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OBJECTIVE Preoperative treatment of rectal cancer with combined chemotherapy and radiation therapy has become a widely accepted strategy. The current challenge is to improve outcomes whereas minimizing morbidity and maximizing the potential for a sphincter sparing procedure. This study sought to evaluate the safety and efficacy of a combination of 2 novel approaches-accelerated, hyperfractionated radiation therapy and twice daily oral capecitabine. METHODS Consenting patients with locally advanced T3-T4, N0-1, M0 rectal adenocarcinoma, located no further than 15 cm from the anal verge, were treated with twice daily fractions of 1.2 Gy M-F to a total of 50.4 Gy for T3 lesions and 55.2 Gy for T4 lesions. Concomitantly, the patients received capecitabine 825 mg/m twice per day 7 days per week. Patients were operated on 4 to 6 weeks after completion of therapy. RESULTS Sixteen of 17 enrolled patients were eligible and all 16 completed the full course of treatment including definitive surgery. Eleven patients had a sphincter sparing procedure and 5 had an abdominoperineal resection. Tumor and/or nodal downstaging occurred in 81% of patients, 100% of resections were R0, and the sphincter preservation rate was 68%. There were 18% pathologic complete remissions and 68% of specimens were node negative with an additional 12% Nx owing to transanal excision. The therapy was well tolerated and there were no unexpected toxicities with only diarrhea reaching grade 3 in 4 patients. CONCLUSIONS This novel approach to preoperative treatment of rectal adenocarcinoma was well tolerated and effective. Comparison with more established approaches appears justified.

Purpose The purpose of this study was to determine the tolerability, clinical response rate, and time to disease progression of gemcitabine treatment in patients with low-grade non-Hodgkin lymphoma. (NHL) PATIENTS AND METHODS: Twenty patients with low-grade NHL and progression of disease after at least 1 prior treatment regimen were prospectively enrolled. The treatment regimen consisted of 1200 mg/m2 gemcitabine intravenously administered weekly for 7 weeks followed by a 1-week rest. Subsequent treatment was given weekly for 3 weeks followed by a 1-week rest and repeated for a maximal treatment of 6 cycles until disease progression or unacceptable toxicity. Results The predominant histologic subtypes among our patients were small lymphocytic (8 of 20) and follicular (7 of 20). Grade III/IV hematologic toxicity was observed in 15 of 20 patients and dose reductions or treatment delays occurred in 19 of 20 patients. Fatigue and asthenia were treatment-limiting in many patients. There were no complete or partial responses observed and only 2 patients had stable disease after 12 weeks of treatment. The average time to progression or off-study status was 2.3 months (95% confidence interval, 1.7-2.9) with 8 patients showing progression of disease. Twelve patients were taken off the study as a result of unacceptable toxicity before observed progression of disease. No patient completed the planned course of therapy. With a median follow up of 10.2 months, 10 of 20 patients remained alive. Conclusion Gemcitabine as a single agent, in this dosage and schedule, has minimal clinical activity in relapsed or refractory low-grade lymphomas and was associated with considerable toxicity. Therefore, further study of gemcitabine in this setting is not justified.

Background The management of perioperative anticoagulation therapy for patients having a high risk of thromboembolism who are receiving long-term oral anticoagulant therapy is uncertain. The prevalent approach is to discontinue oral anticoagulation therapy and initiate heparin therapy. Another potential strategy is to continue oral anticoagulation therapy with a temporary adjustment of warfarin intensity to a preoperative international normalized ratio (INR) of 1.5 to 2.0. Such moderate-dose anticoagulation therapy with warfarin has been shown to be hemostatically safe yet effective in the prevention of thromboembolism after hip or knee replacement Methods Over an 11-year period ( ie , 1993 to 2003), our hemostatic consultative service prospectively identified 100 consecutive patients for whom we continued warfarin therapy at adjusted doses during the perioperative period, targeting a goal for the INR of 1.5 to 2.0. Patients were assigned a score for venous thromboembolic risk as well as overall surgical risk using published instruments. Score assignment was based on what was deemed to be extremely high risk for thromboembolism in patients who were receiving long-term warfarin therapy. Although the patients were accrued prospectively, the final retrospective analysis was made after all patients were treated Results The most common indication (62%) for high-risk assignment was a thromboembolic event within the past 6 months. The second most prevalent reason was prior postoperative venous thromboembolism (VTE) [11%]. Indications for long-term anticoagulation therapy were recent VTE (62%), inherited thrombophilia (7%), antiphospholipid syndrome (13%), mechanical heart valves (18%), and prior cerebrovascular accident (4%). The prevalence of inherited thrombophilia probably has been grossly underestimated, as neither factor V Leiden mutation nor prothrombin 20210 mutation had been described during the bulk of the accrual time. Most surgical procedures (58%) were significantly invasive (Johns Hopkins category 3 to 5). The mean INR values were 2.1 on the day prior to surgery (SD, 0.9594; range, 1.2 to 6.5; n=65), 1.8 on the day of surgery (SD, 0.4899; range, 1.2 to 4.9; n=75), and 1.8 on the first postoperative day (SD, 0.4436; range, 1.1 to 3.3; n=70). Two patients had major bleeding, and four patients had minor bleeding. One patient developed deep venous thrombosis. Several weeks after surgery, one patient with a prosthetic heart valve died from an embolic stroke, which was associated with a failure to increase his anticoagulation to therapeutic levels Conclusions Moderate-intensity anticoagulant therapy with warfarin, targeting a goal INR of 1.5 to 2.0, appears to be a safe and feasible method for preventing thromboembolic complications in high-risk surgical patients who are receiving long-term oral anticoagulant therapy. This may be considered a reasonable method to afford thromboprophylaxis in highly selected patients who are occasionally seen in clinical practice. This observational study does not prove equality, let alone superiority, to other proposed methods of anticoagulation therapy

