, folículo estimulante, estradiol, testosterona (T), prolactina y paratohormona (PTH) y densitometría dual de Rx (DXA). Según edad y resultado de la DXA, se crearon 4 grupos (de 40-49 y de 50-59 años, en L1-L4 y fémur). Se identificaron hombres con hueso normal y mala masa ósea (MMO). Se determinaron distribuciones de frecuencia (variables cualitativas), y mediana y rango (cuantitativas). Se empleó chi cuadrado para determinar relación entre variables cualitativas y Mann-Whitney para cuantitativas. Para establecer correlación entre variables cuantitativas, se calculó el test de Pearson. Resultados: En hombres de 50-59 años, con antecedentes patológicos familiares de fracturas por fragilidad, predominó la mala masa ósea (75 por ciento). La mediana del índice de masa corporal en hombres de 40-49 años fue mayor (26,7 Kg/m2sc) en los que tenían hueso normal en L1-L4; en los de 50-59 años con aumento de la circunferencia de la cintura predominó la mala masa ósea (3; 75 por ciento). La presión arterial sistólica y diastólica se correlacionaron positivamente con la densidad mineral ósea en L1-L4 ([r = 0,225; p = 0,009], [r = 0,263; p = 0,002]). Hubo correlación positiva entre colesterol y contenido mineral óseo en fémur (r = 0,164; p = 0,002). La testosterona resultó más baja en hombres con hueso normal (40-49 años: 15,3 nmol/L; 50-59 años: 12,5 nmol/L). Se observó correlación negativa entre paratohormona y contenido mineral óseo en fémur (r = -0,324; p = 0,000). Conclusiones: Se puede concluir que, de los factores biológicos estudiados en los hombres de edad mediana del Policlínico Universitario Vedado, los niveles más elevados de presión arterial y colesterol, y más bajos de paratohormona, se asociaron con mejor masa ósea(AU)

ABSTRACT Introduction: Male osteoporosis is a heterogeneous and underdiagnosed clinical condition and with multiple risk factors, which requires a diagnostic process that is sometimes more complex than for women. Objective: To identify biological factors related to bone mass in middle-aged men from "Vedado" University Polyclinic. Methods: A cross-sectional and descriptive study was carried out with 43 middle-aged (40-59 years old) men, between April 2017 and May 2018. The variables were family pathological history of osteoporosis or fragility fractures, body mass index, waist circumference, blood pressure, glycemia, cholesterol, triglycerides, creatinine, luteinizing hormone, stimulating follicle, estradiol, testosterone, prolactin and parathyroid hormone, and dual x-ray densitometry. According to age and results of the dual x-ray densitometry, four groups were created (40-49 and 50-59 years old, in L1-L4 and femur). The men with normal bone and poor bone mass were identified. Frequency distributions (qualitative variables), as well as median and range (quantitative variables) were determined. The chi-square test was used to determine the relationship between qualitative variables, and the Mann-Whitney test was used for quantitative variables. To establish correlation between quantitative variables, the Pearson test was used. Results: Among men aged 50-59 years and with a family pathological history of fragility fractures, poor bone mass prevailed (75 percent). The median body mass index among men aged 40-49 years was higher (26.7 kg/m2sc) in those with normal bone in L1-L4; among those aged 50-59 years and with increased waist circumference, poor bone mass predominated (3; 75 percent). Systolic and diastolic blood pressure were correlated positively with bone mineral density in L1-L4 [(r = 0.225, p = 0.009), (r = 0.263, p = 0.002)]. There was a positive correlation between cholesterol and bone mineral content in the femur (r = 0.164, p = 0.002). T was lower among men with normal bone (15.3 nmol/L for the group 40-49 years old, and 12.5 nmol/L for the group 50-59 years old). A negative correlation was observed between the parathyroid hormone and bone mineral content values in the femur (r = -0.324, p = 0.000). Conclusions: Among the biological factors studied in middle-aged men from "Vedado" University Polyclinic, higher levels of blood pressure and cholesterol, as well as lower levels of the parathyroid hormone were concluded to be associated with better bone mass(AU)

Factores relacionados con la masa ósea en hombres de edad mediana / Factors related to bone mass in middle-aged men

