Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis

Somatic hypermutation (SHM) features in a series of 1967 immunoglobulin heavy chain gene (IGH) rearrangements obtained from patients with chronic lymphocytic leukemia (CLL) were examined and compared with IGH sequences from non-CLL B cells available in public databases. SHM analysis was performed for all 1290 CLL sequences in this cohort with less than 100% identity to germ line. At the cohort level, SHM patterns were typical of a canonical SHM process. However, important differences emerged from the analysis of certain subgroups of CLL sequences defined by: (1) IGHV gene usage, (2) presence of stereotyped heavy chain complementarity-determining region 3 (HCDR3) sequences, and (3) mutational load. Recurrent, "stereotyped" amino acid changes occurred across the entire IGHV region in CLL subsets carrying stereotyped HCDR3 sequences, especially those expressing the IGHV3-21 and IGHV4-34 genes. These mutations are underrepresented among non-CLL sequences and thus can be considered as CLL-biased. Furthermore, it was shown that even a low level of mutations may be functionally relevant, given that stereotyped amino acid changes can be found in subsets of minimally mutated cases. The precise targeting and distinctive features of somatic hypermutation (SHM) in selected subgroups of CLL patients provide further evidence for selection by specific antigenic element(s).     

Beitrag zum klinischen und bacteriologischen Studium der brasilianischen Framboesie oder „Boubas”

Ohne ZusammenfassungHierzu Taf. I–IV.     

The in-vivo effect of sodium-potassium citrate on the crystal growth rate of calcium oxalate and other parameters in human urine

Summary In this study, an efficient microtechnique (gel crystallization method) was used to investigate the in-vivo effect of sodium-potassium citrate on the crystal growth rate of calcium oxalate (Vcr) in human urine samples of 6 healthy volunteers. With a daily dose of 3x11 mmol of alkali citrate, Vcr decreased by 70%. This could have been due to the decrease of calcium excretion, which caused 50–60% of the total change, and to the increase of citrate and pH, each contributing about 20–25% to the decline of Vcr. The findings explain the clinical advantages of alkali citrates in the prevention of recurrent calcium oxalate stone formation.     

Changes in coronary flow reserve following stent implantation in the swine descending thoracic aorta.

PURPOSE: To evaluate coronary flow reserve (CFR) changes following stent implantation in the descending thoracic aorta (DTA) of a porcine model. METHODS: Six pigs (3 males; 40 to 44 kg) were anesthetized and kept on mechanical ventilation. A 6-F guiding right Judkins catheter was advanced under fluoroscopy to the right coronary artery, and a pressure wire with a temperature sensor was placed within the vessel lumen at a distance of 4 cm from the ostium. CFR was estimated by the thermodilution method before and after maximal coronary vasodilation with 20 mg of intracoronary papaverine. Aortography was also performed to measure aortic diameter. Subsequently, a self-expanding vascular stent was deployed into the DTA just below the left subclavian artery (LSA), and CFR was measured again. All animals were maintained for 3 weeks; at the end of this period, a further CFR was calculated using the same procedure. RESULTS: The mean aortic diameter below the LSA was 12.15+/-0.15 mm. Following stent deployment, the mean aortic diameter measured at the stented segment was 12.58+/-0.11 (p=0.001 versus baseline). The mean CFR value was 4.70+/-2.00 before stent implantation, 2.68+/-0.86 immediately after, and 4.05+/-1.15 at 3 weeks after stenting. Accordingly, CFR values were significantly depressed immediately after stent placement compared with baseline (p=0.027). However, CFR values obtained 3 weeks following stent deployment were similar to the initial values (p=0.59). CONCLUSION: Stent deployment in the normal swine DTA produces a significant immediate decrease in CFR, which is attenuated 3 weeks later. The clinical impact of CFR changes following DTA endografting remain to be elucidated.     

A Pilot Study of Piracetam in Cuprophan Hemodialysis

Twelve patients, 8 male and 4 female, aged from 26 to 70 years were studied. They were on hemodialysis (HD) 4 h three times weekly with cuprophan hollow fiber dialyzers (Gambro 120M) and dialysate containing 35 mEq/L of acetate. The study compares two random HD sessions on each patient. Sixty minutes prior to one random session a placebo was administered orally, and prior to another random session piracetam was given at a dose of 8 g. Heparin dosage was not reduced during HD using QB 200 ml, QD 500 ml, and no ultrafiltration. Blood samples for leukocyte and platelet counts, serum C3, arterial paO2 and paCO2, thromboxane-B2 (TxB2), and beta-thromboglobulin (beta-TG) were taken from the arterial line before and at 15, 60, and 240 min during HD. Leukopenia at 15 min of HD was found to be less severe (p less than 0.01) in the piracetam study than in the placebo, whereas platelet count did not change. Serum C3 was slightly increased in both studies. Arterial oxygen was preserved close to the initial levels by piracetam (91.66 mm Hg versus 81.08, p less than 0.01 at 60 min, and 93.08 versus 80.17 mm Hg, p less than 0.01 at 240 min of HD sessions) but paCO2 did not change significantly. TxB2 increased less with piracetam in comparison to placebo (p less than 0.01 or p less than 0.001), but beta-TG was reduced significantly by piracetam at any time during HD (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of Gamma Knife Radiosurgery in the management of unresectable gross disease or gross residual disease after surgery in ependymoma

SummaryPurpose/Objective To evaluate the efficacy and the toxicity of Gamma Knife (GK)-based stereotactic radiosurgery (SRS) in the management of gross disease in ependymoma.Materials and methods Eight patients with 13 ependymomas were treated with GK-based SRS in our institution for gross disease. Five patients were treated for recurrent disease that developed after surgery and external beam radiotherapy (EBRT), two received SRS to the gross disease after surgery and EBRT, and one received SRS alone (in a 1.3 year old child). Median EBRT dose was 54.4 Gy (range 50–55.8 Gy). Median SRS dose was 14 Gy (range 12–20 Gy). Seven of eight (87.5%) patients had SRS to a single lesion and one of eight (12.5%) patients had treatment to six tumors in three different sessions.Results The median follow up was 30.2 months (range 8–65.4 months). Out of the eight patients treated with SRS, six (75%) were alive, four (50%) were alive with no recurrence, two (25%) were alive with recurrence, and two (25%) died of recurrent disease. Both patients treated with SRS as a boost were alive and without recurrence. Out of the five patients who received SRS as salvage treatment, three (60%) were alive, two (40%) were alive without recurrence, two (40%) developed distant failure, and three (60%) had in-field control. Two patients who received SRS to their brainstem lesions developed symptoms related to radionecrosis and were successfully treated with steroid with good control of symptoms.Conclusions GK-based SRS appears to be a feasible and safe treatment modality for patients with ependymoma with unresectable gross disease or gross residual disease after surgery. SRS provides reasonable local control but out-of-field tumor progression remains an issue. For patients who receive SRS as a boost, the local control appears to be excellent. This paper has been presented in the American Society for Therapeutic Radiology and Oncology Meeting in Denver, CO in October 2005.