Citations

AbstractWe examined the chronic lymphocytic leukemia (CLL) cells of 2457 patients evaluated by the CLL Research Consortium (CRC) and found that 63 (2.6%) expressed immunoglobulin (Ig) encoded by the Ig heavy-chain-variable-region gene (IGHV), IGHV3-21. We identified the amino acid sequence DANGMDV (motif-1) or DPSFYSSSWTLFDY (motif-2) in the Ig heavy-chain (IgH) third complementarity-determining region (HCDR3) of IgH, respectively, used by 25 or 3 cases. The IgH with HCDR3 motif-1 or motif-2, respectively, was paired with Ig light chains (IgL) encoded by IGLV3-21 or IGKV3-20, suggesting that these Ig had been selected for binding to conventional antigen(s). Cases that had HCDR3 motif-1 had a median time from diagnosis to initial therapy comparable with that of cases without a defined HCDR3 motif, as did cases that used mutated IGHV3-21 (n = 27) versus unmutated IGHV3-21 (n = 30). Of 7 examined cases that used Ig encoded by IGHV3-21/IGLV3-21, we found that 5 had a functionally rearranged IGKV allele that apparently had incurred antigendriven somatic mutations and subsequent rearrangement with KDE. This study reveals that CLL cells expressing IGHV3-21/IGLV3-21 most likely were derived from B cells that had experienced somatic mutation and germinal-center maturation in an apparent antigen-driven immune response before undergoing Ig-receptor editing and after germinal-center leukemogenic selection.

Background and Purpose— Evidence supports a substantial genetic contribution to the risk of intracranial aneurysm (IA). The purpose of this study was to identify chromosomal regions likely to harbor genes that contribute to the risk of IA. Methods— Multiplex families having at least 2 individuals with “definite” or “probable” IA were ascertained through an international consortium. First-degree relatives of individuals with IA who were at increased risk of an IA because of a history of hypertension or present smoking were offered cerebral magnetic resonance angiography. A genome screen was completed using the Illumina 6K SNP system, and the resulting data from 192 families, containing 1155 genotyped individuals, were analyzed. Narrow and broad disease definitions were used when testing for linkage using multipoint model-independent methods. Ordered subset analysis was performed to test for a gene×smoking (pack-years) interaction. Results— The greatest evidence of linkage was found on chromosomes 4 (LOD=2.5; 156 cM), 7 (LOD=1.7; 183 cM), 8 (LOD=1.9; 70 cM), and 12 (LOD=1.6; 102 cM) using the broad disease definition. Using the average pack-years for the affected individuals in each family, the genes on chromosomes 4 (LOD=3.5; P =0.03), 7 (LOD=4.1; P =0.01) and 12 (LOD=3.6; P =0.02) all appear to be modulated by the degree of smoking in the affected members of the family. On chromosome 8, inclusion of smoking as a covariate did not significantly strengthen the linkage evidence, suggesting no interaction between the loci in this region and smoking. Conclusions— We have detected possible evidence of linkage to 4 chromosomal regions. There is potential evidence for a gene×smoking interaction with 3 of the loci.

Background Isolated meniscal tears in the skeletally immature patient are infrequent but well-recognized injuries. Although few studies have evaluated the pediatric and adolescent population, arthroscopic surgical repair remains the standard of care for Patients in this age group with unstable meniscal tears. Purpose To review our results of arthroscopic repair of isolated meniscal tears in pediatric and adolescent patients to further define future management of these injuries. Study Design Case series; Level of evidence, 4. Methods The records of all patients 18 years old or younger who underwent isolated meniscal repair between 1990 and 2005 were retrospectively reviewed. Forty-four patients (6 girls, 38 boys) with an average age of 15.8 years (range, 9.9-18.7 years) were included in this study, for a total of 45 isolated meniscal tears. Clinical examinations were performed, International Knee Documentation Committee forms were administered, and Tegner scores were determined at an average of 5.8 years (range, 2.5 months-13.8 years) postoperative follow-up. Three patients were lost to follow-up. Results The clinical success rate of arthroscopic meniscal repair was 80% for simple tears, 68% for displaced bucket-handle tears, and 13% for complex tears. Seventeen menisci (38% overall) failed initial repair at a mean of 17 months (range, 3-61 Months) postoperatively and underwent repeat arthroscopic surgery (15 partial meniscectomies, 2 rerepair). The average Tegner and International Knee Documentation Committee scores were 8 (range, 5-9) and 89.4 (range, 79-99), respectively, at the time of final follow-up. Risk factors for failure included complex tears and rim width greater than 3 mm. Conclusion Clinically successful repair of an isolated meniscal tear in patients 18 years or younger was variable depending on tear type, with complex tears and rim width 3 mm or greater being negative prognostic factors.