Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy

The immune-mediated graft-versus-leukemia effect is important to prevent relapse after allogeneic progenitor cell transplantation. This process requires engraftment of donor immuno-competent cells. The objective of this study was to assess the feasibility of achieving engraftment of allogeneic peripheral blood or bone marrow progenitor cell after purine analog containing nonmyeloablative chemotherapy. Patients with advanced leukemia or myelodysplastic syndromes (MDS) who were not candidates for a conventional myeloablative therapy because of older age or organ dysfunction were eligible. All patients had an HLA-identical or one-antigen-mismatched related donor. Fifteen patients were treated (13 with acute myeloid leukemia and 2 with MDS). The median age was 59 years (range, 27 to 71 years). Twelve patients were either refractory to therapy or beyond first relapse. Eight patients received fludarabine at 30 mg/m2/d for 4 days with idarubicin at 12 mg/m2/d for 3 days and ara-c at 2 g/m2/d for 4 days (n = 7) or melphalan at 140 mg/m2/d (n = 1). Seven patients received 2-chloro-deoxyadenosine at 12 mg/m2/d for 5 days and ara-C 1 at g/m2/d for 5 days. Thirteen patients received allogeneic peripheral blood stem cells and 1 received bone marrow after chemotherapy. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methyl-prednisolone. Treatment was generally well tolerated, with only 1 death from multiorgan failure before receiving stem cells. Thirteen patients achieved a neutrophil count of greater than 0.5 x 10(9)/L a median of 10 days postinfusion (range, 8 to 17 days). Ten patients achieved platelet counts of 20 x 10(9)/L a median of 13 days after progenitor cell infusion (range, 7 to 78 days). Eight patients achieved complete remissions (bone marrow blasts were < 5% with neutrophil recovery and platelet transfusion independence) that lasted a median of 60 days posttransplantation (range, 34 to 170+ days). Acute GVHD grade > or = 2 occurred in 3 patients. Chimerism analysis of bone marrow cells in 6 of 8 patients achieving remission showed > or = 90% donor cells between 14 and 30 days postinfusion, and 3 of 4 patients remaining in remission between 60 and 90 days continued to have > or = 80% donor cells. We conclude that purine analog-containing nonmyeloablative regimens allow engraftment of HLA-compatible hematopoietic progenitor cells. This approach permits us to explore the graft-versus-leukemia effect without the toxicity of myeloablative therapy and warrants further study in patients with leukemia who are ineligible for conventional transplantation with myeloablative regimens either because of age or concurrent medical conditions.     

Staff attitudes to oral health care. A comparative study of registered nurses, nursing assistants and home care aides

The diagnosis of early ectopic pregnancy remains challenging for the gynecologist. Although early detection of a suspected pregnancy has been facilitated by quantitative beta human chorionic gonadotropin studies and ultrasonography, a patient subgroup remains with an ambiguous presentation. In this group of patients, the clinician must rely on microscopic examination of products of conception in a uterine curettage specimen to rule out the presence of an extrauterine pregnancy. The presence of an implantation site, chorionic villi, or trophoblastic tissue in uterine curettage samples is conventionally held as definitive evidence of an intrauterine pregnancy. We present a series of four cases that challenge this convention. In these cases, chorionic villi or an implantation site were identified in uterine samples of pregnant women who each ultimately proved to have an ectopic pregnancy. If clinical suspicion is high, the finding of either chorionic villi or an implantation site should not preclude further workup of a possible ectopic pregnancy. In cases where only a few villi or a single chorionic villus are identified, other signs of intrauterine implantation such as intermediate trophoblastic cells, hyalinized vessels, and a fibrinoid matrix should be sought to establish firmly the diagnosis of an intrauterine pregnancy.     

Simulating sliding wear with finite element method

Wear of components is often a critical factor influencing the product service life. Wear prediction is therefore an important part of engineering. The wear simulation approach with commercial finite element (FE) software ANSYS is presented in this paper. A modelling and simulation procedure is proposed and used with the linear wear law and the Euler integration scheme. Good care, however, must be taken to assure model validity and numerical solution convergence. A spherical pin-on-disc unlubricated steel contact was analysed both experimentally and with FEM, and the Lim and Ashby wear map was used to identify the wear mechanism. It was shown that the FEA wear simulation results of a given geometry and loading can be treated on the basis of wear coefficient−sliding distance change equivalence. The finite element software ANSYS is well suited for the solving of contact problems as well as the wear simulation. The actual scatter of the wear coefficient being within the limits of ±40–60% led to considerable deviation of wear simulation results. These results must therefore be evaluated on a relative scale to compare different design options.     

