Assessment of calcinosis in Portuguese patients with systemic sclerosis - a multicenter study.

INTRODUCTION/OBJECTIVES: The study aims to define the clinical and subclinical calcinosis prevalence, the sensitivity of radiographed site and clinical method for its diagnosis, and the phenotype of Portuguese systemic sclerosis (SSc) patients with calcinosis. METHOD: A cross-sectional multicenter study was conducted with SSc patients fulfilling Leroy/Medsger 2001 or ACR/EULAR 2013 classification criteria, registered in the Reuma.pt. Calcinosis was assessed through clinical examination and radiographs of hands, elbows, knees, and feet. Independent parametric or non-parametric tests, multivariate logistic regression, and sensitivity calculation of radiographed site and clinical method for calcinosis detection were performed. RESULTS: We included 226 patients. Clinical calcinosis was described in 63 (28.1%) and radiological calcinosis in 91 (40.3%) patients, of which 37 (40.7%) were subclinical. The most sensitive location to detect calcinosis was the hand (74.7%). Sensitivity of the clinical method was 58.2%. Calcinosis patients were more often female (p = 0.008) and older (p < 0.001) and had more frequently longer disease duration (p < 0.001), limited SSc (p = 0.017), telangiectasia (p = 0.039), digital ulcers (p = 0.001), esophageal (p < 0.001) and intestinal (p = 0.003) involvements, osteoporosis (p = 0.028), and late capillaroscopic pattern (p < 0.001). In multivariate analysis, digital ulcers (OR 2.63, 95% CI 1.02-6.78, p = 0.045) predicted overall calcinosis, esophageal involvement (OR 3.52, 95% CI 1.28-9.67, p = 0.015) and osteoporosis (OR 4.1, 95% CI 1.2-14.2, p = 0.027) predicted hand calcinosis, and late capillaroscopic pattern (OR 7.6, 95% CI 1.7-34.9, p = 0.009) predicted knee calcinosis. Anti-nuclear antibody positivity was associated with less knee calcinosis (OR 0.021, 95% CI 0.001-0477, p = 0.015). CONCLUSIONS: Subclinical calcinosis high prevalence suggests that calcinosis is underdiagnosed and radiographic screening might be relevant. Multifactorial pathogenesis may explain calcinosis predictors' variability. Key Points • Prevalence of subclinical calcinosis in SSc patients is substantial. • Hand radiographs are more sensitive to detect calcinosis than other locations or clinical method. • Digital ulcers were associated with overall calcinosis, esophageal involvement and osteoporosis were associated with hand calcinosis, and late sclerodermic pattern in nailfold capillaroscopy was associated with knee calcinosis. • Anti-nuclear antibody positivity may be a protective factor for knee calcinosis.

Pharmacological modulation of ventral tegmental area neurons elicits changes in trigeminovascular sensory processing and is accompanied by glycemic changes: Implications for migraine.

BACKGROUND: Imaging migraine premonitory studies show increased midbrain activation consistent with the ventral tegmental area, an area involved in pain modulation and hedonic feeding. We investigated ventral tegmental area pharmacological modulation effects on trigeminovascular processing and consequent glycemic levels, which could be involved in appetite changes in susceptible migraine patients. METHODS: Serotonin and pituitary adenylate cyclase-activating polypeptide receptors immunohistochemistry was performed in ventral tegmental area parabrachial pigmented nucleus of male Sprague Dawley rats. In vivo trigeminocervical complex neuronal responses to dura mater nociceptive electrical stimulation, and facial mechanical stimulation of the ophthalmic dermatome were recorded. Changes in trigeminocervical complex responses following ventral tegmental area parabrachial pigmented nucleus microinjection of glutamate, bicuculline, naratriptan, pituitary adenylate cyclase-activating polypeptide-38 and quinpirole were measured, and blood glucose levels assessed pre- and post-microinjection. RESULTS: Glutamatergic stimulation of ventral tegmental area parabrachial pigmented nucleus neurons reduced nociceptive and spontaneous trigeminocervical complex neuronal firing. Naratriptan, pituitary adenylate cyclase-activating polypeptide-38 and quinpirole inhibited trigeminovascular spontaneous activity, and trigeminocervical complex neuronal responses to dural-evoked electrical and mechanical noxious stimulation. Trigeminovascular sensory processing through modulation of the ventral tegmental area parabrachial pigmented nucleus resulted in reduced circulating glucose levels. CONCLUSION: Pharmacological modulation of ventral tegmental area parabrachial pigmented nucleus neurons elicits changes in trigeminovascular sensory processing. The interplay between ventral tegmental area parabrachial pigmented nucleus activity and the sensory processing by the trigeminovascular system may be relevant to understand associated sensory and homeostatic symptoms in susceptible migraine patients.

