Effect of intrabronchial platelet rich plasma on the exercise-induced pulmonary hemorrhage endoscopic score in thoroughbred racehorses using furosemide: a preliminary study / [Efeito da instilação intrabronquial de plasma rico em plaquetas no escore endoscópico da hemorragia pulmonar induzida por exercício em cavalos Puro-Sangue Inglês de corrida e usuários de furosemida: um estudo preliminar]

The high prevalence of exercise-induced pulmonary hemorrhage (EIPH) in athletic horses constitutes to be a challenge to the racing industry and a source of major concern to animal welfare. Both experimental and clinical evidence indicate that the use of autologous platelet-rich plasma (PRP) is a promising effector of repair in a variety of pulmonary conditions. The present study evaluated the effect of intrabronchial instillation of PRP on EIPH endoscopic scores from 37 Thoroughbred racehorses. Inclusion criteria were for animals to be EIPH-positive in, at least, two consecutive post-exercise endoscopic exams and to receive 250mg of furosemide IV four hours before racing. Animals were randomly assigned into 3 groups: placebo, control, and PRP instillation. All 37 Thoroughbred racehorses included had EIPH endoscopic scores pre- and post- treatment compared by statistical analysis. The bleeding score from the group receiving PRP was significantly lower than in the control and placebo groups. No adverse effects were observed in any animal during or after the experiment. It was possible to conclude that the intrabronchial instillation of autologous PRP was effective in reducing EIPH scores in racehorses receiving furosemide and that this bioproduct can be considered as a promising coadjuvant in controlling EIPH in athletic horses.(AU)

A alta prevalência de hemorragia pulmonar induzida por exercício (HPIE) em cavalos atletas é um desafio de longa data para a indústria de corridas, além de figurar como grande preocupação sobre o bem-estar animal. As evidências experimentais e clínicas indicam que o uso do plasma rico em plaquetas (PRP) de fonte autógena é promissor na terapêutica de diversas lesões pulmonares. O presente estudo objetivou avaliar as mudanças após corrida no escore endoscópico de HPIE de 37 cavalos Puro-Sangue Inglês que receberam instilação intrabronquial de PRP autólogo. Os animais selecionados eram HPIE-positivos em, ao menos, dois exames endoscópicos consecutivos e recebiam 250mg de furosemida IV administrado quatro horas antes de cada corrida. Na comparação dos escores endoscópicos pré e pós-tratamento, verificou-se que o escore de HPIE do grupo tratado com PRP foi significantemente menor que o dos grupos controle e placebo. Nenhum efeito adverso foi observado nos animais durante ou após o experimento. Concluiu-se que a instilação intrabronquial de PRP autólogo foi efetiva na redução do escore de HPIE de cavalos de corrida usuários de furosemida e que este bioproduto pode ser considerado uma alternativa promissora no controle de HPIE em cavalos atletas.(AU)

[Pharmaceutical care for older adults. Application of STOPP-START criteria]. / Atención farmacéutica de adultos mayores. Aplicación de los criterios STOPP-START.

INTRODUCTION: Drug-related problems can be caused by potentially inappropriate prescribing (PIP), one of the most used tools for its identification are the STOPP (Older Persons' potentially inappropriate Prescriptions) - START (Screening Tool to Alert doctors to Right Treatment) criteria. The objective of this study is to determine PIP in older adults who receive pharmaceutical care in the Pharmacotherapy Optimization Unit (POU)-Rosario. MATERIALS AND METHODS: Pharmacoepidemiological observational study, which evaluates the quality of medication use. Workplace: POU-Rosario. Population under study: adults over 60 years of age, who received pharmacotherapy follow-up during the period March 2017 to February 2018. PIPs were identified using the STOPP-START criteria, 2014 version; selecting the most appropriate criteria to assess outpatient pharmacotherapy. Prevalence of PIP and amount of PIP per active principle were estimated. RESULTS: 50 patients older than 60 years received pharmacotherapy follow-up in the POU; 47 patients (94.0%) had at least one PIP corresponding to a STOPP criterion; 17 STOPP criteria were found among the 41 initially selected, leading to 145 PIPs identified. And 7 START criteria among the 11 initially selected, leading to 50 PIPs identified. Medications with a higher amount of PIPs: benzodiazepines and proton pump inhibitors. CONCLUSIONS: This study allowed the identification of a high prevalence of PIP. The data obtained show the usefulness of these criteria. The STOPP-START criteria have been included to support decision making during pharmacotherapy follow-up to propose pharmaceutical interventions, in order to enhance pharmacotherapy. These activities contribute to patient safety, a dimension of health quality.

