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Biomedical subjects

L Uziel

Publications and source records attributed to L Uziel.

At least 19 recordsLinked to original sources
PubMed2001

DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) is an effective regimen for peripheral blood stem cell collection in multiple myeloma.

DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) has proved to be an effective salvage therapy for refractory-relapsed MM patients. Little is known, however, about its potential as mobilizing therapy. The aim of this study was to evaluate the efficacy of DCEP in mobilizing PBSC and to define its toxicity. Fifty-five MM patients received DCEP followed by G-CSF as part of high-dose programs including autologous transplantation. At the time of mobilization, 40 patients had previously received VAD only, and 15 alkylating agents. Mobilization was successful (minimum number of CD34(+) cells 2 x 10(6)/kg) in 48/55 patients (87%), and 41/55 patients (75%) collected >4 x 10(6)/kg CD34(+) cells. Of the seven patients who did not mobilize stem cells, five (71%) had been previously exposed to alkylating agents. The median number of CD34(+) cells harvested was 5.8 x 10(6)/kg (range 2.1-22.4). There was no treatment-related mortality. The side-effects of DCEP were always tolerable. No neutropenia <1000/microl nor thrombocytopenia <50,000/microl were observed. No patient required transfusion as a consequence of therapy, or hospitalization for septic complications. In conclusion, DCEP, in addition to its demonstrated anti-tumor activity, is an effective regimen for mobilizing peripheral blood progenitor cells in myeloma patients, with little or no side-effects. These properties render DCEP a useful regimen for the debulking and mobilization phase of high-dose programs for multiple myeloma.

Adult↗
PubMed1994

Effects of recombinant human stem cell factor (rh-SCF) on colony formation and long-term bone marrow cultures (LTBMC) in patients with myelodysplastic syndromes.

Stem cell factor (SCF), the ligand of the c-kit receptor, is a potent enhancing cytokine for haematopoietic cells in the presence of IL-3, GM-CSF and erythropoietin (Epo). In the clonogenic assays of 63 MDS patients, the addition of rh-SCF + GM-CSF and/or IL-3 induced a significant increase (p < 0.001) in the number and size of CFU-GM. Never reaching the levels of controls, this increase was seen in all FAB subtypes, but particularly in RA. There was no significant increase in cluster formation, even in RAEB or RAEBt. Rh-SCF (10 ng/ml) led to mean increases of up to 26 times in the number of Epo-dependent BFU-E colonies, particularly in RA (p < 0.001) and RAEB (p < 0.05). Individual responses varied widely (especially in RA) from no response to supranormal levels. Added to the weekly refeed of 37 MDS LTBMC, SCF (10 ng/ml) induced only a 7% mean increase in both cell output and the number of clonogenic cells recovered in the supernatant. Immunohistochemical examination of the supernatant showed significant increases in differentiating myeloid cells in all examined cases, and in erythroid cells in 3 cases; blast cells increased in only 3 cases. These data suggest that rh-SCF is capable of at least partially reversing defective MDS myeloid haematopoiesis, and leads no overt risk of leukaemic transformation. Its potent effect on erythroid cells is encouraging for future clinical applications in patients, particularly if they are selected by means of in vitro tests.

Bone Marrow Cells↗
PubMed1990

Physiopathology and management of coagulation during long-term extracorporeal respiratory assistance.

Thrombohemorrhagic risk is one of the main limiting factors in extracorporeal circulation. We describe here our experience in managing some life-threatening hematological complications in 58 patients with acute respiratory failure treated with long-term extracorporeal assistance. These patients were studied by clinical and laboratory means to assess questions related to heparin monitoring, coagulation complications and bleeding incidence. We found that two clotting tests, activated partial thromboplastin time (APTT) and activated clotting time (ACT) can be easily used to assess the safety of anticoagulant treatment (therapeutic ranges: APTT from 55 to 95 sec and ACT from 170 to 220 sec). A certain degree of coagulation activation, despite heparin, was indicated by the constant finding of thrombin-antithrombin complexes, while fibrinolytic activation, measured as plasminogen activator activity, was confined to the time of bypass connection and was of no clinical consequence. Platelet function was always impaired without relation to the platelet loss. Disseminated intravascular coagulation (DIC) (13 episodes) and severe bleeding (11 episodes) were major complications. DIC was corrected with a good outcome for 8 of 13 patients, while severe bleeding was correlated with a poor outcome in 8 of the 11 patients, probably because of the severity of the underlying disease.

Adolescent↗
PubMed1989

Fibrinolytic response in normal subjects to venous occlusion and DDAVP infusion.

