Small cell undifferentiated carcinoma of the pancreas

Small cell undifferentiated carcinoma of the pancreas is a rare neoplasm: Only 12 cases have previously been documented. This paper describes the clinical evolution, immunohistochemical profile, and ultrastructural features of a case occurring in a 37-year-old woman.     

Decellularised Human Umbilical Artery as a Vascular Graft Elicits Minimal Pro-Inflammatory Host Response Ex Vivo and In Vivo

Small diameter (<6 mm) vessel grafts still pose a challenge for scientists worldwide. Decellularised umbilical artery (dUA) remains promising as small diameter tissue engineered vascular graft (TEVG), yet their immunogenicity remains unknown. Herein, we evaluated the host immune responses, with a focus on the innate part, towards human dUA implantation in mice, and confirmed our findings in an ex vivo allogeneic human setup. Overall, we did not observe any differences in the number of circulating white blood cells nor the number of monocytes among three groups of mice (1) dUA patch; (2) Sham; and (3) Mock throughout the study (day −7 to 28). Likewise, we found no difference in systemic inflammatory and anti-inflammatory cytokine levels between groups. However, a massive local remodelling response with M2 macrophages were observed in the dUA at day 28, whereas M1 macrophages were less frequent. Moreover, human monocytes from allogeneic individuals were differentiated into macrophages and exposed to lyophilised dUA to maximize an eventual M1 response. Yet, dUA did not elicit any immediate M1 response as determined by the absence of CCR7 and CXCL10. Together this suggests that human dUA elicits a minimal pro-inflammatory response further supporting its use as a TEVG in an allogeneic setup.     

Ultraviolet radiometry with synchrotron radiation and cryogenic radiometry

The combination of a cryogenic radiometer and synchrotron radiation enables detector scale realization in spectral regions that are otherwise difficult to access. Cryogenic radiometry is the most accurate primary detector-based standard available to date, and synchrotron radiation gives a unique broadband and continuous spectrum that extends from x ray to far IR. We describe a new cryogenic radiometer-based UV radiometry facility at the Synchrotron Ultraviolet Radiation Facility II at the National Institute of Standards and Technology. The facility is designed to perform a variety of detector and optical materials characterizations. The facility combines a high-throughput, normal incidence monochromator with an absolute cryogenic radiometer optimized for UV measurements to provide absolute radiometric measurements in the spectral range from 125 nm to approximately 320 nm. We discuss results on photodetector characterizations, including absolute spectroradiometric calibration, spatial responsivity mapping, spectroreflectance, and internal quantum efficiency. In addition, such characterizations are used to study UV radiation damage in photodetectors that can shed light on the mechanism of the damage process. Examples are also given for UV optical materials characterization.     

Maximum-tolerated dose, toxicity, and efficacy of (131)I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma

PURPOSE: Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced remissions in patients with non-Hodgkin's lymphoma (NHL) when labeled with iodine 131 ((131)I). Based on the strategy of fractionating the total dose, this study was designed to define the maximum-tolerated dose (MTD) and efficacy of the first two, of a maximum of four, doses of (131)I-Lym-1 given 4 weeks apart. Additionally, toxicity and radiation dosimetry were assessed. MATERIALS AND METHODS: Twenty patients with advanced NHL entered the study a total of 21 times. Thirteen (62%) of the 21 entries had diffuse large-cell histologies. All patients had disease resistant to standard therapy and had received a mean of four chemotherapy regimens. (131)I-Lym-1 was given after Lym-1 and (131)I was escalated in cohorts of patients from 40 to 100 mCi (1.5 to 3.7 GBq)/m2 body surface area. RESULTS: Mean radiation dose to the bone marrow from body and blood (131)I was 0.34 (range, 0. 1 6 to 0.63) rad/mCi (0.09 mGy/MBq; range, 0.04 to 0.17 mGy/ MBq). Dose-limiting toxicity was grade 3 to 4 thrombocytopenia with an MTD of 100 mCi/m2 (3.7 GBq/m2) for each of the first two doses of (131)I-Lym-1 given 4 weeks apart. Nonhematologic toxicities did not exceed grade 2 except for one instance of grade 3 hypotension. Ten (71 %) of 14 entries who received at least two doses of (131)I-Lym-1 therapy and 11 (52%) of 21 total entries responded. Seven of the responses were complete, with a mean duration of 14 months. All three entries in the 100 mCi/m2 (3.7 MBq/m2) cohort had complete remissions (CRs). All responders had at least a partial remission (PR) after the first therapy dose of (131)I-Lym-1. CONCLUSION: (131)I-Lym-1 induced durable remissions in patients with NHL resistant to chemotherapy and was associated with acceptable toxicity. The nonmyeloablative MTD for each of the first two doses of (131)I-Lym-1 was 100 mCi/m2 (total, 200 mCi/m2) (3.7 GBq/m2; total, 7.4 GBq/m2).     

