Current Issue : January - March Volume : 2018 Issue Number : 1 Articles : 5 Articles
Positron emission tomography (PET) imaging of P-glycoprotein (P-gp) in the blood-brain\nbarrier can be important in neurological diseases where P-gp is affected, such as Alzheimer�´s disease.\nRadiotracers used in the imaging studies are present at very small, nanomolar, concentration,\nwhereas in vitro assays where these tracers are characterized, are usually performed at micromolar\nconcentration, causing often discrepant in vivo and in vitro data. We had in vivo rodent PET data of\n[11C]verapamil, (R)-N-[18F]fluoroethylverapamil, (R)-O-[18F]fluoroethyl-norverapamil, [18F]MC225\nand [18F]MC224 and we included also two new molecules [18F]MC198 and [18F]KE64 in this\nstudy. To improve the predictive value of in vitro assays, we labeled all the tracers with tritium\nand performed bidirectional substrate transport assay in MDCKII-MDR1 cells at three different\nconcentrations (0.01, 1 and 50 �¼M) and also inhibition assay with P-gp inhibitors. As a comparison,\nwe used non-radioactive molecules in transport assay in Caco-2 cells at a concentration of 10 �¼M and\nin calcein-AM inhibition assay in MDCKII-MDR1 cells. All the P-gp substrates were transported\ndose-dependently. At the highest concentration (50 �¼M), P-gp was saturated in a similar way as after\ntreatment with P-gp inhibitors. Best in vivo correlation was obtained with the bidirectional transport\nassay at a concentration of 0.01 �¼M. One micromolar concentration in a transport assay or calcein-AM\nassay alone is not sufficient for correct in vivo prediction of substrate P-gp PET ligands....
Primary aortoduodenal fistula (ADF) is a direct communication between the abdominal aorta and the gastrointestinal tractwithout\nany previous vascular intervention and represents a rare but critical cause of repeated and massive gastrointestinal bleeding. Primary\nADF often occurs as a result of atherosclerotic aneurysm and infection, but ADF involving a normal-size aorta is rare; furthermore,\nADF related to radiation therapy is extremely rare. We present the case of a 56-year-old man with a history of bowel obstruction\ndue to radiation enteritis who was admitted with severe hematemesis and hemorrhagic shock. Gastroduodenal endoscopy and\ncontrast-enhanced computed tomography findings were unremarkable. Aortoduodenal fistula was suspected based on the diffuse\ncalcification of the abdominal aorta confined to the radiation field and the presence of an aortoduodenal communication on\nangiography. Endovascular repair with a stent graft seemed to be a safer option than open surgery andwas suited to the rapid control\nof bleeding from ADF because of the patients� unstable hemodynamic state and the presence of intestinal adhesions. The fistula\nwas successfully sealed by endovascular stent graft placement. Hematemesis did not recur postoperatively and anemia gradually\nimproved.The patient died from pneumonia 33 days later....
Background: The risk factors for radiation pneumonitis (RP) in patients with chronic obstructive pulmonary disease\n(COPD) are unclear. Mean lung dose (MLD) and percentage of irradiated lung volume are common predictors of\nRP, but the most accurate dosimetric parameter has not been established. We hypothesized that the total lung\nvolume irradiated without emphysema would influence the onset of RP.\nMethods: We retrospectively evaluated 100 patients who received radiotherapy for lung cancer. RP was graded\naccording to the Common Terminology Criteria for Adverse Events (version 4.03). We quantified low attenuation\nvolume (LAV) using quantitative computed tomography analysis. The association between RP and traditional\ndosimetric parameters including MLD, volume of the lung receiving a dose of �2 Gy, � 5 Gy, � 10 Gy, � 20 Gy, and\n�30 Gy, and counterpart measurements of the lung without LAV, were analyzed by logistic regression. We\ncompared each dosimetric parameter for RP using multiple predictive performance measures including area under\nthe receiver operating characteristic curve (AUC) and integrated discrimination improvement (IDI).\nResults: Of 100 patients, RP of Grades 1, 2, 3, 4, and 5 was diagnosed in 24, 12, 13, 1, and 1 patients, respectively.\nCompared with traditional dosimetric parameters, counterpart measurements without LAV improved risk prediction\nof symptomatic RP. The ratio of the lung without LAV receiving �30 Gy to the total lung volume without LAV most\naccurately predicted symptomatic RP (AUC, 0.894; IDI, 0.064).\nConclusion: Irradiated lung volume without LAV predicted RP more accurately than traditional dosimetric parameters....
