Diagnosis and treatment of giant cell arteritis

Giant cell arteritis (GCA) is a chronic granulomatous vasculitis of unknown aetiology occurring in the elderly. It affects the cranial branches of the arteries originating from the aortic arch and is usually associated with markedly elevated acute-phase reactants. In 10-15% of cases the extra-cranial branches of the aortic arch are involved. GCA is closely related to polymyalgia rheumatica (PMR), although the relationship between the two disorders is still unclear. New-onset headache, scalp tenderness, jaw claudication, temporal artery abnormalities on physical examination, visual symptoms and associated PMR represent the most typical and frequent features of the disease. Systemic manifestations, including fever, anorexia and weight loss, are observed in 50% of cases. Less frequent manifestations are related to the central or peripheral nervous systems, the respiratory tract and extra-cranial large-vessel involvement. As GCA is characterized by a wide spectrum of clinical manifestations, it is important to recognize the different onset patterns of the disease and related diagnostic steps. The diagnosis is relatively straightforward in the presence of typical cranial manifestations, but it may be challenging in the case of a normal erythrocyte sedimentation rate, occult GCA or in patients with isolated extra-cranial features. Temporal artery biopsy still represents the gold standard for diagnosis, while the role of ultrasonography, high-resolution magnetic resonance imaging and positron emission tomography should be better addressed. Corticosteroids remain the therapy of choice. Data supporting the usefulness of antiplatelet agents and anticoagulants combined with corticosteroids to prevent ischaemic complications as well as the corticosteroid-sparing effect of methotrexate and anti-tumour necrosis factor-alpha drugs are limited and non-conclusive.     

Cyclosporin and organ specific toxicity: clinical aspects, pharmacogenetics and perspectives

Cyclosporine (CsA) has considerably modified the graft survival in solid organ and bone marrow transplantations. It is also the treatment of choice in chronic diseases such as steroid resistance and/or dependence nephrotic syndrome and autoimmune-diseases, especially in those cases that require long term treatments. Renal toxicity is the major adverse effect of chronic CsA administration. Deterioration of renal function and renal histopathology are the basic elements of the diagnosis. Overall, available studies suggest a good degree of safety related to appropriate drug dosages even if they require an adequate degree of surveillance in case of rapid changes of renal functions and long term evaluation of renal pathology. CsA neurotoxicity is the second major problem that seems underestimated especially in case of subtle manifestations in children. The full blown picture of the acute form is characterized by convulsion and sudden alteration of mental function that are reversible upon drug withdrawal. The diagnosis is based on typical CT and MRI aspects of extensive bilateral white-matter abnormalities in the occipital region of the brain that mimics the posterior encephalopathy syndrome. Prospective evaluations of drug tolerance include renal histology in case of chronic renal toxicity and neuro-imaging to identify and block acute neurotoxicity.     

Development and validation of a LC-MS method with electrospray ionization for the determination of the imidazole H3 antagonist ROS203 in rat plasma

A rapid, simple and sensitive liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for the determination of the imidazole H(3) antagonist ROS203 in rat plasma, using the superior homologue ROS287 as internal standard. Analyses were performed on an Agilent 1100 Series HPLC system employing a Supelco Ascentis C(18) column and isocratic elution with acetonitrile-10mM ammonium acetate buffer pH 4.0 (30:70, v/v) at a flow rate of 0.25 mL/min. An Applied Biosystems/MDS Sciex 150-EX single quadrupole mass spectrometer, equipped with an electrospray ionization interface was employed, operating in the positive ion mode. Plasma samples were deproteinized with acetonitrile (1:2), evaporated under nitrogen stream, reconstituted in the mobile phase and 5 microL were injected into the system. The retention times of ROS203 and IS were 2.20 and 2.90 min, respectively. Calibration curves in spiked plasma were linear over the concentration range of 2610-2.61 ng/mL with determination coefficients >0.99. The lower limit of quantification (LLOQ) was 2.61 ng/mL. The accuracy of the method was within 15%. Intra- and inter-day relative standard deviations were less or equal to 9.50% or 7.19%, respectively. The applicability of the LC-MS method was tested employing plasma samples obtained after i.p. administration of ROS203 to female Wistar rats to support a behavioral in vivo study. The specificity of the method was confirmed by the absence of interferences from endogenous substances. The reported method can provide the necessary sensitivity, linearity, precision, accuracy and specificity to allow the determination of ROS203 in rat plasma samples to support further pharmacokinetic assays.     

