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Biomedical subjects

S Filip

Publications and source records attributed to S Filip.

28 records · Page 2Linked to original sources

The increase of the rate of hemopoietic recovery and clinical benefit of the erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) with peripheral blood progenitor cells (PBPC) after intensive cyclic chemotherapy in high-risk breast cancer patients.

The role of erythropoietin (EPO) plus granulocyte-colony stimulating factor (G-CSF) combination in hemopoietic recovery was studied in patients with high-risk breast carcinoma and compared to a control group of previously treated identical patients who were not given EPO plus G-CSF. Eleven consecutive patients admitted to this study had Stage III or IV breast cancer. They received 6 cycles of intensive chemotherapy (epirubicin 150 mg/m2 and cyclophosphamide 1300 mg/m2). The 1st cycle served for mobilization of peripheral blood progenitor cells (PBPC). At its end leukaphereses collections of PBPC were performed to be used as hematologic support (PBPCT) in the 5 remaining cycles. The administration of EPO plus G-CSF was started when leukocyte (WBC) count in peripheral blood dropped below 1 x 10(9)/l and hemoglobin (Hb) level fell below 100 g/l. The treatment was stopped when leukocyte count rose to 5 x 10(9)/l and Hb to 130 g/l. EPO plus G-CSF combination after PBPCT produced significant effects in terms of hemopoietic recovery, clinical benefit and supportive care requirements when compared with 12 historic control patients: Periods of leukopenia were shorter which resulted in reduced risk of infectious complications. The grades of leukopenia in the study and control groups were as follows: grade 4 (36 vs. 18%), grade 3 (57 vs. 30%), grade 2 (7 vs. 13%) respectively. Significantly shorter was the time of PLT recovery < 50 x 10(9)/l (p < 0.001). The grades of thrombocytopenia were: grade 4 (29 vs. 11%), grade 3 (21 vs. 12%), grade 2 (25 vs. 36%) respectively. The number of necessary transfusions was significantly reduced as well as the length of hospital stay (p < 0.001). In conclusion, our results obtained in this study confirm that combination of EPO plus G-CSF not only increases the rate of hemopoietic recovery, reduces the number of necessary red blood cell and platelet transfusions but, at the same time, simplifies the clinical management and is more tolerable for the patients.

Adult↗

Mobilization of peripheral blood progenitor cells (PBPC) through a combination of chemotherapy and G-CSF in breast cancer patients and a possibility of unprocessed whole blood collection.

To support multicyclic, dose-intensive chemotherapy in breast cancer, we assessed the effects of reinfusing hematopoietic progenitors either as a leukapheresis product or as mobilized unprocessed whole blood. In this clinical study, 16 consecutive female breast cancer patients were given six cycles of chemotherapy regimen EC (epirubicin (150 mg/m2) and cyclophosphamide (1250 mg/m2) on day 1). In the first cycle, 24 h after chemotherapy, mobilization of the peripheral blood progenitor cells (PBPC) was started with growth factor G-CSF (Neupogen; Amgen-Roche) at a dose of 5 microg/kg/day for 13 days. In all other cycles G-CSF had been given at the same dose from day 7. On days 11, 12 and 13 the leukaphereses were performed and their products cryopreserved. On day 14 whole blood was collected. The median peak incidence of CFU-GM (granulocyte-macrophage colony-forming unit) in peripheral blood was approximately 50 times the baseline level. The leukapheresed PBPC were divided into portions and reinfused after the fourth, fifth and sixth chemotherapy courses. The support with mobilized whole blood was given after the second and third cycles. The effects of the support of whole blood vs leukapheresed PBPC on hematopoietic recovery were compared. The best yields of leukaphereses were achieved on day 13 after initiation of the chemotherapy. The mean number of CD34+ cells was 4.93 x 10(6)/kg (s.d. 2.7; range 0.36-10.54 x 10(6)/kg) the amount of CFU-GM was 2.18 x 10(5)/kg (s.d. 1.3; range 0.07-4.2 x 10(5)/kg). The yields of CFU-GM in 450 ml whole blood collected on day 14 reached 0.51 x 10(5)/kg (s.d. 0.28; range 0.05-1.5 x 10(5)/kg) and of CD34+ cells were 1.3 x 10(6)/kg (s.d. 0.8, range 0.18-2.58 x 10(6)/kg). PBPC yields in 450 ml of unprocessed whole blood were in some cases not sufficient for good hematopoietic recovery after the EC cycles. Grade 4 leukopenias and thrombocytopenias were two times higher in cycles with whole blood support than in cycles with cryopreserved PBPC support. An increase of PBPC harvest can be simply achieved by collecting larger amounts of unprocessed blood, as used by some authors.