Was it something I ate? Understanding the bidirectional interaction of migraine and appetite neural circuits.

Migraine attacks can involve changes of appetite: while fasting or skipping meals are often reported triggers in susceptible individuals, hunger or food craving are reported in the premonitory phase. Over the last decade, there has been a growing interest and recognition of the importance of studying these overlapping fields of neuroscience, which has led to novel findings. The data suggest additional studies are needed to unravel key neurobiological mechanisms underlying the bidirectional interaction between migraine and appetite. Herein, we review information about the metabolic migraine phenotype and explore migraine therapeutic targets that have a strong input on appetite neuronal circuits, including the calcitonin gene-related peptide (CGRP), the pituitary adenylate cyclase-activating polypeptide (PACAP) and the orexins. Furthermore, we focus on potential therapeutic peptide targets that are involved in regulation of feeding and play a role in migraine pathophysiology, such as neuropeptide Y, insulin, glucagon and leptin. We then examine the orexigenic - anorexigenic circuit feedback loop and explore glucose metabolism disturbances. Additionally, it is proposed a different perspective on the most reported feeding-related trigger - skipping meals - as well as a link between contrasting feeding behaviors (skipping meals vs food craving). Our review aims to increase awareness of migraine through the lens of appetite neurobiology in order to improve our understanding of the earlier phase of migraine, encourage better studies and cross-disciplinary collaborations, and provide novel migraine-specific therapeutic opportunities.

Erdheim-Chester Disease: A Rare Clinical Entity.

Pericardial effusion represents a diagnostic challenge. Erdheim-Chester disease (ECD), though a rare cause, should be considered in the differential diagnosis. An 88-year-old woman was admitted to the hospital due to retrosternal pain, dyspnoea and constitutional symptoms. Hypoxaemic respiratory failure and increased inflammatory markers were documented. A chest x-ray revealed an increased cardiothoracic ratio. An echocardiogram showed a moderate-volume pericardial effusion, without signs of cardiac tamponade. A thoraco-abdomino-pelvic CT scan found a bilateral perirenal soft tissue halo. Perirenal mass biopsy showed diffuse infiltration by foamy histiocytes (CD68+), without IgG4, compatible with ECD. The correlation of anamnesis, radiology and histology is crucial for the diagnosis of ECD. LEARNING POINTS: Erdheim-Chester disease is a non-Langerhans cell histiocytosis that affects multiple organs and systems.Thorough study of a pericardial effusion is important as it is still considered idiopathic in 10-20% of cases.It is a rare disease so high diagnostic suspicion is important. The diagnosis is established through clinical manifestations, radiologic findings and histological confirmation.

PAC1 receptor blockade reduces central nociceptive activity: new approach for primary headache?

Pituitary adenylate cyclase activating polypeptide-38 (PACAP38) may play an important role in primary headaches. Preclinical evidence suggests that PACAP38 modulates trigeminal nociceptive activity mainly through PAC1 receptors while clinical studies report that plasma concentrations of PACAP38 are elevated in spontaneous attacks of cluster headache and migraine and normalize after treatment with sumatriptan. Intravenous infusion of PACAP38 induces migraine-like attacks in migraineurs and cluster-like attacks in cluster headache patients. A rodent-specific PAC1 receptor antibody Ab181 was developed, and its effect on nociceptive neuronal activity in the trigeminocervical complex was investigated in vivo in an electrophysiological model relevant to primary headaches. Ab181 is potent and selective at the rat PAC1 receptor and provides near-maximum target coverage at 10 mg/kg for more than 48 hours. Without affecting spontaneous neuronal activity, Ab181 effectively inhibits stimulus-evoked activity in the trigeminocervical complex. Immunohistochemical analysis revealed its binding in the trigeminal ganglion and sphenopalatine ganglion but not within the central nervous system suggesting a peripheral site of action. The pharmacological approach using a specific PAC1 receptor antibody could provide a novel mechanism with a potential clinical efficacy in the treatment of primary headaches.

