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Los tumores de la región pineal representan el 0,1-0,4% de los tumores cerebrales primarios 1) Los más frecuentes son los de células germinales, seguidos por los originados de células del parénquima pineal. Menos frecuente, tumores de estirpe glial y misceláneos; 2) De los gliomas, el más frecuente es el astrocitoma bien diferenciado; 3) Los glioblastomas son un hallazgo infrecuente. Reportamos el caso de un paciente de 62 años, cuya clínica se caracteriza por diplopía altitudinal y cefalea. En estudio de imágenes a su ingreso destacan hidrocefalia supratentorial; lesión pineal de aspecto infiltrativo; y aspectos sugerentes de diseminación leptomeningea. En la región espinal se encuentran lesiones metastásicas. Los biomarcadores resultaron negativos. El tratamiento inicial consiste en realizar fenestración de lámina terminalis para manejo de hidrocefalia. Se practica una biopsia de lesión intradural extramedular T10-T11 que es informada como Glioma de alto grado IDH 1 no mutado, con microproliferacion vascular y numerosas figuras mitóticas. Su historia natural permite una sobrevida solo de 5 meses. Las lesiones pineales de estirpe glial son poco frecuentes. Los casos con características de Gliomas Malignos pueden corresponder a Astrocitomas grado 3 OMS y menos frecuentemente a Glioblastomas. Su diagnóstico requiere estudios histológicos y inmunohistologicos detallados, la presencia de diseminación leptomeningea es de mayor frecuencia en los Glioblastomas. Pese a todas las opciones terapéuticas disponibles, este tipo de tumores tienen baja sobrevida.

Background This study evaluated the efficacy, safety and tolerability of the novel inhaled phosphodiesterase-4 inhibitor CHF6001 added-on to formoterol in patients with chronic obstructive pulmonary disease (COPD). Methods Randomised, double-blind, placebo- and active-controlled, parallel-group study. Eligible patients had symptomatic COPD, post-bronchodilator forced expiratory volume in 1 s (FEV1) 30–70% predicted, and history of ≥1 moderate/severe exacerbation. Patients were randomised to extrafine CHF6001 400, 800, 1200 or 1600 μg twice daily (BID), budesonide, or placebo for 24 weeks. Primary objectives: To investigate CHF6001 dose-response for pre-dose FEV1 after 12 weeks, and to identify the optimal dose. Moderate-to-severe exacerbations were a secondary endpoint. Results Of 1130 patients randomised, 91.9% completed. Changes from baseline in pre-dose FEV1 at Week 12 were small in all groups (including budesonide), with no CHF6001 dose-response, and no significant treatment–placebo differences. For moderate-to-severe exacerbations, CHF6001 rate reductions versus placebo were 13–28% (non-significant). In post-hoc analyses, CHF6001 effects were larger in patients with a chronic bronchitis phenotype (rate reductions versus placebo 24–37%; non-significant), and were further increased in patients with chronic bronchitis and eosinophil count ≥150 cells/μL (49–73%, statistically significant for CHF6001 800 and 1600 μg BID). CHF6001 was well tolerated with no safety signal (including in terms of gastrointestinal adverse events). Conclusions CHF6001 had no effect in the primary lung function analysis, although was well-tolerated with no gastrointestinal adverse event signal. Post-hoc analyses focused on exacerbation risk indicate specific patient subgroups who may receive particular benefit from CHF6001. Trial registration ClinicalTrials.gov (NCT02986321). Registered 8 Dec 2016.

Highlights • Cancer management adapting to the current state of health during COVID-19 pandemic. • Collaborative strategic action plan for cancer management and workflow in a developing country. • Algorithm in cancer center management during COVID-19 in a developing country. • Measures to be adopted in cancer management and workflow after COVID-19 pandemic.

Objective: Apply three prognostic models “online” (Nothingham index (NPI), Adjuvantonline! (AO) and PREDICT used in routine oncology practice in order to stratify patients and define the use of adjuvant therapies in patients with stage I breast cancer (BC) to evaluate its correlation and overall survival (OS) in our population. Methods: We obtained patients’ medical records data with invasive BC T1N0M0, treated at the Cancer Center of the Pontificia Universidad Catolica de Chile, Santiago, Chile, from January 1997 to December 2003. Results: We analyzed data from 125 patients. Median age was 55 years (3580). Most tumors were infiltrating ductal carcinoma (72.8%), estrogen receptor positive (88.8%), 80% received endocrine therapy (ET). The estimated ET and chemotherapy benefit was not significantly different according to the AO and PREDICT models (1.3% and 1% for CT, p = 0.13, 0.9% and 1% for ET p = 0.8, respectively). The estimated median OS on NPI (96%) was higher than calculated by AO (90.9%) and PREDICT (92.5%). Interestingly diseasespecific mortality estimated was 3%, similar to that observed (3.2%). While the estimated median OS by all models in the group of deceased patients was lower than in surviving, this difference did not reach statistical significance (p = 0.85). Conclusion: The prognostic models applied effectively predict OS in Chilean patients with T1N0M0 BC, but in this series, they do not sufficiently discriminate patients with poor prognosis. The addition of co- morbidities to AO does not alter the results.

Se investigó la relación entre el colesterol total (Colt) y la dopamina (DA) a fin de disponer de un examen accesible en consulta como es la medición del colesterol total (Colt) de manera de proyectar el comportamiento de la DA sérica. Se determinó el Colt a 50 caninos y con base a los resultados se formaron tres grupos estudio, Grupo I: 6 pacientes con Colt entre 77 y 200 mg/dl; Grupo II: 6 pacientes entre 250 y 300 mg/dl; Grupo III: 6 pacientes entre 400 y 470 mg/dl. A los 18 pacientes se les midió la DA sérica a través de HPLC acoplado a un detector electroquímico. Se encontró una amplia distribución de datos respecto de la determinación de Colt (291.8 ± 62.0 mg/ dl) y DA (68.8 ± 17.8 μg/ml) con una baja correlación entre ellos. El análisis por grupo de estudio muestra una mayor correlación de DA para bajas concentraciones de colesterol sérico, y el análisis de pendientes muestra que la variación en la concentración de DA es mayor ante pequeñas variaciones de colesterol en el grupo II., The relationship between total cholesterol (Colt) and dopamine (DA) was investigated for the possibility of having an accessible exam in consultation such as the measurement of total cholesterol (Colt) to project the behavior of serum DA. The Colt was determined in 50 dogs and based on the results three study groups were formed, Group I: 6 patients with Colt between 77 and 200 mg/dl; Group II: 6 patients between 250 and 300 mg/dl; Group III: 6 patients between 400 and 470 mg/dl. Serum DA was measured in the 18 patients through HPLC coupled to an electrochemical detector. It was found a wide distribution of data regarding the determination of Colt (291.8 ± 62.0 mg/dl) and DA (68.8 ± 17.8 μg/ml) with a low correlation between them. The analysis by study group shows a greater correlation of DA for low concentrations of serum cholesterol, and the analysis of slopes shows that the variation in the concentration of DA is greater in cases of small variations of cholesterol in group II.

