PubMed Health⌕ Search

Biomedical subjects

Per Grøttum

Publications and source records attributed to Per Grøttum.

6 recordsLinked to original sources
PubMed2006

Contribution of the Na+/Ca2+ exchanger to rapid Ca2+ release in cardiomyocytes.

Trigger Ca(2+) is considered to be the Ca(2+) current through the L-type Ca(2+) channel (LTCC) that causes release of Ca(2+) from the sarcoplasmic reticulum. However, cell contraction also occurs in the absence of the LTCC current (I(Ca)). In this article, we investigate the contribution of the Na(+)/Ca(2+) exchanger (NCX) to the trigger Ca(2+). Experimental data from rat cardiomyocytes using confocal microscopy indicating that inhibition of reverse mode Na(+)/Ca(2+) exchange delays the Ca(2+) transient by 3-4 ms served as a basis for the mathematical model. A detailed computational model of the dyadic cleft (fuzzy space) is presented where the diffusion of both Na(+) and Ca(2+) is taken into account. Ionic channels are included at discrete locations, making it possible to study the effect of channel position and colocalization. The simulations indicate that if a Na(+) channel is present in the fuzzy space, the NCX is able to bring enough Ca(2+) into the cell to affect the timing of release. However, this critically depends on channel placement and local diffusion properties. With fuzzy space diffusion in the order of four orders of magnitude lower than in water, triggering through LTCC alone was up to 5 ms slower than with the presence of a Na(+) channel and NCX.

Animals↗
PubMed2004

Mathematical modeling of granulocyte reconstitution after high-dose chemotherapy with stem cell support: effect of post-transplant G-CSF treatment.

Cancer patients treated with high-dose chemotherapy and autotransplanted with peripheral blood progenitor cells most often reconstitute neutrophils (> 0.5 x 10(9)c/l) 8-16 days after the initiation of treatment. By means of a mathematical model of human granulopoiesis, the present work assesses the effect of administering granulocyte colony stimulating factor (G-CSF) post-transplant to reduce engraftment time, and also assesses the effect of delaying initiation of G-CSF treatment relative to a general schedule. Hematopoietic progenitor cells from 21 breast cancer patients were mobilized by chemotherapy followed by G-CSF injections. Purified CD34+ cells taken from the mobilized blood were infused 3 days after termination of chemotherapy. Patients were given subcutaneous injections of G-CSF post-transplant (5 microg/kg every 12 h). Neutrophil counts calculated from a mathematical model were compared with data from individual patients. These results were also compared with data and modeling results from a group of 19 lymphoma patients given no post-transplant G-CSF therapy. The observed engraftment times were associated with the number of CFU-GM cells in the reinfused blood graft and the administration of post-transplant G-CSF. The latter finding was most predominant in patients given < 5.0 x 10(5) CFU-GM/kg bw. These tendencies were well captured by the model. Interestingly, the model showed no major differences in time to engraft neutrophils if the initiation of G-CSF was postponed for up to 5 days after transplantation. Our findings indicate that the present mathematical model of neutrophil recovery following high-dose therapy correlates with clinical observations and can potentially be used to predict time to neutrophil recovery.

Antineoplastic Agents↗
PubMed2004

Changes in student approaches to learning with the introduction of computer-supported problem-based learning.

OBJECTIVES: To study changes in student approaches to learning following the introduction of computer-supported, problem-based learning. SETTING: Medical students at the University of Oslo undertake a 12-week period of clinical placement during their 10th term. In this period they continue to undertake problem-based learning (PBL) in the form of distributed problem-based learning (DPBL) in a computer-supported learning environment. DESIGN: A questionnaire focusing on learning styles, PBL, and information and communication technology (ICT) was distributed before and after the DPBL period. SUBJECTS: All students in their 10th term at the University of Oslo (n = 61). RESULTS: The introduction of DPBL did not seem to affect the participants' use of regulating strategies or their mental models of learning. After the DPBL period, group discussion and tutor input were reported to have less influence on students' self-study, while the students perceived themselves as being less active in groups and as expecting less from tutors. There was a relationship between perceived tutor influence and students' familiarity with ICT. The DPBL period seemed to increase students' task-related web accesses and use of experts, and to decrease their task-related use of textbooks and discussions with students outside the group. CONCLUSIONS: Students' general approaches to learning were not affected by the introduction of DPBL. However, there was a decrease in students' expectations concerning activity in the group and the importance of the tutor. These changes were related to students' familiarity with the use of computers. Web-based resources and experts became more important resources to the students during the DPBL period.

Adult↗
PubMed2003

A mathematical model for reconstitution of granulopoiesis after high dose chemotherapy with autologous stem cell transplantation.

High dose chemotherapy supported with hematopoietic progenitor cells gives a characteristic neutropenic period (blood neutrophils < 0.5 x 10(9) c/l) ranging from 10 to 16 days. The question of a correlation between the CFU-GM content of the transplanted CD34+ cells and time to neutrophil recovery by patients having been given high-dose chemotherapy (HD-CT) with stem cell support was addressed by means of a mathematical model of granulopoiesis. The model utilizes a convection-reaction partial differential equation (PDE) with feedback from a cytokine compartment on proliferation, maturation, and mobilization of granulocytes from bone marrow to blood. The observed number of CFU-GM cells in the transplanted CD34+ cell autograft was used as input to the model. Using this approach, the observed gross relationship between CFU-GM content in the reinfused blood product and engraftment time could be reproduced. At the same time, the effects of assumed physiological mechanisms, especially some of the effects of G-CSF on proliferation rate, maturation rate, mobilization, and cell death, could be investigated and discussed relative to observed engraftment. The model makes it possible to explain how cytokines interfere with progenitor cell mobilization from bone marrow to blood, and it points out the implications of a regulating mechanism for the granulocyte maturation rate.

Adult↗
PubMed2003

Mathematical modeling of human granulopoiesis: the possible importance of regulated apoptosis.

Steady state human granulopoiesis was modeled by a convection-reaction differential equation of the Rubinow type for the bone marrow granulocyte precursors and an ordinary differential equation for the blood granulocytes. Measured values reported from several laboratories were used as sources for the model proliferation, maturation, and mobilization rates. Due to the large variability in the measured input data, four alternative models were constructed initially, each one with a specific combination of proliferation rate and maturation rate. They were all able to produce output values for the bone marrow neutrophil count and turnover rate close to accepted data, but neither of them could reproduce good values for the differential fractions of the neutrophil precursor stages. The model output was especially sensitive to changes in transit time in the mitotic relative to the postmitotic precursor compartments. When the net proliferation rate was modeled to optimize the bone marrow differential fractions according to published data, the total bone marrow neutrophil count would not fit with published data. However, a composite model optimizing differential fractions, bone marrow neutrophil count, and turnover rate yielded plausible output values and a reduced proliferation rate in the myelocyte stage. This result opens for a possibly substantial apoptosis rate at the myelocyte stage in accordance with results from earlier investigators. However, the result was based on a special choice of precursor transit times, taken from the literature. More precise data concerning granulocyte precursor cycle times, transit times, and differential fractions would radically improve the model's ability to clarify the role of apoptosis during granulocyte production and storage.

Apoptosis↗