Low-Dose Coronary CT Angiography in Patients with Atrial Fibrillation: Comparison of Image Quality and Radiation Exposure with Two Different Approaches.

RATIONALE AND OBJECTIVES: To evaluate image quality, coronary interpretability and radiation exposure of coronary CT angiography (CCTA) performed in patients with atrial fibrillation (AF) with the latest scanner generation, comparing two different technical approaches. A new scanner that combines a 0.23 mm spatial resolution, a new generation of iterative reconstruction, fast gantry rotation time and the intracycle motion-correction algorithm to improve the temporal resolution was recently introduced in the clinical field. MATERIALS AND METHODS: We enrolled 105 consecutive patients with chronic AF who performed CCTA with a whole-heart coverage high-definition CT scanner (16-cm z-axis coverage with 256 detector rows, 0.28 s gantry rotation time). Five of them were excluded for impaired renal function. Patients were randomized between a double acquisition protocol (50 patients, group 1) or a single acquisition protocol (50 patients, group 2). The image quality, coronary segment interpretability and effective dose (ED) of CCTA were assessed. RESULTS: The mean HR during the scan was 85.6±21 bpm in group 1 vs. 83.7±23 bpm in Group 2, respectively (p < ns). In group 2, overall image quality was high and comparable with that of group 1 (Likert scale =3.2 ± 1.4 vs. 3.3 ± 1.2, p = ns, in group 1 and 2, respectively). Coronary interpretability was high and similar between the two groups (97.5% and 97.1% in group 1 and 2, p = ns, respectively). Mean ED was significantly higher in group 1 than in group 2 (5.3 ± 1.8 mSv vs. 2.7 ± 0.7 mSv, p < 0.001). CONCLUSION: The novel whole-heart coverage CT scanner allows to perform CCTA with a single-acquisition protocol with high image quality and low radiation exposure in AF patients.

Predicting prognosis in patients with advanced cancer: A prospective study.

BACKGROUND: Prognosis is one of the most challenging questions with which physicians are confronted. Accuracy in the prediction of survival is necessary for clinical, ethical, and organizational reasons. AIM: Evaluate young doctors' clinical prediction of survival and the aids they could get: expert opinion, Palliative Prognostic score, and Palliative Prognostic Index. DESIGN: Prospective, observational study. SETTING/PARTICIPANTS: Advanced cancer patients under observation of an inhospital palliative care team, from April to July 2014. A total of 38 patients were included, mostly male (65.8%), average age 68.5 years. Average survival time was 24 days. Follow-up concluded with death or after 90 days. RESULTS: Young doctors' clinical prediction of survival was adequate at 10.5%, with 55.3% severe errors in an optimistic direction. Palliative care experts were more adequate (23.7%) and made less severe errors (42.1%). Palliative Prognostic score and Palliative Prognostic Index were even more adequate (47% and 55%, respectively) and made even less severe errors (0% and 11%, respectively). The best correlation with observed survival was achieved when palliative care experts used palliative prognostic score ( rs = -0.629; p < 0.01). CONCLUSION: Young doctors' clinical prediction of survival is often inadequate. Palliative Prognostic score, which includes clinical prediction of survival, calculated by palliative care experts had the best performance. Our results support the recommendation of using clinical prediction of survival together with prognostic scores.

Pulmonary Embolism and Intracardiac Type A Thrombus with an Unexpected Outcome.