Breast cancer is the leading cause of cancer death in Chilean women. While most patientes are cured, five percent of cases present with advanced disease initially and up to 20-30% of patients with localized disease may suffer systemic recurrences. The majority of breast neoplasms are dependent on the estrogenic stimulus, hence the deprivation of estrogen is the main therapeutic strategy. Recently, the use of molecular targeted therapies in combination with endocrine therapy has been successful in improving the survival outcomes of advanced breast cancer, with fewer side effects than those produced by conventional chemotherapy. Knowledge of the mechanisms of action of these new therapies, their toxicities, resistance pathways and patient selection to achieve the best therapeutic benefits are relevant aspects in the management of the disease. We present a review of the current state of management of hormone-dependent metastatic breast cancer with emphasis on the use of endocrine therapies combined with molecular therapies.

We investigated whether high adherence to the Dietary Approaches to Stop Hypertension (DASH) diet was independently associated with lower risk of incident hypertension. Participants included 5632 adults, without hypertension at the baseline (2008–2010) of the Longitudinal Study of Adult Health, who took part in the second follow-up visit (2012–2014). Adherence to the DASH diet was estimated at baseline using a score based on eight food items (final scores from 8 to 40 points) and was categorised as high adherence (≥30 points, or ≥75 %) and low adherence (

Rationale: COPD is a progressive disease, often co-existing with other chronic diseases contributing to increased risk of fatal events. The efficacy of ICS-containing medications in reducing mortality in COPD patients has been suggested. Aims and objectives: We performed a stratified safety pooled analysis of fatal adverse events (AEs) comparing extrafine ICS-containing combinations vs ICS-free treatments. Methods: Three 52-week studies in moderate/severe COPD patients compared the fixed combination of extrafine beclometasone dipropionate, formoterol fumarate, glycopyrronium (BDP/FF/G) to extrafine BDP/FF (TRILOGY study), to tiotropium (TIO) and extrafine BDP/FF + TIO (TRINITY study), or to Indacaterol/Glycopyrronium bromide (IND/GLY) (TRIBUTE study). All fatal AEs stratified by causes (respiratory vs non-respiratory) were considered. Results: No differences were seen between treatments for respiratory fatal events. For non-respiratory fatal events, time to death was delayed for extrafine ICS-containing treatments vs ICS-free treatments (Table 1). Conclusions: These results may suggest that extrafine ICS-containing medications compared to ICS-free treatments could be associated with a lower rate of non-respiratory mortality in symptomatic COPD patients at risk for exacerbations.

The American Society of Breast Surgeons (ASBrS) sought to provide an evidence-based guideline on the use of neoadjuvant systemic therapy (NST) in the management of clinical stage II and III invasive breast cancer. A comprehensive nonsystematic review was performed of selected peer-reviewed literature published since 2000. The Education Committee of the ASBrS convened to develop guideline recommendations. A performance and practice guideline was prepared to outline the baseline assessment and perioperative management of patients with clinical stage II–III breast cancer under consideration for NST. Preoperative or NST is emerging as an important initial strategy for the management of invasive breast cancer. From the surgeon’s perspective, the primary goal of NST is to increase the resectability of locally advanced breast cancer, increase the feasibility of breast-conserving surgery and sentinel node biopsy, and decrease surgical morbidity. To ensure optimal patient selection and efficient patient care, the guideline recommends: (1) baseline breast and axillary imaging; (2) minimally invasive biopsies of breast and axillary lesions; (3) determination of tumor biomarkers; (4) systemic staging; (5) care coordination, including referrals to medical oncology, radiation oncology, plastic surgery, social work, and genetic counseling, if indicated; (6) initiation of NST; (7) post-NST breast and axillary imaging; and (8) decision for surgery based on extent of disease at presentation, patient choice, clinical response to NST, and genetic testing results, if performed.

Rationale COPD often co-exists with other chronic diseases that can contribute to patients’ health status and prognosis. In particular, patients with COPD are at greater risk of cardiovascular disease compared with age and sex-matched controls. Methods Two 52 week multi-centre, randomised, double-blind, active-controlled studies recruited patients with symptomatic COPD, severe to very severe airflow limitation, and an exacerbation history. In TRILOGY, patients were randomised (1:1) to an extrafine fixed triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB; 100/6/12.5 mcg, two actuations twice daily [BID] via pressurised metered dose inhaler [pMDI]; ‘fixed triple’) or an extrafine fixed combination of BDP/FF (100/6 mcg, two actuations BID via pMDI; Fostair) (Singh et al. Lancet 2016; 388: 963–73). In TRINITY patients were randomised 2:2:1 to BDP/FF/GB, tiotropium (18 mcg once daily via single-dose dry powder inhaler [SDDPI]), or BDP/FF+tiotropium: free triple (Vestbo et al. Lancet 2017; 389: 1919–29). In this analysis, we evaluated the occurrence of Major Adverse Cardiovascular Events (MACEs). MACEs included acute myocardial infarction, stroke, cardiovascular death, arrhythmias, and heart failure. Results MACE incidence and rate in the two BDP/FF/GB groups was similar to the BDP/FF and tiotropium groups (Table 1). The majority of reported MACEs were severe in intensity, with a slightly higher percentage of fatal events in the Tiotropium only group. Importantly, in patients with relevant concomitant cardiovascular diseases, the trend was similar to that seen in the overall populations. None of the other subgroup analyses (by age, spacer use and gender) highlighted relevant differences in the safety profiles compared with the overall population. Conclusions These Results provide further reassurance that the additional clinical benefits of this extrafine fixed triple compared to standard treatment are not associated with a greater impact on the cardiovascular safety in severe to very severe COPD patients, further supporting its positive benefit/risk ratio. Importantly, the presence of concomitant cardiac comorbidities did not influence the rate of cardiovascular events. Please refer to page A261 for declarations of interest in relation to abstract P276.

