Natural killer (NK) and lymphokine-activated killer (LAK) cell functions from healthy dogs and 29 dogs with a variety of spontaneous neoplasms

To investigate natural killer (NK) and lymphokine-activated killer (LAK) cell functions from 10 healthy dogs and 29 dogs with a variety of spontaneous neoplasms, large granular lymphocytes (LGLs) from blood samples were separated by a 58.5% Percoll density gradient. LGLs were stimulated with a low dose of recombinant human interleukin 2 (rhIL-2) for 7days. Cytotoxicity of effector cells against the susceptible CTAC cell line was measured before and after stimulation. Compared with those before stimulation, the percentage of LGLs after stimulation with rhIL-2 was found to be significantly increased (P<0.01) in both dogs with tumors and controls. However, the increase was significantly higher in control animals, indicating a defect in proliferation ability of NK cells in canine tumor patients. After stimulation with rhIL-2, lymphokine-activated killer (LAK) cell activity in dogs with tumors was significantly lower (P<0.01) when compared with controls. Reduced cytotoxicity of rhIL-2-activated NK cells in dogs with tumors seems to be attributable to the presence of a diminished proliferative capacity of NK cells and a decreased ability of LAK cells to lyse target cells. Further knowledge of the precise function of IL-2-activated NK cells in dogs with tumors may help to optimize new and therapeutically beneficial treatment strategies in canine and human cancer patients. Our findings suggest that the dog could also serve as a relevant large animal model for cancer immunotherapy with IL-

Contrail cirrus supporting areas in model and observations

Contrails form and persist dependent on the surrounding moisture, temperature and pressure fields and on fuel and aircraft specific variables. After formation, contrail persistence requires only supersaturation relative to ice. The fractional area in which contrails can form is called potential contrail coverage. We introduce a potential contrail cirrus coverage equivalent to the cloud free supersaturated area. This field, simulated by the ECHAM4 climate model, agrees fairly well with estimates of supersaturation frequency as inferred from aircraft and satellite measurements. In areas where the two potential coverages are different, especially at lower flight levels, potential contrail coverage is not a valid estimate of maximum attainable contrail cirrus coverage. We parameterize both potential coverages consistently with the ECHAM4 cloud cover parameterization. A comparison of the potential contrail coverage with an earlier estimate reveals substantial differences especially at upper height levels in the tropics

Evaluation of Arctic land snow cover characteristics, surface albedo and temperature during the transition seasons from regional climate model simulations and satellite data

This paper evaluates the simulated Arctic land snow cover duration, snow water equivalent, snow cover fraction, surface albedo and land surface temperature in the regional climate model HIRHAM5 during 2008-2010, compared with various satellite and reanalysis data and one further regional climate model (COSMO-CLM). HIRHAM5 shows a general agreement in the spatial patterns and annual course of these variables, although distinct biases for specific regions and months are obvious. The most prominent biases occur for east Siberian deciduous forest albedo, which is overestimated in the simulation for snow covered conditions in spring. This may be caused by the simplified albedo parameterization (e.g. non-consideration of different forest types and neglecting the effect of fallen leaves and branches on snow for deciduous tree forest). The land surface temperature biases mirror the albedo biases in their spatial and temporal structures. The snow cover fraction and albedo biases can explain the simulated land surface temperature bias of ca. -3 °C over the Siberian forest area in spring

Tumour assessment in advanced melanoma: value of FDG-PET/CT in patients with elevated serum S-100B

