Osler-Weber-Rendu Syndrome with Severe Hepatic Manifestations: A Rare Clinical Case.

Rendu-Osler-Weber syndrome is a rare inherited syndrome with autosomal dominant transmission characterized by systemic arteriovenous malformations (AVMs) with multi-organ involvement. Its incidence is 1-2/100,000 and it is predominant in females (the male/female ratio varies from 1:2 to 1:4.5). Clinical manifestations and complications are related to recurrent bleeding and, in some cases, the development of end-organ failure. Management is mostly supportive care and it is essential to promote control of the disease as much as possible and screen eventual complications. We describe the case of a 67-year-old male patient with Rendu-Osler-Weber syndrome admitted to the emergency department with decompensated heart failure due to acute anaemia because of severe epistaxis. During hospitalization, the patient progressed to acute-on-chronic liver failure with hepatic encephalopathy and an abdominal computed tomography scan showed multiple hepatic AVMs considered to be the cause of the chronic liver disease. LEARNING POINTS: Rendu-Osler-Weber syndrome is a rare autosomal dominant syndrome characterized by systemic arteriovenous malformations (AVMs) with multi-organ involvement, in which the most common manifestation is recurrent epistaxis.In more severe cases the prognosis is determined by organ dysfunction caused by AVMs, including hepatic involvement, which happens in 74-79% of cases, leading to poor outcomes.The treatment is mainly supportive care so early recognition of major organ involvement is fundamental to prevent severe complications.

Body-Packing: A Rare Diagnosis to Keep in Mind.

Body packing was first described in 1973 and refers to the intracorporeal concealment of illegal drugs, which are swallowed or placed in anatomical cavities and/or body orifices. The body packer can be asymptomatic or can have signs of systemic drug toxicity (neurological, cardiac, abdominal, renal and cutaneous) due to rupture of the packet(s) or symptoms of gastrointestinal obstruction or perforation. The diagnosis is established based on a suggestive history, findings on physical examination and laboratory findings and/or imaging. The vast majority of patients are asymptomatic and are treated conservatively. However, complex situations may require surgical intervention. We present a case of a 50-year-old man who was admitted in the emergency department with a generalized tonic-clonic seizure and vomiting with plastic film, which raised the suspicion of foreign body ingestion, confirmed by imaging and laboratory tests. He underwent exploratory laparotomy to remove the packages. LEARNING POINTS: Body packing is a potentially lethal activity.Body-packers can be asymptomatic, or have signs/symptoms of systemic drug toxicity or gastrointestinal obstruction or perforation.It is essential to recognize this condition so that the correct clinical approach, diagnosis and management can be established.

When radiology determines the success of removal of a retained epidural catheter: A case report.

The epidural block is an anesthetic procedure that can have possible complications upon insertion or removal. Epidural catheter retention is a rare complication; its etiology may come from lateral migration with kinking of the catheter or from involvement with bone, ligamentous, muscular, vascular structures, or nerve roots. Up until today, there is not a standard approach to this complication; however, there are some recommendations for the management of retained epidural catheters. Here, we describe a case report of epidural catheter retention, in which we followed the published recommendations. Although computed tomography scanning may be the best option to visualize the anatomical position of the distal extremity of an epidural catheter, with this case report we intend to reinforce the fundamental contribution of the contrast radiograph in the successful catheter removal. Posteriorly, a protocol for clinical orientation of epidural catheter retention was developed in our institution.

Antioxidant Activity of Blueberry (Vaccinium spp.) Cultivar Leaves: Differences Across the Vegetative Stage and the Application of Near Infrared Spectroscopy.