Pharmacological treatment of COPD - New evidence.

Chronic Obstructive Pulmonary Disease (COPD) is currently the 4th leading cause of death worldwide but is projected to be the 3rd leading cause of death by 2020. In Portugal, the estimated prevalence of COPD in the Lisbon region is 14.2%, and a large proportion of underdiagnosed disease has been detected. In 2016, a Portuguese panel of experts proposed pharmacological treatment approaches to COPD based on the evidence available at the time. However, given that the GOLD 2017 report introduced considerable changes to the 2016 version, and that new evidence has emerged regarding treatment options, these proposals need to be updated. Also, and based on several studies, the concept of Pre-GOLD patients, which has diagnostic, prognostic and therapeutic implications, is introduced, along with a proposed algorithm for the identification and treatment of these patients.

Carcinoma mucoepidermoide bronquial: a propósito de dos casos clínicos / Bronchopulmonary mucoepidermoid carcinoma: apropos of two clinical cases

Resumen El carcinoma mucoepidermoide bronquial es una neoplasia infrecuente, representando el 0,1 a 0,2% de los tumores malignos primarios del pulmón. En general tiene un buen pronóstico, sin embargo, existe un subtipo de alto grado de pronóstico más ominoso. En este artículo se presentan dos casos clínicos de carcinoma mucoepidermoide bronquial de bajo grado, enfocado en su diagnóstico y manejo quirúrgico.

ABSTRACT Bronchopulmonary mucoepidermoid carcinoma is an uncommon neoplasm, accounting for 0.1 to 0.2% of primary malignant tumors of the lung. In general it has a good prognosis, however there is a subtype of high grade of more ominous prognosis. In this paper we present two clinical cases of low grade pulmonary mucoepidermoid carcinoma, focused on their diagnosis and surgical management.

Prevalence of late-onset pompe disease in Portuguese patients with diaphragmatic paralysis - DIPPER study.

Pompe disease is a rare autosomal recessive neuromuscular disorder caused by acid α-glucosidase enzyme (GAA) deficiency and divided into two distinct variants, infantile- and late-onset. The late-onset variant is characterized by a spectrum of phenotypic variation that may range from asymptomatic, to reduced muscle strength and/or diaphragmatic paralysis. Since muscle strength loss is characteristic of several different conditions, which may also cause diaphragmatic paralysis, a protocol was created to search for the diagnosis of Pompe disease and exclude other possible causes. METHODS: We collected a sample size of 18 patients (10 females, 8 males) with a median age of 60 years and diagnosis of diaphragmatic paralysis of unknown etiology, followed in the Pulmonology outpatient consultation of 9 centers in Portugal, over a 24-month study period. We evaluated data from patient's clinical and demographic characteristics as well as complementary diagnostic tests including blood tests, imaging, neurophysiologic and respiratory function evaluation. All patients were evaluated for GAA activity with DBS (dried blood test) or serum quantification and positive results confirmed by serum quantification and sequencing. RESULTS: Three patients were diagnosed with Pompe's disease and recommended for enzyme replacement therapy. The prevalence of Pompe, a rare disease, in our diaphragmatic paralysis patient sample was 16.8%. CONCLUSION: We conclude that DBS test for GAA activity should be recommended for all patients with diaphragmatic paralysis which, despite looking at all the most common causes, remains of unknown etiology; this would improve both the timing and accuracy of diagnosis for Pompe disease in this patient population. Accurate diagnosis will lead to improved care for this rare, progressively debilitating but treatable neuromuscular disease.

Optimal treatment sequence in COPD: Can a consensus be found?