Adult↗

Circulation of progenitor cells after intensive chemotherapy followed by combination G-CSF and EPO in breast carcinoma.

Hematologic effects of granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) combination after printing intensive chemotherapy in the treatment of female breast carcinoma are presented. In a previous group treated with G-CSF alone, 36% of patients became anemic and had to be transfused for correction of their anemia. To the present study 11 consecutive patients with different stages of breast carcinoma were admitted. All were given priming intensive chemotherapy (epirubicin 150 mg/m2 and cyclophosphamide 1300 mg/m2 followed by subcutaneous application of G-CSF at a dose of 5 micrograms/kg/day and EPO 250 IU/kg/day. In cases where leucocyte counts dropped below 1 x 10(9)/l and hemoglobin levels fell to 85 g/l administration of growth factors was started. The therapy stopped when normal leucocyte count reached 4 x 10(9)/l for G-CSF and hemoglobin level rose to 115 g/l for EPO. Our results show significant difference between MNC/T1 (min.), CD34+ cells/microliters (min.), CFU-GM/ml (min.), BFU-E/ml (min.) and MNC/microliters (max.), CD34+ cells/microliters (max.), CFU-GM/ml (max.), BFU-E/ml (max.) p < 0.01, with mean peak values of 16.9-fold for circulating MNC/microliters, 7.8-fold for CD34+ cells/microliters 23.4-fold for CFU-GM/ml and 28.7-fold increase for BFU-E/ml. Side effects were minimal, no infectious complications occurred, body temperature did not rise over 38 degrees C and no corrections of anemia were needed. It is concluded that the administration of G-CSF plus EPO combination following intensive chemotherapy reduces hematologic toxicity and induces large amount of hemopoietic progenitors suitable for autologous transplantation in women with breast carcinoma.

Adult↗

[A fully implantable port system for venous access. Personal experience with 91 patients].

A fully implantable venous port system with a cannula inserted into the central venous system was implanted to 91 patients. The system was used for the administration of different types of intravenous preparations, incl. transfusions of erythrocyte mass and parenteral nutrition. With in the framework of autologous transplantation via the port system haematopoietic progenitor cells from the peripheral blood stream were administered. Part of the introduced systems was used for monitoring of the central venous overpressure and for collecting blood samples. The system was introduced on an average for 289 days, with a median of 245 days, range 82-872 days. During the implantation seven complications developed, in three instances the port was removed prematurely. During treatment 16 complications were observed, which in six instances led to early explantation of the venous port. The number of complications in total amounted to 0.87 per 1000 treatment days. The system was well tolerated by the patients because of its functional effectiveness and minimal cosmetic changes, and because it is not demanding it was also accepted well by the nursing staff.

Catheterization, Central Venous↗

[Bleeding time in incisions in patients with thrombocyte transfusion].

The authors used the Simplate test (Organon Teknika) to examine the bleeding time from an incision in 15 healthy blood donors and found normal values of 3.45 +/- 0.90 min. The authors proved a close correlation between the improvement of the number of platelets in 10 patients with thrombocytopenia, treated with thrombocyte infusions and the improvement of the bleeding time when using the Simplate R test after one hour and after 24 hours following thrombocyte administration. Examination of the bleeding time by means of the Simplate R test (Organon Teknika) was well tolerated by the authors' patients and the test does not produce any side-effects.

Adult↗

[Treatment of the leukostasis syndrome in chronic lymphadenosis using leukapheresis].