Blueberries production has increased in the last few years boosted somehow by the World Health Organization (WHO) recommendations for a healthier nutrition and their recognized potential to treat several diseases. The production increase lead to high amounts of discarded leaves that could be very valuable. In this context, the antioxidant activity of Vaccinium spp. leaves, by means of the total phenolic (TPC) and flavonoid (TFC) content and total antioxidant capacity (TAC) was determined. Adult leaves of twenty-seven Vaccinium cultivars collected in three geographic regions and three seasons of the year were included. The antioxidant activity was additionally estimated with near infrared (NIR) spectroscopy and data transferability across the regions and seasons was evaluated. The TPC, TFC and TAC ranged from 39.6-272.8 mg gallic acid, 41.2-269.1 mg catechin and 22.6-124.8 mM Trolox per g of dry leaf, respectively. Globally through the seasons, the higher values of the three parameters were obtained in December. Regarding the geographic region, region A provided the cultivars with the higher antioxidant content. Titan was the cultivar with higher TPC and TAC and Misty the one with the higher TFC. NIR spectroscopy combined with the partial least squares analysis was able to successfully predict the antioxidant activity with coefficients of determination and range error ratios ranging from 0.84-0.99 and 11.2-26.8. Despite some identified limitations on data transferability, NIR spectroscopy proved to be a reliable, low cost and quick method to predict the antioxidant activity of the considered cultivar leaves.

In vivo biodistribution of venlafaxine-PLGA nanoparticles for brain delivery: plain vs. functionalized nanoparticles.

Background: Actually, no drugs provide therapeutic benefit to approximately one-third of depressed patients. Depression is predicted to become the first global disease by 2030. So, new therapeutic interventions are imperative.Research design and methods: Venlafaxine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were surface functionalized with two ligands against transferrin receptor to enhance access to brain. An in vitro blood-brain barrier model using hCMEC/D3 cell line was developed to evaluate permeability. In vivo biodistribution studies were performed using C57/bl6 mice. Particles were administered intranasal and main organs were analyzed.Results: Particles were obtained as a lyophilized powder easily to re-suspend. Internalization and permeability studies showed the following cell association sequence: TfRp-NPs>Tf-NPs>plain NPs. Permeability studies also showed that encapsulated VLF was not affected by P-gP pump efflux increasing its concentration in the basolateral side after 24 h. In vivo studies showed that 25% of plain NPs reach the brain after 30 min of one intranasal administration while less than 5% of functionalized NPs get the target.Conclusions: Plain NPs showed the highest ability to reach the brain vs. functionalized NPs after 30 min by intranasal administration. We suggest plain NPs probably travel via direct nose-to-brian route whereas functionalized NPs reach the brain by receptor-mediated endocytosis.

A Rare Presentation of Ogilvie's Syndrome.

Ogilvie's syndrome or acute colonic pseudo-obstruction is characterized by massive colon dilation in the absence of mechanical obstruction or toxic megacolon. The phenotype associated with secretory diarrhoea is rare and is related to increased potassium channel activity in the colon, inducing excessive potassium loss, with increased sensitivity to normal serum aldosterone levels. The recommended therapy is potassium-sparing agents. We present the case of an 85-year-old patient who was admitted at the emergency department with prostration, abdominal distension and diarrhoea, corresponding to functional colonic dilation precipitated by severe hypokalaemia. Resolution of the condition only occurred after spironolactone was administered for suspected primary hyperaldosteronism, which was not proved as the patient showed normal aldosterone serum levels. The pathophysiological mechanism of abnormal potassium secretion in this scenario corresponds to 'relative hyperaldosteronism' caused by increased sensitivity of colonocytes to aldosterone. LEARNING POINTS: Colonic pseudo-obstruction is not usually associated with secretory diarrhoea and severe hypokalaemia.Although serum aldosterone levels are normal, the treatment of choice is spironolactone due to its effect on the potassium channels in colonocytes.It is essential to recognize this specific phenotype so that the correct clinical approach, diagnosis and management can be established.

Using microfluidic platforms to develop CNS-targeted polymeric nanoparticles for HIV therapy.

