Invariant natural killer T cells are not affected by lysosomal storage in patients with Niemann-Pick disease type C

Invariant natural killer T (iNKT) cells are a specialised subset of T cells that are restricted to the MHC class I like molecule, CD1d. The ligands for iNKT cells are lipids, with the canonical superagonist being α-galactosylceramide, a non-mammalian glycosphingolipid. Trafficking of CD1d through the lysosome is required for the development of murine iNKT cells. Niemann-Pick type C (NPC) disease is a lysosomal storage disorder caused by dysfunction in either of two lysosomal proteins, NPC1 or NPC2, resulting in the storage of multiple lipids, including glycosphingolipids. In the NPC1 mouse model, iNKT cells are virtually undetectable, which is likely due to the inability of CD1d to be loaded with the selecting ligand due to defective lysosomal function and/or CD1d trafficking. However, in this study we have found that in NPC1 patients iNKT cells are present at normal frequencies, with no phenotypic or functional differences. In addi-tion, antigen-presenting cells derived from NPC1 patients are functionally competent to present several different CD1d/iNKT-cell ligands. This further supports the hypothesis that there are different trafficking requirements for the development of murine and human iNKT cells, and a functional lysosomal/late-endosomal compartment is not required for human iNKT-cell development.     

Laboratory diagnosis of specific antibody deficiency to pneumococcal capsular polysaccharide antigens

BACKGROUND: Measurement of postimmunization antibody response to pneumococcal capsular polysaccharide (caps-PS) is the standard method to identify deficiency of antipolysaccharide antibody production. However, no standardized criteria have been defined for classification of patients into responders or nonresponders to caps-PS. METHODS: We vaccinated 37 healthy children and 39 healthy adults with Pneumovax and measured the anti-caps-PS antibody response to 5 serotypes. We also measured antipneumococcal antibody titers in 82 patients with increased susceptibility to airway infection. The ELISA was performed according to the 3rd-generation assay format. RESULTS: The lower 5th percentile (cutoff) concentrations for the postimmunization antibody titer in healthy individuals were 0.67 mg/L, 0.45 mg/L, 0.46 mg/L, 0.31 mg/L, and 1.04 mg/L for serotypes 3, 4, 9N, 18C, and 19F, respectively. In 96% of healthy individuals, antibody responses higher than the cutoff concentration were seen for at least 3 of the 5 serotypes. Nine of 82 patients (11%) failed to mount an adequate antibody response for at least 4 of the 5 serotypes tested, whereas only 1 control (1.3%) failed to do so. CONCLUSION: The cutoffs for antibody responses to caps-PS identified in this study appear useful for identifying individuals with an inadequate response to vaccine.     

Burnout intervention among Dutch dentists: long-term effects

The aim of the present study was to determine the long-term effects of a burnout-intervention program among Dutch dentists using a longitudinal design. Using the Maslach Burnout Inventory (Dutch version: MBI-NL), at the initial measurement in 1997 a 'burnout risk group' (n = 171) was identified. This group received feedback on their scores and was invited to participate in an intervention program. Of the total group. 19 dentists participated in an intervention program. After the end of the intervention program, 92 dentists (the 19 participants and a control group) responded to a post-intervention survey in 1998. These dentists were approached once more 1 yr later, and this time 78 dentists (84.8%) returned a questionnaire. While demonstrating an improvement on all subscales of the MBI-NL at the first post-test, results show that the program participants showed a relapse at the second post-test. Controls who took action on their own initiative, on the other hand, reported a beneficial effect in the long run. Finally, controls that did not take any preventive action showed little or no progress. Possible causes for these findings are discussed, including the influence of coping style. perceived control, confounding factors, demand characteristics, and the necessity of post-intervention follow-up.     

Validation of anatomical landmarks-based registration for image-guided surgery: An in-vitro study

IntroductionPerioperative navigation is a recent addition to orthognathic surgery. This study aimed to evaluate the accuracy of anatomical landmarks-based registration.Materials and methodsEighty-five holes (1.2 mm diameter) were drilled in the surface of a plastic skull model, which was then scanned using a SkyView cone beam computed tomography scanner. DICOM files were imported into BrainLab ENT 3.0.0 to make a surgical plan. Six anatomical points were selected for registration: the infraorbital foramena, the anterior nasal spine, the crown tips of the upper canines, and the mesial contact point of the upper incisors. Each registration was performed five times by two separate observers (10 times total).ResultsThe mean target registration error (TRE) in the anterior maxillary/zygomatic region was 0.93 ± 0.31 mm (p < 0.001 compared with other anatomical regions). The only statistically significant inter-observer difference of mean TRE was at the zygomatic arch, but was not clinically relevant.ConclusionWith six anatomical landmarks used, the mean TRE was clinically acceptable in the maxillary/zygomatic region. This registration technique may be used to access occlusal changes during bimaxillary surgery, but should be used with caution in other anatomical regions of the skull because of the large TRE observed.