Distribution, function, and prognostic value of cytotoxic T lymphocytes in follicular lymphoma: a 3-D tissue-imaging study

CD8+ CTLs are thought to play a role in the control of follicular lymphoma (FL). Yet, the link between CTL tissue distribution, activation status, ability to kill FL cells in vivo, and disease progression is still elusive. Pretreatment lymph nodes from FL patients were analyzed by IHC (n = 80) or by 3-color confocal microscopy (n = 10). IHC revealed a rich infiltrate of CD8+ granzyme B+ (GrzB) cells in FL interfollicular spaces. Accordingly, confocal microscopy showed an increased number of CD3+CD8+GrzB+ CTLs and a brighter GrzB staining in individual CTL in FL samples compared with reactive lymph nodes. CTLs did not penetrate tumor nodules. In 3-dimensional (3-D) image reconstructions, CTLs were detected at the FL follicle border where they formed lytic synapse-like structures with FL B cells and with apoptotic cells, suggesting an in situ cytotoxic function. Finally, although GrzB expression in CTLs did not correlate with risk factors, high GrzB content correlated with prolonged progression free-survival (PFS) after rituximab-combined chemotherapy. Our results show the recruitment of armed CTLs with a tumor-controlling potential into FL lymph nodes and suggest that CTL-associated GrzB expression could influence PFS in FL patients having received rituximab-combined chemotherapy.     

The effects of thyroid hormone abnormalities on periodontal disease status

Thyroid hormones play an important role in the regulation of physiologic processes. Thyroid disease can lead to imbalance in the homeostasis of the body and affect the healing capacity of tissues. However, limited data are available regarding the relationship between thyroid hormone imbalance (thyroid disease) and periodontal health. This review is carried out to summarize the relationship between thyroid disease and periodontal status. PUBMED and MEDLINE searches of both human and animal studies were performed to investigate the relationship between thyroid disease, periodontal status, and dental implants. Results suggest that thyroid diseases may affect the status of periodontal diseases, especially in hypothyroid conditions. The duration from disease onset to treatment of thyroid disorders may be critical, since uncontrolled thyroid disease may result in destruction of the periodontium. Further controlled studies are needed to explore the relationship between thyroid hormone imbalance and periodontal status. Periodontal therapies, including dental implant placement, appear to be safe with no increase in treatment failure, so long as the status of the thyroid gland is controlled.     

Vascular complications with newer generations of angioseal vascular closure devices

OBJECTIVES: To evaluate the safety and efficacy of newer generations of a single vascular closure device (VCD), Angioseal, compared to contemporaneous manual compression. BACKGROUND: Previous assessment of VCD safety and efficacy has been based primarily on outcomes associated with the original VCD. Few data exist comparing safety and efficacy of modifications of the original VCDs. METHODS: We evaluated in-hospital outcomes of patients undergoing diagnostic cath and percutaneous coronary intervention at a single center: 3,898 with manual compression and 3,898 with the Angioseal VCD. Three generations of the Angioseal device were studied: Generation 1, 7/97-4/00; Generation 2, 5/00-6/02; and Generation 3, 7/02-12/03. Propensity analysis was used to match patients within each generation for clinical and procedural covariates. RESULTS: Closure success was 98.5% for Generation 1, 98.6% for Generation 2, and 98.1% for Generation 3, P = NS. The odds ratio for any vascular complication comparing Angioseal to manual compression was 0.92 (0.42-2.01) for Generation 1; 0.83 (0.49-1.41) for Generation 2; and 0.75 (0.32-1.77) for Generation 3. Multivariate logistic regression identified closure success and Angioseal device Generation 3 versus Generation 1 as predictive of reduced vascular complications during the entire study period. CONCLUSION: These data indicate that the newest generation of the Angioseal VCD is at least as effective as the original device. Moreover, use of the Angioseal VCD was associated with vascular complications similar to or lower than vascular complications following manual compression for each generation of Angioseal device analyzed.     

Contribution of microdissection for the detection of microsatellite instability in colorectal cancer

The determination ofmicrosatellite instability (MSI) is an important step in the identification of familial colorectal cancer such as hereditary nonpolyposis colon cancer. It could also be of interest in the therapeutic management of sporadic cancer. International criteria for the determination of MSI have been published, recommending the use of microdissection. The aim of this work was to evaluate the impact of contaminant normal DNA in tumor samples for MSI assessment in colorectal cancer using a microdissection technique. We performed a comparative analysis of the microsatellite status between total DNA (DNA extracted from whole tumor samples) and microdissected DNA in 3 different regions from 23 cases of colorectal cancer. Six microsatellites were amplified using fluorescent polymerase chain reaction. We analyzed 9 cases with MSI and 14 cases without instability, with similar results between total DNA and microdissected DNA. Moreover, within a same tumor, the MSI phenotype was observed regardless of the region analyzed. Thus, this work shows the reproducibility of the MSI phenotype throughout a tumor. However, we observed a regional heterogeneity of the MSI profile, consisting of variations in the number and the size of unstable alleles within different regions. This result reflects the genetic heterogeneity of colorectal cancer with MSI. In the 14 cases without instability, we observed an increase of more than 60% in the loss of heterozygosity detection rate after microdissection. Thus, this work confirms the contribution of microdissection for loss of heterozygosity assessment.