ALBERT

Description: Fractionation of the noble gases should occur during formation of a Structure I gas hydrate from water and CH4 such that CH4 hydrate is greatly enriched in Xenon. Noble gas concentrations and fractionation factors (F[4He], F[22Ne], F[86Kr], and F[132Xe] as well as R/Ra) were determined for eight gas hydrate specimens collected on Leg 164 to evaluate this theoretical possibility and to assess whether sufficient quantities of Xe are hosted in oceanic CH4 hydrate to account for Xe "missing" from the atmosphere. The simplest explanation for our results is that samples contain mixtures of air and two end-member gases. One of the end-member gases is depleted in Ne, but significantly enriched in Kr and Xe, as anticipated if the source of this gas involves fractionation during Structure I gas hydrate formation. However, although oceanic CH4 hydrate may be greatly enriched in Xe, simple mass balance calculations indicate that oceanic CH4 hydrate probably represents only a minor reservoir of terrestrial Xe. Noble gas analyses may play an important role in understanding the dynamics of gas hydrate reservoirs, but significantly more work is needed than presented here.

Description: Patients with fludarabine refractory CLL have a median survival of 10 months with conventional chemotherapy. Intravenous (IV) alemtuzumab is approved in fludarabine refractory CLL resulting in 33 to 50% responses. Combined alemtuzumab and fludarabine can induce responses in CLL refractory to both agents. Infusion reactions and 2-hour infusions 3x a week for 12 weeks are problems with IV alemtuzumab. Subcutaneous (SC) alemtuzumab is more convenient but pharmacokinetics suggest the need for prolonged therapy with little efficacy data in fludarabine-refractory CLL. We report on the UKCLL02 study to assess the safety and effectiveness of SC alemtuzumab in fludarabine-refractory CLL. SC alemtuzumab was given at a dose of 30mg 3x a week (after dose escalation) for up to 24 weeks depending on 6-weekly marrow assessments. Patients failing to respond to alemtuzumab in the trial could receive oral fludarabine (40mg/m2/day for 3 days every 4 weeks) combined with SC alemtuzumab. In this planned interim analysis of the first 44 patients (median age 66, range 41 to 79) 2 patients died before receiving alemtuzumab, and 5 remain on therapy. Of the remaining 37 patients, one withdrew consent and 36 patients have completed therapy. Responses to alemtuzumab monotherapy (n=36) were 2 MRD negative CR, 1 MRD positive CR, 11 PR (including 1 MRD negative patient who remained cytopenic), 20 NR and 2 died. Alemtuzumab was given for a median 12 weeks (range: 2–24) with a median dose of 913mg (range 106 to 2173mg). 12 patients (8 NR and 4 PR) received concurrent fludarabine and SC alemtuzumab (median 2.5 courses fludarabine [range 1–3]). 2 non-responders achieved a PR and one of the partial reponders achieved a CR (MRD positive). Therefore the overall response rate for the whole cohort was 16/36 (44%) including 3 MRD negative patients (2 CRs and 1 PR). IgVH gene was unmutated (〉98% homology to germ line DNA) in 11/14. FISH revealed poor risk deletions (11q and/or 17p) in 21/34 patients (17p- in 9; 11q- in 6 and both in 6). p53 functional analysis is available for 23. 20/23 had p53/ATM dysfunction or deletion. 10/21 evaluable cases with del (11q23)/del (17p) responded to therapy. The initial alemtuzumab dose was associated with localised erythematous skin reactions in 20 patients (diameter 1 to 18cm), fever in 7 and rigors in 3. All reactions subsided in

Description: Cyclic fluctuations of the leukocyte and platelet counts were observed in five patients with chronic myelogenous leukemia during treatment with hydroxyurea. The cyclic periods ranged from 30 to 50 days, were similar in each individual, but the peak-to-trough values of single cycles varied in magnitude. A second biorhythm was a cyclic undulation of the leukocyte count with heights of the peaks at nine-to-20-month intervals. Rhythmic variations of the platelet counts were also observed; the period and phase of the cycle being the same as that of the leukocyte cycle. No cyclic oscillations were noted in the hemoglobin or reticulocyte counts. The recognition of the phenomenon may aid in the use of hydroxyurea or other chemotherapeutic agents in the control of myelogenous leukemia. Chronopharmacology may more accurately develop the use of antitumor agents by its investigation of drug effects on biologic characteristics as a function of biologic timing.

Description: A series of Cu-substituted goethites, single and co-substituted with Cr, Zn, Cd and/or Pb was prepared, having molar ratios equal to 2.00, 3.33 and 5.00 mol%. All the samples contained only goethite, except Cu-, (Cu,Zn)- and (Cu,Pb)-samples synthesized at 5.00 mol% where hematite was also formed. The presence of Cr/Cd suppressed the hematite-forming effects of Cu. The general sequence of metal entry into the single-metal-substituted goethites was Zn = Cr 〉 Cd 〉 Cu 〉 Pb and in di- (5.00 mol%) and tri- (3.33 mol%) metal-substituted goethites was Cu 〉 Zn 〉 Cd 〉 Cr 〉〉 Pb. Cu incorporation increased all the unit-cell parameters in single-metal-substituted goethite, and these parameters increased in combination with other metals as follows: Cd 〉 Zn 〉 Cr 〉 Pb in the multimetal-substituted goethites. The Cu-substituted goethite dissolved faster than pure goethite. Co substitutions of Cr/Pb reduced the dissolution rate (kFe), while substitutions of Cd/Zn increased kFe.