Osificación heterotópica de cadera asociada a pancreatitis aguda severa: reporte de un caso / Hip heterotopic ossification associated with severe acute pancreatitis: a case report

La osificación heterotópica (OH), es la formación anormal de hueso maduro dentro de tejidos blandos extra esqueléticos donde normalmente no existe tejido óseo. Varias formas de OH han sido descritas de acuerdo a su presentación clínica, localización y ocurrencia progresiva o aislada. Su presentación en pacientes sometidos a inmovilización prolongada en el contexto de coma farmacológicamente inducido, en ausencia de lesiones del sistema nervioso central, es poco habitual. Presentamos el caso de una paciente de 40 años, sexo femenino, sin antecedentes mórbidos, que presenta episodio de pancreatitis aguda grave, manejada en UCI. Producto de lo anterior, requiere coma farmacológicamente inducido por 3 meses y hospitalizaciones reiteradas y prolongadas durante los 10 meses siguientes. Durante 3 años desde la resolución de su cuadro inicial evoluciona con alteración progresiva de la marcha y rigidez de la extremidad inferior derecha, sin eventos traumáticos durante ese período. Se objetiva mediante radiografía y TAC foco de OH coxofemoral derecha. Se resuelve de forma quirúrgica y biopsia de pieza operatoria confirma el diagnóstico. La paciente logra buena recuperación posterior. NIVEL DE EVIDENCIA: IV

Heterotopic ossification (HO) is the abnormal formation of mature bone within extraskeletal soft tissues where bone does not exist. Various presentation of HO have been described according to the clinical settings and location of the lesions, and progressive or isolated occurrence. A rare form of presentation occurs in induced coma patients with long-term immobilization and without central nervous system injuries. We present the case of a 40 years old female patient, without previous morbidity, who develop a severe acute pancreatitis. The patient requires an intensive care unit management (ICU) and a 3-month pharmacology induced coma and reiterative and prolonged hospitalizations during the next 8 months. During 3 years after resolution of her base disease, patient develops a progressive step claudication and a hip rigidity in adduction and external rotation. A coxofemoral HO focus is confirmed by radiology and CT. A surgical treatment of HO was performed, and the initial diagnose confirmed by anatomic pathology after biopsy of the injury. Patient had a favorable outcome.

Leydig cell dysfunction is associated with post-transcriptional deregulation of CYP17A1 in men with Sertoli cell-only syndrome.

STUDY QUESTION: Is the expression of steroidogenic enzyme 17α-Hydroxylase/17,20-Lyase (CYP17A1) down-regulated in Leydig cells (LCs) of men with spermatogenic failure and compensated impairment of LC function, i.e. a low testosterone to LH (T/LH) ratio? SUMMARY ANSWER: Although the transcriptional expression of CYP17A1 is increased, its protein expression is decreased, in isolated LCs of men with spermatogenic failure and reduced serum T/LH. WHAT IS KNOWN ALREADY: Primary spermatogenic defects have been associated with functional and morphological abnormalities of LCs, characterized by decreased serum testosterone (T) levels, decreased T/LH, increased 17ß-estradiol (E2) and E2/T ratio, and larger clusters of LCs (LC hyperplasia). CYP17A1 is a key enzyme in the testosterone pathway and has been implicated in the steroidogenic lesion produced by E2 stimulation. STUDY DESIGN, SIZE, DURATION: We studied 18 azoospermic patients with Sertoli cell-only syndrome (SCOS) and signs of LC dysfunction (cases) and 10 obstructive azoospermic/oligozoospermic men with normal spermatogenesis (controls). The SCOS patients were sub-grouped into 9 cases with T/LH <2 and 9 cases with T/LH ≥2. All of the men underwent testicular biopsy for sperm retrieval at the Reproductive Unit of a University Hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS: The transcriptional expression of CYP17A1 and SF-1 (steroidogenic factor 1) was quantified by SYBR®Green-based qPCR in LCs isolated by laser capture microdissection (LCM), and relative expression to the control pool was assessed. CYP17A1 protein expression was semi-quantified by indirect immunofluorescence (IFI) using Image-Pro Plus v7.0 (Media Cybernetics) in testicular tissue. FSH and LH serum concentrations, and serum and intratesticular T (ITT) and E2 (ITE2) were measured by IRMA and RIA, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Relative CYP17A1 mRNA expression was increased in cases with T/LH <2 compared to cases with T/LH ≥2, by a mean of 3.3-fold (P = 0.002). No corresponding increase in protein expression was found; in fact, CYP17A1 immunostaining intensity assessed by the Integrated Optical Density (IOD) parameter was lower in the cases with T/LH <2 compared to controls (P = 0.008). Relative SF-1 mRNA expression was similar in both case subgroups. CYP17A1 mRNA expression correlated with ITE2 and intratesticular E2/T (r = 0.536; P = 0.026 and r = 0.542; P = 0.016, respectively), while an inverse association was observed for ITE2 and protein level expression (r = -0.421; P = 0.05). LARGE SCALE DATA: Not applicable. LIMITATIONS REASONS FOR CAUTION: We should interpret the results of the semi-quantification of immunofluorescent staining by Image-Pro Plus software with caution, because it is a semi-quantitative method that may have certain difficulties regarding the disposition of protein in the cells. However, it is not influenced by variations in the number of cells that express the protein, as could be the case of western blot analysis in testicular tissue. WIDER IMPLICATIONS OF THE FINDINGS: Dysfunctional LCs of men with SCOS show post-transcriptional deregulation of CYP17A1, with increased mRNA and decreased protein expression, which may be modulated by increased ITE2 levels. In addition, transcriptional expression of CYP17A1 was not associated with changes in SF-1 mRNA expression. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Fund for Scientific and Technological Development (FONDECYT) of Chile to A.C. [grant number 1120176]. The authors declare no conflict of interest.