RESUMEN Introducción: La osteoporosis representa un problema de salud debido al impacto en la morbilidad, mortalidad, calidad de vida y altos costos. Los factores de riesgo asociados a la osteoporosis han sido poco abordados en hombres cubanos. Objetivo: Determinar la masa ósea y su posible relación con factores sociodemográficos y del estilo de vida en hombres de edad mediana del Policlínico Universitario "Vedado". Métodos: Se realizó un estudio descriptivo transversal que incluyó hombres de edad mediana. De la planilla de recolección de datos se extrajeron: sociodemográficos, estilo de vida y elementos del examen físico. Se realizó densitometría para determinar la masa ósea. Se crearon 4 grupos (de 40-49 y de 50-59 años en L1-L4 y fémur, solo se analizó L1-L4), se determinaron las personas con hueso normal y mala masa ósea (MMO) y se asociaron con los factores de riesgo. Resultados: En los hombres estudiados predominó el hueso normal: L1-L4 (27 = 62,8 por ciento) y fémur (38 = 88,4 por ciento). En los hombres entre 50-59 años, el 85,7 por ciento de los que tenían piel mestiza presentaron MMO, el 100 de los que tenían piel blanca y el 83,3 por ciento de los de piel negra, tuvieron hueso normal (p = 0,017). En los dos grupos, se observó un predominio del hueso normal, en los que tenían alimentación adecuada (100 por ciento) y aceptable (66,6 por ciento). En los de 40-49 años que realizaban actividad física, predominó el hueso normal; de 50-59 la mala masa ósea (6 = 60 por ciento). En ambos grupos, los que consumían bebidas alcohólicas y fumaban, predominaron en el grupo con hueso normal. Conclusiones: La mayoría de los hombres estudiados tenían masa ósea normal, la afectación fue mayor en L1-L4. La mayor edad y el color de piel mestiza, en hombres de 50-59 años, se asociaron con mayor daño óseo; factores del estilo de vida no se relacionaron con la masa ósea(AU)

ABSTRACT Introduction: Osteoporosis represents a health problem due to the impact on morbidity, mortality, quality of life and high costs. The risk factors associated with osteoporosis have been poorly addressed in Cuban men. Objective: To determine the bone mass and its possible relationship with sociodemographic and lifestyle factors in middle-aged men at Vedado University Polyclinic. Methods: A descriptive cross-sectional study was carried out in middle-aged men. From the data collection form were extracted sociodemographic, lifestyle and physical examination elements. Densitometry was performed to determine bone mass. Four groups (40-49 and 50-59 years in L1-L4 and femur were created, only L1-L4 was analyzed). People with normal bone and poor bone mass were identified and associated with risk factors. Results: Normal bone predominated in the studied men, L1-L4 (27 = 62.8 percent) and femur (38 = 88.4 percent). 85.7 percent between 50-99 years with meztizo skin color presented poor bone mass. Normal bone was evidenced in white and black skin subjects (100 and 83.3 percent) (p = 0.017). In both groups, predominance of normal bone was observed in those with adequate (100 percent) and acceptable diet (66.6 percent). In those 40-49 year-old subjects who had physical activity, normal bone predominated; but in those 50-59 year-old subjects, bad bone mass predominated (6 = 60 percent). In both groups, normal bone predominated in those who consumed alcoholic beverages and smoked in both groups. Conclusions: Most of the men studied had normal bone mass, the affectation was greater in L1-L4. Older age and mestizo skin color in 50-59 year-old men were associated with greater bone damage. Lifestyle factors were not related to bone mass(AU)

Assessment of the quality of medication information for patients in Spain.

OBJECTIVE: To analyze the extent to which Spanish leaflets and drug information on the Net met quality criteria. RESEARCH DESIGN AND METHODS: A descriptive study was conducted comparing readability (REA) and comprehensibility (COM) criteria of a random sample of 77 marketed products of the 12 active ingredients most frequently sold in 2010 in Spain. Leaflets were approved by the Spanish Agency for Medication (AEMPS). Flesch index, DISCERN, ELF, MIDAS and CIRF scales were used to evaluate quality criteria. RESULTS: COM assessment yielded between 63 and 77% of the maximum possible scores on the scales. None of the websites or leaflets met all the quality criteria of the DISCERN, CIRF or MIDAS scales. Four (3%) leaflets met all the 22 quality criteria of ELF. The leaflets showed shortcomings regarding: medication benefits (17 required substantial improvements, 31.5%), correct forms of storage (13, 24.1%), contraindications (12, 22.2%), side effects (11, 20.4%) and precautions to be taken (9, 16.7%). CONCLUSIONS: The quality of the information approved by the AEMPS is superior to that which can be found by surfing the Net. More specific information on precautions, complications and how to avoid common patient errors would allow patients the best chance to contribute to their own clinical safety.