Rationale Treatment with extrafine triple therapy in a single inhaler has beneficial effects compared to LAMA monotherapy on lung function and symptoms. This analysis focuses on rescue medication use (as this is associated with symptoms) and lung function responder analysis identifying clinically relevant effects. Methods In this 52 week multicentre, randomised, double-blind, active-controlled study, 2691 patients with severe to very severe COPD, exacerbations history, and CAT total score ≥10 were randomised (2:2:1) to tiotropium, fixed triple (beclometasone/formoterol/glycopyrronium), or free triple (beclometasone/formoterol+tiotropium). Secondary endpoints included FEV1 responders at week 26 and 52 using different thresholds for response and change from baseline in average use of rescue medication. Results Both fixed and free triple FEV1 responder percentages were significantly greater than tiotropium at weeks 26 and 52 regardless of the threshold used to define the response (p Conclusions Extrafine triple therapy in a single inhaler provides superior clinical benefits in severe to very severe COPD patients in terms of lung function (by individual responder analysis) and rescue medication use compared with tiotropium alone. Please refer to page A260 for declarations of interest in relation to abstract P271.

Rationale Efficacy and safety of extrafine fixed triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB; 100/6/12.5 mcg, two actuations BID via pMDI; ‘fixed triple’) has been recently demonstrated in two phase III trials. Fixed triple has shown superiority in improving lung function and reducing moderate/severe exacerbations versus BDP/FF (Fostair 100/6 mcg, two actuations BID via pMD; TRILOGY – Singh et al. Lancet 2016; 388: 963–73) and versus tiotropium (18 mcg one inhalation OD via DPI; TRINITY – Vestbo et al. Lancet 2017; 389: 1919–29). Increase in pneumonia risk associated with ICS containing medications is a known class effect. The risk/benefit balance of extrafine fixed triple was evaluated by comparing variations in pneumonia and exacerbation events. Methods Information on moderate/severe exacerbations and confirmed pneumonia was extracted from TRINITY and TRILOGY. A frequency plot was generated considering days in the study versus cumulative number of events. Results In TRILOGY study, the number of recorded events was 288 exacerbations (rate: 0.448 exacerbations per patient per year) versus 25 pneumonias (rate: 0.039 events per patient per year) with fixed triple and 353 exacerbations (0.565) versus 18 pneumonias (0.029) with Fostair (figure 1A). In TRINITY study, the number of events was 485 exacerbations (0.472) versus 30 pneumonias (0.029) with fixed triple and 569 exacerbations (0.583) versus 20 pneumonias (0.020) with tiotropium (figure 1B). Overall, treatment with fixed triple therapy reduced exacerbations by 65 events compared to Fostair (adjusted rate ratio: 0.773, p=0.005) and by 84 events compared to tiotropium (0.801, p=0.003). No fatal pneumonias occurred in TRILOGY while 5 pneumonias led to death in TRINITY (1 with fixed triple versus 4 with tiotropium). All pneumonias were classified as non-related to treatment. Conclusions This analysis confirms that, in two independent populations of COPD patients treated with an ICS containing extrafine fixed triple combination, the number of incident pneumonia remains very small compared to that of moderate/severe exacerbations. The benefit observed in reducing the absolute number of exacerbations outweighs the increase observed in absolute number of pneumonias, thus confirming the positive risk benefit balance of extrafine fixed triple in severe/very severe COPD patients. Please refer to page A260 for declarations of interest in relation to abstract P273.

Made available in DSpace on 2018-12-11T16:47:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-08-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The crossbreeding of two or more breeds from the Bos taurus and Bos indicus species is an alternative for obtaining high-quality meat from animals adapted to tropical climates. Quality and sensory attributes of beef, mainly its tenderness and flavour, are very important with regard to the consumer’s point of view. This study aimed to evaluate the physico-chemical and sensory characteristics of crossbred young bulls and heifers, the offspring of Angus or Limousin bulls and 1/2 Angus + 1/2 Nellore or 1/2 Simental + 1/2 Nellore cows that were finished on feedlot or pasture. Meat quality traits (pH, colour, cooking loss, water holding capacity and shear force) and sensory parameters (characteristic beef aroma/flavour intensity, strange aroma/flavour intensity, tenderness and juiciness descriptive attributes, flavour, texture (tenderness) and overall acceptance) were evaluated. The genetic group had an effect on the beef pH, but it was not as relevant as the effect of the combination between the production system and the sex or genetic group, which affected many of the quality and sensory traits. Embrapa Pecuária Sudeste, Rodovia Washington Luiz, km 234, P.O. box 339 Faculdade de Ciências Farmacêuticas (FCFAr) Universidade Estadual Paulista (UNESP) Departamento de Zootecnia Universidade do Estado de Santa Catarina – UDESC Faculdade de Ciências Farmacêuticas (FCFAr) Universidade Estadual Paulista (UNESP) CNPq: 472344/2012-9

Aim: To establish the association between the obstruction site, whether it is unilateral or bilateral, age group, and sex. Methods: A retrospective observational study of 1000 lacrimal ducts of 500 consecutive patients seen in the Emilio Amorim Radiological Clinic, who were suspected of having lacrimal duct obstructions, was performed. Results: Of the studied patients, 121 were men and 379 were women. Their ages varied between 2 years and 93 years. 148 of the examinations were normal; in 298 the obstructions were unilateral and in 54 they were bilateral. The majority of the obstructions occurred at the valve of Krause. There was a significant difference in the correlation of the obstruction site with sex. The obstruction was total in 378 valves and partial in 28. Other findings included sinusitis, osteomas, bone fractures, fistulae, diverticulum, and lacrimal stones. Conclusion: Obstruction of the lacrimal ducts is normally total, unilateral, and sited at the valve of Krause. The obstruction of this valve predominantly affects women, whereas obstruction of the valve of Hasner mainly affects men. There was no significant difference in the distribution of obstructions by age group.

BACKGROUND: Limited data are available for the efficacy of triple therapy with two long-acting bronchodilators and an inhaled corticosteroid in chronic obstructive pulmonary disease (COPD). We compared treatment with extrafine beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB; fixed triple) with tiotropium, and BDP/FF plus tiotropium (open triple).METHODS: For this double-blind, parallel-group, randomised, controlled trial, eligible patients had COPD, post-bronchodilator forced expiratory volume in 1 s (FEV1) of less than 50%, at least one moderate-to-severe COPD exacerbation in the previous 12 months, and a COPD Assessment Test total score of at least 10. After a 2-week run-in period receiving one inhalation per day via single-dose dry-powder inhaler of open-label 18 μg tiotropium, patients were randomised (2:2:1) using a interactive response technology system to 52 weeks treatment with tiotropium, fixed triple, or open triple. Randomisation was stratified by country and severity of airflow limitation. The primary endpoint was moderate-to-severe COPD exacerbation rate. The key secondary endpoint was change from baseline in pre-dose FEV1 at week 52. The trial is registered with ClinicalTrials.gov, number NCT01911364.FINDINGS: Between Jan 21, 2014, and March 18, 2016, 2691 patients received fixed triple (n=1078), tiotropium (n=1075), or open triple (n=538). Moderate-to-severe exacerbation rates were 0·46 (95% CI 0·41-0·51) for fixed triple, 0·57 (0·52-0·63) for tiotropium, and 0·45 (0·39-0·52) for open triple; fixed triple was superior to tiotropium (rate ratio 0·80 [95% CI 0·69-0·92]; p=0·0025). For week 52 pre-dose FEV1, fixed triple was superior to tiotropium (mean difference 0·061 L [0·037 to 0·086]; pINTERPRETATION: In our TRINITY study, treatment with extrafine fixed triple therapy had clinical benefits compared with tiotropium in patients with symptomatic COPD, FEV1 of less than 50%, and a history of exacerbations.FUNDING: Chiesi Farmaceutici SpA.

