A quick and universal method for stereotactic visualization of the subthalamic nucleus before and after implantation of deep brain stimulation electrodes

For deep brain stimulation (DBS) of the subthalamic nucleus (STN), it would be an advantage if the STN could be visualized with fast acquisition of MR images, allowing direct and individual targeting. We present a protocol for T2-weighted, nonvolumetric fast-acquisition MRI, implemented at 8 centers in 6 countries. Acquisition time varied between 3 min 5 s and 7 min 48 s according to the center, and imaging often provided visualization of the STN on axial and coronal scans. Postoperatively, the same imaging protocol permitted visualization of the target area and DBS electrodes with minimum artifacts. This imaging technique may contribute to a decrease in the number of electrode passes at surgery.     

Home versus Office blood pressure MEasurements: Reduction of Unnecessary treatment Study: rationale and study design of the HOMERUS trial

The Home versus Office MEasurements, Reduction of Unnecessary treatment Study (HOMERUS) is a multicentre prospective study, primarily designed to examine in subjects with mild to moderate hypertension whether treatment decisions based on home blood pressure measurements can lead to reduction in the use of antihypertensive drugs and the associated costs, compared to office blood pressure measurements. After inclusion, 360 patients are randomized to two groups. In one group, antihypertensive therapy is based on blood pressure measured in the outpatient clinic: the office pressure (OP) group. In the other group, antihypertensive therapy is based on home blood pressure measurements: the self-pressure (SP) group. All readings, both in OP and in SP, are obtained with the same validated oscillometric device, the Omron 705 CP. Treatment decisions are taken by an independent physician at the coordinating centre, who is unaware whether the patient belongs to the SP or OP group. Following a standardized treatment schedule, blood pressure is targeted at 120-139 mmHg for systolic and 80-89 mmHg for diastolic pressure. Patients are followed for 1 year. At the start and at the end of the study, ambulatory blood pressure measurements are obtained as a reference. Microalbuminuria and echocardiography are assessed to evaluate the possible development of target organ damage. It is expected that, at the end of the trial, patients in both groups will have the same blood pressure, at the expense of more medication in the OP group. Therefore, a cost-minimization analysis will be performed first. If short-term effects appear not to be comparable for OP and SP, a cost-effectiveness analysis will be performed to assess the value of the SP strategy in comparison to standard practice. In addition, medication compliance is recorded within random subgroups of the SP and OP groups by means of Medication Event Monitoring System (MEMS) V TrackCaps.     

Cue combination in a combined feature contrast detection and figure identification task

Target figures defined by feature contrast in spatial frequency, orientation or both cues had to be detected in Gabor random fields and their shape had to be identified in a dual task paradigm. Performance improved with increasing feature contrast and was strongly correlated among both tasks. Subjects performed significantly better with combined cues than with single cues. The improvement due to cue summation was stronger than predicted by the assumption of independent feature specific mechanisms, and increased with the performance level achieved with single cues until it was limited by ceiling effects. Further, cue summation was also strongly correlated among tasks: when there was benefit due to the additional cue in feature contrast detection, there was also benefit in figure identification. For the same performance level achieved with single cues, cue summation was generally larger in figure identification than in feature contrast detection, indicating more benefit when processes of shape and surface formation are involved. Our results suggest that cue combination improves spatial form completion and figure-ground segregation in noisy environments, and therefore leads to more stable object vision.     

SERPINE2 (protease nexin I) promotes extracellular matrix production and local invasion of pancreatic tumors in vivo