Evaluation of atypical cytochrome P450 kinetics with two-substrate models: evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites

Some cytochrome P450 catalyzed reactions show atypical kinetics, and these kinetic processes can be grouped into five categories: activation, autoactivation, partial inhibition, substrate inhibition, and biphasic saturation curves. A two-site model in which the enzyme can bind two substrate molecules simultaneously is presented which can be used to describe all of these observed kinetic properties. Sigmoidal kinetic characteristics were observed for carbamazepine metabolism by CYP3A4 and naphthalene metabolism by CYPs 2B6, 2C8, 2C9, and 3A5 as well as dapsone metabolism by CYP2C9. Naphthalene metabolism by CYP3A4 and naproxen metabolism by CYP2C9 demonstrated nonhyperbolic enzyme kinetics suggestive of a low Km, low Vmax component for the first substrate molecule and a high Km, high Vmax component for the second substrate molecule. 7, 8-Benzoflavone activation of phenanthrene metabolism by CYP3A4 and dapsone activation of flurbiprofen and naproxen metabolism by CYP2C9 were also observed. Furthermore, partial inhibition of 7, 8-benzoflavone metabolism by phenanthrene was observed. These results demonstrate that various P450 isoforms may exhibit atypical enzyme kinetics depending on the substrate(s) employed and that these results may be explained by a model which includes simultaneous binding of two substrate molecules in the active site.     

Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma

PURPOSE: To evaluate the toxicities, radiographic and pathologic responses, and event-free outcomes with combined modality treatment that involves preoperative rapid-fractionation chemoradiation, pancreaticoduodenectomy, and electron-beam intraoperative radiation therapy (EB-IORT) for patients with resectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with radiographically resectable localized adenocarcinoma of the pancreatic head were entered onto a preoperative protocol that consisted of a 2-week course of fluorouracil (5-FU) 300 mg/m2 daily 5 days per week and concomitant rapid-fractionation radiation 30 Gy, 3 Gy daily 5 days per week. Radiographic restaging was performed 4 weeks after chemoradiation, and patients with localized disease underwent pancreaticoduodenectomy with EB-IORT 10 to 15 Gy. RESULTS: Thirty-five patients were entered onto the study and completed chemoradiation, 34 (97%) as outpatients. Three patients (9%) experienced grade 3 nausea and vomiting; no other grade 3 or 4 toxicities were observed. Of the 27 patients taken to surgery, 20 patients (74%) underwent pancreaticoduodenectomy with EB-IORT. All patients had a less than grade III pathologic response to preoperative chemoradiation. At a median follow-up of 37 months, the 3-year survival rate in patients who underwent combined modality therapy was 23%. CONCLUSION: Combined modality treatment with preoperative rapid-fractionation chemoradiation, pancreaticoduodenectomy, and EB-IORT is associated with minimal toxicity and excellent locoregional control. This represents one approach to maximize the proportion of patients who receive all components of combined modality therapy and avoids the toxicity of pancreaticoduodenectomy in patients found to have metastatic disease at the time of restaging.     

Canine neosporosis: clinical signs, diagnosis, treatment and isolation of Neospora caninum in mice and cell culture

Clinical signs, diagnosis, treatment and isolation of Neospora caninum from two littermate dogs are described. Three of six pups from a Labrador bitch developed paralysis. Neosporosis was diagnosed ante mortem by serological examination in two of the affected pups. At necropsy, tissue cysts were seen in unstained smears and in histologic sections of their brains. Tissue cysts were often thin-walled (approximately 1 micron) but antigenically and ultrastructurally identified as N. caninum. Furthermore, N. caninum (isolates NC-4, NC-5) was isolated in mice and in cell cultures inoculated with neural tissues of these two dogs. Serological diagnosis of neosporosis using a variety of tests is discussed.