The Cassini-Huygens Cosmic Dust Analyzer (CDA) is intended to provide direct observations of dust grains with masses between 10(-19) and 10(-9) kg in interplanetary space and in the jovian and saturnian systems, to investigate their physical, chemical and dynamical properties as functions of the distances to the Sun, to Jupiter and to Saturn and its satellites and rings, to study their interaction with the saturnian rings, satellites and magnetosphere. Chemical composition of interplanetary meteoroids will be compared with asteroidal and cometary dust, as well as with Saturn dust, ejecta from rings and satellites. Ring and satellites phenomena which might be effects of meteoroid impacts will be compared with the interplanetary dust environment. Electrical charges of particulate matter in the magnetosphere and its consequences will be studied, e.g. the effects of the ambient plasma and the magnetic held on the trajectories of dust particles as well as fragmentation of particles due to electrostatic disruption. The investigation will be performed with an instrument that measures the mass, composition, electric charge, speed, and flight direction of individual dust particles. It is a highly reliable and versatile instrument with a mass sensitivity 106 times higher than that of the Pioneer 10 and I I dust detectors which measured dust in the saturnian system. The Cosmic Dust Analyzer has significant inheritance from former space instrumentation developed for the VEGA, Giotto, Galileo, and Ulysses missions. It will reliably measure impacts from as low as I impact per month up to 104 impacts per second. The instrument weighs 17 kg and consumes 12 W, the integrated time-of-flight mass spectrometer has a mass resolution of up to 50. The nominal data transmission rate is 524 bits/s and varies between 50 and 4192 bps

TA-1 is a monoclonal antibody identifying a cell surface molecule with a broad distribution on normal and malignant human leukocytes. Preliminary structural studies performed by using radioimmunoprecipitation and sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated that TA-1 recognizes a two-chain polypeptide of approximately 170 kilodaltons (KD) and 95 KD under reducing conditions. The same experiment conducted under nonreducing conditions yielded bands of approximately 155 KD and 110 KD, suggesting the existence of intrachain disulfide bonds in both subunits. Both polypeptide chains were labeled with tritiated sodium borohydride after treatment of cells with neuraminidase and galactose oxidase, thereby demonstrating that both were glycosylated. Tryptic peptide mapping indicated that the 170-KD and 95-KD subunits did not have significant homology in peptide composition. We are designating this newly defined human leukocyte bimolecular complex gp 170/95.

Considerable progress has been achieved in HgI_2 detector fabrication technology and amplification electronics. An energy resolution of 198 eV (full width at half maximum) has been obtained for the Mn K_α line of 5.9 keV in a practical X-ray probe without the use of cryogenic cooling. Detectors prepared with Parylene-C encapsulation have demonstrated perfect reliability in two-year tests under high vacuum and temperature and bias cycling. Other HgI_2 detectors have been used to demonstrate proton-radiation-damage resistance to levels of 10^(12) protons/cm^2 at 10.7 MeV. It is concluded that HgI_2 detectors are suitable for the ordinary requirements of energy dispersive detectors in X-ray spectroscopy systems.

An ion microprobe has been used to observe ^(26)Mg/^(24)Mg in excess of normal values in anorthite crystals from Allende refractory inclusions. In one crystal, ^(26)Mg excesses up to 40% above normal, correlated with Al/Mg, were observed, These excesses are many times larger than those observed by other techniques. The correlation with Al/Mg indicated that the excess ^(26)Mg in the Allende anorthite is uniformly distributed in the anorthite crystal. Analytical procedures and conditions were carefully controlled. Nevertheless, small but significant apparent ^(26)Mg/^(24)Mg anomalies in isotopically normal samples were observed in analyses by one ion microprobe. A repetition of the isotopic analyses using another ion probe produced normal ratios in the normal samples and confirmed large ^(26)Mg excesses in the Allende anorthite.

We have produced a new monoclonal antibody designated BA-3. An extensive side-by-side serologic comparison of BA-3 with the anti-common acute lymphoblastic leukemia antigen (CALLA) monoclonal antibody J-5 was undertaken. Cells examined included established leukemic cell lines, malignant cells from patients with newly diagnosed leukemia/lymphoma, and normal hematopoietic tissues. In all experiments the cellular distribution of the antigens recognized by BA-3 and J-5 were identical when analyzed by immunofluorescent microscopy and the FACS. Iodination of NALM-6 cells, followed by radioimmunoprecipitation and SDS-PAGE, indicated that BA-3 (like J-5) precipitated a glycoprotein of approximately 100,000 daltons. Competitive binding studies using 125I-labeled BA-3 indicated that BA-3 and J-5 were binding to closely associated (if not identical) epitopes on CALLA. Calculation of the equilibrium constant (K value) for BA-3 and J-5, and the approximate number of CALLA molecules per cell, was graphically determined using Scatchard plots. BA-3 and J-5 were shown to have K values of approximately 2.7 x 10(7) M-1 and 7.2 x 10(7) M-1, respectively, with NALM-6 cells expressing 1 x 10(5) to 2 x 10(5) CALLA molecules per cell. Additional studies with BA-3 failed to demonstrate significant antigenic modulation of CALLA in vitro using fresh leukemic cells and leukemic cell lines. Thus, we suggest that antibody affinity may be a significant factor influencing antigenic modulation of CALLA in vitro.