The human immunodeficiency virus (HIV) uses the brain as reservoir, which turns it as a promising target to fight this pathology. Nanoparticles (NPs) of poly(lactic-co-glycolic) acid (PLGA) are potential carriers of anti-HIV drugs to the brain, since most of these antiretrovirals, as efavirenz (EFV), cannot surpass the blood-brain barrier (BBB). Forasmuch as the conventional production methods lack precise control over the final properties of particles, microfluidics emerged as a prospective alternative. This study aimed at developing EFV-loaded PLGA NPs through a conventional and microfluidic method, targeted to the BBB, in order to treat HIV neuropathology. Compared to the conventional method, NPs produced through microfluidics presented reduced size (73 nm versus 133 nm), comparable polydispersity (around 0.090), less negative zeta-potential (-14.1 mV versus -28.0 mV), higher EFV association efficiency (80.7% versus 32.7%) and higher drug loading (10.8% versus 3.2%). The microfluidics-produced NPs also demonstrated a sustained in vitro EFV release (50% released within the first 24 h). NPs functionalization with a transferrin receptor-binding peptide, envisaging BBB targeting, proved to be effective concerning nuclear magnetic resonance analysis (δ = -0.008 ppm; δ = -0.017 ppm). NPs demonstrated to be safe to BBB endothelial and neuron cells (metabolic activity above 70%), as well as non-hemolytic (1-2% of hemolysis, no morphological alterations on erythrocytes). Finally, functionalized nanosystems were able to interact more efficiently with BBB cells, and permeability of EFV associated with NPs through a BBB in vitro model was around 1.3-fold higher than the free drug.

Development of a PEGylated-Based Platform for Efficient Delivery of Dietary Antioxidants Across the Blood-Brain Barrier.

The uptake and transport of dietary antioxidants remains the most important setback for their application in therapy. To overcome the limitations, a PEGylated-based platform was developed to improve the delivery properties of two dietary hydroxycinnamic (HCA) antioxidants-caffeic and ferulic acids. The antioxidant properties of the new polymer-antioxidant conjugates (PEGAntiOxs), prepared by linking poly(ethylene glycol) (PEG) to the cinnamic acids by a one-step Knovenagel condensation reaction, were evaluated. PEGAntiOxs present a higher lipophilicity than the parent compounds (caffeic and ferulic acids) and similar, or higher, antioxidant properties. PEGAntiOxs were not cytotoxic at the tested concentrations in SH-SY5Y, Caco-2, and hCMEC/D3 cells. By contrast, cytotoxic effects in hCMEC/D3 and SH-SY5Y cells were observed, at 50 and 100 µM, for caffeic and ferulic acids. PEGAntiOxs operate as antioxidants against several oxidative stress-cellular inducers in a neuronal cell-based model, and were able to inhibit glycoprotein-P in Caco-2 cells. PEGAntiOxs can cross hCMEC/D3 monolayer cells, a model of the blood-brain barrier (BBB) endothelial membrane. In summary, PEGAntiOxs are valid antioxidant prototypes that can uphold the antioxidant properties of HCAs, reduce their cytotoxicity, and improve their BBB permeability. PEGAntiOxs can be used in the near future as drug candidates to prevent or slow oxidative stress associated with neurodegenerative diseases.

The role of sleepiness on arterial stiffness improvement after CPAP therapy in males with obstructive sleep apnea: a prospective cohort study.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk. This study aim to assess differences in changes in arterial stiffness of two groups of patients, defined as having daytime sleepiness or not, after continuous positive airway pressure (CPAP) treatment. METHODS: A selected cohort of consecutive male patients, under 65 years old, with moderate to severe OSA and without great number of comorbidities was studied. The diagnosis was confirmed by home respiratory poligraphy. Sleepiness was considered with an Epworth Sleepiness Scale (ESS) > 10. An ambulatory blood pressure (BP) monitoring and carotid-femoral pulse wave velocity (cf-PWV) measurements were performed, before and after four months under CPAP. Compliant patients, sleepy and non-sleepy, were compared using linear mixed effects regression models. A further stratified analysis was performed with non-sleepy patients. RESULTS: Thirty-four patients were recruited, with mean age 55.2 (7.9) years, 38.2% were sleepy, 79.4% with hypertension, 61.8% with metabolic syndrome and 82.4% with dyslipidaemia. In univariable analysis, cf-PWV was strongly related to systolic BP parameters and age, but also to antihypertensive drugs (p = 0.030), metabolic syndrome (p = 0.025) and daytime sleepiness (p = 0.004). Sleepy patients had a more severe OSA, with AHI 44.8 (19.0) vs 29.7 (15.7) events/h (p = 0.018), but sleep study parameters were not associated with cf-PWV values. On multivariable regression, a significant interaction between time (CPAP) and sleepiness (p = 0.033) was found. There was a weak evidence of a cf-PWV reduction after CPAP treatment (p = 0.086), but the effects of treatment differed significantly between groups, with no changes in non-sleepy patients, while in sleepy patients a significant decrease was observed (p = 0.012). Evaluating non-sleepy patients group under CPAP therapy, results showed that both higher pulse pressure (p = 0.001) and lower LDL-cholesterol levels (p = 0.015) at baseline were associated to higher cf-PWV changes. CONCLUSIONS: Patients with daytime sleepiness had a more severe OSA and presented a greater arterial stiffness improvement after CPAP therapy, independently from age and BP. Besides sleepiness, cf-PWV reduction after CPAP therapy was mainly associated to CV risk factors, and less to sleep study parameters. TRIAL REGISTRATION: Clinicaltrials.gov NCT02273089 23.10.2014 retrospectively registered.