In large-scale expression profiling analyses, we have previously identified genes differentially expressed between subclones of the pancreatic cancer cell line SUIT-2. One of the genes most strongly overrepresented in the highly metastatic subclone S2-007 as compared with the rarely metastatic subclone S2-028 was the serine proteinase inhibitor SERPINE2 (protease nexin I), suggesting that this protein may play an important part in the process of metastasis. The aim of this study was to functionally characterize SERPINE2 for its potential to influence the invasive and metastatic phenotype of cancer cells in vitro and in vivo. SERPINE2 expression was weak or absent in all normal pancreas and chronic pancreatitis tissue samples examined. In contrast, it was strongly overexpressed in the majority of pancreatic carcinoma as well as gastric and colorectal cancer samples. [(3)H]Thymidine incorporation, soft agar, two chamber migration, Matrigel invasion, and zymography assays of SERPINE2-transfected S2-028 cells revealed no significant effects on metastasis-related cellular characteristics of isolated cancer cells. Although overall metastatic activity of the transfected cells in vivo was also unaltered, SERPINE2 overexpression greatly enhanced the local invasiveness of the s.c. xenograft tumors, accompanied by a massive increase in extracellular matrix (ECM) production in the invasive tumors. ECM deposits were positive for type I collagen, fibronectin, and laminin, thus resembling the desmoplastic reaction commonly observed in pancreatic cancer. Moreover, cancer cells in invasive SERPINE2-expressing tumors tended to adopt a spindle-shaped morphology and strongly expressed the mesenchymal intermediate filament marker vimentin. We propose that SERPINE2 overexpression enhances the invasive potential of pancreatic cancer cells in nude mouse xenografts by altering ECM production and organization within the tumors. Thus, our experimental system for the first time provides the opportunity to effectively model the desmoplastic reaction of pancreatic cancer and represents a valuable new tool for the study of tumor-stroma interactions.     

Assessment of focal liver reaction by multiphasic CT after stereotactic single-dose radiotherapy of liver tumors

PURPOSE: To characterize and quantitatively assess focal radiation reactions in the liver after stereotactic single-dose radiotherapy for liver malignancies. METHODS AND MATERIALS: A total of 131 multiphasic CT scans were performed in 36 patients before and after stereotactic radiotherapy for liver tumors. The examination protocol included a nonenhanced scan and contrast-enhanced scans at different times after contrast injection. The volume of the reaction was determined in each scan and the threshold dose calculated using the dose-volume histogram of the treatment plan. RESULTS: Every patient showed a focal radiation reaction on at least one follow-up examination. In 74% of the posttherapeutic scans, a sharply demarcated hypodense area surrounded the treated tumor in the nonenhanced scans. The reaction occurred at a median of 1.8 months (range 1.2-4.6) after radiotherapy. The median threshold dose was 13.7 Gy (range 8.9-19.2). The threshold dose strongly correlated with the time of detection after therapy (r = 0.7). Radiologically, three reaction types were found on the enhanced scans: type 1, portal-venous phase: hypodense and late phase: isodense; type 2, portal-venous phase: hypodense and late phase: hyperdense; and type 3, portal-venous phase: isodense/hyperdense and late phase: hyperdense. Type 1 or 2 reactions were observed significantly earlier than type 3 (p <0.05). The median threshold dose for type 1 or 2 reactions was significantly lower than for type 3 (p <0.05). The reaction volume decreased with longer follow-up (2-4 months: median 40% of initial volume). The reaction types shifted with follow-up: 58% were of type 1 at the initial manifestation and 58% were of type 3 at the next examination thereafter. CONCLUSION: A focal radiation reaction occurs after stereotactic single-dose therapy in the liver. The volume of the reaction decreases and changes its radiologic appearance during follow-up. This reaction has to be differentiated from recurrent tumor.     

Evaluation of non-radioactive temperature gradient SSCP analysis and of temperature gradient gel electrophoresis for the detection of HPV 6-variants in condylomata acuminata and Buschke-Loewenstein tumours

A modified non-radioactive single strand conformation polymorphism analysis incorporating a temperature gradient (TG-SSCP) and temperature gradient gel electrophoresis (TGGE) were evaluated for the detection of human papillomavirus type 6 (HPV 6)-variants in 41 condylomata acuminata and 5 Buschke-Loewenstein tumours. TG-SSCP and TGGE analysed part of the transforming ORF E6 of HPV 6 spanning nucleotides 10 to 495. TG-SSCP distinguished between 8 HPV 6-variants whereas TGGE demonstrated 6 different DNA-species. HPV 6-strains found in Buschke-Loewenstein tumours did not vary in the analysed portion of the E6 ORF as compared to ordinary condylomata acuminata. TG-SSCP and TGGE further showed absence of double infection with different HPV 6-strains in the analysed samples. Our results demonstrated that both methods may be successfully used for the detection of different strains of microbiological agents, although TG-SSCP seemed to provide easier execution and to confer a higher degree of flexibility than TGGE.