Erratum to "Immunocytochemical detection of cytokines and chemokines in Langerhans cells and in vitro derived dendritic cells"

We have developed a direct immunocytochemical technique to identify cytokine and chemokine production in epidermal Langerhans cells (LC) and in vitro derived CD14-, CD1a+, CD83+, CD40+ dendritic cells (DC) at the single cell level. Formaldehyde fixation combined with saponin permeabilization preserved cellular morphology and generated a characteristic juxtanuclear staining signal due to the accumulation of cytokine to the Golgi organelle. This approach was used for the assessment of TNF-alpha, IL-6, IL-8, IL-10, IL-12, GM-CSF, MIP-1alpha, MIP-1beta and RANTES producing cells. In contrast, a diffuse cytoplasmic staining was evident for IL-1ra, IL-1alpha and IL-1beta production. IL-1ra and IL-1alpha were expressed in 10-25% of unstimulated cultured cells, while all the other cytokines were undetectable. IL-1ra, IL-1alpha and IL-1beta were also the dominating cytokines, expressed in up to 85% of the DC, after 3 h of LPS stimulation. A significantly lower number of cells (0-5%) synthesized TNF-alpha, IL-6, IL-10, IL-12 and GM-CSF. The incidence of chemokine producing cells (IL-8, RANTES, MIP-1alpha, MIP-1beta) peaked 10 h after LPS stimulation in up to 60% of the DC. Both immature CD83- and mature CD83+ DC as well as LC had a similar cytokine production pattern. Thus, in comparison to monocytes, LPS stimulation of DC generated a lower incidence of TNF-alpha, IL-6, IL-10 and IL-12 producing cells while IL-1 was expressed in a comparable number of cells.     

Achievement of specificational information usage with true and false feedback in learning a visual relative-mass discrimination task.

Participants' usage of informational variables in learning visual relative-mass discrimination in collisions was tracked by means of PROBIT correlations. Four groups received feedback that was true or accorded with either of three nonspecificational cue variables. A majority in each group adopted the feedback, but several participants defied the false feedback. Unlike in previous research, the fit to data of the relative-mass invariant could not be bettered by post hoc linear combinations of the cues. Discriminability was lower in the use of the invariant. Analytic complexity was rejected as an explanation for discriminability differences. A "smart mechanism" for pickup of the relative-mass invariant was developed as an extension of G. Johansson's (1950/1994) vector model. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of macrophage overactivation in the development of acute pancreatic injury in rats

PURPOSE: To report quantitative changes in the anterior chamber configuration after small-incision cataract surgery with implantation of a posterior chamber intraocular lens by means of ultrasound biomicroscopy. METHODS: We examined the anterior chamber configuration of 20 eyes of 20 patients before and 3 months after small-incision cataract surgery (phacoemulsification and aspiration plus foldable intraocular lens implantation through a 3.0- to 4.0-mm self-sealing wound) by means of ultrasound biomicroscopy. The following variables were measured: the anterior chamber depth at the center of the cornea, the angle-opening distance 250 microns from the scleral spur (AOD250), the angle-opening distance 500 microns from the scleral spur (AOD500), and the trabecular-iris angle. RESULTS: The anterior chamber depth at the center of the cornea, AOD250, AOD500, and trabecular-iris angle increased significantly after surgery. The preoperative anterior chamber depth at the center of the cornea and trabecular-iris angle were negatively correlated with the differences between the postoperative and preoperative values (P < .01). The preoperative values of all variables examined were negatively correlated with the ratios of the postoperative value to the preoperative value (P < .002). CONCLUSIONS: The present results showed that small-incision cataract surgery significantly deepened the anterior chamber and widened its angle. The more shallow the preoperative anterior chamber was, the greater the postoperative change of the chamber was; and the more narrow the preoperative angle was, the greater the postoperative change of the angle was.     

Fusion Generated Fast Particles by Laser Impact on Ultra-Dense Deuterium: Rapid Variation with Laser Intensity

Nuclear fusion D+D processes are studied by nanosecond pulsed laser interaction with ultra-dense deuterium. This material has a density of 10²⁹ cm^?3 as shown in several previous publications. Laser power is <2 W (0.2 J pulses) and laser intensity is <10¹⁴ W cm^?2 in the 5–10 μm wide beam waist. Particle detection by time-of-flight energy analysis with plastic scintillators is used. Metal foils in the particle flux to the detector remove slow ions, and make it possible to convert and count particles with energy well above 1 MeV. The variation of the signal of MeV particles from D+D fusion is measured as a function of laser power. At relatively weak laser-emitter interaction, the particle signal from the laser focus varies as the square of the laser power. This indicates collisions in the ultra-dense deuterium of two fast deuterons released by Coulomb explosions. During experiments with stronger laser-emitter interaction, the signal varies approximately as the sixth power of the laser power, indicating a plasma process. At least 2 × 10⁶ particles are created by each laser pulse at the maximum intensity used. Our results indicate break-even in fusion at a laser pulse energy of 1 J with the same focusing, in approximate agreement with theoretical results for ignition conditions in ultra-dense deuterium. Radiation loss at high temperature will however require higher laser energy at break-even.