Purpose: To evaluate the usefulness of PET/CT in melanoma patients with an elevated serum S-100B tumour marker level. Methods: Out of 165 consecutive high-risk melanoma patients referred for PET/CT imaging, 47 had elevated (>0.2μg/l) S-100B serum levels and a contemporaneous 18F-FDG PET/CT scan. PET/CT scans were evaluated for the presence of metastases. To produce a composite reference standard, we used cytological, histological, MRI and PET/CT follow-up findings as well as clinical and S-100B follow-up. Results: Among the 47 patients with increased S-100B levels, PET/CT correctly identified metastases in 38 (30 distant metastases and eight lymph node metastases). In one patient with cervical lymph node metastases, PET/CT was negative. Eight patients had no metastases and PET/CT correctly excluded metastases in all of them. Overall sensitivity for metastases was 97% (38/39), specificity 100% (8/8) and accuracy 98% (46/47). S-100B was significantly higher in patients with distant metastases (mean 1.93μg/l, range 0.3-14.3μg/l) than in patients with lymph node metastases (mean 0.49μg/l, range 0.3-1.6μg/l, p = 0.003) or patients without metastases (mean 0.625μg/l, range 0.3-2.6μg/l, p = 0.007). However, 6 of 14 patients with a tumour marker level of 0.3μg/l had no metastases. Conclusion: In melanoma patients with elevated S-100B tumour marker levels, FDG-PET/CT accurately identifies lymph node or distant metastases and reliably excludes metastases. Because of the significant number of false positive S-100B tumour marker determinations (17%), we recommend repetition of tumour marker measurements if elevated S-100B levels occur before extensive imaging is use

ICON in Climate Limited-area Mode (ICON release version 2.6.1): a new regional climate model

For the first time, the Limited-Area Mode of the new ICON (Icosahedral Nonhydrostatic) weather and climate model has been used for a continuous long-term regional climate simulation over Europe. Built upon the Limited-Area Mode of ICON (ICON-LAM), ICON-CLM (ICON in Climate Limited-area Mode, hereafter ICON-CLM, available in ICON release version 2.6.1) is an adaptation for climate applications. A first version of ICON-CLM is now available and has already been integrated into a starter package (ICON-CLM_SP_betal). The starter package provides users with a technical infrastructure that facilitates long-term simulations as well as model evaluation and test routines. ICON-CLM and ICON-CLM_SP were successfully installed and tested on two different computing systems. Tests with different domain decompositions showed bit-identical results, and no systematic outstanding differences were found in the results with different model time steps. ICON-CLM was also able to reproduce the large-scale atmospheric information from the global driving model. Comparison was done between ICON-CLM and the COnsortium for Small-scale MOdeling (COSMO)-CLM (the recommended model configuration by the CLM-Community) performance. For that, an evaluation run of ICON-CLM with ERA-Interim boundary conditions was carried out with the setup similar to the COSMO-CLM recommended optimal setup. ICON-CLM results showed biases in the same range as those of COSMO-CLM for all evaluated surface variables. While this COSMO-CLM simulation was carried out with the latest model version which has been developed and was carefully tuned for climate simulations on the European domain, ICON-CLM was not tuned yet. Nevertheless, ICON-CLM showed a better performance for air temperature and its daily extremes, and slightly better performance for total cloud cover. For precipitation and mean sea level pressure, COSMO-CLM was closer to observations than ICON-CLM. However, as ICON-CLM is still in the early stage of development, there is still much room for improvement

Combined PET/CT-perfusion in patients with head and neck cancers

Objectives: Computed tomography perfusion (CTP) can provide information about angiogenesis and blood-flow characteristics in tumours. [18F]Fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) is one of the major oncological imaging techniques which provides information about viability of the tumour cell and partly also about its aggressiveness. The aim of the study was to investigate the relationship between FDG and CTP data in patients with head and neck cancers. Materials and methods: Forty-one patients with a clinically suspected head and neck cancer were prospectively included. All patients underwent a combined PET/CT with an integrated CTP examination in the area of the head and neck tumour. CTP data (BF, BV and MTT) and PET data (SUVmax, SUVmean, TLG, PETvol) were compared between tumours and (1) healthy contralateral tissue, (2) inflammatory lesions, (3) metastatic lymph nodes, and CTP data and PET data were correlated in tumours. Results: Thirty-five patients had a head and neck cancer. All CTP data were statistically different between tumours, inflammatory lesions, healthy tissue and metastatic lymph nodes; PET/CT data were in part significantly different. CTP and PET parameters were not significantly correlated. Conclusion: CTP and PET parameters were not significantly correlated; thus, the additional CTP values provide additional insights into tumour behaviour and their glycolytic status. Key Points : • Computed tomography perfusion (CTP) can be performed in combined positron emission tomography (PET)/CT. • CTP in addition to PET provides additional insights into tumour behaviour. • CTP can possibly differentiate between head and neck tumours and inflammatory lesions. • PET/CT with integrated CTP is possible without additional contrast medi