Detection of right heart thrombi (RHT) in the context of pulmonary thromboembolism (PE) is uncommon (4-18%) and increases the risk of mortality beyond the presence of PE alone. Type A thrombi are serpiginous and highly mobile and are thought to be originated from large veins and captured in-transit within the right heart. Optimal management of RHT is still uncertain. A 79-year-old woman, with a history of recent total hysterectomy with adnexectomy and a Wells procedure, presented to the emergency department following an episode of syncope. Computed tomography revealed bilateral PE and the presence of a right atrial thrombus. Transthoracic echocardiography demonstrated a free-floating type A thrombus in the right atrium, protruding into the right ventricle, and signs of pulmonary hypertension and right ventricle dysfunction. Considering the recent surgery and clinical stability, treatment with heparin alone was decided. Subsequent clinical improvement was observed and echocardiographic follow-up revealed complete thrombus dissolution and complete recovery of right ventricle function. Most authors recommend treatment of PE with RHT with thrombolysis or embolectomy followed by anticoagulation, although evidence is scarce. Individual risk of hemorrhage and operatory-related mortality should be taken into account when defining the treatment strategy especially when benefit is not firmly established.

The concerted action of a positive charge and hydrogen bonds dynamically regulates the pKa of the nucleophilic cysteine in the NrdH-redoxin family.

NrdH-redoxins shuffle electrons from the NADPH pool in the cell to Class Ib ribonucleotide reductases, which in turn provide the precursors for DNA replication and repair. NrdH-redoxins have a CVQC active site motif and belong to the thioredoxin-fold protein family. As for other thioredoxin-fold proteins, the pK(a) of the nucleophilic cysteine of NrdH-redoxins is of particular interest since it affects the catalytic reaction rate of the enzymes. Recently, the pK(a) value of this cysteine in Corynebacterium glutamicum and Mycobacterium tuberculosis NrdH-redoxins were determined, but structural insights explaining the relatively low pK(a) remained elusive. We subjected C. glutamicum NrdH-redoxin to an extensive molecular dynamics simulation to expose the factors regulating the pK(a) of the nucleophilic cysteine. We found that the nucleophilic cysteine receives three hydrogen bonds from residues within the CVQC active site motif. Additionally, a fourth hydrogen bond with a lysine located N-terminal of the active site further lowers the cysteine pK(a). However, site-directed mutagenesis data show that the major contribution to the lowering of the cysteine pK(a) comes from the positive charge of the lysine and not from the additional Lys-Cys hydrogen bond. In 12% of the NrdH-redoxin family, this lysine is replaced by an arginine that also lowers the cysteine pK(a). All together, the four hydrogen bonds and the electrostatic effect of a lysine or an arginine located N-terminally of the active site dynamically regulate the pK(a) of the nucleophilic cysteine in NrdH-redoxins.

2011 Portuguese recommendations for the use of biological therapies in patients with psoriatic arthritis.

OBJECTIVE: To develop recommendations for the treatment of psoriatic arthritis (PsA) with biological therapies, endorsed by the Portuguese Society of Rheumatology. METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. A draft of the recommendations was first circulated to all Portuguese rheumatologists and their suggestions were incorporated in the draft. At a national meeting the recommendations were discussed and all attending rheumatologists voted on the level of agreement for each recommendation. A second draft was again circulated before publication. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching biological therapies in patients with PsA. Specific recommendations were developed for several disease domains: peripheral arthritis, axial disease, enthesitis and dactylitis. CONCLUSION: These recommendations may be used for guidance in deciding which patients with PsA should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated.

Avaliação de risco potencial para estabelecimentos processadores de alimentos artesanais / Evaluation of potential risk to food processors craft establishments

A exigência de Boas Práticas de Fabricação ao longo da cadeia produtiva na produção de alimentos tem procurado garantir melhor qualidade e segurança. Com o presente trabalho, objetivou-se avaliar o potencial de risco de estabelecimentos processadores de alimentos artesanais. Foram aplicados questionários num total de 20 estabelecimentos produtores de queijo minas frescal, rapadura, farinha de mandioca e doces na região do Alto Jequitinhonha. As perguntas eram pertinentes à avaliação das condições de infra-estrutura, higienização e processamento adotados nas unidades de produção artesanal. Para a produção de farinha de mandioca, rapadura e doces, os estabelecimentos foram considerados de Alto Risco. O maior risco estava nas instalações e nos manipuladores de alimentos, que não atenderam aos itens considerados imprescindíveis no processamento dos alimentos. Nas avaliações das queijarias, observou-se que se apresentavam dentro dos padrões recomendados. Em 100% dos estabelecimentos não realizavam nenhum controle de qualidade do processo. Portanto para minimizar os riscos e garantir a obtenção de alimentos dentro dos padrões de qualidade e segurança é fundamental a adoção de sistemas e programas de controle.