Introduction: Free triple therapy is commonly used and recommended by guidelines in the treatment of COPD. CHF5993 is a novel fixed dose combination (FDC) of extrafine BDP/FF/GB pMDI developed for the treatment of COPD. Objectives: Primary objective was to show superiority of CHF5993 vs. Tio (via Handihaler®) in terms of moderate/severe COPD exacerbation rate. Key secondary objectives were to show superiority of CHF5993 vs. Tio and non-inferiority vs. Foster® (pMDI FDC of BDP/FF) + Tio in pre-dose FEV1. Methods: In this phase III, double-blind, 52-week study, 2691 severe/very severe COPD patients (post-bronchodilator FEV1 Results: Compared to Tio, CHF5993 significantly reduced the rate of moderate/severe exacerbations by 20% (p=0.003) and improved pre-dose FEV1 by 0.061 L (95% CI: 0.037, 0.086; p Conclusion: This study is the first to demonstrate that a novel triple FDC is superior to Tio in reducing exacerbations and improving pulmonary function while providing a comparable clinical efficacy with a free triple combination in COPD patients.

Introduction: Free triple therapy is commonly used in COPD. CHF5993 is a novel fixed dose triple combination (FDC) of extrafine BDP/FF/GB delivered via a pMDI. Main Objectives: To demonstrate the superiority of CHF5993 vs. Foster® (a marketed pMDI FDC of BDP/FF) in pre-dose and 2-hour post-dose FEV1 and Transition Dyspnoea Index (TDI) score at Week 26 (co-primary endpoints), to evaluate the effect on COPD exacerbations over 52 weeks and to assess safety and tolerability. Methods: In this phase III, double-blind, 52-week study, 1368 severe/very severe COPD patients (post-bronchodilator FEV1 Results: CHF5993 improved pre-dose FEV1 by 0.081 L (95% CI: 0.052, 0.109; p Conclusion: This study demonstrated that a novel triple FDC is superior to an approved double FDC treatment in terms of lung function and reduction of exacerbations in severe/very severe COPD patients at risk for exacerbations.

To evaluate whether soybean extracts and estrogens present additive effects on adult rat uterus.Fifty ovariectomized rats were randomly divided into five equal groups of ten animals: Control, treated with vehicle; SE46 and SE120, treated with 46 and 120 mg/kg soybean concentrated extract (SE), respectively; EE, treated with conjugated equine estrogens (CE) 50 μg/kg; SE120 + EE, treated with 50 μg/kg (CE) plus 120 mg/kg SE. The substances were administered daily by gavage for 21 consecutive days. Thereafter the animals were weighed and killed by decapitation; trunk blood was collected for hormone determinations. Uteri were removed immediately and fixed in 10% formaldehyde, followed by dehydration, embedding in paraffin and 6-m sections staining with hematoxylin and eosin for histomorphometric analyses of myometrium and endometrium. After ANOVA analysis of the data, the study was complemented with the Tukey-Kramer test for multiple comparisons.The concentrated extract of soybean at high concentration (SE 120 kg/mg) and estrogens proved to have a trophic effect on the uterus (endometrium and myometrium) of castrated rats. In groups SE120, EE and SE120 + EE, all morphometric parameters examined (number of glands, eosinophils, blood vessels and the glandular area) were increased. No significant addictive effects of soybean extract plus estrogens were detected in the SE120 + EE group.Our results indicate that soy extract has a trophic effect on rat uterine structures. Treatment of ovariectomized rats with a concentrated soy extract in combination with conjugated estrogens had no addictive effect on the uterine response.

ResumenSe presenta una visión personal del jefe de la unidad de trauma ocular, en la cual se describen los hechos históricos más importantes, y los pasos que se dieron para la creación del primer centro nacional de referencia en Chile de trauma ocular severo. También en estudios previos se han mencionado las características principales de los pacientes que se atienden en este centro.El objetivo del artículo es revisar los hitos históricos más importantes que participaron en la creación de la Unidad de Trauma Ocular del hospital el Salvador hasta ahora, haciendo énfasis en los resultados epidemiológicos en estudios previos.Desde 1971, el primer esfuerzo por dar atención de urgencia oftalmológica, se concentró en el en la Urgencia de la asistencia pública Dr. Alejandro del Río. Con solo 12 oftalmólogos, y muchas dificultades para operar como un departamento de urgencia independiente. El servicio tuvo una lento deterioro, hasta mediados de los 80, en que comenzaron a colapsar otros servicios oftalmológicos. Sin embargo, diversos personajes de la esfera oftalmológica presionaron a las autoridades para la creación de una unidad de trauma ocular.De este modo en 1994 se creó la primera unidad de trauma ocular con dos oftalmólogos con turno de medio día, una pequeña sala de emergencia, que fue gradualmente creciendo y prosperando hasta como se conoce hoy día. Desde el 2007, fue declarada por ley, el centro de referencia del trauma ocular severo, en el nuevo régimen de garantías explícitas de salud. Actualmente, desde el 2010, nuestra unidad se convertido el Centro Nacional de trauma ocular severo y accidentes del trabajo, con más de 33.000 atenciones y 1.500 cirugías al año.La creación del Centro Nacional de Trauma Ocular severo es el resultado de largos años de trabajo y representa el esfuerzo conjunto para prevenir la ceguera por trauma en Chile.SummaryPurposeTo review the main historical landmarks of the creation of the Ocular Trauma Unit of Hospital del Salvador until nowadays, making emphasis in epidemiological findings of previous studies.MethodsA personal point of view, made by the Ocular Trauma Unit head chief is presented here describing the most important historical facts that they took step to the creation of the First Center of National Reference for Severe Ocular in Chile. Also, a previous epidemiological study is mentioned in order to reference main characteristics of patients attended here.ResultsSince 1971, the first effort to provide ophthalmological emergency attention was concentrated in its beginnings in the Emergency Department of The Public Assistance Dr. Alejandro del Río. With only 12 ophthalmologists and many difficulties to operate as an independent emergency department, the service had a slow deterioration until middle eighties, starting to collapse other Ophthalmology Services. Nevertheless, diverse personages of the ophthalmological sphere, pressed to the authorities for the creation of a unit of ocular trauma. Thus, in 1994 it was created the first ocular trauma unit with only two ophthalmologists with half-day shifts in a small emergency room that gradually prospered to which we know now. Since 2007, it was declared by law as The Referral Center for Severe Ocular Trauma in the new regimen of Explicit Guaranties in Health, and currently (since 2010) our unit has become the National Center for Severe Ocular Trauma and Work-Related accidents, with more than 33,000 attentions and 1,500 surgeries per year.ConclusionThe creation of The National Center for Severe Ocular Trauma has been the result of long years of work and represents a joint effort in preventing the blindness by ocular trauma in Chile.