Pseudoautosomal abnormalities in terminal AZFb+c deletions are associated with isochromosomes Yp and may lead to abnormal growth and neuropsychiatric function.

STUDY QUESTION: Are copy number variations (CNVs) in the pseudoautosomal regions (PARs) frequent in subjects with Y-chromosome microdeletions and can they lead to abnormal stature and/or neuropsychiatric disorders? SUMMARY ANSWER: Only subjects diagnosed with azoospermia factor (AZF)b+c deletions spanning to the end of the Y chromosome (i.e. terminal deletions) harbor Y isochromosomes and/or cells 45,X that lead to pseudoautosomal gene CNVs, which were associated with abnormal stature and/or neuropsychiatric disorders. WHAT IS KNOWN ALREADY: The microdeletions in the long arm of the Y chromosome (Yq) that include the loss of one to three AZF regions, referred to as Yq microdeletions, constitute the most important known etiological factor for primary spermatogenic failure. Recently, controversy has arisen about whether Yq microdeletions are associated with gain or loss of PAR genes, which are implicated in skeletal development and neuropsychiatric function. STUDY DESIGN, SIZE, DURATION: We studied a cohort of 42 Chilean patients with complete AZF deletions (4 AZFa, 4 AZFb, 23 AZFc, 11 AZFb+c) from a university medical center, diagnosed over a period of 15 years. The subjects underwent complete medical examinations with special attention to their stature and neuropsychiatric function. PARTICIPANTS/MATERIALS, SETTING, METHODS: All subjects were characterized for Yq breakpoints by PCR, and for CNVs in PARs by multiplex ligation-dependent probe amplification (MLPA), followed by qPCR analysis for genes in PAR1 (SHOX and ZBED1), PAR2 (IL9R) and two single copy genes (SRY and DDX3Y, respectively located in Yp11.3 and AZFa). In addition, karyotypes revision and fluorescence in situ hybridization (FISH) for SRY and centromeric probes for X (DXZ1) and Y (DYZ3) chromosomes were performed in males affected with CNVs. MAIN RESULTS AND THE ROLE OF CHANCE: We did not detect CNVs in any of the 35 AZF-deleted men with interstitial deletions (AZFa, AZFb, AZFc or AZFb+c). However, six of the seven patients with terminal AZFb+c deletions showed CNVs: two patients showed a loss and four patients showed a gain of PAR1 genes, with the expected loss of VAMP-7 in PAR2. In these patients, the Yq breakpoints localized to the palindromes P8, P5 or P4. In the four cases with gain of PAR1, qPCR analysis showed duplicated signals for SRY and DDX3Y and one copy of IL9R, indicating isodicentric Yp chromosomes [idic(Y)] with breakpoint in Yq11.22. The two patients who had loss of PAR1, as shown by MLPA, had an additional reduction for SRY and DDX3Y, as shown by qPCR, associated with a high proportion of 45,X cells, as determined by FISH and karyotype. In agreement with the karyotype analysis, we detected DYZ3++ and DYZ3+ cells by FISH in the six patients, confirming idic(Y) and revealing additional monocentric Y chromosome [i(Y)]. Five patients had a history of major depressive disorders or bipolar disorder, and three had language impairment, whereas two patients showed severe short stature (Z score: -2.75 and -2.62), while a man with bipolar disorder was very tall (Z score: +2.56). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The number of males studied with Y-chromosome microdeletions and normozoospermic controls with normal karyotypes may not be enough to rule out an association between AZF deletions and PAR abnormalities. The prevalence of Y isochromosomes and/or 45,X cells detected in peripheral blood does not necessarily reflect the variations of PAR genes in target tissues. WIDER IMPLICATIONS OF THE FINDINGS: This study shows that CNVs in PARs were present exclusively in patients with terminal AZFb+c deletions associated with the presence of Y isochromosomes and 45,X cells, and may lead to neuropsychiatric and growth disorders. In contrast, we show that men with interstitial Yq microdeletions with normal karyotypes do not have an increased risk of PAR abnormalities and of phenotypical consequences. Moreover, our results highlight the importance of performing molecular studies, which are not considered in the usual screening for patients with Yq microdeletions. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Fund for Scientific and Technological Development of Chile (FONDECYT), grant no. 1120176 (A.C.). The authors declare that no conflicting interests exist.

Overexpression of CYP19A1 aromatase in Leydig cells is associated with steroidogenic dysfunction in subjects with Sertoli cell-only syndrome.