PpRab1, a Rab GTPase from maritime pine is differentially expressed during embryogenesis.

Rab-related small GTP-binding proteins are known to be involved in the regulation of the vesicular transport system in eukaryotic cells. We report the characterization of a previously isolated full-length cDNA PpRab1 from Pinus pinaster. Amino acid sequence analysis revealed the presence of G1-G5 conserved domains of the GTPase Ras superfamily and a double cysteine motif in the C-terminal, characteristic of Rab proteins. The PpRab1 protein shows high sequence similarity to several Rab1 GTP-binding proteins in plants. Phylogenetic analysis showed that, within the Ras superfamily, PpRab1 is more closely related to the Rab family and within this, PpRab1 protein was found to cluster with Arabidopsis subfamily AtRABE, whose members are known to regulate ER-to-Golgi membrane trafficking steps. PpRab1 transcripts were expressed at constitutively high levels for the initial stages of zygotic embryo development, and then their relative abundance decreased as embryo matures. The PpRab1 transcript is not embryo-specific as it was found in roots, cotyledons and hypocotyls. An increase in PpRab1 expression level was observed when seeds are germinated and collected at successive time points of development. In situ RT-PCR analysis revealed an expression signal in early zygotic embryos. In view of the proposed roles of Rab1 GTP-binding protein, the possible function of the protein encoded by PpRab1 in embryogenesis is discussed.

[Tuberculosis in rheumatic patients treated with tumour necrosis factor alpha antagonists: the Portuguese experience]. / Tubereulose em doentes reumáticos tratados com antagonistas do factor de necrose tumoral alfa: a experiência Portuguesa.

In Portugal, 13 cases of tuberculosis (TB) were reported, in the period between 1999 and 2005, in 960 patients exposed to anti-TNFalpha treatment (1.35%), 8 females and 5 males. Mean age was 46.7 +/- 13.8 years. 9 patients had rheumatoid arthritis (RA), in 639 exposed patients (1.4%), 3 had ankylosing spondylitis (AS), in 200 exposed patients (1.5%) and 1 had psoriatic arthritis (PA), in 101 exposed patients (1%). The anti-TNFa used was in 8 cases infliximab (in 456 patients exposed, 1.5%), in 4 adalimumab (in 171 patients exposed, 2.3%) and in 1 etanercept (in 333 exposed, 0.3%). Treatment with a biological agent was started 11.1 +/- 8.7 months (min 3 and max 50) before TB onset. Tuberculin skin test (TST) was performed in 9 out of the 13 patients (the other 4 had started biological therapy before 2002). In 3 cases the TST response was 0 mm, in 3 less than 10 mm, in one was 14 mm and in two 20 mm. In the 3 cases with a TST response superior to 10 mm, isoniazid treatment 300 mg/d was prescribed, during 9 months. The time between first symptoms and TB diagnosis was 2.6 +/- 2.9 months. TB involvement was pulmonary in 6 patients, lymph node disease in 2, peritoneal and pulmonary in 2, osteoarticular in one case, lymph node disease and splenic in another and miliar TB in the last case. One death was reported; all of the other cases had a good outcome after anti-TB treatment. In two cases (one treated with adalimumab and the other with infliximab), paradoxical response to treatment occurred. None of the patients has restarted biological therapy after TB treatment.

Reabilitação na hemipelvectomia traumática / Rehabilitation for traumatic hemipelvectomy

A hemipelvectomia traumática constitui um evento raro, catastófico, cujos mecanismos de lesão e prognóstico são bem descritos na literatura. O crescente número de acidentes motociclísticos têm elevado a prevalência desta amputação, definindo o grupo de vítimas como jovens do sexo masculino sem comorbidade. Acarreta múltiplas sequelas físicas, psicológicas e sociais. Através da reabilitação, o paciente poderá recuperar independência funcional. A protetização é de grande valia, uma vez que os pacientes são jovens com prognóstico de marcha. Neste relato é apresentado o caso de uma vítima de hemipelvectomia traumática do sexo feminino, que se tornou independente para as atividades da vida diária após processo de reabilitação, que incluiu prótese, com melhora da qualidade de vida observada sob diversos aspectos. A protetização adequada não devolveu à paciente todas as finções perdidas, mas se constituiu em um instrumento capaz de melhorar-lhe a qualidade de vida.