The authors draw attention to the leukostasis syndrome which develops in haematological patients in case of enormous leucocyte proliferation. It occurs most frequently in chronic myelosis but may occur also in other types of leukaemia. The diagnosis is not easy. Most frequently disorders of the microcirculation develop in the lungs and brain. These are frequently very urgent clinical situations which can be resolved by leukapheresis. The authors described a patient where during chronic lymphadenosis proliferation of lymphocytes occurred to values of 1432 x 10(9)/l. After leukapheresis and cytostatic treatment rapid improvement of the condition occurred and the leucocyte values were approximately 30 x 10(9)/l. The patient's condition improved for a long period of time and became stabilized.

Humans↗

Differentiation potential of murine neural stem cells in vitro and after transplantation.

We examined the differentiation potential of murine neural stem cells (NSCs) grown in vitro and transplanted into intact and irradiated recipients. NSCs were isolated from neonatal Balb/c mice using the neurosphere assay. On in vitro differentiation assays, NSCs produced beta-III tubulin(+) neurons, glial fibrillary acidic protein (GFAP(+)) astrocytes, and O4(+) oligodendrocytes. After neural grafting to histocompatible adult mice, NSCs gave rise to neuronal and glial cells. When cells were transplanted in the form of solid neurospheres, they reached terminal differentiation and spatial arrangements that mimicked the three-dimensional organization of nervous tissue. To create conditions that would allow us to assess the potential for generation of nonneural cells, NSCs were intravenously injected into irradiated mice. Transplantation of NSCs stimulated hematopoiesis because the number of colony-forming units of granulocyte-monocyte lineage (CFU-GM) colonies isolated from the spleen and bone marrow of transplanted mice was greater than that from irradiated, nontransplanted animals. Moreover, transplanted cells tagged with beta-galactosidase were identified in the thymus of animals grafted with labelled NSCs. NSCs harvested from the neurosphere assay produced viable and transplantable cells. In vitro differentiation assays and neural grafting confirmed the multipotency of NSCs and their commitment to generate neuronal and glial cells. Following intravenous injection of NSCs, the transplanted cells colonized hematopoietic and lymphatic organs, facilitating hematopoiesis in irradiated animals.

Animals↗

Endovascular brachytherapy potentiated by hyperthermia in the prevention of vascular restenosis. A case report.

BACKGROUND: The combination of hyperthermia and radiotherapy has additive or synergistic effects. This combination has been studied extensively in radiation oncology, but not in the prevention of vascular restenosis. CASE REPORT: A patient with restenosis of cephalic vein underwent percutaneous transluminal angioplasty (PTA) followed by endovascular irradiation with 192Iridium (12 Gy) using a high dose rate afterloading technique. After endovascular irradiation, one fraction of external ultrasound hyperthermia was administered to the irradiated segment. There was no restenosis in the treated vessel segment according to duplex sonography performed 192 days after treatment. No radiation or hyperthermia associated side effects were observed. CONCLUSIONS: Present observations suggest that endovascular brachytherapy of restenosis potentiated by hyperthermia is a technically feasible and well-tolerated treatment. The additive and synergistic effects of hyperthermia, in conjunction with radiation, could be of benefit in the prevention of vascular restenosis.

Angioplasty, Balloon↗

Issues in stem cell plasticity.

Experimental biology and medicine work with stem cells more than twenty years. The method discovered for in vitro culture of human embryonal stem cells acquired at abortions or from "surplus" embryos left from in vitro fertilization, evoked immediately ideas on the possibility to aim development and differentiation of these cells at regeneration of damaged tissues. Recently, several surprising observations proved that even tissue-specific (multipotent) stem cells are capable, under suitable conditions, of producing a whole spectrum of cell types, regardless, whether these tissues are derived from the same germ layer or not. This ability is frequently called stem cell plasticity but other authors also use different names - "non-orthodox differentiation" or "transdifferentiation". In this paper we wish to raise several important questions and problems related to this theme. Let us remind some of them: Is it possible to force cells of one-type tissue to look and act as cells of another tissue? Are these changes natural? Could these transformations be used to treat diseases? What about the bioethic issue? However, the most serious task "still remains to be solved - how to detect, harvest and culture stem cells for therapy of certain diseases".

Animals↗