Several observational studies have showed a combination of lower testosterone (T) to LH ratio and higher estradiol (E2 ) to T ratio in secretory infertile men compared to men with normal spermatogenesis, suggesting a steroidogenic dysfunction of Leydig cells (Lc) that may involve increased aromatase activity. Low T/LH ratio is associated with Lc hyperplasia, which together with LH hyperstimulation may represent compensation for impaired T production. Aromatase expression and oestrogen production are mainly detected in Lc of the testis, although Sertoli and germ cells also contribute to testicular aromatase activity. The aim of this study was to assess the transcriptional expression of CYP19A1 (aromatase) in isolated Lc of subjects with Sertoli cell-only syndrome (SCOS) and signs of Lc impairment. Nineteen patients with SCOS and 10 controls with normal spermatogenesis who had medical indication of testicular biopsy for sperm retrieval were studied. Leydig cells were isolated by Laser Capture Microdissection (LCM) and CYP19A1 mRNA expression was quantified by SYBR® Green-based qPCR. In addition, testicular T and E2 and serum hormonal levels were measured. Relative to control group, CYP19A1 was overexpressed more than twofold in 10/19 cases (2.3-12.2-fold increase), showing a significant increment in cases with low T/LH ratio (T/LH < 2) compared to cases with T/LH ≥ 2 (p = 0.038, REST® ). Moreover, Rq data for CYP19A1 had a direct correlation with testicular levels of E2 and the E2 /T ratio (r = 0.869; p < 0.001 and r = 0.633; p = 0.005). In summary, Lc from infertile patients with signs of Lc dysfunction overexpressed aromatase and showed an increment of testicular E2 . Our results suggest that increased expression of aromatase in Lc leads to higher E2 production and may account for the functional impairment of the Lc in patients with SCOS.

Bronquio cardíaco accesorio y otras variantes de la anatomía tráqueo-bronquial / Accessory cardiac bronchus and others variations of the tracheobronchial anatomy

Entre las variantes de la anatomía bronquial nos podemos encontrar con ramas bronquiales displásicas, ramas ausentes o ramas supernumerarias. Aunque gran parte son asintomáticas, es esencial reconocerlas porque se pueden asociar a hemoptisis, infecciones recurrentes, empiema o a complicaciones secundarias a procedimientos (por ejemplo intubaciones endotraqueales, fibrobroncoscopías, lavado broncoalveolar, biopsias, tratamientos endobronquiales, instalación de stent, braquiterapia y cirugías pulmonares entre otros). En este articulo describimos las variantes bronquiales más prevalentes en tomografia computada, incluyendo al bronquio cardíaco accesorio, bronquio traqueal y bronquio puente, entre otras.

Among the variations of bronchial anatomy, we can find dysplastic bronchial branches, an absence of bronchial branches, or supernumerary branches. Although many of them are asymptomatic, it is essential to know them because they may be associated with hemoptysis, recurrent infections, empyema, or complications secondary to various procedures (e.g. endotracheal intubation, brochoscopy, bronchoalveolar lavage, biopsy, endobronchial treatments, stent installation, brachytherapy and lung surgeries among others). In this study we used computed tomography to describe some of the most prevalent bronchial variations, including accessory cardiac bronchus, tracheal bronchus, and bridge bronchus among others.

Production of versatile peroxidase from Pleurotus eryngii by solid-state fermentation using agricultural residues and evaluation of its catalytic properties.

Interest in production of ligninolytic enzymes has been growing over recent years for their use in various applications such as recalcitrant pollutants bioremediation; specifically, versatile peroxidase (VP) presents a great potential due to its catalytic versatility. The proper selection of the fermentation mode and the culture medium should be an imperative to ensure a successful production by an economic and available medium that favors the process viability. VP was produced by solid-state fermentation (SSF) of Pleurotus eryngii, using the agricultural residue banana peel as growth medium; an enzymatic activity of 10,800 U L(-1) (36 U g(-1) of substrate) was detected after 18 days, whereas only 1800 U L(-1) was reached by conventional submerged fermentation (SF) with glucose-based medium. The kinetic parameters were determined by evaluating the H2O2 and Mn(2+) concentration effects on the Mn(3+)-tartrate complex formation. The results indicated that although the H2O2 inhibitory effect was observed for the enzyme produced by both media, the reaction rates for VP obtained by SSF were less impacted. This outcome suggests the presence of substances released from banana peel during the fermentation, which might exhibit a protective effect resulting in an improved kinetic behavior of the enzyme.

The acute phase response induced by Escherichia coli lipopolysaccharide modifies the pharmacokinetics and metabolism of florfenicol in rabbits.

The aim of this study was to determine the effect of Escherichia coli lipopolysaccharide (LPS)-induced acute phase response (APR) on the pharmaco-kinetics and biotransformation of florfenicol (FFC) in rabbits. Six rabbits (3.0 ± 0.08 kg body weight (bw)) were distributed through a crossover design with 4 weeks of washout period. Pairs of rabbits similar in bw and sex were assigned to experimental groups: Group 1 (LPS) was treated with three intravenous doses of 1 µg/kg bw of E. coli LPS at intervals of 6 h, and Group 2 (control) was treated with an equivalent volume of saline solution (SS) at the same intervals and frequency of Group 1. At 24 h after the first injection of LPS or SS, an intravenous bolus of 20 mg/kg bw of FFC was administered. Blood samples were collected from the auricular vein before drug administration and at different times between 0.05 and 24.0 h after treatment. FFC and florfenicol-amine (FFC-a) were extracted from the plasma, and their concentrations were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic model was used for data analysis, and data were compared using the paired Student t-test. The mean values of AUC0-∞ in the endotoxaemic rabbits (26.3 ± 2.7 µg·h/mL) were significantly higher (P < 0.05) than values observed in healthy rabbits (17.2 ± 0.97 µg·h/mL). The total mean plasma clearance (CLT ) decreased from 1228 ± 107.5 mL·h/kg in the control group to 806.4 ± 91.4 mL·h/kg in the LPS-treated rabbits. A significant increase (P < 0.05) in the half-life of elimination was observed in the endotoxaemic rabbits (5.59 ± 1.14 h) compared to the values observed in healthy animals (3.44 ± 0.57 h). In conclusion, the administration of repeated doses of 1 µg/kg E. coli LPS induced an APR in rabbits, producing significant modifications in plasma concentrations of FFC leading to increases in the AUC, terminal half-life and mean residence time (MRT), but a significant decrease in CLT of the drug. As a consequence of the APR induced by LPS, there was a reduction in the metabolic conversion of FFC to their metabolite FFC-a in the liver, suggesting that the mediators released during the APR induced significant inhibitory effects on the hepatic drug-metabolizing enzymes.

