Depth and direction effects in the prediction of static and shifted reaching goals from kinematics.

The kinematic parameters of reach-to-grasp movements are modulated by action intentions. However, when an unexpected change in visual target goal during reaching execution occurs, it is still unknown whether the action intention changes with target goal modification and which is the temporal structure of the target goal prediction. We recorded the kinematics of the pointing finger and wrist during the execution of reaching movements in 23 naïve volunteers where the targets could be located at different directions and depths with respect to the body. During the movement execution, the targets could remain static for the entire duration of movement or shifted, with different timings, to another position. We performed temporal decoding of the final goals and of the intermediate trajectory from the past kinematics exploiting a recurrent neural network. We observed a progressive increase of the classification performance from the onset to the end of movement in both horizontal and sagittal dimensions, as well as in decoding shifted targets. The classification accuracy in decoding horizontal targets was higher than the classification accuracy of sagittal targets. These results are useful for establishing how human and artificial agents could take advantage from the observed kinematics to optimize their cooperation in three-dimensional space.

Rheumatic immune-related adverse events of checkpoint therapy for cancer: case series of a new nosological entity.

Immunotherapy of cancer with checkpoint inhibitors has been associated with a spectrum of autoimmune and systemic inflammatory reactions known as immune-related adverse events (irAEs). Rheumatic irAEs are infrequently reported and extensively described. Here, we report our experience over an 18-month period with 15 patients evaluated in the rheumatology department for rheumatic irAEs. We identified 13 patients without pre-existing autoimmune disease (AID) who subsequently developed rheumatic irAEs, and two with established AID referred pre-emptively. irAEs encountered included: inflammatory arthritis, sicca syndrome, polymyalgia rheumatica-like symptoms and myositis. All cases required glucocorticoids, and three required a biological agent. Rheumatic irAEs led to temporary or permanent cessation of immunotherapy in all but five patients. One patient with pre-existing AID experienced a flare after starting immunotherapy. Our findings underscore that rheumatic irAEs are complex, at times require additional immunosuppressive therapy, and may influence ongoing immunotherapy regimens for the primary disease. Similar irAEs will be increasingly seen as checkpoint inhibitors adopted as standard of care in the community.

Global color estimation of special-effect coatings from measurements by commercially available portable multiangle spectrophotometers.

Colors of special-effect coatings have strong dependence on illumination/viewing geometry and an appealing appearance. An open question is to ask about the minimum number of measurement geometries required to completely characterize their observed color shift. A recently published principal components analysis (PCA)-based procedure to estimate the color of special-effect coatings at any geometry from measurements at a reduced set of geometries was tested in this work by using the measurement geometries of commercial portable multiangle spectrophotometers X-Rite MA98, Datacolor FX10, and BYK-mac as reduced sets. The performance of the proposed PCA procedure for the color-shift estimation for these commercial geometries has been examined for 15 special-effect coatings. Our results suggest that for rendering the color appearance of 3D objects covered with special-effect coatings, the color accuracy obtained with this procedure may be sufficient. This is the case especially if geometries of X-Rite MA98 or Datacolor FX10 are used.

Chest CT findings in EBUS-TBNA-proven anthracosis in enlarged mediastinal lymph nodes.

PURPOSE: We demonstrate the multislice computed tomography (MSCT) findings of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)-proven hilar and mediastinal lymph node enlargement with signs of anthracosis. MATERIALS AND METHODS: 53 enlarged lymph nodes in 39 patients (28 male, 11 female) with EBUS-TBNA-confirmed anthracosis were analyzed retrospectively. RESULTS: The mean short axis diameter of the enlarged lymph nodes with signs of anthracosis was 13.7  mm. Lymph nodes most often showed an oval shape (84  %) and were well defined in 66  % of cases. Lymph node confluence was observed in 32  % of cases. Calcifications were documented in 24.5  % of cases. Contrast enhancement and fatty involution were seen seldom (3.8  %). Lymph node necrosis was not seen. CONCLUSION: Lymph node anthracosis may be found most often in enlarged, well defined lymph nodes with an oval shape, frequently associated with confluence and calcifications.

The "dirty chest"--correlations between chest radiography, multislice CT and tobacco burden.

