Humoral and Cellular Responses to Influenza Vaccination in Human Recipients Naturally Tolerant to a Kidney Allograft

Rare kidney allograft recipients enjoy unaltered graft function years after interruption of their immunosuppressive treatment. To assess the extent to which this state of 'operational tolerance' (TOL) is specific to the graft and not the result of a global immunodeficiency, we analyzed the response of such patients following influenza vaccination. Hemagglutination inhibition titers and frequency of IFNgamma-secreting T cells were measured before 1 and 3 months after vaccination. The proportion of healthy volunteers (HV) responding to vaccine was significantly higher than that of immunosuppressed (IS) patients. Three 'TOL' patients presented a humoral response similar to that of HV, whereas the two others had a poor response, like the IS recipients. Although the small number of patients does not allow for definitive conclusions to be made, these data suggest that the status of tolerance may be heterogeneous, with some patients with a global immunodeficiency and others with an adapted response to vaccination.     

心理群体干预对缓解体外受精妇女焦虑作用的随机对照研究

目的：评价东部身体-智力-精神（EBMS）群体干预对进行体外受精（IVF）的中国妇女焦虑缓解的作用。设计：随机对照研究。机构：三级辅助生殖机构。受试者：227例接受第1个IVF周期治疗的妇女。干预：干预组（n=69）接受4次EBMS群体咨询，而对照组（n=115）无任何干预。主要观察指标：状态-特质焦虑问卷。结果：与对照组相比，干预组在干预后状态焦虑平均分显著下降。每组移植同样数目的卵子，但干预组没有明显更高妊娠率的倾向。     

A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.     

PET imaging of the dopamine transporter with 18F-FECNT: a polar radiometabolite confounds brain radioligand measurements.

18F-2beta-Carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (18F-FECNT), a PET radioligand for the dopamine transporter (DAT), generates a radiometabolite that enters the rat brain. The aims of this study were to characterize this radiometabolite and to determine whether a similar phenomenon occurs in human and nonhuman primate brains by examining the stability of the apparent distribution volume in DAT-rich (striatum) and DAT-poor (cerebellum) regions of the brain. METHODS: Two rats were infused with 18F-FECNT and sacrificed at 60 min. Extracts of brain and plasma were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometric (LC-MS) techniques. Two human participants and 3 rhesus monkeys were injected with 18F-FECNT and scanned kinetically, with serial arterial blood analysis. RESULTS: At 60 min after the injection of rats, 18F-FECNT accumulated to levels about 7 times higher in the striatum than in the cortex and cerebellum. The radiometabolite was distributed at equal concentrations in all brain regions. The LC-MS techniques identified N-dealkylated FECNT as a major metabolite in the rat brain, and reverse-phase HPLC detected an equivalent amount of radiometabolite eluting with the void volume. The radiometabolite likely was 18F-fluoroacetaldehyde, the product expected from the N-dealkylation of 18F-FECNT, or its oxidation product, 18F-fluoroacetic acid. The distribution volume in the cerebellum increased up to 1.7-fold in humans between 60 and 300 min after injection and 2.0 +/- 0.1-fold (mean +/- SD; n = 3) in nonhuman primates between 60 and 240 min after injection. CONCLUSION: An 18F-fluoroalkyl metabolite of 18F-FECNT originating in the periphery confounded the measurements of DAT in the rat brain with a reference tissue model. Its uniform distribution across brain regions suggests that it has negligible affinity for DAT (i.e., it is an inactive radiometabolite). Consistent with the rodent data, the apparent distribution volume in the cerebellum of both humans and nonhuman primates showed a continual increase at late times after injection, a result that may be attributed to entry of the radiometabolite into the brain. Thus, reference tissue modeling of 18F-FECNT will be prone to more errors than analysis with a measured arterial input function.     

Analysis of surgical management of calvarial tumours and first results of a newly designed robotic trepanation system.