Pharmacokinetics of florfenicol after intravenous administration in Escherichia coli lipopolysaccharide-induced endotoxaemic sheep.

Experiments in different animal species have shown that febrile conditions, induced by Escherichia coli lipopolysaccharide (LPS), may alter the pharmacokinetic properties of drugs. The objective was to study the effects of a LPS-induced acute-phase response (APR) model on plasma pharmacokinetics of florfenicol (FFC) after its intravenous administration in sheep. Six adult clinically healthy Suffolk Down sheep, 8 months old and 35.5 ± 2.2 kg in body weight (bw), were distributed through a crossover factorial 2 × 2 design, with 4 weeks of washout. Pairs of sheep similar in body weight were assigned to experimental groups: Group 1 (LPS) was treated with three intravenous doses of 1 µg/kg bw of E. coli LPS before FFC treatment. Group 2 (control) was treated with an equivalent volume of saline solution (SS) at similar intervals as LPS. At 24 h after the first injection of LPS or SS, an intravenous bolus of 20 mg/kg bw of FFC was administered. Blood samples (5 mL) were collected before drug administration and at different times between 0.05 and 48.0 h after treatment. FFC plasma concentrations were determined by liquid chromatography. A noncompartmental pharmacokinetic model was used for data analysis, and data were compared using a Mann-Whitney U-test. The mean values of AUC0-∞ in the endotoxaemic sheep (105.9 ± 14.3 µg·h/mL) were significantly higher (P < 0.05) than values observed in healthy sheep (78.4 ± 5.2 µg·h/mL). The total mean plasma clearance (CLT ) decreased from 257.7 ± 16.9 mL·h/kg in the control group to 198.2 ± 24.1 mL·h/kg in LPS-treated sheep. A significant increase (P < 0.05) in the terminal half-life was observed in the endotoxaemic sheep (16.9 ± 3.8 h) compared to the values observed in healthy sheep (10.4 ± 3.2 h). In conclusion, the APR induced by the intravenous administration of E. coli LPS in sheep produces higher plasma concentrations of FFC due to a decrease in the total body clearance of the drug.

Should thyroid-stimulating hormone goals be reviewed in patients with type 1 diabetes mellitus? Results from the Brazilian Type 1 Diabetes Study Group.

AIMS: To investigate if thyroid-stimulating hormone (TSH) levels are associated with any differences in glycaemic control or diabetes-related complications in individuals with Type 1 diabetes. METHODS: This observational, cross-sectional and multicentre study included patients with Type 1 diabetes for ≥ 5 years, with a recent TSH measurement and without a known previous thyroid disease. Patients were divided into three groups according to TSH levels: 0.4-2.5 mU/l; 2.5-4.4 mU/l; and ≥ 4.5 mU/l. RESULTS: We included 1205 individuals with a mean ± sd age of 23.8 ± 11.3 years. Seven patients had TSH levels <0.4 mU/l and were excluded from the comparison between groups. HbA1c levels, systolic and diastolic blood pressure, LDL cholesterol and disease duration were similar in all groups (P = 0.893, P = 0.548, P = 0.461, P = 0.575 and P = 0.764, respectively). The rates of diabetic retinopathy and GFR < 60/mL/min/1.73 m(2) differed between groups (P = 0.006 and P < 0.001, respectively) and were lower in those with lower TSH levels. Multivariate analysis confirmed these associations. The frequencies of retinopathy and GFR < 60 mL/min/1.73 m(2) were higher not only in patients with TSH ≥ 4.5 mU/l (odds ratio 1.878 and 2.271, respectively) but also in those with TSH levels of 2.5-4.4 mU/l (odds ratio 1.493 and 2.286, respectively), when compared with patients with TSH levels of 0.4-2.5 mU/l. CONCLUSIONS: TSH levels of 0.4-2.5 mU/l are associated with a lower risk of diabetic retinopathy and renal failure in individuals with Type 1 diabetes, independently of glycaemic control and duration of the disease.

Plasma disposition kinetics of moxidectin after subcutaneous administration to pregnant sheep.

The plasma kinetic profile of moxidectin (MXD) in ewes during the last third of pregnancy was studied after the subcutaneous dose of 0.2 mg/kg of body weight (bw). Two groups of sheep (n = 7) that were equally balanced in body weight were used. Group I (control) was maintained unmated, while Group II (pregnant) was estrous-synchronized and mated with fertile rams. Both groups were maintained under similar conditions regarding management and feeding. When the ewes from Group II fulfilled 120 days of pregnancy, both groups were treated with a subcutaneous injection of 0.2 mg of MXD/kg bw. Blood samples were collected at different set times between 1 h and 40 days post-treatment. After plasma extraction and derivatization, the samples were analyzed using high-performance liquid chromatography with fluorescence detection. A noncompartmental pharmacokinetic analysis was performed, and the data were compared using Student's t-test. The mean pharmacokinetic parameters, including Cmax , Tmax , and the area under the concentration-time curve (AUC), were similar for both groups of sheep. The average of elimination half-life was significantly lower (P = 0.0023) in the pregnant (11.49 ± 2.2 days) vs. the control (17.89 ± 4.84 days) sheep. Similarly, the mean residence time (MRT) for the pregnant group (20.6 ± 3.8 days) was lower (P = 0.037) than that observed in the control group (27.4 ± 9.1 days). It is concluded that pregnancy produces a significant decrease in mean values of half-life of elimination of MXD, indicating that pregnancy can increase the rate of elimination of the drug reducing their permanence in the body.

