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Biomedical subjects

M Wysocki

Publications and source records attributed to M Wysocki.

At least 73 records · Page 4Linked to original sources

Animal serum-free culture of purified human CD34+ cells: amplification of progenitors from G-CSF and GM-CSF-mobilized peripheral blood.

The isolation and culture of human CD34+ cells could have broad clinical application for hematologic support following high-dose chemotherapy or bone marrow transplantation. The need for reproducible, animal product-free conditions for the culture of progenitors is crucial to the widespread clinical implementation of ex vivo cell therapies. In these studies, we explored the use of animal serum-free (ASF) medium for the culture of isolated human bone marrow and peripheral blood CD34+ cells. In this ASF system, isolated CD34+ cells were cultured using a variety of different growth factor combinations. Such ASF culture conditions yielded equivalent to superior cell and progenitor growth when directly compared with culture containing 10% fetal calf serum (FCS). In cultures containing IL-1, IL-3, and stem cell factor, total cell numbers increased, on average, 33-fold over the first 2 weeks. On phenotypic analysis, the ASF cultures demonstrated sustained proliferation of CD33+ myeloid cells throughout the culture period. CD34+ cell numbers increased during the first 7-10 days of culture, with a mean 3.4-fold expansion. Concomitant with the CD34+ cell expansion was an average 8.2-fold expansion of colony-forming unit-granulocyte-macrophage (CFU-GM) and a 102.0-fold increase in burst-forming units-erythrocytes (BFU-E). Likewise, a mean 4929-fold expansion of CD41a+ megakaryocyte progenitors was observed in these CD34+ cultures. Different combinations of growth factors affected the fold increase in cell and progenitor number. When CD34+ cell cultures from normal healthy volunteers mobilized with either G-CSF or GM-CSF were compared, similar expansions of total cell and progenitor cells resulted. However, CD41+ cells expansions were greater in those samples from G-CSF-mobilized volunteers in every case tested. These studies established the feasibility of this ASF CD34+ cell culture system to generate a population of maturing progenitors for potential use in transfusion support during cytopenic periods following high-dose chemotherapy or bone marrow transplantation.

Animals↗

Elastic energy as an index of right ventricular filling.

BACKGROUND: Right ventricle (RV) preload assessment remains controversial because the complexity of RV geometry is an obstacle to wall stress modeling. We developed a method to evaluate end-diastolic RV elastic energy (EL), a variable that integrates all the stretching effects of venous return and that can be easily estimated at the bedside from the area under the diastolic RV pressure-volume curve. The purpose of this study was to compare the clinical utility of EL and of the two conventional variables used to assess RV filling, ie, right atrial pressure (Pra) and RV end-diastolic volume (EDV). METHOD: We studied 26 postoperative patients who required a rapid fluid challenge. Energetics were evaluated by constructing the RV pressure-volume loop at the bedside using right heart catheterization with RV ejection fraction (EF) derivation. Correlations between RV filling and RV performance (ejection and mechanical efficiency) were studied. RV filling indexes were Pra, EDV, and EL. Indexes of RV ejection were stroke volume (SV), RV stroke work (RVSW), mechanical energy expenditure during ejection (EM), and total energy expenditure of contraction (ET). Indexes of RV mechanical efficiency were EF and the EM/ET ratio. RESULTS: Three important results were obtained. First, among RV ejection indexes, those that correlated best with RV filling indexes were EM and ET. Second, we found significant linear relationships between improved RV filling, as assessed by changes in EDV and EL, and improved RV ejection, as assessed by changes in SV, RVSW, EM, or ET. Third, changes in EDV and EL also predicted improved mechanical efficiency, as assessed by changes in EF and EM/ET. In, all situations, changes in EL yielded the strongest correlations. CONCLUSIONS: Derivation of EL is simple and appears to be the best clinical means of assessing Starling's law of the heart for the RV.

Adult↗

Hemorheologic effects of vasodilation in essential hypertension.