There is currently no consensus on the treatment sequence in chronic obstructive pulmonary disease (COPD), although it is recognized that early diagnosis is of paramount importance to start treatment in the early stages of the disease. Although it is fairly consensual that initial treatment should be with an inhaled short-acting beta agonist, a short-acting muscarinic antagonist, a long-acting beta-agonist or a long-acting muscarinic antagonist. As the disease progresses, several therapeutic options are available, and which to choose at each disease stage remains controversial. When and in which patients to use dual bronchodilation? When to use inhaled corticosteroids? And triple therapy? Are the existing non-inhaled therapies, such as mucolytic agents, antibiotics, phosphodiesterase-4 inhibitors, methylxanthines and immunostimulating agents, useful? If so, which patients would benefit? Should co-morbidities be taken into account when choosing COPD therapy for a patient? This paper reviews current guidelines and available evidence and proposes a therapeutic scheme for COPD patients. We also propose a treatment algorithm in the hope that it will help physicians to decide the best approach for their patients. The authors conclude that, at present, a full consensus on optimal treatment sequence in COPD cannot be found, mainly due to disease heterogeneity and lack of biomarkers to guide treatment. For the time being, and although some therapeutic approaches are consensual, treatment of COPD should be patient-oriented.

Measurement of salivary cortisol by a chemiluminescent organic-based immunosensor.

A highly sensitive chemiluminescent immunoassay (CLIA) using a sensitive organic photodetector was developed to detect human cortisol, an important biomarker for stress-related diseases. The developed CLIA was performed onto gold-coated glass chips, on which anti-cortisol antibodies were immobilised and chemiluminescent horseradish peroxidase-luminol-peroxide reactions were generated. Using cortisol-spiked artificial saliva samples, the CLIA biosensor showed a linear range of detection between 0.1 ng/mL and 175 ng/mL and a detection limit of 80 pg/mL. The sensor response was highly specific to cortisol and did not vary significantly between assays. The results indicate the potential clinical application of the CLIA sensor. Furthermore, the simple layered structure of the organic photodetector may encourage the realisation of integrated optical biosensors for point-of-use measurement of salivary cortisol levels.

An integrated passive-flow microfluidic biosensor with organic photodiodes for ultra-sensitive pathogen detection in water.

This work reports on integrated passive-flow optical microfluidic devices to detect waterborne pathogens in the field. Ring-shaped organic photodiodes were integrated to a capillary-induced flow microfluidic channel for monitoring chemiluminescent sandwich immunoassays enhanced by gold nanoparticles. The integrated device yielded a resolution of 4×10(4) cells/mL for the detection of Legionella pneumophila, which represented a 25-fold improvement over chemiluminescence detection devices employing no gold-nanoparticle enhancement. This work demonstrates the feasibility of a low-cost but highly sensitive lab-on-a-chip device amenable for point-of-use applications.

Dexamethasone-eluting stents for the prevention of in-stent restenosis: evidence for a differential effect in insulin-dependent and non-insulin-dependent diabetic patients.

UNLABELLED: Diabetes mellitus (DM) is a strong predictor of in-stent restenosis. This may be due to a higher level of vascular inflammation. We hypothesized that diabetic patients will benefit from dexamethasone-eluting stents, since local inflammation and consequently neointimal growth are suppressed and no systemic side effects will occur. METHODS: 21 consecutive patients with DM with 32 lesions were treated with dexamethasone-eluting stents. Excluded were patients with triple vessel disease, bifurcation lesions, previous revascularization of the culprit vessel, and reference diameter smaller than 2.5 or larger than 3.75 mm. MACE (death, myocardial infarction, and revascularization) was counted at 12 months. At 6 months, angiographic follow-up was performed. RESULTS: Of the patients, 38% had insulin-dependent DM. Lesion type was type A/B1 in 56% and B2/C in 44%. Lesion length was 15.7+/-8.4 mm and the reference diameter was 2.83+/-0.53 mm. Event-free survival at 12 months was 62%. Any revascularization procedure was performed in 33% and target lesion revascularization in 24% of the patients. At 6 months in-stent late loss was 1.07+/-0.64 mm. Binary restenosis occurred in 28.1% of the lesions. The event-free survival in insulin-dependent DM was worse compared to non-insulin-dependent DM (92.1 vs. 37.8%; p<0.01). Patients with insulin-dependent DM had higher in-stent late loss compared to non-insulin-dependent DM patients (1.44+/-0.83 vs. 0.83+/-0.51 mm; p<0.01). CONCLUSION: Treatment with dexamethasone-eluting stents in patients with DM is associated with a relatively high restenosis rate. Our data suggest a differential effect of dexamethasone-eluting stents in insulin-dependent compared to non-insulin-dependent DM.