Delivery of siRNA silencing P-gp in peptide-functionalized nanoparticles causes efflux modulation at the blood-brain barrier.

AIM: Explore the use of transferrin-receptor peptide-functionalized nanoparticles (NPs) targeting blood-brain barrier (BBB) as siRNA carriers to silence P-glycoprotein (P-gp). MATERIALS & METHODS: Permeability experiments were assessed through a developed BBB cell-based model; P-gp mRNA expression was evaluated in vitro; rhodamine 123 permeability was assessed after cell monolayer treatment with siRNA NPs. RESULTS: Beyond their ability to improve siRNA permeability through the BBB by twofold, 96-h post-transfection, functionalized polymeric NPs successfully reduced P-gp mRNA expression up to 52%, compared with nonfunctionalized systems. Subsequently, the permeability of rhodamine 123 through the human BBB model increased up to 27%. CONCLUSION: Developed BBB-targeted NPs induced P-gp downregulation and consequent increase on P-gp substrate permeability, revealing their ability to modulate drug efflux at the BBB.

Tailoring Lipid and Polymeric Nanoparticles as siRNA Carriers towards the Blood-Brain Barrier - from Targeting to Safe Administration.

Blood-brain barrier is a tightly packed layer of endothelial cells surrounding the brain that acts as the main obstacle for drugs enter the central nervous system (CNS), due to its unique features, as tight junctions and drug efflux systems. Therefore, since the incidence of CNS disorders is increasing worldwide, medical therapeutics need to be improved. Consequently, aiming to surpass blood-brain barrier and overcome CNS disabilities, silencing P-glycoprotein as a drug efflux transporter at brain endothelial cells through siRNA is considered a promising approach. For siRNA enzymatic protection and efficient delivery to its target, two different nanoparticles platforms, solid lipid (SLN) and poly-lactic-co-glycolic (PLGA) nanoparticles were used in this study. Polymeric PLGA nanoparticles were around 115 nm in size and had 50 % of siRNA association efficiency, while SLN presented 150 nm and association efficiency close to 52 %. Their surface was functionalized with a peptide-binding transferrin receptor, in a site-oriented manner confirmed by NMR, and their targeting ability against human brain endothelial cells was successfully demonstrated by fluorescence microscopy and flow cytometry. The interaction of modified nanoparticles with brain endothelial cells increased 3-fold compared to non-modified lipid nanoparticles, and 4-fold compared to non-modified PLGA nanoparticles, respectively. These nanosystems, which were also demonstrated to be safe for human brain endothelial cells, without significant cytotoxicity, bring a new hopeful breath to the future of brain diseases therapies.

Use of CPAP to reduce arterial stiffness in moderate-to-severe obstructive sleep apnoea, without excessive daytime sleepiness (STIFFSLEEP): an observational cohort study protocol.