Arterial hypertension is often associated with plasma volume contraction and hemoconcentration, which negatively affect the vascular flow resistance and microcirculation. Since some antihypertensive drugs can affect blood rheology, the purpose of this study was to evaluate whether acute and long-term arterial vasodilation with cadralazine influences rheologic parameters in essential hypertension. Twelve patients with unsatisfactorily controlled essential hypertension were studied. In the acute double-blind phase of the study the patients were allocated to treatment with either cadralazine or placebo. Intraarterial blood pressure, cardiac output (dye dilution), and blood rheology (viscosity, hematocrit) were registered before and after the first dose of cadralazine. Then 9 patients (3 dropouts) were treated with cadralazine and placebo during two four-week crossover periods and continued with cadralazine medication during the eight-week open phase of the study. Blood pressure and blood hemoglobin were followed during long-term treatment. A single oral dose of cadralazine caused vasodilation (total peripheral resistance index decreased from 45 to 33 U x m2, P < 0.05), which was accompanied by hemodilution (hematocrit declined from 46.9% to 42.5%, P < 0.05) and a blood viscosity reduction of more than 10%. Viscosity of 45% suspension of erythrocytes in plasma was also reduced, suggesting a possible modification of the microrheologic factors. The changes in total peripheral resistance correlated negatively with the changes in hematocrit. An antihypertensive effect of cadralazine was still observed during the chronic phase of the study, which was not accompanied by hemodilution. It is concluded that arterial vasodilation with cadralazine reduces flow resistance in the circulatory system in hypertension and has acute rheologic effects that disappear during chronic medication.

Antihypertensive Agents↗

[Experience in the use of Broviac catheters in children with hematologic neoplastic diseases].

Between 1990 and 1994, 61 Broviac catheters were implanted in 53 children with haematological neoplastic diseases. The mean duration of catheter function was 206 days (range 14-615 days). The total observation time was 12544 days, during which 84 catheter-related complications were recorded, i.e. 6.7 per 1000 catheter use days. Infections occurred with a frequency of 3.8 episodes/1000 cath, days, the majority of which were bacteriemias (2.6/1000 cath, days). Gram-positive and Gram-negative strains were the isolated etiologic agents with equal frequency. Most of infectious episodes (85%) responded well to initial empiric antibiotics treatment without removal of the catheters. Mechanica complications (occlusion, displacement or catheter leakage) occurred significant less frequently and were managed by repairing or replacing the device or clearing the block. No deaths were related to catheter complications. In conclusion indwelling Broviac catheters offer a safe and effective method of long-term venous access. Infections are the most frequent catheter-related complications.

Bacteremia↗

[Treatment of acute immune thrombocytopenic purpura in children--intravenous immunoglobulin or treatment with corticosteroids?].

The results of treatment of newly diagnosed patients with immune thrombocytopenic purpura are described. Forty seven patients were treated with prednisone 1-2 mg/kg body weight/24 hours and 13 with simplified methods of giving immunoglobulins (2 x 0.4 g/kg body weight/24 hours). An increase of platelet number to 150 G/l was achieved in 43/47 patients treated with prednisone after 3-104 days (mean 22 days) and significantly faster in 12/13 treated with immunoglobulins (after 3-17 days, mean 7 days). The effect was stable in 30/43 patients in group I (prednisone) and in 11/13 in group II (Igiv). The disease evolved to the chronic form in 15/47 patients treated with prednisone and in 1/13 treated with immunoglobulins. No life-threatening bleedings were observed.

Adolescent↗

Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: In patients with acute exacerbations of chronic obstructive pulmonary disease, noninvasive ventilation may be used in an attempt to avoid endotracheal intubation and complications associated with mechanical ventilation. METHODS: We conducted a prospective, randomized study comparing noninvasive pressure-support ventilation delivered through a face mask with standard treatment in patients admitted to five intensive care units over a 15-month period. RESULTS: A total of 85 patients were recruited from a larger group of 275 patients with chronic obstructive pulmonary disease admitted to the intensive care units in the same period. A total of 42 were randomly assigned to standard therapy and 43 to noninvasive ventilation. The two groups had similar clinical characteristics on admission to the hospital. The use of noninvasive ventilation significantly reduced the need for endotracheal intubation (which was dictated by objective criteria): 11 of 43 patients (26 percent) in the noninvasive-ventilation group were intubated, as compared with 31 of 42 (74 percent) in the standard-treatment group (P < 0.001). In addition, the frequency of complications was significantly lower in the noninvasive-ventilation group (16 percent vs. 48 percent, P = 0.001), and the mean (+/- SD) hospital stay was significantly shorter for patients receiving noninvasive ventilation (23 +/- 17 days vs. 35 +/- 33 days, P = 0.005). The in-hospital mortality rate was also significantly reduced with noninvasive ventilation (4 of 43 patients, or 9 percent, in the noninvasive-ventilation group died in the hospital, as compared with 12 of 42, or 29 percent, in the standard-treatment group; P = 0.02). CONCLUSIONS: In selected patients with acute exacerbations of chronic obstructive pulmonary disease, noninvasive ventilation can reduce the need for endotracheal intubation, the length of the hospital stay, and the in-hospital mortality rate.