This article presents a case of intrapelvic migration of a Gamma nail lag screw (Stryker, Mahwah, New Jersey) in an 82-year-old woman 7 months after fixation of an unstable pertrochanteric fracture. Two of the most common complications associated with the use of the Gamma nail and other sliding intramedullary devices, as well as lag screw and side plate devices, relate to the lag screw: cut out and medial migration in the femoral head. As compared to lag screw migration in the femoral head, intrapelvic migration of the Gamma lag screw is a rare complication. To our knowledge, intra-pelvic migration after disengagement of the lag screw from the Gamma nail has been reported in the literature only 3 times. Several risk factors can be associated with Gamma nail failure, most importantly damage to femoral head leading to lag screw migration, plate/lag or nail/lag screw interface dysfunction, technical mistakes, and additional subsequent trauma. This article reviews the literature and the theories for such device failures.

Se evaluó la capacidad ulcerogénica a dosis única de tres drogas antiinflamatorias no esteroideas (AINES) de amplio uso en Terapéutica como son el celecoxib, ibuprofeno e indometacina. Se utilizaron ocho (08) ratas macho albinas de la raza Sprague-Dawley, de 4 meses de edad, con un peso vivo entre 250-3oog, mantenidas en ayuno durante 24h previo al ensayo. Fueron distribuidas al azar en 4 grupos y se les administró vía oral (orogástrica) Grupo 1: Indometacina 15 mg/kg, Grupo 2: Ibuprofeno 100 mgj kg, Grupo 3: Celecoxib 100 mg/kg, Grupo 4: Suero Fisiológico (Control). Los animales fueron sacrificados 24h después del tratamiento y se evaluaron lesiones macroscópicas en yeyuno. En el grupo control se observaron lesiones de grado 2. Estas lesiones se ubicaron en el lado mesentérico del yeyuno. En los animales tratados se observaron lesiones de grado 1, 3 Y 4 (Tabla 1). Las lesiones estuvieron caracterizadas por el engrosamiento de la pared intestinal, pérdida de la mucosa, hiperemia y presencia de úlceras circulares. El tratamiento concelecoxib fue el que presentó menor daño. El mayor grado de lesión fue observado en el tratamiento con indometacina. En la mucosa gástrica el mayor daño se observó en los tratamientos con indometacina e ibuprofeno.

BACKGROUND: Few data are available for the efficacy of "triple therapy" with two long-acting bronchodilators and an inhaled corticosteroid in chronic obstructive pulmonary disease (COPD). We designed this study to assess efficacy of single-inhaler combination of an extra fine formulation of beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB) in COPD compared with beclometasone dipropionate and formoterol fumarate (BDP/FF) treatment.METHODS: TRILOGY was a randomised, parallel group, double-blind, active-controlled study done in 159 sites across 14 countries. The sites were a mixture of primary, secondary, and tertiary care providers, and specialist investigation units. Eligible patients with COPD had post-bronchodilator forced expiratory volume in 1 s (FEV1) of lower than 50%, one or more moderate-to-severe COPD exacerbation in the previous 12 months, COPD Assessment Test total score of 10 or more, and a Baseline Dyspnea Index focal score of 10 or less. Patients who met the inclusion and exclusion criteria at screening entered a 2-week open-label run-in period where they received beclometasone dipropionate (100 μg) and formoterol fumarate (6 μg) in two actuations twice daily. Patients were then randomly assigned (1:1) with an interactive response technology system to either continue BDP (100 μg) and FF (6 μg) or step-up to BDP (100 μg), FF (6 μg), and GB (12·5 μg) in two actuations twice daily for 52 weeks via pressurised metered-dose inhaler. The three co-primary endpoints were pre-dose FEV1, 2-h post-dose FEV1, and Transition Dyspnea Index (TDI) focal score, all measured at week 26 in the intention-to-treat population (all patients who were randomly assigned and received at least one dose of study drug and had at least one post-baseline efficacy assessment). Safety outcomes were measured in the safety population (all patients who were randomly assigned and received at least one dose of study drug). Secondary endpoints included moderate-to-severe COPD exacerbation rate over 52 weeks. This study is registered with ClinicalTrials.gov number NCT01917331.FINDINGS: Between March 21, 2014, and Jan 14, 2016, 1368 patients received either BDP/FF/GB (n=687) or BDP/FF (n=681). At week 26, BDP/FF/GB improved pre-dose FEV1 by 0·081 L (95% CI 0·052-0·109; pINTERPRETATION: We provide evidence for the clinical benefits of stepping up patients with COPD from an inhaled corticosteroid/long-acting β2-agonist combination treatment to triple therapy using a single inhaler.FUNDING: Chiesi Farmaceutici SpA.

The objective of this study was to examine relationships among metabolic and endocrine factors that may influence ovarian activity during early lactation. Holstein cows (n=19) were bled twice each week to determine plasma concentrations of insulin (INS), glucose, cholesterol, insulin-like growth factor-1 (IGF-I), and progesterone (P 4 ). Feed intake and milk production were recorded daily while body weights and milk composition were recorded weekly. Relationships among plasma cholesterol and P 4 , and days to first and second postpartum ovulation were modeled with energy balance (EB), dry matter intake, milk yield and composition, plasma metabolites, and hormones using the backward elimination technique of multivariate regression analysis. Variables that contributed the most to predicting plasma cholesterol concentrations were dry matter intake×SNF using model 1 (production variables) and the square of glucose (i.e., glucose 2 ) using model 3 (plasma hormones and metabolites). For plasma P 4 concentrations, EB (model 2, production variables) and IGF-I (model 3, plasma hormones and metabolites) were the major predictors. The production variables EB and percentage of milk lactose were the greatest contributors to the models predicting days to first and second postpartum ovulations, respectively. Of the plasma hormones and metabolites evaluated, IGF-I 2 was the most significant predictor of days to first postpartum ovulation, whereas glucose 2 and INS were the significant predictors of days to second postpartum ovulation. Plasma IGF-I, glucose, and INS have been implicated in ovarian functions and their significant contributions to these models are consistent with possible important roles in postpartum return to ovarian competence.