A set of fibrinolytic parameters was measured in 40 healthy subjects before and after a venous occlusion (VO) test lasting 10 min. After VO, plasma levels of tissue-type plasminogen activator (t-PA) antigen increased in all subjects, t-PA activity increased only in 25 subjects who were considered responders and remained unchanged in 15 (non-responders). High levels of plasminogen activator inhibitor (PAI) in the non-responder group explain this discrepancy. The non-responders had basal levels of PAI activity and t-PA antigen higher than responders (p less than 0.0001) and their basal levels of t-PA activity were lower (p less than 0.001). DDAVP infusion elicited good responses in 7 of 9 non-responders to VO with a fall of PAI activity to 0. Our data indicate that a high proportion of healthy subjects do not have a fibrinolytic response after VO, that a lack of fibrinolytic response to VO is due to high plasma levels of PAI and that DDAVP infusion appear to be more selective than VO for detecting non-responders.

Adult↗
PubMed1988

Haemostasis contact system and fibrinolysis in hereditary angioedema (C1-inhibitor deficiency).

Factors of the classical complement pathway, the contact system and fibrinolysis were evaluated both with functional and immunochemical methods, in patients with inherited deficiency of C1-inhibitor. Evaluations were performed under basal conditions, during acute attacks and during prophylaxis with low doses of anabolic steroids. Patients in the basal state showed no significant abnormalities of any of the parameters that we investigated. During acute attacks a slightly reduced prekallikrein concentration was registered. During treatment with low doses of danazol and stanozolol, protein C and plasminogen were found to be increased. Our data suggest that C1-inhibitor deficiency per se does not lead to a derangement of the fibrinolysis and coagulation contact system, and that the kinin system may be involved during acute attacks of angioedema.

Adolescent↗
PubMed1986

Low-frequency positive-pressure ventilation with extracorporeal CO2 removal in severe acute respiratory failure.

Forty-three patients were entered in an uncontrolled study designed to evaluate extracorporeal membrane lung support in severe acute respiratory failure of parenchymal origin. Most of the metabolic carbon dioxide production was cleared through a low-flow venovenous bypass. To avoid lung injury from conventional mechanical ventilation, the lungs were kept "at rest" (three to five breaths per minute) at a low peak airway pressure of 35 to 45 cm H2O (3.4 to 4.4 kPa). The entry criteria were based on gas exchange under standard ventilatory conditions (expected mortality rate, greater than 90%). Lung function improved in thirty-one patients (72.8%), and 21 patients (48.8%) eventually survived. The mean time on bypass for the survivors was 5.4 +/- 3.5 days. Improvement in lung function, when present, always occurred within 48 hours. Blood loss averaged 1800 +/- 850 mL/d. No major technical accidents occurred in more than 8000 hours of perfusion. Extracorporeal carbon dioxide removal with low-frequency ventilation proved a safe technique, and we suggest it as a valuable tool and an alternative to treating severe acute respiratory failure by conventional means.

Acute Disease↗
PubMed1986

Evaluation of tests for heparin control during long-term extracorporeal circulation.

Two coagulation tests, Recalcified Activated Clotting Time (RACT) and Hemochron, were compared with the activated partial thromboplastin time (APTT) in in vitro heparinization experiments and in patients heparinized for long term extracorporeal circulation (ECC) to determine their suitability as guidelines for heparin administration. All tests had good precision, with a small variability between methods. There was satisfactory correlation with the heparin level in vivo (r = 0.77 for RACT; r = 0.80 for Hemochron and r = 0.82 for APTT) too, while the in vitro r was always greater than or equal to 0.94. Nevertheless, APTT values for plasma heparin levels higher than 1.5 U/ml were markedly prolonged, with a large standard deviation, and often "unclottable". The good correlation between the three tests, makes it possible to substitute RACT and Hemochron for APTT, during long-term ECC.

Analysis of Variance↗
PubMed1981

Effect of PGI2 infusion during long term extracorporeal circulation with membrane lung in sheep.

PGI2 plus very low dose of heparin was infused in 6 lambs connected for long term extracorporeal circulation with a membrane lung. Hemodynamic and hemostasis parameters were compared to those of a control group treated only with standard doses of heparin. PGI2 efficacy in inhibiting platelet aggregation and platelet fall was confirmed. A small platelet release, measured as antiheparin activity, was observed during all the by-pass, but did not influence platelet capacity of recovering when PGI2 effect dissolved. Heparin needed resulted less than a quarter of the quantity used for the control group. In our experimental conditions the hemodynamic changes were mainly limited to a decrease in diastolic blood pressure.

Animals↗