Long-term follow-up of a randomized post-induction therapy trial in acute myelogenous leukemia (a Southeastern Cancer Study Group trial)

A phase III clinical trial was designed to determine if more intensive induction and consolidation therapy for acute myeloblastic leukemia increases the remission rate and prolongs survival. A minor objective was to determine if the use of non-cross resistant drugs was more effective than the same drugs used for induction. Patients with untreated leukemia between the ages of 15 and 50 were given daunorubicin 45 mg/m2 for the first 3 days of a 10-day continuous infusion of cytosine arabinoside, initially at a dose of 2000 mg/m2 but reduced to 100 mg/m2 because of toxicity. Those under 36 achieving a complete remission and with an histocompatible donor were assigned to a transplant arm. The rest were randomized to receive one of three consolidation arms: A, cytosine arabinoside, 200 mg/m2 daily for 7 days and daunorubicin 45 mg/m2 daily for 3 days for three courses; B, one course as in Arm A followed by amsacrine, 120 mg/m2 daily for 5 days followed by a 5-day continuous infusion of azacytidine, 150 mg/m2/day; C, thioguanine and cytosine arabinoside, 100 mg/m2 every 12 h and daunorubicin 10 mg/m2 daily for 5 days for three courses followed by four maintenance courses of cytosine arabinoside, 100 mg/m2 daily for 5 days and daunorubicin, 45 mg/m2 for 2 days every 13 weeks. From 1981 to 1986, 398 eligible patients were enrolled and 219 achieved a complete remission. The initial induction dose of cytosine arabinoside was reduced after five of 29 patients exhibited fatal gastrointestinal toxicity. Only 11 patients were assigned to the transplant arm. There were no significant differences in the consolidation arms. The 5 year disease-free survivals were 38, 31 and 27% in arms A, B, and C respectively. Intensive consolidation therapy with the same or different drugs used in induction was as effective as lower dose consolidation followed by maintenance therapy.     

In situ bypass and diabetes

From 1986 through to 1990 a total of 483 in situ bypass procedures were performed in 444 patients. Preoperative risk-factors were equally distributed among diabetic (DM) and non-diabetic (NDM) patients, except for smoking habits (DM:48%, NDM:64%, p = 0.002) and cardiac disease (DM:45%, NDM:29%, p = 0.005). Critical limb-ischaemia was more often present in diabetic than non-diabetic patients (DM:57%, NDM:36%, p = 0.0002). Diabetic patients had a significantly lower distal anastomosis than non-diabetic patients (p = 0.00001). There were no differences among diabetic and non-diabetic patients regarding three years primary and secondary patency (58% and 64% respectively), and regarding major amputations. However, the rate of minor amputations was higher in insulin-dependent compared with non-insulin-dependent diabetics, who in turn had a higher rate than non-diabetics (p < 0.00001). A markedly decreased survival rate was found in diabetics (p < 0.00005). We found the in situ bypass technique very useful in the treatment of critical ischaemia of the lower limb in diabetic patients. The overall results in diabetic patients, whether insulin-dependent or not, were equal to those in non-diabetic patients.     

Fabrication and characterization of planar and channel polymer wave guides. I. Plasma-polymerized HMDS films

Plasma-polymerized hexamethyldisiloxane (HMDS) films have been prepared as both planar and channel wave guides. The optical attenuation results measured in both the planar and channel HMDS wave guides were found to be similar, thus demonstrating that the inherent solvent resistance and chemical inertness of the plasma polymerized films allows the use of common photoresist techniques, including application of the photoresist, photomasking, and subsequent etching. This may be contrasted with wave guides made from conventional polymers, where careful consideration must be given to photoresist/polymer compatibility, because the photoresist solvents may adversely affect the underlying polymer and lead to degradation of the material during processing. © 1995 John Wiley & Sons, Inc.     

