Cardiac magnetic resonance imaging parameters as surrogate endpoints in clinical trials of acute myocardial infarction

Cardiac magnetic resonance (CMR) offers a variety of parameters potentially suited as surrogate endpoints in clinical trials of acute myocardial infarction such as infarct size, myocardial salvage, microvascular obstruction or left ventricular volumes and ejection fraction. The present article reviews each of these parameters with regard to the pathophysiological basis, practical aspects, validity, reliability and its relative value (strengths and limitations) as compared to competitive modalities. Randomized controlled trials of acute myocardial infarction which have used CMR parameters as a primary endpoint are presented

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

Bilateral paramedian midbrain infarct: an uncommon variant of the ``top of the basilar&apos;&apos; syndrome

Occlusion of the rostral portion of the basilar artery can result in ischaemia of the midbrain and thalami, as well as of the temporal and occipital lobes. The so called “top of the basilar” syndrome manifests clinically as numerous combinations of abnormalities of alertness, sleep-wake cycle, and behaviour and oculomotor or pupillomotor functions. A 67 year old man presented with bilateral internuclear ophthalmoplegia, rubral tremor, and daytime somnolence. He was awake during the night and mostly agitated and aggressive. An ischaemic lesion was visible on the magnetic resonance (MR) image in the central portion of the midbrain just ventral to the aqueduct, clearly affecting the paramedian structures bilaterally. MR angiographic images demonstrated a hypoplastic basilar artery ending in both superior cerebellar arteries. Both posterior cerebral arteries were seen to arise from the corresponding internal carotid arteries via the posterior communicating branches. This unique case of an acute bilateral paramedian infarct represents a highly uncommon variant of the “top of the basilar” syndrome and was due to the affected ischaemic territory - that is, the “distal field” of the variant basilar artery

Terapia fotodinâmica com ftalocianina de zinco tópica: avaliação da intensidade de fluorescência, absorção cutânea, alterações histológicas e imuno-histoquímicas na pele do modelo animal Topical photodynamic therapy with zinc phthalocyanine: evaluation of fluorescence intensity, skin absorption, skin histological and immunohistochemical changes in animal model

FUNDAMENTOS - Ftalocianinas são promissores agentes fotossensibilizadores na terapia fotodinâmica (TFD). OBJETIVOS - Avaliar intervalos, veículos e a incorporação de promotor de absorção na formulação tópica da ftalocianina de zinco (FC-Zn). Avaliar alterações macro e micromorfológicas e a expressão de Fas promovidas pela TFD com FC-Zn tópica no modelo murino. MÉTODOS - Por meio da espectrometria de fluorescência, foram avaliadas combinações de diferentes períodos de oclusão tópica das formulações gel ou emulsão de FC-Zn (1mg/dl), com ou sem monoleína 5%, no dorso do camundongo hairless. Após oito horas das diferentes formulações, os camundongos foram expostos ao laser de diodo de 670nm, dose de 50J/cm-². RESULTADOS - A fluorescência foi discretamente superior após oito horas e com a emulsão nos intervalos de uma, duas e quatro horas de oclusão. A intensidade do edema e da erosão correspondeu à necrose da epiderme e à imunoexpressão de Fas nos cortes histológicos de pele. CONCLUSÕES - Os achados indicam a ação fotodinâmica promovida pela interação entre FC-Zn e fonte de luz de 670nm. As alterações macro e micromorfológicas foram correspondentes e mais substanciais com a emulsão FC-Zn e monoleína, sugerindo a acentuação dos efeitos com essa formulação. A imunoexpressão de Fas e as alterações histológicas sugeriram a apoptose como mecanismo de morte celular na TFD com FC-Zn tópica.<br>BACKGROUND - Phthalocyanines are promising photosensitizers used in photodynamic therapy (PDT). OBJECTIVES - To evaluate the following parameters: intervals, vehicles and enhancer using topical zinc-phthalocyanine (Zn-PC) formulation. To examine macro and micromorphological changes and Fas expression induced by topical Zn-PC-PDT on murine skin. MATERIAL AND METHODS - Using fluorescence spectrometry, different intervals of topical occlusion employing Zn-PC gel or emulsion, with or without monolein 5% were studied. After an 8-hour occlusion of different formulations, the mice were exposed to 670 nm laser, at a 50 J.cm-² dose. RESULTS - Fluorescence was slightly higher after 8 hours, and also with emulsion formulation at one-, two- and four-hour occlusion periods. The intensity of edema and erosion were correlated to epidermal necrosis and to Fas immunoexpression in skin histological specimens. CONCLUSIONS - The results show the effects of photodynamic action promoted by the interaction between Zn-PC formulation and a 670-nm light source. Macro and micromorphological alterations were correlated and more substantial with monolein and Zn-PC emulsion, suggesting more marked effects with this formulation. The Fas immunoexpression and histological changes suggested that apoptosis plays a role in the mechanism of cell death caused by PDT based in Zn-PC