OBJECTIVES: Cigarette smoking-induced airway disease commonly results in an overall increase of non-specific lung markings on chest radiography. This has been described as "dirty chest". As the morphological substrate of this condition is similar to the anthracosilicosis of coal workers, we hypothesised that it is possible to quantify the radiological changes using the International Labour Organization (ILO) classification of pneumoconiosis. The aims of this study were to evaluate whether there is a correlation between the extent of cigarette smoking and increased lung markings on chest radiography and to correlate the chest radiographic scores with findings on CT studies. METHODS: In a prospective analysis a cohort of 85 smokers was examined. The cigarette consumption was evaluated in pack years (defined as 20 cigarettes per day over 1 year). Film reading was performed by two board-certified radiologists. Chest radiographs were evaluated for the presence of thickening of bronchial walls, the presence of linear or nodular opacities, and emphysema. To correlate the smoking habits with the increase of overall lung markings in chest radiography, the ILO profusion score was converted to numbers ranging from zero to nine. Chest radiographs were rated according to the complete set of standard films of the revised ILO classification. RESULTS: 63/85 (74%) of the smokers showed an increase in overall lung markings on chest radiography; 32 (37%) had an ILO profusion score of <1/1, 29 (34%) had an ILO profusion score of <2/2 and 2 (2%) had an ILO score of ≥ 2/2. There was a significant positive linear correlation between the increase of overall lung markings on chest radiography and the cigarette consumption quantified as pack years (r=0.68). The majority of the heavy smokers (>40 pack years) showed emphysema; there was no significant difference between the prevalence of emphysema as diagnosed by CT (62%) or chest radiography (71%) (p<0.05).The most common findings in CT were thickening of bronchial walls (64%) and the presence of emphysema (62%) and of intralobular opacities (61%). Ground-glass opacities were seen in only 7% of our patients. CONCLUSION: Bronchial wall thickening and intralobular opacities as seen in CT showed a positive linear correlation with the increase of overall lung markings on chest radiography.

Enlarged hilar and mediastinal lymph nodes in chronic obstructive pulmonary disease.

INTRODUCTION: To evaluate the frequency of enlarged hilar or mediastinal lymph nodes in patients suffering from chronic obstructive pulmonary disease (COPD). METHODS: In a retrospective study, 89 patients with proven COPD were analysed. Exclusion criteria were history of malignant disease or clinical evidence of pneumonia. Prevalence, size, and localisation of enlarged lymph nodes were assessed by multi-slice computed tomography (MSCT) and correlated with the clinical stages following the GOLD classification as well as the MSCT findings of bronchitis and emphysema. RESULTS: 44/89 (49%) of our patients showed enlarged lymph nodes. Lymph node enlargement was more often seen in the mediastinum (48%) than the hilar region (20%). The most common localisation of enlarged mediastinal lymph nodes was the regional station 7 following the ATS mapping (infracarinal). Patients with a stage I following the GOLD classification showed enlarged lymph nodes in 49% (18/37), stage II in 46% (12/26), stage III in 58% (7/12) and stage IV in 50% (7/14). These findings did not differ significantly (P > 0.05). Severe airway wall thickening (42/89) was significantly more often associated with an increase of nodal enlargement (64%) (P < 0.05). CONCLUSION: The present study demonstrates that enlarged hilar and mediastinal lymph nodes may occur in a rather high percentage of patients suffering from COPD, especially in those with the MSCT finding of severe bronchitis.

In a study for acne vulgaris, sequence-based HLA typing showed a novel DPB1 allele, DPB1*2402.

In this paper, we characterize the novel human leucocyte antigen (HLA)-DPB1*2402 allele that we found in a patient suffering from acne vulgaris. In comparison to the closest related allele DPB1*0401, HLA-DPB1*2402 has a single nucleotide exchange at position 115 (202), T replaces G. In consequence, codon 39 (68) TAC encodes for tyrosine in the novel allele instead of aspartic acid 39 (68) GAC in DPB1*0401.

Reduced activation of immunomodulatory transcription factors during positive end-expiratory pressure adjustment based on volume-dependent compliance in isolated perfused rabbit lungs.