Clostridium septicum is a rare organism, accounting for approximately 1.3% of clostridial infections and is associated with synchronous colonic malignancy. This case report describes a patient successfully treated for a mycotic aortic aneurysm secondary to C. septicum bacteremia. Subsequent evaluation confirmed a colonic malignancy, prompting early intervention. A systematic literature review revealing a rate of gastrointestinal malignancy in this patient population is 71%, and hematologic malignancy is 3.9%, with the remaining cohort of patients having an unknown source. Infectious involvement of the aorta and associated vascular structures portends a poor prognosis with a 57% mortality rate. Our case and updated review demonstrates the implications of C. septicum vascular seeding and subsequent treatment outcomes.

Background The fixed combination of extrafine beclomethasone dipropionate and formoterol fumarate (BDP/FF) pMDI (Foster®) is approved for treatment of adult asthmatic patients. In order to provide an alternative drug delivery system for BDP/FF to physicians and patients, a dry powder inhaler (NEXThaler®) has been developed, capable to deliver extrafine particles to the lungs and therefore improve the dosing of the drugs, especially in patients with poor hand-breath coordination. Objective This trial was performed to compare efficacy and safety of extrafine BDP/FF NEXThaler® with extrafine BDP/FF pMDI or non-extrafine BDP DPI alone in adult patients with controlled asthma. Methods In this 8-week randomised, double-blind, parallel-group trial, patients were randomized to receive either extrafine BDP/FF NEXThaler® 100/6 μg bid, extrafine BDP/FF 100/6 μg pMDI bid or non-extrafine BDP DPI 100 μg bid. The primary efficacy variable was change from baseline to the entire 8-week randomised treatment period in average pre-dose morning PEF. Results The ITT population comprised 754 patients. Extrafine BDP/FF NEXThaler® was non-inferior (pre-defined margin: −15 L/min) relative to extrafine BDP/FF pMDI (mean difference: −1.84; 95% CI: −6.73, 3.05) in terms of the primary efficacy variable, change from baseline in average pre-dose morning PEF. Statistical superiority of both extrafine BDP/FF formulations over non-extrafine BDP DPI was demonstrated for the primary efficacy variable (providing evidence of assays sensitivity of the trial), ACQ score and percentage of rescue medication use-free days. No significant safety signals were observed. Conclusion NEXThaler® is an effective and well-tolerated delivery device for treatment of patients with asthma who need a regular treatment.

The goal of this study was to evaluate the effectiveness of a number of shin guards in protecting against tibia fracture in soccer players. A secondary purpose was to determine the relationship between the material and structural differences in shin guard design and the protection provided. Twenty-three commercially available shin guards were tested on a model leg containing a synthetic tibia that had been calibrated against human cadaver specimens. Each guard was categorized into one of four material types: plastic (N 9), fiberglass (N 6), compressed air (N 4), and Kevlar (N 4). The maximum combined force at the ends of the tibia, the principal strain on the posterior side of the tibia, and the contact time of the impact were measured using a drop track impact simulation. Shin guards provided significant protection from tibia fracture at all drop heights. The average guard reduced force by 11% to 17% and strain by 45% to 51% compared with the unguarded leg. At the higher drop heights, material composition and structural characteristics of the shin guards showed significant differences in protective abilities. These findings indicate that all shin guards provide some measure of protection against tibia fracture, although the level of protection may vary significantly among the different guards.

To test the hypothesis that leptin signals metabolic information to the reproductive system in cattle by directly affecting IGF-I-induced ovarian cell function, granulosa and thecal cells from bovine ovarian follicles were cultured for 2 d in serum-free medium with added hormones. Recombinant human leptin at 30 and 300 ng/mL had no effect on basal thecal cell steroidogenesis or thecal cell numbers. However, 300 but not 30 ng/mL of leptin attenuated (p < 0.05) luteinizing hormone-induced androstenedione production by 24% in the absence of IGF-I and by 16% in the presence of IGF-I. Leptin had no effect on IGF-I-induced estradiol production in the presence of follicle-stimulating hormone (FSH), but at 100 ng/mL, leptin inhibited (p < 0.05) FSH plus IGF-I-induced progesterone production and granulosa cell proliferation by 29 and 31%, respectively. Leptin did not compete for 125I-IGF-I binding to granulosa or thecal cells, whereas unlabeled IGF-I did. In conclusion, leptin has weak inhibitory effects on gonadotropin- and/or IGF-I-induced steroidogenesis of thecal and granulosa cells.

Leptin, a recently-discovered hormonal product of the obese (ob) gene, circulates in the blood at levels paralleling those of fat reserves and regulates satiety. Although noninsulin-dependent diabetics are insulin-resistant and have greater levels of leptin than normal subjects, little evidence existed previously to support the notion that leptin can influence insulin action, particularly in the ovary. Therefore, we tested the hypothesis that leptin signals metabolic information to the reproductive system by directly affecting insulin-induced thecal cell function. Thecal cells from bovine ovarian follicles were cultured for 2 days in the presence of 10% fetal calf serum, and then cultured for an additional 2 days in serum-free medium with added hormones. Doses of 10 to 300 ng/ml of leptin increased (p 0.10) on thecal cell viability. Specific high-affinity, low-capacity binding of 125I-leptin was also demonstrable in thecal cells. Furthermore, leptin did not compete for [125I]insulin binding to thecal cells, whereas unlabeled insulin did. In conclusion, leptin can directly attenuate insulin-induced steroidogenesis of thecal cells while stimulating proliferation of the same cell type. This inhibitory effect of leptin on steroidogenesis does not appear to be mediated through inhibiting binding of insulin to its receptor but rather appears to be mediated through leptin binding to its own receptor. These results provide evidence for a role of leptin as a metabolic signal to the reproductive system via direct action in the ovary.

The tropical marine cyanobacteriumLyngbya majuscula produces a series of cytotoxic and antimicrobial cyclic peptides. The total structure of the two major components, laxaphycins A and B, was determined by interpretation of physical data, principally high field NMR, FAB MS and MS/MS, in combination with chemical derivatization and degradation schemes. Absolute stereochemistries of the natural and ‘exotic’ amino acids were determined. The two cyclic peptides exhibited an unusual biological synergism when tested for antifungal or cytotoxic effects.

