Lipopolysaccharide endotoxemia induces amyloid-ß and p-tau formation in the rat brain.

Amyloid beta (Aß) plaques are not specific to Alzheimer's disease and occur with aging and neurodegenerative disorders. Soluble brain Aß may be neuroprotective and increases in response to neuroinflammation. Sepsis is associated with neurocognitive compromise. The objective was to determine, in a rat endotoxemia model of sepsis, whether neuroinflammation and soluble Aß production are associated with Aß plaque and hyperphosphorylated tau deposition in the brain. Male Sprague Dawley rats received a single intraperitoneal injection of 10 mg/kg of lipopolysaccharide endotoxin (LPS). Brain and blood levels of IL-1ß, IL-6, and TNFα and cortical microglial density were measured in LPS-injected and control animals. Soluble brain Aß and p-tau were compared and Aß plaques were quantified and characterized. Brain uptake of [18F]flutemetamol was measured by phosphor imaging. LPS endotoxemia resulted in elevations of cytokines in blood and brain. Microglial density was increased in LPS-treated rats relative to controls. LPS resulted in increased soluble Aß and in p-tau levels in whole brain. Progressive increases in morphologically-diffuse Aß plaques occurred throughout the interval of observation (to 7-9 days post LPS). LPS endotoxemia resulted in increased [18F]flutemetamol in the cortex and increased cortex: white matter ratios of activity. In conclusion, LPS endotoxemia causes neuroinflammation, increased soluble Aß and Aß diffuse plaques in the brain. Aß PET tracers may inform this neuropathology. Increased p-tau in the brain of LPS treated animals suggests that downstream consequences of Aß plaque formation may occur. Further mechanistic and neurocognitive studies to understand the causes and consequences of LPS-induced neuropathology are warranted.

18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury.

INTRODUCTION: Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18F-fluoro-2-deoxyglucose (18F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14C-2DG uptake in activated neutrophils. METHODS: Lung uptake of 18F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24h following the intraperitoneal injection of 10mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. RESULTS: Significant uptake of 18F-FDG occurred by 2h following LPS, and progressively increased to 24h. Lung uptake of 18F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. CONCLUSION: Systemic endotoxin-induced ALI results in very early and progressive uptake of 18F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: 18F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14C-2DG uptake in activated neutrophils. 18F-FDG PET may provide a potential mechanism for early diagnosis and therapeutic assessment of ALI/ARDS.

MR imaging of hypervascular lesions in the cirrhotic liver: a diagnostic dilemma.

Cirrhosis is characterized by a spectrum of hepatocellular nodules that mark the progression from regenerative nodules to low- and high-grade dysplastic nodules, followed by small and large hepatocellular carcinomas (HCCs). Characterization of small nodules on the basis of imaging and histopathologic findings is complicated by an overlap in findings associated with each type of nodule, a reflection of their multistep transitions. Vascularity patterns change gradually as the nodules evolve, with an increasing shift from predominantly venous to predominantly arterial perfusion. Regenerative and low-grade dysplastic nodules demonstrate predominantly portal perfusion and contrast enhancement similar to that of surrounding parenchyma. Differentiation of high-grade dysplastic nodules and well-differentiated HCCs on the basis of dynamic imaging and histologic findings is challenging, with a high rate of false-negative results. Some small nodules that lack hypervascularity may be early HCCs. Progressed small and large HCCs usually present no diagnostic difficulty because of their characteristic findings. Although characterization of hypervascular lesions in the cirrhotic liver is difficult, it is a key step in disease management and is the radiologist's responsibility.

Thoracic paracoccidioidomycosis: radiographic and CT findings.

Paracoccidioidomycosis (PCM) is the most common systemic mycosis in Latin America. Although most cases occur in developing countries, recent immigration patterns and an increase in travel have led to a growing number of PCM cases in the United States and Europe. PCM is caused by the dimorphic fungus Paracoccidioides brasiliensis, and the chronic form may progress to severe pulmonary involvement. Several radiologic patterns have been described for pulmonary PCM, including linear and reticular opacities, variable-sized nodules, patchy ill-defined opacities, airspace consolidation, and cavitary lesions. Fibrosis and paracicatricial emphysema are common associated findings. Chest computed tomography (CT) is the method of choice for evaluating pulmonary PCM, with the most common CT findings being ground-glass attenuation, consolidation, small or large nodules, masses, cavitations, interlobular septal thickening, emphysema, and fibrotic lesions. PCM is also an important cause of the "reversed halo" sign at high-resolution CT and should be considered in the differential diagnosis. Awareness of the multiple radiologic manifestations of PCM as well as its epidemiologic and clinical characteristics may permit early diagnosis and initiation of specific treatment, thereby reducing associated morbidity and mortality.

Effect of continuous positive airway pressure on fluid absorption among patients with pleural effusion due to tuberculosis.

BACKGROUND: Tuberculosis (TB) remains as an important public health problem worldwide. The most common type is pulmonary TB, and the most prevalent form of extra-pulmonary disease among HIV-negative patients is pleural disease. OBJECTIVE: The objective of the present study was to determine the effect of continuous positive airway pressure (CPAP) on fluid absorption among patients with pleural effusion due to TB. METHODS: Twenty patients were randomized into two groups. The interventional group (n=10) received CPAP three times a week during the initial four weeks of anti-TB treatment, and the control group (n=10) received anti-TB drugs only. The primary endpoint was the volume of pleural fluid after four weeks of treatment. Both groups were submitted to thoracic computed tomography using three-dimensional image reconstruction. The Mann-Whitney test for independent samples and the Wilcoxon paired samples test were used for statistical analysis. The normal distribution samples were analyzed using the unpaired t test. RESULTS: The reduction of pleural effusion volume was significantly greater in the intervention group (83.5%+/-SD 3.6) than in the control group (36.9%+/-SD 2.9; p<0.001), and the final dyspnea index was lower in the Intervention group than in the control group (p=0.002). CONCLUSION: Our findings indicate that CPAP during the first month of TB treatment accelerates the absorption of pleural effusion, however, additional studies are needed to confirm these findings and evaluate the impact of CPAP on pleural sequelae after the end of anti-TB treatment. Article registered in the Clinical Trials under the number NCT00560521.