BACKGROUND: Repeated alveolar collapse and cyclic alveolar overdistension with associated activation of inflammatory signalling cascades contribute to ventilator-induced lung injury (VILI). The appropriate positive end-expiratory pressure (PEEP) which prevents or ameliorates VILI is unknown. In the isolated perfused lung, repeated adjustments of PEEP based on the continuously analysed intratidal compliance-volume curve have previously been shown to result in full end-expiratory alveolar recruitment and low risk of cyclic alveolar overdistension. Accordingly, we tested the hypothesis that such ventilatory management reduces intrapulmonary activation of the immunomodulatory transcription factors nuclear factor kappaB (NF-kappaB), activator protein 1 (AP-1) and cAMP-responsive element binding protein (CREB) which induce the expression of various chemokines and cytokines. METHODS: Isolated perfused rabbit lungs were randomly allocated to one of three groups: zero end-expiratory pressure (ZEEP) to induce repeated alveolar collapse (n=6), high PEEP to induce cyclic alveolar overdistension (n=6) and repeated PEEP adjustments based on intratidal compliance-volume curve analysis by the slice method to minimize repeated alveolar collapse and overdistension (n=9). All lungs were ventilated with a tidal volume of 6 ml kg(-1) bodyweight for 120 min. Thereafter, activation of transcription factors NF-kappaB, AP-1 and CREB in lung tissue was analysed by electrophoretic mobility shift assay. RESULTS: High PEEP was associated with the highest activation of NF-kappaB and AP-1 and repeated PEEP adjustments with the lowest activation when compared with the other two study groups (P<0.001). In contrast, activation of CREB did not differ between groups. Activated NF-kappaB and AP-1 protein complexes consisted mainly of the transactivators p50/p65 and c-Fos/Jun, respectively. CONCLUSIONS: In isolated perfused rabbit lungs, repeated adjustments of PEEP based on the continuously analysed intratidal compliance-volume curve were associated with less activation of early steps of inflammatory signalling cascades than ventilation with ZEEP or high PEEP.

[Observing the density increase curve after intravenous contrast medium administration using a bolus triggering system: a method for detection cardiovascular disorders?]. / Beobachtung der Dichteanstiegskurve nach intravenöser Kontrastmittelapplikation unter Verwendung eines Bolustriggerungsystems: eine Methode zur Detektion kardiovaskulärer Störungen?

PURPOSE: Recently bolus tracking systems were developed to improve the timing of intravenous contrast media application in helical computed tomography. We investigated the benefit of this new method as a parameter of the cardiac function. MATERIAL AND METHODS: Retrospective analysis of 64 patients which incidentally underwent bolus triggered contrast enhanced helical CT and invasive investigation of the heart within one week. All examinations were performed on the CT scanner Somatom Plus 4 Volume Zoom (Siemens Corp., Forchheim, Germany) using the C.A.R.E. Bolus software. This performs repetitive low-dose test scans (e.g. for the abdomen: 140 kV, 20 mA, Tl 0.5 s) and measures the Hounsfield attenuation (increase over the baseline) in a preselected region of interest. The displayed increase of vascular density over the time after peripheral contrast media injection (75 ml lopromid (300 mg/ml), 2 ml/s) was categorised to three types: (a) rapid increase, (b) deceleration before a 100 HE threshold was reached and (c) one or more peaks. The findings of the invasive investigation of the heart were correlated to the findings of the bolus-tracking measurements. RESULTS: The examinations were categorized as follows: 19 type A, 34 type B, 11 type C. We found a high significant correlation between the type of the Hounsfield attenuation and systolic pressure in the left ventricle. There was no correlation between the type of the Hounsfield attenuation and the diastolic pressure in the left ventricle, the pressures related to the right ventricle or the ejection fraction. The bolus-tacking system showed a sensitivity of 53, a specificity of 82, an accuracy of 70%, a positive predictive value of 70% and a negative predictive value of 70% in detection of left heart failure. CONCLUSION: The bolus tracking system C.A.R.E.-bolus often shows atypical Hounsfield attenuation in cases of cardiac failure but is not suitable as a screening method of the cardiopulmonary function.

Sequential immunochemotherapy and edrecolomab in the adjuvant therapy of breast cancer: reduction of 17-1A-positive disseminated tumour cells.