Vasectomía sin bisturí: resultados de una cohorte de 309 pacientes / No-scalpel vasectomy

Introducción: La vasectomía es una técnica segura y efectiva para el control de la fertilidad masculina. A pesar de esto, en el mundo se realizan el doble de esterilizaciones femeninas respecto a vasectomías, lo cual es más acentuado en países en vías de desarrollo. Objetivos: El objetivo de este trabajo es presentar nuestra experiencia y resultados en pacientes sometidos a una vasectomía sin bisturí. Materiales y Métodos: Se incluyó un total de 309 pacientes sometidos a una vasectomía sin bisturí entre junio de 2009 y mayo de 2010. En cada caso se evaluó la edad, tiempo operatorio, espermiograma a los 3 y 6 meses (en caso de ser necesario) y la morbilidad perioperatoria. Resultados: 281 pacientes (91 por ciento) se controlaron con al menos un espermiograma. En 189 pacientes (67 por ciento) se evidenció azoospermia en el espermiograma a los 3 meses. En 81 pacientes (29 por ciento) se evidenció un recuento con < 100.000 espermatozoides 100 por ciento inmóviles. En 9 pacientes (3,2 por ciento) se necesitó un segundo espermiograma para obtener menos de 100.000 espermatozoides 100 por ciento inmóviles. Seis pacientes (2 por ciento) consultaron por complicaciones menores: orquialgia, epididimitos o hematoma del sitio operatorio. A 2 años de seguimiento, no se registraron embarazos. Conclusiones: La vasectomía sin bisturí es un método seguro y reproducible de anticoncepción masculina, presentando tasas de efectividad superiores al resto de los métodos anticonceptivos. Un espermiograma de control debe ser realizado a los 3 meses de realizado el procedimiento. La tasa de falla temprana se estima en 0,3 por ciento de los pacientes.

Introduction: Vasectomy is a safe and effective technique of male fertility control. Despite this, in the world are carried out more than double female sterilization in comparison with vasectomies, that is more pronounced in less developed countries. Aims: To present our experience and results in patients undergoing a no-scalpel vasectomy. Methods and Material: A total of 309 patients undergoing a no-scalpel vasectomy between June 2009 and May 2010 were included. For each case was record age, operative time, sperm count at 3 months post vasectomy and peri-operative morbidity. Results: 309 vasectomies were performed, 281 patients (91%) were controlled with at least one sperm count. Azoospermia was obtained in the first sperm count at 3 months in 189 patients (67%). In 81 patients (29%) were observed ≤ 100,000 sperm 100% immobile. 9 patients (3.2%) needed a second semen analysis and 2 patients a third one for less than 100,000 sperm that were 100% immobile. 6 patients (2%) consulted by minor complications such as postoperative pain, epididymitis or hematoma with spontaneous resolution. Conclusions: Vasectomy is a safe and reproducible method of male contraception, presenting an effectiveness rates higher than others contraceptive methods. There are no absolute contraindications for performing the procedure. A sperm count should be done at 3 months of the procedure. The early failure rate in our study is 0.3%.

[Strengths and difficulties in emotional adjustment of Aymara children from the perspective of children, parents and teachers]. / Fortalezas y dificultades para el ajuste emocional en niños aymara desde la perspectiva de los menores, padres y profesores.

OBJECTIVE: To describe capabilities and difficulties in emotional adjustment experienced by children living in the Chilean Aymara city of Arica. PATIENTS AND METHOD: 610 students between 5th and 8th grade, in addition to their parents and teachers were surveyed using the Strengths and Difficulties Questionnaire (SDQ), comparing Aymara children to those without indigenous heritage. 25 items divided into five scales were evaluated: Emotional, behavioral problems, hyperactivity, relationship problems with peers and prosocial behaviors, classifying the respondents into three levels, Normal, Border and Abnormal. RESULTS: There were no significant differences among the groups studied, where discrepancies in almost all cases show a slight effect (d≥|0.2|). Also, no relevant effects were observed regarding the type of assessor on the assessment of each dimension. Despite this, it was observed that Aymara children showed lower scores than their peers in "behavioral problems" according to their teachers, but this difference was also mild (partial η2>0.01). CONCLUSIONS: Aymara Children showed similar strengths and difficulties than non-Aymara students in situations that require emotional adjustment.

Percretismo placentario: manejo con oclusión de arterias ilíacas internas, embolización de arterias uterinas y oclusión de arterias ilíacas comunes / Placenta previa percreta: handling with occlusion of internal iliac artery, uterine artery embolization and occlusion of common iliac arteries

Presentamos el caso de una embarazada con placenta ístmica, percreta, previa central, con extensas anastomosis vasculares y flujo de alta velocidad. En la resolución mediante cesárea-histerectomía, para prevenir la hemorragia intraoperatoria, se utilizó una intervención radiológica en secuencia de oclusión temporal de las ilíacas internas, embolización de las arterias uterinas, reposicionamiento e insuflación de balones en ilíacas comunes. Se logró mantener estabilidad hemodinámica y el control del sangrado; estando ocluida la circulación uterina hubo pérdidas moderadas en la parte final de la operación. Se discuten la característica poco común de la implantación y percretismo ístmico, y el beneficio del uso combinado de la oclusión vascular con la cirugía expedita para minimizar el riesgo materno.