Chemotherapy response assessment in stage IV melanoma patients—comparison of 18F-FDG-PET/CT, CT, brain MRI, and tumormarker S-100B

Purpose: This study aims to compare the use of 18F-FDG-PET/CT, CT, brain MRI, and tumormarker S-100B in chemotherapy response assessment of stage IV melanoma patients. Methods: In 25 patients with stage IV melanoma, FDG-PET/CT and S-100B after 2-3months (three cycles) of chemotherapy was compared with baseline PET/CT and baseline S-100B. Retrospectively, the response was correlated with the outcome. In patients with clinical suspicion for brain metastases, MRI or CCT was performed. Results: There was agreement between FDG-PET/CT and CT regarding response to chemotherapy in all patients. There was a clear trend to a longer OS of PET/CT responders (n = 10) compared with PET/CT non-responders (n = 15; p = 0.072) with remarkably better 1-year OS of 80% compared to 40% (p = 0.048). There was a significant longer PFS of PET/CT responders compared with PET/CT non-responders (p = 0.002). S-100B was normal at baseline in eight of 22 patients where it was available. Chemotherapy response assessment with S-100B failed to show correlation with OS or PFS. Eleven patients developed brain metastases during treatment, first detected by PET/CT in two and by MRI or CCT in nine of 11 patients. Appearance of brain metastases was associated with a poor survival. Conclusions: 18F-FDG-PET/CT and CT alone are equally suitable for chemotherapy response assessment in melanoma patients and clearly superior to S-100B. PET/CT responders have better early survival, but this is shortlived due to late therapy failure—often with brain recurrence. Additional brain MRI for therapy response assessment in such high-risk patients is mandatory to detect brain metastases missed by PET/C

Myeloid-related protein 8/14 complex describes microcirculatory alterations in patients with type 2 diabetes and nephropathy

<p>Abstract</p> <p>Background</p> <p>Inflammation contributes to cardiovascular complications in type 2 diabetes, which are often characterized by microvascular alterations. We investigated whether myeloid-related protein 8/14 complex (MRP8/14) secreted by transmigrating monocytes and granulocytes may represent a biomarker for microvascular alterations in patients with type 2 diabetes and nephropathy.</p> <p>Methods</p> <p>MRP8/14 was measured in 43 patients with type 2 diabetes and nephropathy. Additionally, the inflammatory markers Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were quantified. To detect microvascular alterations proteinuria and retinal vessel caliber were used as classical and novel marker, respectively. Proteinuria was quantified by protein-creatinine ratio (PCR); retinal vessel caliber was quantified after retina photography on digitalized retina pictures.</p> <p>Results</p> <p>MRP8/14 was positively associated with inflammation (<it>r </it>= 0.57), proteinuria (<it>r </it>= 0.40) and retinal arterial caliber (<it>r </it>= 0.48). Type 2 diabetic patients with MRP8/14 values above the median of 5.8 μg/ml demonstrated higher proteinuria and larger retinal artery caliber than patients with MRP8/14 values below the median (logPCR: -0.51 ± 0.52 versus -0.96 ± 0.46, <it>P </it>< 0.01; retinal artery lumen (μm): 178.3 ± 14.1 versus 162.7 ± 14.9 <it>P </it>< 0.01). Both groups did not differ with regard to metabolic factors and blood pressure. MRP8/14 was an independent predictor of retinal artery caliber in multivariate stepwise regression analysis (<it>β </it>= 0.607) and was positively associated with IL-6 (<it>r </it>= 0.57, <it>P </it>< 0.001) and TNF-α (<it>r </it>= 0.36, <it>P </it>< 0.05).</p> <p>Conclusion</p> <p>MRP8/14 – a marker for transendothelial migration – describes not only the state of inflammation in diabetic nephropathy, but additionally the degree of microvascular alterations in the glomerular and retinal bed. Therefore, MRP8/14 may be a potentially selective novel biomarker for microcirculatory defects in diabetic nephropathy.</p

