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After identification of an insulinoma, surgery is indicated for all localized tumors. The choice of procedure will depend on the features of the tumor mass, such as type, size, and localization. Atypical resection, including enucleation, partial pancreatectomy, or middle pancreatectomy, has the advantage of preserving the pancreatic parenchyma as much as possible, thereby reducing the risk of late exocrine/endocrine insufficiency[62]. To date, laparoscopic resection has often been performed for insulinomas that are benign, small, and/or located in the body or tail of the pancreas[63]. Radical resection should be considered for patients in whom the lesion is not single, not well-capsulated, > 4 cm in diameter, and involves or is near the main pancreatic duct. Lymphadenectomy is not usually performed. Although the cure rate after resection for insulinoma is very high, it is necessary to be aware of the potential for postoperative complications after pancreatic surgery, especially postoperative pancreatic fistula[64-66].

However, there is a considerable risk of morbidity and mortality associated with the surgical management of insulinomas, which precludes surgery in high-risk patients. Alcohol ablation and RFA have been established as minimally invasive procedures in the treatment of primary liver tumors and hepatic metastases. Recently, successful EUS-guided alcohol ablation and CT-guided RFA of pancreatic insulinomas have been reported in humans[56,57]. These two patients were in poor general condition and were experiencing recurrent symptomatic episodes of hypoglycemia. Because it was considered that surgical management for benign insulinoma of the pancreas was impossible in both cases, ablation of the solitary mass was performed. Both patients were discharged without any complications and reported no further hypoglycemic episodes. Embolization of an insulinoma of the pancreas is another non-surgical alternative[55,67,68]. Because angiographically the insulinoma is demonstrated in the arterial phase as a hypervasculated mass, embolization could be performed using flow to direct particles exclusively into the tumor. Although it remains contentious as to whether these procedures are a viable treatment for patients with an insulinoma, they may be offered as an alternative for certain patients, such as those who refuse surgery, those who are of advanced age, those with a poor general condition, those who have already undergone multiple abdominal surgeries, or those with an increased risk of postoperative complications due to other reasons.

Whether the exposures were by inhalation or instillation was a significant predictor of cellular composition and protein concentration in the BAL fluid (p < 0.01 (% of neutrophils), p < 0.001 (% of macrophages), p < 0.001 (protein concentration), nested ANOVA, respectively). The inhalation of CB was only associated with a marginally altered distribution between neutrophils and macrophages, whereas the i.t. instillation dose-dependently shifted the distribution towards increased representation of neutrophils in the BAL fluid. The concentration of protein was significantly elevated following inhalation and instillation at both doses. Inhalation of CB resulted in 108.1 and 118.5 μg protein/ml BAL fluid (high/low dose, respectively) compared to 91.2 μg/ml for the controls. This corresponds to a 1.2- and 1.3-fold induction, respectively. In comparison, the i.t. instillation of CB was associated with markedly larger concentration of protein in the BAL fluid of both the low and high dose of CB (1.4- and 1.7-fold, respectively). We did not detect any differences in LDH content of the BAL fluid when CB inhalations were compared to HEPA air inhalation or CB instillations were compared to control instillations (data not shown).

Increased levels of neutrophils and decreased levels of macrophages were detected at both time points following exposure for CB and SWCNT. However, the altered cell composition was only significant following 24 h. Au and C60 instillations did not result in statistically different cell composition at any time point. The comet assay was used for determining DNA damage in BAL cells. BAL cells obtained 3 h after CB and SWCNT instillation, but not following Au and C60 instillation, had elevated level of DNA damage measured as % DNA in the tail. When we analysed the data by tail length, all four particles induced significant DNA damage (p < 0.001). SWCNT and CB exposure significantly increased the amount of protein in BAL fluid at both 3 h (1.7 and 1.4-fold, respectively) and 24 h (2.6 and 1.6-fold, respectively). Unexpectedly, the exposure for C60 caused a significant decrease in measured protein in BAL fluid. Since this was visible at both time points, it may be a genuine effect on the lung by C60 or it may be caused by C60 assay interference. Au exposure did not alter level of protein in BAL fluid. We did not detect any differences in LDH content of the BAL fluid (data not shown).

We here present results that show that particle instillation induced a faster and stronger lung inflammatory response in hyperlipidemic ApoE-/- mice compared to wild-type mice. Instillation produced stronger effects than inhalation. SWCNT, CB, C60 and gold nanoparticles showed inflammatory effects corresponding to their surface areas after instillation, whereas QDs were highly toxic, possibly due to cadmium leakage.

The mice were anesthetized using Hypnorm® (fentanyl citrate 0.315 mg/ml and fluanisone 10 mg/ml from Janssen Pharma) and Dormicum® (Midazolam 5 mg/mL from Roche). Both were mixed with equal vol. sterile water. A volume of 0.2 ml was injected subcutaneously in the neck of each mouse. The sedated mice were kept on 37°C heating plates. During instillation the mice were placed on their backs on a 40 degree slope. A diode light was placed touching the larynx. The tongue was pressed towards the lower jaw by a small spatula. The trachea was intubated using a 24 gauge BD Insyte catheter (Ref: 381212, Becton Dickinson, Denmark) with a shortened needle. The correct location of each intubation was tested by a small but highly sensitive pressure transducer developed by our laboratory in collaboration with John Frederiksen (FFE/P, Copenhagen, Denmark). The particle suspensions were rigorously mixed by pipetting immediately before instillation. A 50 μl suspension was instilled followed by 150 μl air with a 250 μl SGE glass syringe (250F-LT-GT, MicroLab, Aarhus, Denmark). The intubation catheter was removed and the mouse transferred to a vertical hanging position with the head up. This ensures that the delivered material is maintained in the lung and does not block the airways. After 5 to 10 min the mice were transferred to the 37°C heating plate until they recovered from anaesthesia. The deposition and distribution of instilled material was verified installing Evans blue, radioactive gold (18 nm) and QDs (data not shown).

The Klondike Kings quickly became very rich. It is estimated that over one billion dollars worth of gold was found, adjusted to late 20th century standards. Others found their fame and fortune in different manners. Jack London became well-known by writing of his experiences in the Klondike. Nor were the successful Klondikers limited to men. Belinda Mulroney became wealthy by running a hotel and selling supplies. Many women found their riches running dance halls. Martha Black bought a sawmill and went on to become Canada's second female Member of Parliament. Even some those who didn't travel to the Klondike managed to get rich from the Gold Rush. Over 1,000 miles away, Seattle businesses made over $1 million (not adjusted) selling the needed food and supplies for the trip to the gold fields. Seattle mayor W.D. Wood should have stayed in Seattle and taken advantage of the wealth the Klondikers brought to the city. Instead, he resigned his post as mayor and set off for the Yukon. He was one of the many who turned back.

It was a historic moment, meant to commemorate the golden anniversary of Oregon Pinot Noir. To taste such a comprehensive vertical of these rare wines was a huge treat for the 150-odd wine writers, retailers, wine-club members and friends of the winery who were present at the Portland Art Museum Fields ballroom, where the tasting was held on February 22. 2b1af7f3a8