Opioid binding in DYT1 primary torsion dystonia: an 11C-diprenorphine PET study.

The opioid transmitters enkephalin and dynorphin are known to regulate pallidal output and consequently cortical excitability. Indeed, abnormal basal ganglia opioid transmission has been reported in several involuntary movement disorders, including levodopa-induced dyskinesias in Parkinson's disease (PD), tardive dyskinesias/dystonia, Huntington's disease, and Tourette's syndrome. Moreover, a previous 11C-diprenorphine PET study investigating levodopa-induced dyskinesias found reduced opioid receptor availability in PD with but not without dyskinesias. We wished to investigate if a similar alteration in basal ganglia opioid binding was present in DYT1 primary torsion dystonia (PTD). Regional cerebral 11C-diprenorphine binding was investigated in 7 manifesting carriers of the DYT1 gene and 15 age-matched normal controls using a region-of-interest (ROI) approach and statistical parametric mapping (SPM). No difference in regional mean 11C-diprenorphine binding was found between DYT1-PTD and controls, and no correlation between the severity of dystonia and opioid binding was seen. We conclude that aberrant opioid transmission is unlikely to be present in DYT1-PTD and altered opioid transmission is not a common mechanism underlying all disorders of involuntary movement.     

Reference and target region modeling of [11C]-(R)-PK11195 brain studies.

PET with [(11)C]-(R)-PK11195 is currently the modality of choice for the in vivo imaging of microglial activation in the human brain. In this work we devised a supervised clustering procedure and a new quantification methodology capable of producing binding potential (BP) estimates quantitatively comparable with those derived from plasma input with robust quantitative implementation at the pixel level. METHODS: The new methodology uses predefined kinetic classes to extract a gray matter reference tissue without specific tracer binding and devoid of spurious signals (in particular, blood pool and muscle). Kinetic classes were derived from an historical database of 12 healthy control subjects and from 3 patients with Huntington's disease. BP estimates were obtained using rank-shaping exponential spectral analysis (RS-ESA) (both plasma and reference input) and the simplified reference tissue model (SRTM). Comparison between plasma- derived BPs and those produced with the new reference methodology was performed using 6 additional healthy control subjects. Reliability of the new methodology was performed on 4 test-retest studies of patients with Alzheimer's disease. RESULTS: The new algorithm selected reference voxels in gray matter tissue avoiding regions with specific binding located, in particular, in the venous and arterial circulation. Using the new reference, BP values obtained using a plasma input and a reference input were in excellent agreement and highly correlated (r = 0.811, P < 10(-5)) when calculated with RS-ESA and less so (r = 0.507, P < 0.005) when SRTM was used. In the production of parametric maps, SRTM was used with the new reference extraction, resulting in test-retest variability (10.6%; mean ICC = 0.878) that was superior to that obtained using the previous unsupervised clustering approach (mean ICC = 0.596). CONCLUSION: Reference region modeling combined with supervised reference tissue extraction produces a robust and reproducible quantitative assessment of [(11)C]-(R)-PK11195 studies in the human brain.     

Introduction of a novel proliferation assay for pharmacological studies allowing the combination of BrdU detection and phenotyping

A recently developed technology for the non-enzymatic detection of the thymidine analog 5-bromo-2-deoxyuridine (BrdU) has been evaluated. In contrast to previous enzymatic approaches, Ultraviolet-Induced Detection (UVID) of halogenated pyrimidines allows for a mild detection procedure which enables the simultaneous detection of cellular markers and DNA-synthesis without enzyme-specific disadvantages. Superantigen-stimulated peripheral blood mononuclear cells (PBMNCs) have been treated with two different inhibitors of proliferation and the cell cycle of different lymphocyte subsets has been analysed. Both pentoxifylline (POF) and 2-methoxyestradiol (2ME2) exhibited strong antiproliferative activity, but led to distinctive changes in the cell cycle distribution. This study shows that the UVID technology is a simple and viable method which should find a wide range of applications in immunological and pharmacodynamic assays.     