Purpose/objective: Local treatment options for patients with in-field non-small cell lung cancer (NSCLC) recurrence\nfollowing conventionally fractionated external beam radiation therapy (CF-EBRT) are limited. Stereotactic body radiation\ntherapy (SBRT) is a promising modality to achieve reasonable local control, although toxicity remains a concern.\nMaterials/methods: Patients previously treated with high-dose CF-EBRT (ââ?°Â¥59.4 Gy, ââ?°Â¤3 Gy/fraction) for non-metastatic\nNSCLC who underwent salvage SBRT for localized ultra-central in-field recurrence were included in this analysis. Ultracentral\nrecurrences were defined as those abutting the trachea, mainstem bronchus, or esophagus and included both\nparenchymal and nodal recurrences. The Kaplan-Meier method was used to estimate local control and overall survival.\nDurable local control was defined as ââ?°Â¥12 months. Toxicity was scored per the CTC-AE v4.0.\nResults: Twenty patients were treated with five-fraction robotic SBRT for ultra-central in-field recurrence following\nCF-EBRT. Fifty percent of recurrences were adenocarcinoma, while 35% of tumors were classified as squamous cell\ncarcinoma. The median interval between the end of CF-EBRT and SBRT was 23.3 months (range: 2.6 ââ?¬â?? 93.6 months).\nThe median CF-EBRT dose was 63 Gy (range: 59.4 ââ?¬â?? 75 Gy), the median SBRT dose was 35 Gy (range: 25 ââ?¬â?? 45 Gy), and\nthe median total equivalent dose in 2 Gy fractions (EQD2) was 116 Gy (range: 91.3 ââ?¬â?? 136.7 Gy). At a median follow-up\nof 12 months for all patients and 37.5 months in surviving patients, the majority of patients (90%) have died. High-dose\nSBRT was associated with improved local control (p < .01), and the one-year overall survival and local control were 77.\n8% and 66.7% respectively in this sub-group. No late esophageal toxicity was noted, although a patient who received\nan SBRT dose of 45 Gy (total EQD2: 129.7 Gy) experienced grade 5 hemoptysis 35 months following treatment.\nConclusions: Although the overall prognosis for patients with in-field ultra-central NSCLC recurrences following CFEBRT\nremains grim, five-fraction SBRT was well tolerated with an acceptable toxicity profile. Dose escalation above\n35 Gy may offer improved local control, however caution is warranted when treating high-risk recurrences with\naggressive regimens....
Theductus venosus serves as an important vascular pathway for intrauterine circulation. This case presents a description of an absent\nductus venosus in a female patient with Noonan syndrome, including both prenatal and postnatal imaging of the anomaly. In the\nsetting of the anomalous vascular connection, the umbilical vein courses inferiorly to the iliac vein in parallel configuration with\nthe umbilical artery. This finding was suspected based on prenatal imaging and the case was brought to attention when placement\nof an umbilical catheter was thought to be malpositioned given its appearance on radiography. Ultrasound imaging confirmed the\nanomalous course. This is in keeping with prior descriptions in the literature of an association between Noonan syndrome and\naberrant umbilical venous drainage. This case illustrates the need for awareness of this condition by the radiologist, allowing for\nidentification on radiographs and the recommendation for further confirmatory imaging. Further, the case illustrates the value\nof paying particular attention to the fetal course of the umbilical vessels in patients with suspected Noonan syndrome, as this\npopulation is particularly at risk for anomalous vasculature....
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