BACKGROUND: The aim of our study was to evaluate the efficacy of the monoclonal antibody edrecolomab after chemo- and radiotherapy in the elimination of disseminated tumour cells in bone marrow in the adjuvant therapy of breast cancer. PATIENTS AND METHODS: The bone marrow of 25 patients with breast cancer was tested for the presence of disseminated tumour cells using the pancytoceratine antibody and the alkaline phosphatase-anti-alkaline-phosphatase (APAAP) technique. To characterize tumour cells simultaneously, immunofluorescent double labelling of pancytoceratine and epithelial cell adhesion molecule (antibody 17-1A) was performed on tumour cells after magneto bead enrichment. Patients positive for the 17-1A antigen in bone marrow after chemotherapy were treated with edrecolomab (500 mg Panorex) initially, then 100 mg/month over 4 months) and investigated for the presence of micrometastases 6 weeks after the last treatment. RESULTS: Of the 17 patients showing bone marrow micrometastases (BM-MM), 14 tested 17-1A positive before adjuvant chemotherapy. After chemotherapy, nine patients remained positive for the 17-1A antigen and were treated with edrecolomab. The final investigation after immunotherapy showed a complete elimination of the 17-1A-positive BM-MM in seven patients and a significant reduction of these cells in two patients. CONCLUSIONS: Sequential treatment of breast cancer with edrecolomab after adjuvant chemotherapy can reduce disseminated tumour cells in the bone marrow and eliminate 17-1A-positive micrometastases.

Melanoptysis: findings on CT and MRI.

The purpose of this study was to demonstrate the CT and MRI features of liquefied progressive massive fibrosis (PMF) in coal worker's pneumoconiosis (CWP). A retrospective analysis was made of the CT and MRI features in five patients suffering from severe CWP with the initial clinical finding of melanoptysis ("black phtisis"). CT showed either an air-fluid level or a fluid-precipitate level with high density in the dependent layer. On pre-contrast T(1) weighted images, liquefied PMF showed a fluid level with isointensity relative to soft tissue in the upper layer and a signal loss in the dependent layer of the lesion. The wall of the PMF showed rim enhancement after administration of iv gadolinium. On T(2) weighted images there was a high signal intensity in the upper layer of the lesion. In conclusion, liquefied PMF results in characteristic features on CT and MRI owing to precipitation of silica in the mucous fluid.

Transformation of Hodgkin's disease to high-grade B-cell lymphoma: remission after Rituximab monotherapy.

PURPOSE: We demonstrate the usefulness of immunotherapy with the CD20 antibody Rituximab in a case of transformation of Hodgkin's disease (HD) to high-grade non-Hodgkin's lymphoma (NHL). CASE REPORT: A 45-year-old women suffering from lymphocyte predominant HD of paragranuloma type (stage IVb) since 1995 showed mediastinal relapse despite of 6 cycles of chemotherapy following the COPP/ABVD-protocol in 1998. Again complete remission could be achieved after escalated BEA-COPP II therapy in May 1998. Six months later chest radiograph and CT depicted pulmonary nodules. The non-typical resection of the lung revealed pulmonary involvement of a high-grade T-cell rich large B-cell lymphoma with 100% of the tumoral cells CD20 positive. Since the symptoms occurred shortly after the BEA-COPP-escalated protocol chemotherapy resistance had to be assumed. Because of this problems and supported by the refusal of a high-dose chemotherapy with stem-cell transplantation by the patient we decided to perform a mono-immunotherapy with the monoclonal CD20 antibody Rituximab. Today, 14 months later, the patient is still in complete remission including the absence of B symptoms. CONCLUSIONS: Immunotherapy against CD20 positive cells in cases of sequential HD and NHL seems to be an effective therapy in chemotherapy resistant cases because of the suspected clonally relation of both diseases.

Rapid exchange of large numbers of donor- and host leukocytes after human liver transplantation.

After liver transplantation, the release of donor leukocytes into the host and the uptake of host leukocytes by the graft is one of the earliest immunologic interactions between donor and host. Using three-color flow cytometry, these interactions were investigated in eight patients from 5 min-24 h after receiving HLA unmatched liver grafts. Five minutes after reperfusion, 5.0 % +/- 1.4 % of all blood leukocytes in the host were of donor origin, decreasing to 1.1 % +/- 0.8 % after 24 h. Donor granulocytes preferentially disappeared from the host circulation, whereas no differences were found between NK-cells and various B- and T cell subpopulations. Furthermore, host granulocytes were preferentially retained in the donor liver. Thus, despite extensive pre-operative perfusion, more than 10(9) donor leukocytes quickly leave the liver graft while host granulocytes preferentially accumulate there. A better understanding of the molecular mechanisms mediating these early interactions might help to develop new strategies for diagnosis and therapy of liver graft rejection.