Imaging of the testicle: the painful scrotum and nonpalpable masses.

Scrotal pain is initially evaluated by color Doppler ultrasonography providing information on the presence or absence of flow within the testis and B Scan imaging providing important complementary information about lesions such as torsion of the appendix testis and testicular abscess. While radioisotope scanning provides similar information to color Doppler about testicular flow, it does not demonstrate the anatomy. Testicular imaging is extremely sensitive for "silent masses" and useful to evaluate palpable ones. Characteristic findings may be seen with simple testicular cysts and epidermoid cysts. Homogeneously hyperechoic masses have a variety of etiologies but are virtually always benign. A major limitation of a ultrasonography is the large number of nonneoplastic lesions which may mimic tumors.     

Expansion of Patient Education Programming Regarding Live Donor Liver Transplantation via Virtual Group Encounters During the COVID-19 Pandemic

During the coronavirus 2019 pandemic we converted our liver transplant waitlist candidate education and support program to a virtual format and expanded it to include ongoing engagement sessions aimed to educate and empower patients to maximize opportunity for live donor liver transplantation. Over a period of 6 months from April 2020 to Sept 2020 we included 21 patients in this pilot quality improvement program. We collected data regarding patient response and potential donor referral activity. Overall, patient response was positive, and some patients saw progress toward live donor liver transplantation by fostering inquiry of potential live liver donors. Optimization of logistical aspects of the program including program flow, technology access, and utilization is required to enhance patient experience. Long-term follow-up is needed to assess impact on the outcome of transplantation rates. Future data collection and analysis should focus on assessment of any potential disparity that may result from utilization of virtual programming. Herein we provide a framework for this type of virtual program and describe our experience.     

Diagnostic classification of arterial spin labeling and structural MRI in presenile early stage dementia

Because hypoperfusion of brain tissue precedes atrophy in dementia, the detection of dementia may be advanced by the use of perfusion information. Such information can be obtained noninvasively with arterial spin labeling (ASL), a relatively new MR technique quantifying cerebral blood flow (CBF). Using ASL and structural MRI, we evaluated diagnostic classification in 32 prospectively included presenile early stage dementia patients and 32 healthy controls. Patients were suspected of Alzheimer's disease (AD) or frontotemporal dementia. Classification was based on CBF as perfusion marker, gray matter (GM) volume as atrophy marker, and their combination. These markers were each examined using six feature extraction methods: a voxel‐wise method and a region of interest (ROI)‐wise approach using five ROI‐sets in the GM. These ROI‐sets ranged in number from 72 brain regions to a single ROI for the entire supratentorial brain. Classification was performed with a linear support vector machine classifier. For validation of the classification method on the basis of GM features, a reference dataset from the AD Neuroimaging Initiative database was used consisting of AD patients and healthy controls. In our early stage dementia population, the voxelwise feature‐extraction approach achieved more accurate results (area under the curve (AUC) range = 86 ? 91%) than all other approaches (AUC = 57 ? 84%). Used in isolation, CBF quantified with ASL was a good diagnostic marker for dementia. However, our findings indicated only little added diagnostic value when combining ASL with the structural MRI data (AUC = 91%), which did not significantly improve over accuracy of structural MRI atrophy marker by itself. Hum Brain Mapp 35:4916–4931, 2014. © 2014 Wiley Periodicals, Inc .     

美国、德国医疗保险服务协议相关法律问题及对中国的启示

重点对美国医疗保险经办机构和医疗机构的关系、医疗保险申请、医疗服务协议的协商谈判机制、工作程序、医疗保险的支付方式,经费报销结算计算及医保纠纷解决五步上诉机制等相关法律问题,以及德国的医疗保险模式和医疗服务协议相关情况进行了综述介绍,在此基础上论述了美、德医疗保险服务协议相关法律问题对我国的启示。