Pé diabético: análise bacteriológica de 141 casos / Diabetic foot infection: bacteriologic analysis of 141 patients

Diabetes mellitus (DM) é uma doença progressiva que apresenta complicações freqüentes, em especial a infecção nos pés. Realizamos um estudo prospectivo com 141 pacientes com DM e úlceras infectadas nos pés, conduzido no Centro Integrado de Diabetes e Hipertensão da UFC no período de março/2000 a novembro/2001. A maioria apresentava infecção avaliada como graus I e II da classificação de Wagner. As amostras foram cultivadas utilizando-se meios seletivos, e a identificação bacteriana e os antibiogramas foram realizados através de metodologia convencional e automatizados. Os patógenos mais freqüentemente isolados foram as enterobactérias (83,7 por cento), Staphylococcus aureus (43,3 por cento) e bactérias anaeróbias (17 por cento). Cepas de Streptococcus pyogenes foram isoladas de 7,8 por cento dos pacientes. Cepas produtoras de beta-lactamase de espectro ampliado e cepas de Staphylococcus aureus resistentes à oxacilina foram isoladas de 6 por cento e 11,6 por cento dos pacientes, respectivamente. A resistência aos antimicrobianos vem se tornando cada vez mais comum, mesmo em pacientes com infecção adquirida na comunidade. Investimentos em diagnóstico etiológico das infecções e estratégias racionais no uso de antimicrobianos fazem-se necessários na tentativa de evitar tratamentos inadequados e suas já conhecidas conseqüências.

Gasto social das três esferas do governo: 1995 / Social expenditure of three government spheres: 1995

Apresenta consolidação do gasto social das três esferas de governo. Tem como objetivo possibilitar o conhecimento da dimensão e estrutura dos gastos com a prestação de serviços dos setores públicos da União, estados e municípios. Analisa o ano de 1995, por áreas de atuação social. Trata da consolidação do gasto público brasileiro com programas voltados para a melhoria das condições de vida da população e para o atendimento mais amplo das demandas sociais colocadas pelo "status" de cidadania. Relata que a obtenção de uma primeira medida relativa do perfil, da estrutura e da responsabilidade de execução desses gastos pode vir a contribuir para confirmar ou desmistificar alguns conceitos que já fazem parte do imaginário presente no debate sobre a questão social.

Dimensionamento e acompanhamento do gasto social federal / Measurement and accompanying to the federal social expenditure

Relata que a mensuração dos dispênidos do governo federal em áreas sociais é um instrumento que ajuda a identificar a forma e a condução da política social no país, e pode servir de subsídio para a correção dos rumos das políticas e/ou como base de projeção para ações futuras. Procura quantificar e analisar os gastos sociais do governo federal, a partir do conceito de "área de atuação social". Observa que a metodologia empregada no levantamento foi definida ainda em acordo com dois critérios: i) os gastos sociais deveriam estar associados aos registros contidos no orçamento, ou seja, à classificação funcional-programática e à natureza da despesa; e ii) a série deveria ser comparável, em nível internacional, com outras séries de gasto social.

Dimensionamento e acompanhamento do gasto social federal / Texto para Discussão (TD) 547: Dimensionamento e acompanhamento do gasto social federal

Analisa e quantifica os gastos sociais do governo federal, a partir do conceito de área de atuação. Emprega metodologia no levantamento dos gastos, baseada nos critérios de: gastos sociais associados à classificação funcional pragmática e à natureza da despesa; série comparável, em nível internacional, com outras séries de gasto social.

Gasto social das três esferas de governo: 1995 / Texto para Discussão (TD) 598: Gasto social das três esferas de governo: 1995

Trata-se da consolidação do gasto público brasileiro com programas voltados para a melhoria, a curto e longo prazos, das condições de vida da população, e também para o atendimento mais amplo das demandas sociais colocadas pelo status de cidadania. A obtenção de uma primeira medida relativa do perfil, da estrutura e da responsbilidade de execução desses gastos pode vir a contribuir para confirmar ou desmistificar alguns conceitos que já fazem parte do imaginário presente no debate sobre a questão social.