[Estimation of the risk of drug-related problems in nursing home residents : A retrospective analysis of routine data].

Background: Polypharmacy and drug-related problems are major challenges in the care and treatment of nursing home residents. Many interventional studies showed disappointing results, which lead to the question if this could also be due to the selection of the target parameters of these studies.

Material And Methods: A routine data set from six long-term care facilities was retrospectively analyzed.

Stem cell therapy clinical research: A regulatory conundrum for academia.

The encouraging pace of discovery and development in the field of regenerative medicine holds tremendous potential for bringing therapies to the clinic that may offer meaningful benefit to patients, particularly in diseases with no or suboptimal therapeutic options. Academic researchers will continue to play a critical role in developing concepts and therapies, thus determining whether regenerative medicine will be able to live up to this potential that clearly excites clinicians, researchers and patients alike. This review summarises recent developments in regulatory frameworks across different countries that aim to ensure adequate oversight of the development of regenerative medicine products, which are unique in structural and functional complexity when compared to traditional chemical drugs and fully characterised biological drugs.

Long-term outcome of patients with metastatic breast cancer treated with high-dose chemotherapy and transplantation of purified autologous hematopoietic stem cells.

Metastatic breast cancer remains a major treatment challenge. The use of high-dose chemotherapy (HDCT) with rescue by autologous mobilized peripheral blood (MPB) is controversial, in part because of contamination of MPB by circulating tumor cells. CD34(+)Thy-1(+) selected hematopoietic stem cells (HSC) represent a graft source with a greater than 250,000-fold reduction in cancer cells.

Primary prevention of childhood obesity: an interdisciplinary analysis.

The primary prevention of childhood obesity requires combined efforts by stakeholders at various societal levels, based on the knowledge from multiple disciplines. The goal of the present study was therefore to analyze current preventive approaches and delineate implications for future prevention research and practice by integrating knowledge from genetics, law, economics, psychology, and social ethics. Inconclusive evidence on the etiology of obesity, a complex, multifactorial condition, likely complicates prevention, leading to a lack of specificity regarding target groups, focus, and techniques.

[Primary prevention of adult obesity. an interdisciplinary analysis].

The primary prevention of adult obesity requires combined efforts by stakeholders at various societal levels, based on the knowledge from multiple disciplines. The goal of the present study was, therefore, to analyze current preventive approaches and delineate implications for future prevention research and practice by integrating knowledge from genetics, law, economics, psychology, and social ethics (Figure 1). Inconclusive evidence on the etiology of obesity, a complex, multifactorial condition, likely complicates prevention, contributing to a lack of specificity regarding target groups, focus, and techniques of prevention.

Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with recurrent indolent non-Hodgkin's lymphoma.

Purpose: To evaluate the results of high-dose chemotherapy and transplantation of highly purified "mobilized" peripheral blood CD34+Thy-1+ hematopoietic stem cells (HSCs) in patients with recurrent indolent non-Hodgkin's lymphoma (NHL) or mantle cell lymphoma (MCL).

Patients And Methods: Twenty-six patients with recurrent indolent NHL or MCL were mobilized witheither granulocyte colony-stimulating factor (G-CSF) alone or cyclophosphamide plus G-CSF. Apheresis was performed, and the product was purified using the Isolex immunomagnetic positive CD34+ cell selection device initially and subsequent high-speed flow-cytometric cell sorting for the final purification of CD34+Thy-1+ HSCs.

Evaluation of the potential causes of epistaxis in dogs with natural visceral leishmaniasis.

Haemostasis was evaluated in 19 dogs with natural Leishmania infection, six of them with a history of epistaxis, and the results were compared with the results from 24 healthy dogs. In addition, the dogs' blood pressure was measured and biopsies were taken from the nasal mucosa. Buccal mucosa bleeding time was prolonged in the dogs with leishmaniasis (P < 0.

Administration of herpes simplex-thymidine kinase-expressing donor T cells with a T-cell-depleted allogeneic marrow graft.

Administration of donor T cells expressing the herpes simplex-thymidine kinase (HS-tk) with a hematopoietic stem cell (HSC) transplantation could allow, if graft-versus-host disease (GVHD) was to occur, a selective in vivo depletion of these T cells by the use of ganciclovir (GCV). The study evaluates the feasibility of such an approach. Escalating numbers of donor HS-tk-expressing CD3(+) gene-modified cells (GMCs) are infused with a T-cell-depleted bone marrow transplantation (BMT).

Transplantation with selected autologous peripheral blood CD34+Thy1+ hematopoietic stem cells (HSCs) in multiple myeloma: impact of HSC dose on engraftment, safety, and immune reconstitution.