O presente artigo apresenta uma revisão bibliográfica sobre a osteoporose, abordando seu conceito, fisiopatologia, tipos e fatores de risco. Enfatiza a assistência que a equipe de saúde deve desenvolver considerando os diferentes tipos, princi palmente as medidas preventivas capazes de retardar ou mesmo estacionar a doenças, sendo elas: a suplementação de cálcio e vitamina D, a terapia hormonal e atividade física This paper presents a bibliog raphic review about osteoporosis, poi nt out the concept, physiopathology, types and risk factors. It emphasizes h owthe health team must developthe assistance according the differents types of osteoporosis, mainly the prevetive measures that can retard or even stop this disease , like: the supplementation of calcium and vitamin D in the diet if necessary, the hormonal therapy and physical activity

Background. The MammaPrint (MP) diagnostic assay stratifies breast cancer patients into high- and low-risk groups using mRNA analysis of a 70-gene profile. The assay is validated for assessment of patients with estrogen receptor positive or negative tumors less than 5 cm with 3 or fewer malignant lymph nodes. TargetPrint (TP) is an assay for assessing estrogen, progesterone, and HER2-neu receptor status based on mRNA expression. A potential limitation of these assays is that they require an evaluation of fresh tissue samples. There is limited published experience describing MP or TP implementation.Methods. Over 10 months, 4 breast surgeons obtained samples from 54 patients for MP/TP analysis. The samples were analyzed by Agendia Labs. The tumors were independently evaluated for receptor status using immunohistochemistry (IHC). Retrospectively, we identified patients who were assessed by MP/TP during this period. Patients who underwent OncotypeDx evaluation were also identified.Results. Of the 54 patients receiving MP, 4 were found ineligible for MP risk assessment because >3 lymph nodes were found to be malignant. Out of all eligible patients, 14/50 (28%) had samples whose quantity of tumor was not sufficient for analysis (QNS). Out of eligible patients with tumors Conclusions. This study indicates that using MP/TP assay is feasible in a tertiary care center but there may be utility in limiting MP testing to patients with tumors between 1 and 5 cm due to high likelihood of uninformative results in subcentimeter tumors. Further study is needed to explore the discordance between oncotype and MP results.

Oxidatively induced stress and DNA damage have been associated with various human pathophysiological conditions, including cancer and aging. Complex DNA damage such as double-strand breaks (DSBs) and non-DSB bistranded oxidatively induced clustered DNA lesions (OCDL) (two or more DNA lesions within a short DNA fragment of 1-10 bp on opposing DNA strands) are hypothesized to be repair-resistant lesions challenging the repair mechanisms of the cell. To evaluate the induction and processing of complex DNA damage in breast cancer cells exposed to radiotherapy-relevant gamma-ray doses, we measured single-strand breaks (SSBs), DSBs, and OCDL in MCF-7 and HCC1937 malignant cells as well as MCF-10A nonmalignant human breast cells. For the detection and measurement of SSBs, DSBs, and OCDL, we used the alkaline single-cell gel electrophoresis, gamma-H2AX assay, and an adaptation of pulsed-field gel electrophoresis with E. coli repair enzymes as DNA damage probes. Increased levels for most types of DNA damage were detected in MCF-7 cells while the processing of DSBs and OCDL was deficient in these cells compared to MCF-10A cells. Furthermore, the total antioxidant capacity of MCF-7 cells was lower compared to their nonmalignant counterparts. These findings point to the important role of complex DNA damage in breast cancer and its potential association with breast cancer development especially in the case of deficient BRCA1 expression.

Bistranded oxidative clustered DNA lesions are closely spaced lesions (1-10 bp) that challenge the DNA repair mechanisms and are associated with genomic instability. The endogenous levels of oxidative clustered DNA lesions in cells of human cancer cell lines or in animal tissues remain unknown, and these lesions may persist for a long time after irradiation. We measured the different types of DNA clusters in cells of two human cell lines, MCF-7 and MCF-10A, and in skin obtained from mice exposed to either 12.5 Gy or sham X radiation. For the detection and measurement of oxidative clustered DNA lesions, we used adaptations of number average length analysis, constant-field agarose gel electrophoresis, putrescine, and the repair enzymes APE1, OGG1 (human) and Nth1 (E. coli). Increased levels of all cluster types were detected in skin tissue from animals exposed to radiation at 20 weeks postirradiation. The level of endogenous (no radiation treatment) oxidative clustered DNA lesions was higher in MCF-7 cells compared to nonmalignant MCF-10A cells. To the best of our knowledge, this is the first study to demonstrate persistence of oxidative clustered DNA lesions for up to 20 weeks in animal tissues exposed to radiation and to detect these clusters in human breast cancer cells. This may underscore the biological significance of clustered DNA lesions.

El siguiente trabajo tiene como finalidad analizar los registros corridos a lo largo de una seccion repetida (13400´ – 13900´), en un pozo exploratorio ubicado al sureste de la Cuenca del Lago de Maracaibo, los cuales fueron grabados a distintos tiempos de exposicion a hoyo desnudo.

From ether extracts of the tunicate Cynthia savignyi , collected in Morocco, a new alkaloid – cynthichlorine – has been isolated. The structure of cynthichlorine has been characterized by extensive 2D-NMR data. Cynthichlorine possesses antifungal activity against two tomato pathogenic fungi: Botrytis cinerea and Verticillium albo atrum and antibacterial activity against Agrobacterium radiobacter , Escherichia coli and Pseudomonas aeruginosa and cytotoxicity against Artemia salina larvae.

To determine the effect of feeding Propionibacteria on energy balance, milk yield, and composition, metabolites and hormones of early-lactating dairy cows, multiparous Holstein cows were individually fed a total mixed ration from -2 to 12 wk postpartum with no addition (control, n = 10) or with an additional 17 g of Propionibacteria culture daily (Treated, n = 9). Daily feed intake and milk production were recorded. Plasma cholesterol, nonesterified fatty acids (NEFA), leptin, insulin, glucose, insulin-like growth factor-I (IGF-I), IGF-binding proteins (IGFBP), and progesterone concentrations were measured up to twice weekly. Cows fed supplemental Propionibacteria had improved energy balance at wk 1 of lactation and had lower DMI per kg of body weight than control cows on wk 3 to 7, 10, and 12. Cows fed Propionibacteria had a greater percentage of milk protein and solids-not-fat and plasma NEFA concentrations than did control cows only at wk 1 of lactation. Treatment did not affect milk production or percentage of milk fat and lactose. Leptin levels were greater in treated than control cows throughout the study. Plasma glucose, insulin, cholesterol, IGFBP-3, and IGF-I concentrations were not affected by feeding Propionibacteria, but those variables increased with week postpartum. Plasma IGFBP-2 and IGFBP-5 levels decreased with week postpartum. Measures of reproductive and ovarian function did not differ between Propionibacteria-treated and control cows. Feeding Propionibacteria culture to transition and early lactating dairy cows may hold potential for improved milk protein production and metabolic efficiency during early lactation, without affecting reproductive function.