Interventional catheterization management of perioperative peripheral pulmonary stenosis: balloon angioplasty or endovascular stenting.

There is limited reported experience of catheterization therapy for peripheral pulmonary stenosis (PPS) at a surgical site in the early postoperative period. We reviewed the clinical course of patients undergoing interventional catheterization for PPS at a surgical site < 7 weeks after surgery. Successful dilation (SD) was defined as > 50% increase in predilation diameter. From 1984 to 2000, 17 patients had 19 proximal pulmonary arteries dilated 1 to 46 (median 8) days postoperatively. Median age and weight were 3.1 year and 12.7 kg. Three arteries were initially occluded. Seventeen arteries had initial BD with postintervention imaging available in 15; 8 arteries had SD. The arterial diameter increased from 3.9 +/- 2.6 to 5.5 +/- 2.8 mm (P < 0.001). Nine of these arteries had stents placed with diameter increasing to 8.7 +/- 3.7 mm (P < 0.001 compared with post-BD diameter). Stents increased the diameter in all arteries and made four of four failed BD successful. In the two most recent procedures, stents were placed without prior BD with diameter increasing from 1.3 to 9 mm and 8.2 to 14 mm. A stent was placed in 1 of 7 arteries prior to 1993 and in 10 of 12 arteries thereafter (P < 0.004). Three patients prior to 1995 had catheterization-related deaths secondary to vessel rupture after BD. BD produces SD in approximately one-half of the procedures but is associated with mortality. Stent placement increases vessel diameter substantially more than BD alone. Stents reduce the acute complication rate and avoid early reoperation in this patient group.

Changes in lysosomal enzyme activities in pre-ovulatory follicles and endometrium of PMSG superovulated rats

Large superovulatory doses of gonadotrophins result in reduced fertility in laboratory and large domestic animals and it has been postulated that some of the superovulated oocytes are derived from abnormal follicles wich would not ovulate under normal physiological stimuli. Follicular growth, follicular maturation and atresia, ovulation and the nidation of the fertilized oocute require intense tissue remodelation which can be accomplished only through the action of hydrolytic enzymen. We have studied the activities and sub-cellular distribution of three lysosomal ensymes (acid phosphatase, N-acetyl-ß-D-glucosaminidase and ß-glucuronidase) in the follicular fluid, granulosa and theca cells of preovulatory follicles and in the endometrial tissue of immature Wistar rats injected with 4 (control) or 40 (superovulated) IU of pregnant mare serum gonadotrophin (PMSG). Enzyme activities were from four to ten time higher in theca than in granulosa cells. This difference was particularly important in the case of ß-glucuronidase. Large preovulatory follicles tended to have higher activities of lysosomal ensymes in the free fraction of all the compartments studied. This difference was remarkable in theca cells where free enzymes could be required to help ovulation. Forty IU of PMSG induced higher activities of acid phosphatase in theca and granulosa cells than 4 IU, but in endometrial tissue this latter dose of PMSG was more efficient to induce higher activities of this enzyme. The endometrial bound fraction of N-acetyl-ß-D-glucosaminidase was almost three times higher than the free activity. This behavior was also observed in endometrial ß-glucosaminidase but only in the control rats. The results observed in follicular fluid were less homogeneous. The activities of glucosaminidase and acid phosphatase were two to three times higher in rats overstimulated with 40 IU of PMSG than int he controls rats, whereas the activities of ß-glucuronidase were lower in the superovulated rats. Our results suggest that alterations in the process of tissue remodeling required for ovulation of mature, normal oocytes and for nidation of the fertilized ovum may be important factors to explain pregnancy failure in the PMSG superovulated female