Postoperative altered plasma growth hormone levels--a predictor for postoperative complications? A case report.

We compared the onset of predictors for postoperative complications (lactate, total T2 (tT2), total T4 (tT4) and cortisone) retrospectively with the onset of altered growth hormone (GH) concentration in a patient who had had a lethal postoperative outcome and in 13 patients who were without postoperative complications for a period of 24 hours postoperatively. Compared with the values of the patients without postoperative complications, GH values were elevated (68-fold) 1 h after surgery to 103 ng/ml and lactate was increased (12-fold) to 12.7 mmol/l at 6 h postoperatively in the patient with the lethal outcome. The other parameters measured (tT3, tT4 and cortisone) showed no rapid alteration during the first hours postoperatively. This case report suggests that the rapid postoperative onset of raised GH concentration in plasma may be an earlier marker for postoperative complications than the 'established' predictors.

Postoperative pattern of various hormonal and metabolic variables. A pilot study in patients without complications following cardiac surgery.

The use of single predictors for threatening postoperative complications are widely accepted. However, a typical pattern of multiple parameters could be more helpful than a single predictor. To study this hypothesis, various variables of normal postoperative changes in patients without postoperative complications were investigated. Secondly, this pattern needs to be compared in the future with those findings in patients with postoperative complications. Blood parameters of 13 patients undergoing cardiovascular surgery without postoperative complications for 24 hours were evaluated. Samples were obtained on the afternoon before the operation and 1, 3, 6, 12 and 24 hours after the end of surgery. At one hour postoperation increased levels of the following parameters were noted: growth hormone (p < 0.0001), glucose (p < 0.0001), insulin (p < 0.001), c-peptide (p < 0.001), lactate (p < 0.002), glutamate (p < 0.0001), aspartate (p < 0.001) and total amino acids (p < 0.05), although the concentration of some amino acids decreased. Three hours postoperatively free fatty acids (p < 0.05) were increased. Total-T3 concentrations were reduced postoperatively. Other parameters were not altered. Most of the parameters returned to normal values during the period of observation.

In vitro evaluation of a glass-ceramic restorative material.

The aim of the present study was to evaluate the clinically relevant properties of the recently introduced ceramic material IPS Empress, which is marketed for all-ceramic restorations. The following parameters were investigated: three- and four-point bending strength, bi-axial flexure strength, compressive and diametral tensile strength, compressive strength and marginal fit of full crowns. The results show that this material is a highly developed glass-ceramic with physical properties making this dental material well suitable for adhesively luted restorations.

[Effect of lidocaine administration mode on decreasing injection pain caused by propofol]. / Einfluss der Applikationsart von Lidocain auf die Verminderung des Injektionsschmerzes durch Propofol.

Pain is a well known complication of propofol injection. Many methods are described to reduce it but often empirical ways are used. In this study we attempt to determine the effects of premixing propofol with lidocaine or to preinjecting lidocaine in a hand vein in combination with using a tourniquet before we applicated propofol. Our study shows that both ways are able to reduce the injection pain but premixing with lidocaine 0.05% is less effective than giving a bolus of lidocaine before the propofol injection.

[Anesthesiologic characteristics of isolated hyperthermic liver perfusion with mitomycin C]. / Anästhesiologische Besonderheiten bei der isolierten hyperthermen Leberperfusion mit Mitomycin C.

The isolated hyperthermic liver perfusion with mitomycin C presents a new technique of regional therapy for irresectable liver tumours. The advantage is a high local concentration of the antitumour agent with reduced systemic side-effects. Isolated hyperthermic liver perfusion is an extensive surgical procedure requiring a veno-venous bypass and a heart-lung machine. Disturbances affecting the base-acid hemostasis, the coagulation system and the cardiocirculatory function can occur. To date, there has been little experience with this technique. The intraoperative changes during the isolated hyperthermic liver perfusion in our series were similar to those seen during orthotopic liver transplantation. In contrast to orthotopic liver transplantation, heparin is given during the anhepatic phase. The reperfusion after isolated hyperthermic liver perfusion was not complicated by severe cardiocirculatory changes. A decrease in body temperature was not observed probably due to the absence of cold, potassium-rich perfusate flowing into the systemic circulation. Two patients developed signs of a reperfusion syndrome within the first hour after reperfusion (decrease in peripheral systemic resistance).