INTRODUCTION: Sleepiness is a cardinal symptom in obstructive sleep apnoea (OSA) but most patients have unspecific symptoms. Arterial stiffness, evaluated by pulse wave velocity (PWV), is related to atherosclerosis and cardiovascular (CV) risk. Arterial stiffness was reported to be higher in patients with OSA, improving after treatment with continuous positive airway pressure (CPAP). This study aims to assess whether the same effect occurs in patients with OSA and without sleepiness. METHODS AND ANALYSIS: This observational study assesses the CV effect of CPAP therapy on a cohort of patients with moderate-to-severe OSA; the effect on the subcohorts of sleepy and non-sleepy patients will be compared. A systematic and consecutive sample of patients advised CPAP therapy will be recruited from a single outpatient sleep clinic (Centro Hospitalar de Lisboa Central-CHLC, Portugal). Eligible patients are male, younger than 65 years, with confirmed moderate-to-severe OSA and apnoea-hypopnea index (AHI) above 15/hour. Other sleep disorders, diabetes or any CV disease other than hypertension are exclusion criteria. Clinical evaluation at baseline includes Epworth Sleepiness Scale (ESS), and sleepiness is defined as ESS above 10. OSA will be confirmed by polygraphic study (cardiorespiratory, level 3). Participants are advised to undertake an assessment of carotid-femoral PWV (cf-PWV) and 24 hours evaluation of ambulatory blood pressure monitoring (ABPM), at baseline and after 4 months of CPAP therapy. Compliance and effectiveness of CPAP will be assessed. The main outcome is the variation of cf-PWV over time. ETHICS AND DISSEMINATION: This protocol was approved by the Ethics Committees of CHLC (reference number 84/2012) and NOVA Medical School (number36/2014/CEFCM), Lisbon. Informed, written consent will be obtained. Its results will be presented at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02273089; Pre-results.

Oral hypoglycaemic effect of GLP-1 and DPP4 inhibitor based nanocomposites in a diabetic animal model.

Glucagon-like peptide-1 (GLP-1), an incretin hormone, is used for type 2 diabetes mellitus (T2DM) treatment because of its ability to stimulate insulin secretion and release in a glucose-dependent manner. Despite of its potent insulinotropic effect, oral GLP-1 delivery is greatly limited by its instability in the gastrointestinal tract, poor absorption efficiency and rapid degradation by dipeptidylpeptidase-4 (DPP4) enzyme leading to a short half-life (~2min). Thus, a multistage dual-drug delivery nanosystem was developed to deliver GLP-1 and DPP4 inhibitor simultaneously. The system comprised of chitosan-modified porous silicon (CSUn) nanoparticles, which were coated by an enteric polymer, hydroxypropylmethylcellulose acetate succinate MF, using aerosol flow reactor technology. A non-obese T2DM rat model induced by co-administration of nicotinamide and streptozotocin was used to evaluate the in vivo efficacy of the nanosystem. The oral administration of H-CSUn nanoparticles resulted in 32% reduction in blood glucose levels and ~6.0-fold enhancement in pancreatic insulin content, as compared to the GLP-1+DPP4 inhibitor solution. Overall, these results present a promising system for oral co-delivery of GLP-1 and DPP4 inhibitor that could be further evaluated in a chronic diabetic study.

siRNA as a tool to improve the treatment of brain diseases: Mechanism, targets and delivery.

As the population ages, brain pathologies such as neurodegenerative diseases and brain cancer increase their incidence, being the need to find successful treatments of upmost importance. Drug delivery to the central nervous system (CNS) is required in order to reach diseases causes and treat them. However, biological barriers, mainly blood-brain barrier (BBB), are the key obstacles that prevent the effectiveness of possible treatments due to their ability to strongly limit the perfusion of compounds into the brain. Over the past decades, new approaches towards overcoming BBB and its efflux transporters had been proposed. One of these approaches here reviewed is through small interfering RNA (siRNA), which is capable to specifically target one gene and silence it in a post-transcriptional way. There are different possible functional proteins at the BBB, as the ones responsible for transport or just for its tightness, which could be a siRNA target. As important as the effective silence is the way to delivery siRNA to its anatomical site of action. This is where nanotechnology-based systems may help, by protecting siRNA circulation and providing cell/tissue-targeting and intracellular siRNA delivery. After an initial overview on incidence of brain diseases and basic features of the CNS, BBB and its efflux pumps, this review focuses on recent strategies to reach brain based on siRNA, and how to specifically target these approaches in order to treat brain diseases.

Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system.