From a hexane extract of the tunicate Cynthia savignyi, collected in Morocco, epidioxysterol or 5,8-alpha-epidioxy-5alpha-cholest-6-en-3beta-ol has been isolated. This is the first example of epidioxysterol found in the tunicate C. savignyi. The structure of epidioxysterol has been characterised by NMR data (1H, 13C and 2D). Epidioxysterol possesses antifungal activity against three tomato pathogenic fungi: Botrytis cinerea, Fusarium oxysporum and Verticillium albo atrum and antibacterial activity against Agrobacterium tumefaciens, Escherichia coli, Staphylococcusfaecalis, Staphylococcus aureus and Pseudomonas aeruginosa and cytotoxicity against Artemia salina larvae.

Strength athletes often employ the deadlift in their training or rehabilitation regimens. The purpose of this study was to quantify kinematic and kinetic parameters by employing a three-dimensional analysis during sumo and conventional style deadlifts.Two 60-Hz video cameras recorded 12 sumo and 12 conventional style lifters during a national powerlifting championship. Parameters were quantified at barbell liftoff (LO), at the instant the barbell passed the knees (KP), and at lift completion. Unpaired t-tests (P0.05) were used to compare all parameters.At LO and KP, thigh position was 11-16 degrees more horizontal for the sumo group, whereas the knees and hips extended approximately 12 degrees more for the conventional group. The sumo group had 5-10 degrees greater vertical trunk and thigh positions, employed a wider stance (70 +/- 11 cm vs 32 +/- 8 cm), turned their feet out more (42 +/- 8 vs 14 +/- 6 degrees). and gripped the bar with their hands closer together (47 +/- 4 cm vs 55 +/- 10 cm). Vertical bar distance, mechanical work, and predicted energy expenditure were approximately 25-40% greater in the conventional group. Hip extensor, knee extensor, and ankle dorsiflexor moments were generated for the sumo group, whereas hip extensor, knee extensor, knee flexor, and ankle plantar flexor moments were generated for the conventional group. Ankle and knee moments and moment arms were significantly different between the sumo and conventional groups, whereas hip moments and moments arms did not show any significantly differences. Three-dimensional calculations were more accurate and significantly different than two-dimensional calculations, especially for the sumo deadlift.Biomechanical differences between sumo and conventional deadlifts result from technique variations between these exercises. Understanding these differences will aid the strength coach or rehabilitation specialist in determining which deadlift style an athlete or patient should employ.

The objective of this study was to qualitatively characterize quadriceps and hamstring muscle activation as well as to determine knee flexion angle during the eccentric motion of sidestep cutting, cross-cutting, stopping, and landing. Fifteen healthy collegiate and recreational athletes performed the four movements while knee angle and electromyographic activity (surface electrodes) of the vastus lateralis, vastus medialis obliquus, rectus femoris, biceps femoris, and medial hamstring (semimembranosus/semitendinosus) muscles were recorded. The results indicated that there is high-level quadriceps muscle activation beginning just before foot strike and peaking in mid-eccentric motion. In these maneuvers, the level of quadriceps muscle activation exceeded that seen in a maximum isometric contraction. Hamstring muscle activation was sub-maximal at and after foot strike. The maximum quadriceps muscle activation for all maneuvers was 161% maximum voluntary contraction, while minimum hamstring muscle activity was 14%. Foot strike occurred at an average of 22° of knee flexion for all maneuvers. This low level of hamstring muscle activity and low angle of knee flexion at foot strike and during eccentric contraction, coupled with forces generated by the quadriceps muscles at the knee, could produce significant anterior displacement of the tibia, which may play a role in anterior cruciate ligament injury.

Spontaneous aortocaval fistulas are rare and thoracoabdominal aneurysms eroding into the inferior vena cava are rarer still. We describe a patient who presented to our hospital with a fistula between a Type IV thoracoabdominal aneurysm and the inferior vena cava. Expanding endovascular capabilities of vascular surgeons enabled us to insert proximal and distal occluding balloon catheters into the vena cava which greatly minimized blood loss.

Leptin, a recently-discovered hormonal product of the obese gene, circulates in the blood at levels paralleling those of fat reserves and regulates satiety and improves reproductive performance if injected into mice lacking circulating leptin. Therefore, we tested the hypothesis that leptin signals metabolic information to the reproductive system by directly affecting granulosa cell function. Doses of 10-300 ng/ml leptin had no effect (P0.10) on basal or insulin-induced numbers of granulosa cells cultured from small (1-5 mm) or large (or = 8 mm) bovine follicles. Similarly, 30 and 300 ng/ml leptin had no effect (P0.10) on basal estradiol production. However, leptin, in a dose-dependent manner, inhibited (P0.05) insulin-induced progesterone and estradiol production by granulosa cells from small and large follicles. Leptin did not compete for specific 125I-insulin binding to granulosa cells. Furthermore, specific binding of 125I-leptin was demonstrable in granulosa cells. In conclusion, leptin, at physiological levels, can directly attenuate insulin-induced steroidogenesis of granulosa cells without affecting proliferation of this ovarian cell type. These results provide evidence to support the hypothesis that leptin can act as a metabolic signal to the reproductive system via direct action at the ovarian level.

Background Rheumatoid arthritis (RA) is an autoimmune disorder, affecting 1% of the population, characterised by pain, joint swelling and progressive destruction of joint tissue. EULAR (European League Against Rheumatism) recommends the use of Tumour Necrosis Factor alpha antagonists (anti-TNFα) if methotrexate or Disease Modifying Antirheumatic Drugs fail. Anti-TNFα treatment imposes a significant financial burden on hospital budgets. Purpose To perform a pharmacoeconomic investigation in the Piedmont region (Italy) to identify the cost of the illness RA. To analyse the payer’s and societal perspectives, investigating direct costs associated with health care use and indirect costs related to productivity loss. Materials and Methods A multidisciplinary group, rheumatologists, hospital pharmacists and pharmacoeconomists, was established to perform a pharmacoeconomic evaluation of the direct and indirect costs of RA, by a systematic literature review. Afterward, we plan a perspective, observational, multicentre, cost-effectiveness analysis of RA biological drugs, involving 100 patients. Each patient will be recorded, every three months for one year, through personal data, disease duration and characterization, systemic manifestations and comorbidities, prescribed biological medicines. A questionnaire will be submitted, in order to assess direct and indirect costs. Results 40 existing pharmacoeconomic evaluations were critically appraised: the overall mean costs of RA amounted to about €15,000 per year, while the direct annual costs of RA were on average about €4,000. The greatest burden of RA costs was the indirect costs. From a societal perspective the superior clinical outcomes achieved with anti-TNFα are worth their higher costs. The most favourable incremental cost-effectiveness ratio was for etanercept compared to methotrexate. Conclusions The cost-effectiveness of an intervention depends on the maximum the decision makers are willing to pay for an extra unit of health effect. It should be considered that treatments with anti-TNFα, in a societal perspective, decrease the use of health resources and increase productivity. No conflict of interest.