We present a patient with placenta previa percreta and oclusive. It had extensive vascular anastomosis with high velocity flow, in which resolution by cesarean-hysterectomy was done for bleeding control and followed by temporal occlusion of iliac arteries, embolization of uterine arteries, reposition and insuflation of balloons in common iliac arteries. The patient was stable and moderated bleeding happened to the end of intervention when the uterine arterial circulation was occluded. We discuss the uncommon of isthmic implantation and percretism and the benefits of both vascular occlusion and expedite surgery for to minimize maternal compromise or damage.

Tratamiento endoscópico de cálculos ureterales: experiencia en una serie de 102 casos / Endoscopic treatment of ureteral stones: experience in a series of 102 cases

INTRODUCCIÓN: La ureterolitectomía endoscópica (URS) es una técnica validada para el manejo de cálculos ureterales, ya que tiene alto poder resolutivo y es poco invasiva. El desarrollo de instrumentos flexibles ha facilitado el manejo endoscópico de los cálculos en uréter medio y proximal. El objetivo de este trabajo es describir la experiencia de nuestro centro en URS. Material y metodos: Análisis retrospectivo de las URS realizadas en nuestro centro entre Diciembre 2009 y Mayo 2012. Se consignaron las características del cálculo, el método de fragmentación, la efectividad del procedimiento y las complicaciones. Se utilizaron los ureteroscopios semirrígido Wolf (6,0-9,5 Fr) y flexible Karl Storz Flex X2. Resultados: Se revisaron 102 ureteroscopías, 85 con ureteroscopio semirrígido y 17 con flexible. Los cálculos tuvieron un promedio de 5,7 mm y 642 UH. El 89,4 por ciento de los cálculos resueltos mediante URS semirrígida se localizaban en uréter distal y 52,9 por ciento de los resueltos con URS flexible en uréter proximal. Se realizó litotripsia con láser Holmium en un 25,9 por ciento y 70,6 por ciento de los casos con URS semirrígida y flexible, respectivamente. Se utilizó litotripsia pneumática en un 4,7 por ciento de los casos de URS semirrígida. En URS semirrígida y flexible, la tasa de stone-free + fragmentos < 2 mm fue de 89,4 por ciento y 88,2 por ciento, respectivamente. Sólo hubo una complicación en nuestra serie (infección urinaria febril en 1 caso con URS flexible). La mediana de hospitalización fue de 1 día (rango 1-5 días). Conclusion: Nuestros resultados reafirman a la URS como una técnica eficaz, segura y poco invasiva para el tratamiento de los cálculos ureterales.

INTRODUCTION: The endoscopic ureterolithotomy (URS) is a validated technique for the management of ureteral calculi, which is highly resolutive and minimally invasive. The development of flexible instruments has facilitated the endoscopic management of stones in the mid and proximal segments of the ureter. The aim of this paper is to describe the experience of our center in endoscopic ureterolithotomy. Material and methods: Retrospective analysis of URS performed at our center between December 2009 and May 2012. We recorded the characteristics of the stones, the fragmentation method, the effectiveness of the procedure and complications. The Wolf semi-rigid (6.0 to 9.5 Fr) and the flexible Karl Storz Flex X2 ureteroscopes were used. RESULTS: We reviewed 102 URS, 85 with semi-rigid and 17 with flexible ureteroscope. The calculi were 5.7 mm and 642 HU in average. 89.4 percent of the stones treated with a semi-rigid URS were localized in the distal ureter and 52.9 percent of the calculi treated with a flexible URS were in the proximal ureter. Holmium laser lithotripsy was performed in 25.9 percent and 70.6 percent of the cases of semi-rigid and flexible URS, respectively. Pneumatic lithotripsy was used in 4.7 percent of the semi-rigid URS. In semi-rigid and flexible URS, the rate of stone-free + fragments < 2 mm was 89.4 percent and 88.2 percent, respectively. There was only one complication in our series (febrile urinary tract infection in 1 case of flexible URS). The median length of stay was 1 day (range 1-5 days). CONCLUSION: Our results confirm that URS is an effective, safe and minimally invasive treatment for ureteral calculi.

Esteroides androgénicos anabolizantes: consecuencias en el hombre / Anabolic androgenic steroids: consequences in the man

El abuso de Esteroides Androgénicos Anabolizantes (EAA) se ha convertido en una práctica frecuente en hombres. Deportistas de alto rendimiento y fisicoculturistas eran los usuarios más frecuentes de este tipo de fármacos, sin embargo, en los últimos 10 años se ha observado una preocupante prevalencia de abuso en hombres jóvenes y usuarios de gimnasios con el fin simplemente de mejorar su aspecto físico. Muchas veces este tipo de fármacos son adquiridos al margen de la legalidad, promocionados en internet, sin la supervisión médica, necesaria al sostener una terapia hormonal. La autoadministración de EAA en altas dosis guarda implicancias negativas poco conocidas o inadvertidas por lo usuarios. Dentro de estas destacan las consecuencias andrológicas propias del abuso de estas sustancias como son la disfunción sexual, alteraciones reproductivas, metabólicas y psicógenas. El objetivo de esta revisión es acercar el conocimiento actual sobre los riesgos e implicancias en el hombre del abuso de los EAA.