[Pathogenic role of PTEN tumor suppressor gene in ovarian cancer associated to endometriosis]. / Rol patogénico del gen supresor de tumores PTEN en cáncer ovárico asociado a endometriosis.

BACKGROUND: Endometrioid carcinoma and clear cell carcinoma of the ovary are associated to endometriosis. Somatic mutations of PTEN (10q23.3) are present in endometrial endometrioid carcinoma. Therefore, these mutations could be also present in ovarian tumors. Molecular studies show that solitary endometriotic cysts are monoclonal, have aneuploid DNA, have a loss of 9p,11q and 22q heterozygosity (LOH) and a higher cellular proliferation index of the epithelial component. AIM: To determine the cellular proliferation index using Ki 67, the immunohistochemical expression of PTEN and LOH in patients with ovarian endometriosis without atypia (EN), ovarian endometriosis with atypia (EA) and endometriosis with adjacent ovarian carcinoma (ET). MATERIAL AND METHODS: Paraffin embedded samples of 37 endometrioid and clear cell carcinomas of the ovary (CC/CE), 15 solitary ovarian EN and 15 ovarian EA, were studied. Expression of Ki 67 and PTEN was measured by immunohistochemistry. LOH of 10q23.3 locus was measured by polymerase chain reaction. RESULTS: Ki 67 was 5.5 and 2.3% in EA and EN, respectively (p <0.005). There was a histological correlation between EA and a higher cellular proliferation index. PTEN was negative in 5 of 15 EN, 9 of 15 EA and 30 of 37 CE/CC. There was a correlation between LOH and loss of PTEN protein in EN, EA and ET (60%). CONCLUSIONS: Negative expression on PTEN in EN; EA; ET and CE/CC is a manifestation of the inactivation of this gene. The mechanisms that cause this inactivation, must be elucidated.

Rol patogénico del gen supresor de tumores PTEN en cáncer ovárico asociado a endometriosis / Pathogenic role of PTEN tumor suppressor gene in ovarian cancer associated to endometriosis

Background: Endometrioid carcinoma and clear cell carcinoma of the ovary are associated to endometriosis. Somatic mutations of PTEN (10q23.3) are present in endometrial endometrioid carcinoma. Therefore, these mutations could be also present in ovarian tumors. Molecular studies show that solitary endometriotic cysts are monoclonal, have aneuploid DNA, have a loss of 9p,11q and 22q heterozygosity (LOH) and a higher cellular proliferation index of the epithelial component. Aim: To determine the cellular proliferation index using Ki 67, the immunohistochemical expression of PTEN and LOH in patients with ovarian endometriosis without atypia (EN), ovarian endometriosis with atypia (EA) and endometriosis with adjacent ovarian carcinoma (ET). Material and methods: Paraffin embedded samples of 37 endometrioid and clear cell carcinomas of the ovary (CC/CE), 15 solitary ovarian EN and 15 ovarian EA, were studied. Expression of Ki 67 and PTEN was measured by immunohistochemistry. LOH of 10q23.3 locus was measured by polymerase chain reaction. Results: Ki 67 was 5.5 and 2.3% in EA and EN, respectively (p <0.005). There was a histological correlation between EA and a higher cellular proliferation index. PTEN was negative in 5 of 15 EN, 9 of 15 EA and 30 of 37 CE/CC. There was a correlation between LOH and loss of PTEN protein in EN, EA and ET (60%). Conclusions: Negative expression on PTEN in EN; EA; ET and CE/CC is a manifestation of the inactivation of this gene. The mechanisms that cause this inactivation, must be elucidated.

Dural arteriovenous fistulas: unusual access routes in the elderly.