Oncogene rearrangement in non-Hodgkin's lymphoma with a 14q+ chromosome of unknown origin

Southern blot analysis was performed with a panel of DNA probes to detect rearrangements of c-myc, bcl-1, bcl-2 and bcl-3 in 14 cases of B-cell non-Hodgkin's lymphoma (NHL) with a clonal cytogenetic rearrangement involving the chromosome 14q32 locus and no known donor chromosome [t(14;?)(q32;?)]. In our experience, 21% of all chromosomal abnormalities involving the 14q32 locus in B-cell NHL are of this type. We found oncogene rearrangements in five of the 14 cases: bcl-1 rearrangement on one mantle zone lymphoma, bcl-2 rearrangements in two follicular lymphomas, and c-myc rearrangements in two small noncleaved cell lymphomas. We conclude that a 14q32+ abnormality of unknown origin is a relatively frequent karyotypic finding in B-cell NHL. In one third of the cases, known oncogenes that have been previously described in reciprocal translocations involving the immunoglobulin heavy chain locus were shown to be involved in the 14q32+ abnormality. The translocations in the other cases are likely to have involved one of the above oncogenes with breakpoints not revealed by the probes employed, other known oncogenes, or oncogenes that have not yet been identified.     

The OKT3 Antibody Response Study: a multicentre study of human anti-mouse antibody (HAMA) production following OKT3 use in solid organ transplantation

Human anti-murine antibody titres following patient exposure to the monoclonal antibody Orthoclone OKT3 (muromonab-CD3) are determined by laboratories using diverse analytical methods which are not standardized and whose concordance is not established. A multicentre study group therefore compared testing for IgG anti-OKT3 antibody among seven laboratories. A set of 270 sera was obtained from 30 heart, 30 kidney and 30 liver transplant recipients with no previous exposure to OKT3 who were receiving OKT3 for induction immunosuppression. Sera were collected from each patient prior to and at 24 +/- 2 days and 31 +/- 2 days following initial OKT3 exposure. Identical aliquots of all 270 sera were tested for IgG anti-OKT3 antibody by each laboratory. In addition, the limit of detection of each laboratory's method was estimated by titration of an affinity-purified IgG anti-OKT3 reference material of known concentration. Anti-OKT3 antibody formation differed greatly among the three organ groups. Cardiac patients demonstrated the least sensitization and almost exclusively lower titres, while kidney recipients had more frequent and higher titre antibody formation. Liver recipients yielded the highest sensitization rate and the most frequent high titre sera. Importantly, the seven laboratories differed widely in the number of pretreatment sera reported as positive (ranging from 0% to 41% among laboratories), the number of post-OKT3 sera reported as positive (17-63%), the number of post-OKT3 samples with titre > or = 1000 (2-31%), and the number of patients sensitized 19-69%). Concordance among laboratories was highly variable, with interlaboratory agreement ranging from 38% to 83% on the sample titres assigned to 180 post-OKT3 sera. Many of the discordant results were consistent with differences in the limit of detection of the analytical methods, which ranged from 0.19 microgram/ml to > or = 15 micrograms/ml, a nearly 100-fold difference among laboratories. This study demonstrated the presence of both good concordance and significant discordance among laboratories in determining human anti-mouse antibody titres, and demonstrated that common titre categories (100, 1000, 10,000) were not equivalent among laboratories. The level of concordance among methods should be considered when comparing anti-OKT3 antibody results from different centres and their correlation with clinical events. Universal comparative testing, patterned after proficiency testing programmes, is needed to assess differences among laboratories and to bring uniformity and a sound interpretative basis to this field of testing.     

Olfactory recognition of nonhosts aspen and birch by conifer bark beetlesTomicus piniperda andHylurgops palliatus

The field response ofTomicus piniperda (L.) andHylurgops palliatus (Gyll.) (Coleoptera: Scolytidae) to the attractant ethanol in combination with volatile wood constituents released from the nonhost tree speciesPopulus tremula L. (Salicaceae) andBetula pendula Roth (Betulaceae) was studied using flight barrier traps. The attraction of both species decreased when aspen or birch wood was added to the ethanol bait. The same was true forRhizophagus depressus (F.) (Coleoptera: Rhizophagidae), a predatory species associated with conifer bark beetles.Glischrochilus quadripunctatus (L-),Epuraea bickhardti St.-Claire Deville,E. unicolor (Oliv.) (Coleoptera: Nitidulidae), andRhizophagus parvutus (Payk.) (Coleoptera: Rhizophagidae) were caught in higher numbers in traps baited with both ethanol and wood of aspen or birch than in traps baited with ethanol alone. In a separate experiment, landings ofT. piniperda andH. palliatus on nonhosts (black plastic tubes) were demonstrated with sticky traps.