Anabolic Androgenic Steroid (EAA) Abuse has turned into a common practice upon men. High performance sportsmen and body builders were the most common users of these drugs, but in the last 10 years there has been a worrying prevalence of abuse in young men and fitness studio users with the aim of obtaining better physical aspect. Many times these drugs are bought at the margins of legality, promoted in Internet, without the medical supervision needed for hormonal therapy. Self-administration of EAA in high doses has negative effects that may be not known or unnoticed by users. Some of them are Sexual Dysfunction, reproductive, metabolic or psychological alterations. The purpose of this revision is to come closer to today’s knowledge of the risks of abuse of EAA in men.

Forced expression of OCT4 influences the expression of pluripotent genes in human mesenchymal stem cells and fibroblasts.

Genetic reprogramming of adult cells to generate induced pluripotent stem (iPS) cells is a new and important step in sidestepping some of the ethical issues and risks involved in the use of embryonic stem cells. iPS cells can be generated by introduction of transcription factors, such as OCT4, SOX2, KLF4, and CMYC. iPS cells resemble embryonic stem cells in their properties and differentiation potential. The mechanisms that lead to induced pluripotency and the effect of each transcription factor are not completely understood. We performed a critical evaluation of the effect of overexpressing OCT4 in mesenchymal stem cells and fibroblasts and found that OCT4 can activate the expression of other stemness genes, such as SOX2, NANOG, CMYC, FOXD3, KLF4, and ßCATENIN, which are not normally or are very weakly expressed in mesenchymal stem cells. Transient expression of OCT4 was also performed to evaluate whether these genes are affected by its overexpression in the first 48 h. Transfected fibroblast cells expressed around 275-fold more OCT4 than non-transfected cells. In transient expression, in which cells were analyzed after 48 h, we detected only the up-regulation of FOXD3, SOX2, and KLF4 genes, suggesting that these genes are the earlier targets of OCT4 in this cellular type. We conclude that forced expression of OCT4 can alter cell status and activate the pluripotent network. Knowledge gained through study of these systems may help us to understand the kinetics and mechanism of cell reprogramming.

Cirugía urológica en pacientes de 80 años y más: ¿es la edad un factor de riesgo para el desarrollo de complicaciones postoperatorias? / Urological surgery in patients 80 years and older: is age a risk factor for the development of postoperative complications?

La expectativa de vida ha ido aumentando en Chile y en el mundo, lo que ha causado un gran impacto a nivel del número de cirugías que se realiza en la población añosa. El objetivo de este trabajo es describir la experiencia de nuestro centro en cirugías urológicas en pacientes mayores de 80 años y analizar que factores aumentan el riesgo de complicaciones postquirúrgicas.Materiales y método: Análisis retrospectivo de 138 cirugías urológicas realizadas en 120 pacientes mayores de 80 años, durante los años 2000 a 2012. Se obtuvo información sociodemográfica, riesgo quirúrgico (ASA), tipo y duración de cirugía realizada, complicaciones post-operatorias (escala de Clavien) y tiempo de hospitalización. Los datos obtenidos fueron analizados mediante el programa SPSS v17. Se realizó análisis multivariado y se estableció el riesgo relativo para el desarrollo de complicaciones. Se consideró signi ficativo p<0,05. Resultado: La edad promedio de los pacientes fue de 84+/-3.7 años, 86.2 por ciento fueron hombres. El 96.7 por ciento presentaba algún tipo de comorbilidad, con predominio de hipertensión arterial (60,84 por ciento) y diabetes mellitus tipo 2 (24,16 por ciento). La mayoría de las intervenciones fue de complejidad intermedia (77.27 por ciento), donde la anestesia regional (56,8 por ciento) y la vía endo urológica (84,78 por ciento) fueron las más utilizadas, con un tiempo operatorio promedio de 62+/-52.4 minutos. El riesgo quirúrgico prevalente fue ASA2 (62.7 por ciento). El promedio de hospitalización fue de 2,8+/-2.7 días. El 15.21 por ciento de los pacientes presentó algún tipo de complicación, con predominio de clasifi cación tipo 1 de Clavien (38 por ciento). En el análisis multivariado se evidenció como factores de riesgo signi ficativos para complicaciones, edad mayor a 90 años (p=0.03), presencia de insu ciencia renal (p=0.01), portar 4 o más comorbilidades (p=0.04), cirugía mayor a 3 horas (p=0.03) y tener riesgo quirúrgico ASA3 (p=0.04)...

Life expectancy has been increasing in Chile and in the World. This has caused a great impact over the number of surgeries being performed in the elderly population. The aim of this paper is to describe the experience of our center in urological surgery in patients older than 80 years and analyze which factors increase the risk of postoperative complications.Materials and methods: Retrospective analysis of 138 urological surgeries performed in 120 patients older than 80 years, during the years 2000-2012. Sociodemographic information, surgical risk (ASA), type and duration of surgery, postoperative complications (Clavien scale) and length of hospitalization was obtained. The data were analyzed using SPSS v17. Multivariate analysis was performed and the relative risk for developing complications was established. Signi cance was p <0.05. Average age of the patients was 84 +/- 3.7 years, 86.2percentwere men. The 96.7 percenct had some kind of comorbidity, with prevalence of hypertension (60.84 percent) and diabetes mellitus type 2 (24.16 percent). Most of the interventions was of intermediate complexity (77.27percent), where regional anesthesia (56.8 percent) and endourological aproach (84.78 percent) were the most used, with average operative time of 62 +/- 52.4 minutes. Most common Surgical risk was ASA2 (62.7 percent). Average hospital stay was 2.8 +/- 2.7 days. 15.21 percent of patients had some type of complication, with a predominance of type 1 Clavien classication (38 percent). The multivariate analysis showed signi cant risk factors for complications: age greater than 90 years (p = 0.03), renal failure (p = 0.01), carrying 4 or more comorbidities (p = 0.04), surgery Langer than 3 hours (p = 0.03) and ASA3 surgical risk (p =.04). No mortality was reported in our series. In this study, although most of our patients underwent endourological procedures, we evidence that surgery in patients older than 80 years is feasible...