MAGUK proteins: new targets for pharmacological intervention in the glutamatergic synapse

In the postsynaptic density of excitatory glutamatergic synapses, membrane associated guanylate kinase (MAGUK) proteins, such as Post-Synaptic Density 95 (PSD-95), organize ionotropic glutamate receptors and their associated signalling proteins regulating the strength of synaptic activity. Modifications of MAGUK proteins function in the glutamatergic synapse such as alterations of MAGUK proteins interaction with N-Methyl-D-Aspartate (NMDA) receptors regulatory subunits are common events in several neurodegenerative disorders. Thus, a better knowledge and understanding of MAGUK structure and function as well as of the molecular events regulating MAGUK-mediated interactions in the glutamatergic synapse could lead to the identification of new targets for pharmaceutical intervention for neurodegenerative diseases.     

Detection of sonographic B-lines in patients with normal lung or radiographic alveolar consolidation.

BACKGROUND: Diffuse comet-tail B-line artifacts in lung ultrasound are a sign of alveolar-interstitial syndrome, but isolated transthoracic scans positive for B-lines (multiple B lines or B+) could be detected in other conditions. The aim was to assess the prevalence and distribution of this sonographic sign in patients with normal lung or isolated alveolar consolidation in chest radiography. MATERIAL/METHODS: Two hundred seventeen patients consecutively admitted to this emergency medicine unit with any diagnosis and without radiographic or clinical evidence of diffuse interstitial syndrome were analyzed. Each patient underwent chest radiography and lung sonographic examination with four anterolateral chest scans per side. RESULTS: Of the 1736 sonographic scans performed, 13.2% were positive for the B+ pattern. Positive scans significantly corresponded to laterobasal areas or radiographic opacities due to lung alveolar consolidations (p<0.005). Twenty percent of the laterobasal scans of 145 patients with radiologically normal lung were positive. The negative predictive value of B+ was 83.9% (95% confidence interval: 78.2-89.7%), with a specificity of 90.3% (95%CI: 85.5-95.1%) for predicting any localized radiographic pulmonary opacity. CONCLUSIONS: B+ scans can be detected in the chest areas surrounding an isolated alveolar consolidation and in the laterobasal scans of a radiographic normal lung. These features should always be considered when lung ultrasound is performed to rule out the alveolar-interstitial syndrome in an emergency setting. Moreover, B+ patterns have a satisfactory negative predictive value for radiographic lung opacities, which could have added diagnostic value in the ED evaluation of dyspneic patients.     

The Provision of Interventional Radiology Services in Europe: CIRSE Recommendations

Interventional Radiology (IR) is an essential part of modern medicine, delivering minimally invasive patient-focused care, which has been proven to be safe and effective in both elective and emergency settings. The aim of this document is to outline the core requirements and standards for the provision of Interventional Radiological services, including training, certification, manpower, and accreditation. The ultimate challenge will be the adoption of these recommendations by different countries and health economies around the world, in turn ensuring equal access to IR treatments for all patients, the appropriate distribution of resources for IR service provision as well as the continued development of safe and high-quality IR services in Europe and beyond.     

Combined Endoscopic-Radiological Rendezvous for Distal Tail Postoperative Pancreatic Fistula (POPF)

Postoperative pancreatic fistula (POPF) with leakage of pancreatic juice is a rare, severe complication following pancreatic resection or, less commonly, splenectomy. Definitive treatment can require multidisciplinary approaches. We report a case of stenosis of the main pancreatic duct with distal tail GRADE C POPF, occurred after splenectomy for Hodgkin lymphoma, successfully treated with combined radiological-endoscopic approach.