Imaging Non-Specific Wrist Pain: Interobserver Agreement and Diagnostic Accuracy of SPECT/CT, MRI, CT, Bone Scan and Plain Radiographs

PURPOSE: Chronic hand and wrist pain is a common clinical issue for orthopaedic surgeons and rheumatologists. The purpose of this study was 1. To analyze the interobserver agreement of SPECT/CT, MRI, CT, bone scan and plain radiographs in patients with non-specific pain of the hand and wrist, and 2. to assess the diagnostic accuracy of these imaging methods in this selected patient population. MATERIALS AND METHODS: Thirty-two consecutive patients with non-specific pain of the hand or wrist were evaluated retrospectively. All patients had been imaged by plain radiographs, planar early-phase imaging (bone scan), late-phase imaging (SPECT/CT including bone scan and CT), and MRI. Two experienced and two inexperienced readers analyzed the images with a standardized read-out protocol. Reading criteria were lesion detection and localisation, type and etiology of the underlying pathology. Diagnostic accuracy and interobserver agreement were determined for all readers and imaging modalities. RESULTS: The most accurate modality for experienced readers was SPECT/CT (accuracy 77%), followed by MRI (56%). The best performing, though little accurate modality for inexperienced readers was also SPECT/CT (44%), followed by MRI and bone scan (38% each). The interobserver agreement of experienced readers was generally high in SPECT/CT concerning lesion detection (kappa 0.93, MRI 0.72), localisation (kappa 0.91, MRI 0.75) and etiology (kappa 0.85, MRI 0.74), while MRI yielded better results on typification of lesions (kappa 0.75, SPECT/CT 0.69). There was poor agreement between experienced and inexperienced readers in SPECT/CT and MRI. CONCLUSIONS: SPECT/CT proved to be the most helpful imaging modality in patients with non-specific wrist pain. The method was found reliable, providing high interobserver agreement, being outperformed by MRI only concerning the typification of lesions. We believe it is beneficial to integrate SPECT/CT into the diagnostic imaging algorithm of chronic wrist pain

Clinical impact of 18F-choline PET/CT in patients with recurrent prostate cancer

Purpose: To investigate the clinical value of 18F-fluorocholine PET/CT (CH-PET/CT) in treatment decisions in patients with recurrent prostate cancer (rPCA). Methods: The study was a retrospective evaluation of 156 patients with rPCA and CH-PET/CT for restaging. Questionnaires for each examination were sent to the referring physicians 14-64months after examination. Questions included information regarding initial extent of disease, curative first-line treatment, and the treatment plan before and after CH-PET/CT. Additionally, PSA values at diagnosis, after initial treatment, before CH-PET/CT and at the end of follow-up were also obtained from the questionnaires. Results: Mean follow-up was 42months. The mean Gleason score was 6.9 at initial diagnosis. Initial treatment was: radical prostatectomy in 110 patients, radiotherapy in 39, and combined prostatectomy and radiotherapy in 7. Median PSA values before CH-PET/CT and at the end of follow-up were 3.40ng/ml and 0.91ng/ml. PSA levels remained stable, decreased or were below measurable levels in 108 patients. PSA levels increased in 48 patients. In 75 of the 156 patients (48%) the treatment plan was changed due to the CH-PET/CT findings. In 33 patients the therapeutic plan was changed from palliative treatment to treatment with curative intent. In 15 patients treatment was changed from curative to palliative. In 8 patients treatment was changed from curative to another strategy and in 2 patients from one palliative strategy to another. In 17 patients the treatment plan was adapted. Conclusion: CH-PET/CT has an important impact on the therapeutic strategy in patients with rPCA and can help to determine an appropriate treatmen