Estudio descriptivo de forma y función del juego libre del niño(a) en etapa preescolar / Descriptive study of the form and function of the unstructured play of the child in pre-school stage

La investigación tiene como principal objetivo conocer la forma y función del juego libre de 7 niños (as) en etapa de transición (4 a 5 años) de la ciudad de Punta Arenas, considerados en establecimientos educacionales pre-escolares en la región de Magallanes y Antártica Chilena. Bajo los fundamentos teóricos de la ciencia de la ocupación, se pretende identificar, a través del juego libre, aspectos relevantes de la conducta del menor, que favorezcan o dificulten su desempeño escolar. La metodología usada es de carácter cualitativo, siendo su método el estudio de caso. Los principales resultados demuestran similitud en la función del juego libre de cada niño(a), siendo estos predominantemente motor-social, los cuales repercuten en su desempeño escolar. Se concluye que, cada juego significa un momento para el aprendizaje y, como herramienta diagnóstica, entrega la posibilidad de visualizar ciertas conductas adaptativas en los niños(as) o, por el contrario, determinar signos de alerta según su edad de desarrollo.

The objective of the this research is to investigate the form and function of the unstructured play of seven children in transition stage (4 to 5 year-old) in the city of Punta Arenas. The children considered in this study are from preschool educational institutions living in the region of Magallanes and the Chilean Antartica. Under the theoretical foundations of occupational science it is expected to identify the relevant aspects of the children’s behavior in unstructured play, especially those that may help, or having negative effects in the school performance. The methodology used in this case is qualitative, being its method the case study. The main results demonstrate similarities regarding the functions of the children’s unstructured play, being these mainly “motor-social” functions that have an effect in the school performance. It can be concluded then, that unstructured play helps to develop the children’s learning strategies. It can be used as a diagnosis tool because it permits the observation of adaptive behaviors in children, and also allows determining signs of alert considering the child’s age of development.

PP131. Regulation of heme oxygenase/carbon monoxide (ho/co) and l-arginine/nitric oxide (no) pathways by human chorionic gonadotropin (hcg) in human fetal endothelium.

INTRODUCTION: HO/CO and l-arginine/NO pathways are critical regulators of vascular function in early human pregnancy. HO is the rate-limiting enzyme in heme catabolism leading to the formation of biliverdin, which is subsequently reduced to bilirubin by biliverdin reductase, carbon monoxide, and free iron. HO-1, the inducible isoform of the enzyme, is essential to promote placental function and fetal development (1). HO-1 is also required to maintain nitric oxide synthesis (2). Human chorionic gonadotropin (hCG) is the first blastocyst-derived hormonal signal playing a significant role in implantation and placentation (3). We hypothesized that hCG upregulates HO-1 and thus positively regulates early vascular events in human pregnancy. OBJECTIVES: In this study we used human umbilical vein endothelial cells (HUVECs) to demonstrate that hCG up-regulates mRNA and protein abundance of HO-1. The effect of hCG on l-arginine transport and the expression of hCAT1, the main cationic amino acid transporter involved in endothelial nitric oxide synthesis were evaluated. METHODS: HUVEC were isolated from normal pregnancies (approval from the Institutional Review Board) by collagenase digestion and grown (37°C, 5% CO2) in medium 199 supplemented with 20% newborn and fetal calf sera. Cells were treated with hCG (0.5-100IU/mL, 0-24hours and CoCl2 (150µM, 6hours) as positive control. Total proteins were separated by SDS-PAGE electrophoresis, transferred to nitrocellulose membranes and incubated with monoclonal anti human HO-1 or anti ß-actin and respective secondary antibody conjugated with horseradish peroxidase. Protein bands were detected by enhanced chemiluminiscence. Total RNA was isolated and cDNA was obtained by reverse transcription. PCR assays were performed in a reaction mix containing 0.5µM primers, dNTPs, Taq DNA polymerase, 2 mM MgCl2. Relative abundance of HO-1, hCAT-1 and 28S were determined. l-[(3)H]Arginine transport (100µM, 2 µCi ml(-1), 37°C, 1min) were determined in HUVECs exposed (30min) to hCG (0.5-100IU/mL) and CORM-2 (CO donor). RESULTS: The highest level of HO-1 protein were obtained at 5IU/mL of hCG and declined at higher concentrations. hCG increased HO-1 protein abundance and maximal response was observed at 6 hours (4-fold), decreasing at 24hours exposure. These effects of hCG on HO-1 protein abundance are well correlated with changes in HO-1 mRNA regarding time of exposure and concentration of hCG. L-arginine transport and hCAT-1 mRNA were also increased (2.8-fold and 4.5-fold, respectively) by hCG. CONCLUSION: Upregulation of HO-1 as well as the increase in l-arginine transport and hCAT-1 mRNA in HUVECs are novel effects of hCG, which occur at physiological plasma concentrations of the hormone, as those found in the first weeks of pregnancy. These changes could be relevant for the maintenance of the NO synthesis in fetal and maternal vasculature, ensuring the predominance of the vasodilator tone. These effects could be also critical for vascular remodelling of uterine circulation and placental vascular development in early stages of pregnancy, the lack of which could result in abnormal placentation as described in preeclampsia and fetal growth restriction.