Antiretroviral drug therapy plays a cornerstone role in the treatment of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients. Despite obvious advances over the past 3 decades, new approaches toward improved management of infected individuals are still required. Drug distribution to the central nervous system (CNS) is required in order to limit and control viral infection, but the presence of natural barrier structures, in particular the blood-brain barrier, strongly limits the perfusion of anti-HIV compounds into this anatomical site. Nanotechnology-based approaches may help providing solutions for antiretroviral drug delivery to the CNS by potentially prolonging systemic drug circulation, increasing the crossing and reducing the efflux of active compounds at the blood-brain barrier, and providing cell/tissue-targeting and intracellular drug delivery. After an initial overview on the basic features of HIV infection of the CNS and barriers to active compound delivery to this anatomical site, this review focuses on recent strategies based on antiretroviral drug-loaded solid nanoparticles and drug nanosuspensions for the potential management of HIV infection of the CNS.

Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies.

Alopecia is a dermatological disorder, commonly known as hair loss, which affects up to half of the Caucasian male population by middle age, and almost all (95%) Caucasian men by old age. Considering that alopecia affects so many people and that there is currently no scientifically proven treatment with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil and finasteride) into the dermis and hair follicles. Lipid nanoparticles, prepared by ultrasonication method, showed mean particle sizes around 200 nm, which is sufficient for reaching the dermis and hair follicles, and zeta potential values around -30 mV, which indicates good physical stability. Over 28 days of storage, no significant variations in these parameters were observed, which indicates that all nanoformulations are stable in storage over that period. Cryo-scanning electron microscope measurements showed that all the lipid nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. Differential scanning calorimetry studies allowed the determination of phase transition temperatures and confirmed the recrystallization of the lipid nanoparticles (recrystallization index between 11% and 86%). A high loading efficiency was achieved for finasteride (between 70% and 90%), while less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics indicating their suitability for dermal delivery of anti-alopecia active compounds.

Contribution of flow-volume curves to the detection of central airway obstruction.

OBJECTIVE: To assess the sensitivity and specificity of flow-volume curves in detecting central airway obstruction (CAO), and to determine whether their quantitative and qualitative criteria are associated with the location, type and degree of obstruction. METHODS: Over a four-month period, we consecutively evaluated patients with bronchoscopy indicated. Over a one-week period, all patients underwent clinical evaluation, flow-volume curve, bronchoscopy, and completed a dyspnea scale. Four reviewers, blinded to quantitative and clinical data, and bronchoscopy results, classified the morphology of the curves. A fifth reviewer determined the morphological criteria, as well as the quantitative criteria. RESULTS: We studied 82 patients, 36 (44%) of whom had CAO. The sensitivity and specificity of the flow-volume curves in detecting CAO were, respectively, 88.9% and 91.3% (quantitative criteria) and 30.6% and 93.5% (qualitative criteria). The most prevalent quantitative criteria in our sample were FEF50%/FIF50% ≥ 1, in 83% of patients, and FEV1/PEF ≥ 8 mL · L(-1) · min(-1), in 36%, both being associated with the type, location, and degree of obstruction (p < 0.05). There was concordance among the reviewers as to the presence of CAO. There is a relationship between the degree of obstruction and dyspnea. CONCLUSIONS: The quantitative criteria should always be calculated for flow-volume curves in order to detect CAO, because of the low sensitivity of the qualitative criteria. Both FEF50%/FIF50% ≥ 1 and FEV1/PEF ≥ 8 mL · L(-1) · min(-1) were associated with the location, type and degree of obstruction.

Contribution of flow-volume curves to the detection of central airway obstruction / Contribuicao da curva de fluxo-volume na deteccao de obstrucao da via aerea central

OBJECTIVE: To assess the sensitivity and specificity of flow-volume curves in detecting central airway obstruction (CAO), and to determine whether their quantitative and qualitative criteria are associated with the location, type and degree of obstruction. METHODS: Over a four-month period, we consecutively evaluated patients with bronchoscopy indicated. Over a one-week period, all patients underwent clinical evaluation, flow-volume curve, bronchoscopy, and completed a dyspnea scale. Four reviewers, blinded to quantitative and clinical data, and bronchoscopy results, classified the morphology of the curves. A fifth reviewer determined the morphological criteria, as well as the quantitative criteria. RESULTS: We studied 82 patients, 36 (44%) of whom had CAO. The sensitivity and specificity of the flow-volume curves in detecting CAO were, respectively, 88.9% and 91.3% (quantitative criteria) and 30.6% and 93.5% (qualitative criteria). The most prevalent quantitative criteria in our sample were FEF50%/FIF50% ≥ 1, in 83% of patients, and FEV1/PEF ≥ 8 mL . L–1 . min–1, in 36%, both being associated with the type, location, and degree of obstruction (p < 0.05). There was concordance among the reviewers as to the presence of CAO. There is a relationship between the degree of obstruction and dyspnea. CONCLUSIONS: The quantitative criteria should always be calculated for flow-volume curves in order to detect CAO, because of the low sensitivity of the qualitative criteria. Both FEF50%/FIF50% ≥ 1 and FEV1/PEF ≥ 8 mL . L–1 . min–1 were associated with the location, type and degree of obstruction. .