SUMMARY: Transvenous embolization is effective in the treatment of an intracranial dural arteriovenous fistula (DAVF). Retrograde venous access to the fistula may be limited by associated sinus thrombosis, as in the two cases here reported. Unusual curative access routes were performed: direct superior ophthalmic vein puncture and through a small craniectomy, packing the sinus with detachable coils. When traditional routes proved impossible, unusual access routes must be devised.

Pubertad precoz periférica por tumor ovárico de las células de la granulosa juvenil: con manifestaciones iso y heterosexuales en una niña de 6 años / Precocious puberty in a six years old girl caused by a juvenile granulosa cell ovaric tumor: report of one case

A six years old girl consulted due to mammary development. On physical examination, clitoris enlargement and a tumor localized in the abdominal-pelvic region were observed. Hormonal study disclosed elevated testosterone and estradiol levels. On exploratory laparotomy, a right ovarian tumor was observed and a right salpingo-oophorectomy was performed. The contemporary biopsy informed a disgerminoma, leading to a surgical staging of the tumor. The definitive pathological diagnosis was a juvenile granular cell tumor, limited to the ovary. In the postoperative period, estradiol and testosterone levels returned to normal values and the pseudopuberty reverted. The patient did not receive adjuvant treatment and after three years of follow up, there is no evidence of tumor recidivism

Humor de celulas de la granulosa del ovario

Se comunican 10 casos de tumor de células de la granulosa diagnósticados y/o tratados en nuestra Institución entre 1991 y 2002. Se revisa la forma de presentación, tipo cirugía, utilidad de la biopsia rápida, histología, distribución por etapas, el tipo de tratamiento y seguimiento posterior. El 70% de los casos se presentó en etapa I. En 4 de 5 casos en que se realizó biopsia contemporánea (80%), hubo concordancia con el informe definitivo. La modalidad terapéutica predominante en etapa temprana fue la cirugía (anexectomía en pacientes con deseo de paridad e histerectomia total más anexectomía bilateral en aquellas con paridad cumplida). En pacientes jóvenes diagnosticadas después de la cirugía inicial privilegiamos la reexploración para completar la etapificación. La mediana de seguimiento fue de 38 meses (12-140 meses). Solo hubo una recurrencia, en ganglios periaórticos, y fue tratada con bloqueo hormonal y quimioterapia. Concluimos que el tumor de la granulosa es una entidad poco frecuente, con diferentes formas de presentación clínica pero de buen pronóstico cuando se presenta en etapa temprana (etapa I) y se trata con cirugía sola.

Diagrama de flujo inmunohistoquímico para la diferenciación entre adenocarcinomas primarios y tumores metastásicos extraginecológicos más frecuente en el ovario / Immunohistochemical flow chart to differentiate between primary adenocarcinomas and the most frequent extragynecological metastases in the ovary

Background: The pathological differential diagnosis between primary and metastatic ovarian malignant tumors is usually difficult, specially for tumors originating in the gastrointestinal system or breast. Aim: To define an immunohistochemical flow chart to discriminate these tumor types. Material and methods: We performed a immunostaining analysis using a panel of six antibodies (CK 7, CA 125, CEA, CK20, BRST-2 and CA 15-3) in 3 tumor groups: 11 ovarian, 14 breast and 12 colonic primary tumors and in a study group of 38 ovarian tumors whose primary origin was unknown. Results: We defined an ovarian immunohistochemical pattern (CEA-/CK20-, 45 percent in ovarian tumors, 0 percent in breast or colonic tumors, p <0.001); an ovary/breast pattern (CEA+/CK20-, 0 percent in colonic tumors, p <0.001): a breast pattern (CEA+/CK20-/BKST-2+, 64 percent in breast tumors and 0 percent in colonic and ovarian tumors, p <0.001) and a colonic pattern (CEA+/ CK20+/CK7-, 67 percent in colonic tumors and 0 percent in breast and ovarian tumors, p <0.001). Conclusions: Employing a simple panel of antibodies, characteristic immunohistochemical patterns were defined for ovarian, breast and colonic tumors. These patterns allowed the identification of the origin of most tumors of the study group