Objective: The aims of our study performed in myeloma were to evaluate the performance and the safety of Systemix's high-speed clinical cell sorter, to assess the safety and efficacy of deescalating cell dose cohorts of CD34+Thyl+ hematopoietic stem cells (HSCs) as autologous grafts by determining engraftment, and to assess the residual tumor cell contamination using polymerase chain reaction (PCR) amplification assays of patient-specific complementarity determining region III (CDR III) analysis for residual myeloma cells.

Materials And Methods: The clinical trial was performed in 31 multiple myeloma patients, using purified human CD34+Thyl+ HSCs mobilized from peripheral blood with cyclosphosphamide and granulocyte-macrophage colony-stimulating factor to support a single transplant after high-dose melphalan 140 mg/m2 alone (cohort 1) and with total body irradiation (TBI) (cohorts 2-5) after an HSC transplant cell dose de-escalation/escalation design.

Results: Twenty-three patients were transplanted.

Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with metastatic breast cancer.

We report here the transplantation of extensively purified "mobilized" peripheral blood CD34Thy-1 hematopoietic stem cells from 22 patients with recurrent or metastatic breast cancer. Patients were mobilized with either high-dose granulocyte colony-stimulating factor (G-CSF) alone or cyclophosphamide plus G-CSE Median purity of the stem cell product at cryopreservation was 95.3% (range, 91.

Optimal conditions for simultaneous measurement of platelet aggregation and ATP secretion in canine whole blood.

This paper describes the optimal conditions for simultaneous evaluation of platelet aggregation and secretion capacity in canine whole blood using a Whole Blood Lumi-Aggregometer (Chrono-Log Corporation, Havertown, Pensylvania). For this purpose, the potential influence of several parameters was investigated using collagen, adenosinediphosphate (ADP), arachidonic acid (AA) and thrombin as platelet agonists. Results indicate that optimal experimental conditions to obtain reliable results include: allowing blood samples to stand at room temperature 60 minutes after blood collection, analysing samples within 3 hours from time of collection, adjusting platelet numbers to a final concentration of 150 000 microl(-1)and mixing the sample with isotonic saline (1:1) before adding the platelet agonist.

Multicycle high-dose chemotherapy and filgrastim-mobilized peripheral-blood progenitor cells in women with high-risk stage II or III breast cancer: five-year follow-up.

Purpose: To determine the safety and efficacy of multiple cycles of dose-intensive, nonablative chemotherapy in women with poor-prognosis breast cancer.

Patients And Methods: Women with stage II breast cancer and 10 or more involved nodes or four or more involved nodes and estrogen receptor-negative tumors and women with stage III disease received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 g/m2, with progenitor cell and filgrastim support every 28 days (n = 79) or 21 days (n = 20). Patients were reviewed at least twice yearly thereafter.

Collection, tumor contamination, and engraftment kinetics of highly purified hematopoietic progenitor cells to support high dose therapy in multiple myeloma.

Unfractionated peripheral blood stem cell (PBSC) grafts contain measurable quantities of myeloma cells and are therefore a potential source of relapse posttransplantation. In contrast, fluorescence-activated cell sorting (FACS)-sorted CD34+ Thy1+ Lin- peripheral blood cells are substantially enriched for stem cell activity, yet contain virtually no clonal myeloma cells. A study was performed in patients with symptomatic myeloma, who had received 12 months or less of preceding standard chemotherapy, to evaluate the feasibility of large scale purification of primitive hematopoietic stem cells in order to study engraftment kinetics posttransplantation and the degree of tumor cell contamination of this cell population, based on polymerase chain reaction (PCR) analysis for the patient-specific complementarity-determining region III (CDR III).

Rapid hematopoietic recovery after multicycle high-dose chemotherapy: enhancement of filgrastim-induced progenitor-cell mobilization by recombinant human stem-cell factor.

Purpose: To assess the mobilization potential and safety of recombinant human stem-cell factor (SCF) when coadministered with filgrastim to untreated women with poor-prognosis breast cancer.

Patients And Methods: Eligible women had breast cancer with 10 or more positive axillary nodes, or estrogen receptor-negative tumor with 4 positive nodes, or stage III disease. Patients were randomized to receive SCF plus filgrastim or filgrastim alone.

Ex vivo culture of peripheral blood CD34+ cells: effects of hematopoietic growth factors on production of neutrophilic precursors.

A major potential application for ex vivo culture of hematopoietic progenitor cells is the treatment of cytopenia following high-dose chemotherapy and hematopoietic transplantation. We have previously postulated that infusion of a sufficient number of neutrophil postprogenitor cells generated by ex vivo culture of CD34+ cells may be able to abrogate neutropenia. In this article, we describe further development of an efficient stromal-free, cytokine-dependent, static culture system for generation of these cells.

Detection of minimal residual disease in an AML patient with trisomy 8 using interphase fish.

Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) often exhibit clonal chromosomal abnormalities. Using a probe for the centromeric region of chromosome 8, fluorescence in situ hybridization (FISH) on interphase cells was used to detect trisomy 8 in an AML patient whose leukemia was characterised by the karyotype 47, XY, +8, del(9) (q21.1q32).

Standardization of the CFU-GM assay using hematopoietic growth factors.

The colony-forming unit-granulocyte-macrophage (CFU-GM) assay is used commonly to assess adequacy of progenitor number in bone marrow transplantation. The assay is poorly standardized, resulting in variability of results between and within laboratories. We assessed three variables that contribute to the lack of standardization.

Partially differentiated ex vivo expanded cells accelerate hematologic recovery in myeloablated mice transplanted with highly enriched long-term repopulating stem cells.

The ability of an infusion of ex vivo expanded hematopoietic cells to ameliorate cytopenia following transplantation of hematopoietic stem cells (HSCs) is controversial. To address this issue, we measured the recovery of circulating leukocytes, erythrocytes, and platelets in lethally irradiated mice transplanted with 10(3) enriched HSCs, with or without their expanded equivalent (EE) generated after 7 days of culture in interleukin-3 (IL-3), IL-6, granulocyte colony-stimulating factor and Steel Factor. Two HSC populations differing in their content of short-term repopulating progenitors were evaluated.

Peripheral blood stem cells mobilized from patients with acute myeloid leukaemia have different platelet repopulating abilities compared with those mobilized from patients with other diseases.

Peripheral blood stem cell (PBSC) transplantation gives rapid recovery of neutrophils and platelets and sustained haemopoiesis. However in patients with acute myeloid leukaemia (AML) platelet recovery has a distinctive rapid rise and then secondary fall between 3 to 8 weeks post-transplant. This study compares platelet and neutrophil recovery after PBSC transplantation in 15 patients with AML and 29 patients with other diseases consecutively transplanted in a single unit.

An incremental response to high-dose therapy in multiple myeloma.

Results of conventional chemotherapy for multiple myeloma are disappointing. High-dose chemoradiotherapy with auto-transplantation is increasingly reported and some results are encouraging. We report the results of peripheral blood stem cell transplantation (PBSCT) for multiple myeloma at a single institution over a 6-year period.

Comparison of myeloma cell contamination of bone marrow and peripheral blood stem cell harvests.

lt could be speculated for patients with myeloma and other lymphoproliferative disorders that peripheral blood stem cells may be preferable to bone marrow for autologous transplantation because they may be less contaminated by neoplastic cells. To test this possibility, the immunoglobulin heavy chain gene rearrangement and limiting dilution polymerase chain reaction were used to sensitively quantify myeloma cells in bone marrow and peripheral blood stem cell collections, taken at a similar time, from eight patients with multiple myeloma. Levels of residual disease in the peripheral blood stem cell harvests were variable and did not reflect the tumour burden in the marrow.

Prophylactic ganciclovir is more effective in HLA-identical family member marrow transplant recipients than in more heavily immune-suppressed HLA-identical unrelated donor marrow transplant recipients. Australasian Bone Marrow Transplant Study Group.

A multi-centre Australasian study of the efficacy of prophylactic ganciclovir in 88 recipients of marrow allografts at high risk for post-transplant cytomegalovirus (CMV) disease was conducted. The actuarial incidence of CMV disease was 10% in 74 recipients of HLA-identical family member transplants given ganciclovir but was 33% in 14 recipients of HLA-identical unrelated donor transplants given more immune-suppression pre- and post-transplant (P = 0.006).

Adjuvant treatment of high-risk breast cancer using multicycle high-dose chemotherapy and filgrastim-mobilized peripheral blood progenitor cells.

Women with primary breast cancer associated with extensive axillary node involvement or large primary tumors have a very poor prognosis despite treatment with standard-dose adjuvant chemotherapy. In an attempt to improve the outlook of these patients, we investigated the safety and feasibility of delivering three cycles of high-dose epirubicin and cyclophosphamide supported with filgrastim-mobilized peripheral blood progenitor cells (PBPC). Fifteen previously untreated women, median age 50 (range, 30-58) years, with poor prognosis early stage breast cancer received filgrastim (12 microgram/kg daily for 6 days) prior to chemotherapy to mobilize progenitor cells.

Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34-35, a region frequently affected in haematological neoplasms.

Developmentally regulated mouse gene Nedd2 encodes a protein similar to the product of the nematode Caenorhabditis elegans cell death gene ced-3 and the mammalian interleukin-1 beta-converting enzyme. Overexpression of Nedd2 in cultured mammalian cells induces apoptosis that can be blocked by proto-oncogene BCL2. We have isolated cDNA clones for the human homologue of the mouse gene and, by using these as probes, mapped the human NEDD2 gene to 7q34-35 by fluorescence in situ hybridisation.