OBJETIVO: Verificar a sensibilidade e especificidade das curvas de fluxo-volume na detecção de obstrução da via aérea central (OVAC), e se os critérios qualitativos e quantitativos da curva se relacionam com a localização, o tipo e o grau de obstrução. MÉTODOS: Durante quatro meses foram selecionados, consecutivamente, indivíduos com indicação para broncoscopia. Todos efetuaram avaliação clínica, preenchimento de escala de dispneia, curva de fluxo-volume e broncoscopia num intervalo de uma semana. Quatro revisores classificaram a morfologia da curva sem conhecimento dos dados quantitativos, clínicos e broncoscopicos. Um quinto revisor averiguou os critérios morfológicos e quantitativos. RESULTADOS: Foram incluídos 82 doentes, 36 (44%) com OVAC. A sensibilidade e especificidade da curva de fluxo-volume na detecção de OVAC foram, respectivamente, de 88,9% e 91,3% (critérios quantitativos) e de 30,6% e 93,5% (critérios qualitativos). Os critérios quantitativos mais frequentes na amostra foram o FEF50%/FIF50% ≥ 1 em 83% e o VEF1/PFE ≥ 8 mL . L–1 . min–1 em 36% dos doentes, e ambos se relacionaram com o tipo, a localização e o grau de obstrução (p < 0,05). Houve concordância dos revisores quanto à existência ou não de OVAC. Existe relação entre o grau de obstrução e o de dispneia. CONCLUSÕES: Os critérios quantitativos devem ser sempre calculados nas curvas de fluxo-volume de forma a detectar OVAC, dado a baixa sensibilidade dos critérios qualitativos. Os critérios FEF50%/FIF50% ...

Rituximab therapy in primary Sjögren's syndrome.

Primary Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltration of glandular tissues leading to sicca symptoms, namely, dry eyes and dry mouth. In the majority of cases, the disease course is benign, albeit with considerable patient discomfort. Some patients, however, have systemic symptoms with arthritis, cutaneous vasculitis, low complement levels, and cryoglobulinemia. A small but not insignificant percentage of those patients evolve to B cell lymphoma. The increased expression of B cell survival factors, such as B cell activating factor, may promote the perpetuation of a B cell clone and precede the lymphoproliferative disease. Rituximab, a chimeric monoclonal antibody to CD20, leads to B cell depletion and may have a role in Sjögren systemic manifestations as well as in preventing and treating Sjögren-associated lymphoma.

Evaluation of the radiographic cephalometry learning process by a learning virtual object.

INTRODUCTION: Radiographic cephalometry is a complex area of study. The literature shows a lack of interobserver reproducibility in the definition and identification of cephalometric landmarks. The aim of this study was to test a learning virtual object (LVO) called ceph learning used in the teaching of radiographic cephalometry and to verify whether it improves performance of the landmarking process. METHODS: A total of 40 undergraduate students were divided into 2 groups. Group A was taught according to the conventional teaching method of theory and practical classes, and group B was taught with an LVO. The students' learning performance was tested by using a multiple-choice questionnaire that covered the knowledge and understanding of cephalometry and by the index of correct landmark identification. The Student t test was used to check statistical differences between the 2 groups. LVO usability was evaluated with a questionnaire based on the system usability scale. RESULTS: In the first posttest, the Student t test showed no significant differences (P >0.05). However, in the second posttest 15 days later, a decrease was observed in the scores of group A, with significant differences (P <0.05). Students approved the LVO usability aspects--effectiveness, efficiency, and satisfaction (82.45% +/- 6.78%). CONCLUSIONS: LVO was shown to be a useful and efficient tool in the learning process and might assist the learning of cephalometry.