The rate of complications after endoscopic biliary sphincterotomy can vary widely in different circumstances and is primarily related to the indication for the procedure and to endoscopic technique, rather than to the age or general medical condition of the patients.

These data support the concept of a dose-response effect for cytarabine in patients with AML who are 60 years of age or younger. The results with the high-dose schedule in this age group are comparable to those reported in similar patients who have undergone allogeneic bone marrow transplantation during a first remission.

Acute myeloid leukemia (AML) remains the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML provide recommendations on the diagnostic evaluation and workup for AML, risk assessment based on cytogenetic and molecular features, treatment options for induction and consolidation therapies for younger and older (age ≥ 65 years) adult patients, and key supportive care considerations.

In many cell systems the interaction of ligands with their receptors causes rapid breakdown and resynthesis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Recent work has focused on the role of the degradation products of PtdIns(4,5)P2 as intermediates in the activation of cell function and growth: inositol trisphosphate (InsP3) can release Ca2+ from intracellular stores and diacylglycerol is thought to activate protein kinase C. This enzyme is also activated by phorbol esters (for example, 12-O-tetradecanoyl phorbol 13-acetate, TPA) and this is assumed to account for the pleiotropic effects of TPA on cell function and growth. Mouse thymocytes are not mitogenically stimulated by TPA alone, but it is a potent co-mitogen in combination with either concanavalin A (Con A) or A23187 (A. N. Corps and J.C.M., unpublished observations). Here we show that mitogenic concentrations of TPA, A23187 and Con A each cause an increase in the net phosphorylation of phosphatidylinositol (PtdIns) to PtdIns(4,5)P2 in mouse thymocytes. This is consistent with simulation by the mitogens of the same phosphoinositide phosphorylations in intact cells as recently demonstrated for the isolated products of the src and ros viral oncogenes in a cell-free system.

Combined treatment with infused PSC 833 and DNR is well tolerated and has activity in patients with poor risk acute myeloid leukemia. Administration of PSC 833 delays elimination of daunorubicinol, but yields variable changes in DNR systemic exposure.

Thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia and disseminated platelet thrombi throughout the microvasculature. Studies by our group have demonstrated calcium- dependent proteolytic activity (calpain) that is no longer detectable in the serum of patients with acute TTP after their recovery. The purpose of this study was to investigate if the protease activity of TTP was detectable in plasma and, therefore, not an in vitro phenomenon secondary to the formation of serum. Additionally, we looked for evidence of membrane association of the active protease in the patients' samples, which would explain the persistence of its activity in the presence of plasma inhibitors. Acute TTP samples, both serum and plasma, were collected from 10 patients with TTP. Calpain was measured using bioassays for enzyme activity and also by detection of the protein using immunoblotting with an anticalpain monoclonal antibody (MoAb). In all instances, calpain could be detected both functionally and antigenically in the acute TTP sera and plasma. No calpain activity could be detected in any of the controls, although antigenic calpain was detectable in one sample from a patient who had undergone cardiopulmonary bypass surgery. To investigate whether the calpain was associated with microparticles in the plasma, the TTP plasma samples were ultrafiltered and ultracentrifuged. Activity was not lost by passage across a 0.2-micron filter but was detectable only in the pellet following ultracentrifugation. Membrane association of the calpain in the microparticles also was demonstrated using solubilization with Triton X-100. Immunoprecipitation studies demonstrated that the calpain activity could be removed by MoAbs against platelet membrane glycoproteins (IX and IIb/IIa) but not by a MoAb against red blood cell membrane glycophorin. These studies indicate that active calpain is associated with platelet microparticles in plasma from patients with TTP.

No abstract

Untreated de novo (n=421) and secondary (n=189) acute myeloid leukemia (AML) patients≥60 years received intensified chemotherapy, including daunorubicin 60mg/m2 and etoposide 100mg/m2 during days 1, 2, 3 with cytarabine 100mg/m2 during days 1–7, with a second induction if needed and one consolidation course with these drugs and doses for 2, 2 and 5 days, respectively. In all, 287 (47%) achieved complete remission (CR), 136 (22%) died and 187 (31%) were non-responders. CR rates were 27, 44 and 52% for complex karyo-types, rare aberrations and neither (P<0.001), 52 and 37% for de novo and secondary AML (P=0.003), and 53 and 42% for age 60–69 and ≥70 years (P=0.015). In multivariable analysis, CR predictors included non-complex/non-rare karyotypes (P<0.001), de novo AML (P<0.001), better performance status (PS) (P<0.001) and younger age (P=0.001). Disease-free (DFS) and overall (OS) survival medians were 6.8 (95% CI: 6.2, 7.8) and 7.2 (95% CI: 6.4, 8.6) months. In multivariable analysis, DFS was shorter for complex karyotypes (P<0.001) and increasing white blood count (WBC) (P<0.001) and age (P=0.038), and OS for complex karyotypes (P<0.001), increasing WBC (P=0.001) and age (P<0.001), poorer PS (P<0.001) and secondary AML (P=0.010). Outcomes and prognostic factors were similar to those in previous Cancer and Leukemia Group B studies.