Effect of continuous positive airway pressure on fluid absorption among patients with pleural effusion due to tuberculosis / Efeito da pressão positiva nas vias aéreas sobre a absorção do derrame pleural em pacientes devido à tuberculose

BACKGROUND: Tuberculosis (TB) remains as an important public health problem worldwide. The most common type is pulmonary TB, and the most prevalent form of extra-pulmonary disease among HIV-negative patients is pleural disease. OBJECTIVE: The objective of the present study was to determine the effect of continuous positive airway pressure (CPAP) on fluid absorption among patients with pleural effusion due to TB. METHODS: Twenty patients were randomized into two groups. The interventional group (n=10) received CPAP three times a week during the initial four weeks of anti-TB treatment, and the control group (n=10) received anti-TB drugs only. The primary endpoint was the volume of pleural fluid after four weeks of treatment. Both groups were submitted to thoracic computed tomography using three-dimensional image reconstruction. The Mann-Whitney test for independent samples and the Wilcoxon paired samples test were used for statistical analysis. The normal distribution samples were analyzed using the unpaired t test. RESULTS: The reduction of pleural effusion volume was significantly greater in the intervention group (83.5 percent±SD 3.6) than in the control group (36.9 percent±SD 2.9; p<0.001), and the final dyspnea index was lower in the Intervention group than in the control group (p=0.002). CONCLUSION: Our findings indicate that CPAP during the first month of TB treatment accelerates the absorption of pleural effusion, however, additional studies are needed to confirm these findings and evaluate the impact of CPAP on pleural sequelae after the end of anti-TB treatment.

CONTEXTUALIZAÇÃO: A tuberculose (TB) permanece como um importante problema de saúde pública no mundo. A forma mais comum de apresentação é a pulmonar e, em pacientes soronegativos, a forma de doença extrapulmonar mais prevalente é a pleural. OBJETIVO: O objetivo deste estudo foi determinar o efeito da pressão positiva contínua em vias aéreas (CPAP) na absorção do derrame pleural em pacientes com tuberculose. MÉTODOS: Vinte pacientes foram randomizados em dois grupos. O grupo intervenção (n=10) recebeu CPAP três vezes por semana durante as quatro primeiras semanas do tratamento anti-TB, e o grupo controle (n=10) recebeu somente droga anti-TB. O ponto final de avaliação foi o volume de líquido pleural após quatro semanas de tratamento. Ambos os grupos foram submetidos à tomografia computadorizada, usando a reconstrução tridimensional (3D) da imagem. A análise estatística foi realizada por meio do teste de Mann-Whitney para amostras independentes e Wilcoxon para amostras pareadas, e as que apresentaram distribuição normal foram analisadas por meio do teste t de Student não pareado. RESULTADOS: A redução do volume de derrame pleural foi significativamente maior no grupo intervenção (83,5 por cento±DP 3,6) que no grupo controle (36,9 por cento±DP 2,9) (p<0,001), e o índice de dispnéia final foi menor no grupo CPAP que no grupo controle (p=0,002). CONCLUSÃO: Tais achados indicam que a CPAP, durante o primeiro mês de tratamento anti-TB, acelera a absorção do derrame pleural, no entanto estudos adicionais são necessários para confirmar estes achados e avaliar o impacto da CPAP na sequela pleural após o término do tratamento anti-TB.

Comparison of whole-body PET/CT, dedicated high-resolution head and neck PET/CT, and contrast-enhanced CT in preoperative staging of clinically M0 squamous cell carcinoma of the head and neck.

UNLABELLED: The purpose of this study was to compare optimized whole-body (WB) and dedicated high-resolution contrast-enhanced PET/CT protocols and contrast enhanced CT in the preoperative staging of primary squamous cell carcinoma of the head and neck. METHODS: A total of 44 patients with clinically M0 squamous cell carcinoma of the head and neck underwent primary tumor resection and neck dissection within 6 wk of diagnostic imaging. Imaging consisted of a standard WB PET/CT protocol without intravenous contrast enhancement, followed by a high-resolution dedicated head and neck (HN) PET/CT protocol, which included diagnostic-quality contrast-enhanced CT (CECT). Imaging results were compared with histopathology. A 5-point scale was used to designate primary tumor localization and the presence of lymph node metastasis on a per-patient and per-level basis. For cervical nodes, receiver-operating-characteristic curves were generated to determine the differences in performance between the WB and HN PET/CT protocols and CECT. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for primary tumor and cervical nodes. RESULTS: No statistical difference was observed between WB and HN PET/CT protocols, both of which significantly outperformed CECT, in the evaluation of the primary tumor. The performance of the HN PET/CT protocol was superior to that of the WB PET/CT in the detection of cervical node metastases, achieving statistical significance on a per-level basis and approaching significance on a per-patient basis, with the greatest advantage in the detection of small positive lymph nodes (<15 mm). No significant difference was observed between the WB PET/CT protocol and CECT in nodal staging, either on a per-patient or on a per-level basis. CONCLUSION: The primary advantage of the dedicated HN PET/CT protocol over the WB protocol or CECT in the staging of head and neck cancer is in the detection of small lymph node metastases.