This study was performed to evaluate the surgical strategy in patients with calvarial tumours, in order to design and modify a robot-assisted trepanation system. A total of 75 patients underwent craniectomy for the treatment of calvarial tumours during the 10-year period from 1993 to 2002. The patients' complaints, the size, location and histology of the tumour, and the various cranioplasty techniques used were analysed retrospectively. In a second procedure several craniectomies at typical locations according to the study's results were performed in a laboratory setting using a hexapod robotic tool, constructed at the Helmholtz-Institute, RWTH Aachen University, and plastic model heads. The workflow was documented and the reproducibility and the accuracy of the procedure were registered. A total of 83 surgical procedures were performed on 75 patients. The majority (87 %) of lesions treated surgically were located in the frontal, temporal and anterior parts of the parietal region. Histological examination revealed benign lesions in 66 % of the patients and dural involvement in 46 %. According to these results craniectomies were performed using the robotic system. Mean positioning accuracy of the robotic system while milling was 0.24 mm, with a standard deviation of 0.04 mm, and maximum error under 1 mm. Craniectomies leaving a 1-mm layer of the tabula interna intact to ensure a healthy dura were performed in several regions successfully. The majority of calvarial tumours, requiring surgical treatment in our patients, were located in cosmetically relevant areas in which drilling can be carried out with the robotic trepanation system. Consequently, the surgical approach had to be planned carefully in order to achieve a good cosmetic outcome.     

Outcomes of low-vision services using optometric and multidisciplinary approaches: a non-randomized comparison

Consecutive patients (n = 215) who were referred to optometric (55%) or multidisciplinary (45%) low-vision services and above 50 years of age were recruited from four hospitals in the Netherlands. They completed two vision-related quality of life questionnaires, the Vision Quality of Life Core Measure (VCM1) and the Low Vision Quality of Life Questionnaire (LVQOL), before their first visit with low-vision services and 1 year later. At follow-up, patients referred to multidisciplinary low-vision services had lower scores on the mobility subscale of the LVQOL than patients referred to optometric low-vision services [5.3 points; 95% confidence interval (CI): 0.2-10.5]. Paired sample t-tests for the two groups of patients taken together show improvement for the VCM1 (3.1 points; 95% CI: 0.6-5.6) and deterioration for the basic aspects of vision (3.5 points; 95% CI: 1.1-5.9) and the mobility (6.6 points; 95% CI: 3.7-9.5) subscales of the LVQOL. In conclusion, people referred to optometric services showed less deterioration in mobility than those referred to multidisciplinary services. No differences were observed for any of the other subscales of the LVQOL and the VCM1. Future research in this field should include randomized controlled designs comparing low-vision services with no treatment or placebo.     

Delayed and persistent suppression of bronchoconstriction by trypsin in the airway lumen.

Mucosal trypsin, a protease-activated receptor (PAR) stimulant, may have an endogenous bronchoprotective role on airway smooth muscle. To test this possibility the effects of lumenal trypsin on airway tone in segments of pig bronchus were tested. Bronchial segments from pigs were mounted in an organ chamber containing Kreb's solution. Contractions were assessed from isovolumetric lumen pressure induced by acetylcholine (ACh) or carbachol added to the adventitia. Trypsin, added to the airway lumen (300 microg x mL(-1)), had no immediate effect on smooth muscle tone but suppressed ACh-induced contractions after 60 min, for at least 3 h. Synthetic activating peptides (AP) for PAR1, PAR2 or PAR3 were without effect, but PAR4 AP caused rapid, weak suppression of contractions. Lumenal thrombin was without effect and did not prevent the effects of trypsin. Effects of trypsin were reduced by N(omega)-nitro-L-arginine methyl ester but not indomethacin. Trypsin, thrombin and PAR4 AP released prostaglandin E2. Adventitially, trypsin, thrombin and PAR4 AP (but not PAR2 AP) relaxed carbachol-toned airways after <3 min. The findings of this study show that trypsin causes delayed and persistent bronchoprotection by interacting with airway cells accessible from the lumen. The signalling mechanism may involve nitric oxide synthase but not prostanoids or protease-activated receptors.