Acute Disease↗

Noninvasive pressure support ventilation in patients with acute respiratory failure. A randomized comparison with conventional therapy.

The benefit of noninvasive pressure support ventilation (NIPSV) in avoiding the need for endotracheal intubation and reducing morbidity and mortality associated with endotracheal intubation was evaluated in 41 patients who presented with acute respiratory failure not related to chronic obstructive pulmonary disease (COPD). Patients were randomly assigned to receive conventional therapy (n = 20) or conventional therapy plus NIPSV (n = 21). NIPSV was delivered to the patient by a face mask connected to a ventilator (Puritan-Bennett 7200a) set in inspiratory pressure support (IPS) mode. The mean levels of IPS, positive end-expiratory pressure (PEEP), and fraction of inspired oxygen (FIO2) were respectively 15 +/- 3 cm H2O, 4 +/- 2 cm H2O, and 57 +/- 22%. The rate of endotracheal intubation (62 vs 70%, p = 0.88), the length of ICU stay (17 +/- 19 days vs 25 +/- 23 days, p = 0.16), and the mortality rate (33 vs 50%, p = 0.46) were not different between patients treated with NIPSV and those treated conventionally. Post hoc analysis suggested that in patients with PaCO2 > 45 mm Hg (n = 17), NIPSV was associated with a reduction in the rate of endotracheal intubation (36 vs 100%, p = 0.02), in the length of ICU stay (13 +/- 15 days vs 32 +/- 30 days, p = 0.04), and in the mortality rate (9 vs 66%, p = 0.06). We conclude that NIPSV is of no benefit when used systematically in all forms of acute respiratory failure not related to COPD. A subgroup of patients, characterized by acute ventilatory failure and hypercapnia, may potentially benefit from this therapy and further studies are needed to focus on this aspect.

Acute Disease↗

[Fever in children with hematologic neoplastic diseases and implanted Broviac-Hickman catheters].

A safe and effective method of venous access is important in the care and treatment of patients with malignancies. Thirty-seven Broviac-Hickman catheters were inserted in 32 children with haematological neoplastic disease. The mean indwelling time of the catheters was 7014 days. The catheters were used to administer chemotherapy and other drugs, blood products, and as well as to draw blood. Fever occurred 96 times. Forty-three percent of fever episodes were related to clinically documented infections and in 15% of cases, to catheter-related bacteremia caused by Gram-positive and Gram-negative strains in equivalent proportions. Fever was observed with a two fold greater incidence in patients with severe granulocytopenia (< 0.5 G/l).

Adolescent↗

[Efficacy of passive and active immunization against HBV infection in children with neoplastic diseases].

The efficacy of 3 schemes of passive and active prevention of HBV infection was evaluated in 47 children with haematologic proliferative diseases. Twenty-six children suffering from leukemia (group I) received passive immunisation (hepatitis B immunoglobulin) in six week intervals during intensive chemotherapy and were vaccinated on maintenance therapy. Thirteen children with Hodgkin or B-non-Hodgkin lymphoma (group II) received active immunisation from the beginning of intensive chemotherapy with two doses of immunoglobulin. Eight children who had completed their therapy (group III) were vaccinated only. Among children who completed vaccinations, 5/8 in group I, 4/7 in group II and 5/5 in group III produced protective anti-HBs levels. Passive/active prophylaxis was successful in most patients suffering from neoplastic diseases and reduced the endemy of HBV infection in our department from 43.3% to 2.56% infected subjects. Among 7 patients vaccinated from the beginning of treatment (group II), 4 of them produced protective levels of anti,-HBs, despite intensive chemotherapy.

Adolescent↗

Additive effect on gas exchange of inhaled nitric oxide and intravenous almitrine bismesylate in the adult respiratory distress syndrome.

OBJECTIVE: To assess the additive effect of inhaled nitric oxide (NO) and intravenous almitrine bismesylate (ALM) on gas exchange. DESIGN: Prospective self-controlled study. SETTING: 3 medico-surgical intensive care units. PATIENTS: 17 patients with severe hypoxemia (PaO2/FIO2 ratio: 88 +/- 30 mmHg, venous admixture: 47 +/- 7%) and elevated mean pulmonary artery pressure (MPAP: 30 +/- 5 mmHg) due to adult respiratory distress syndrome (ARDS). INTERVENTIONS: 5 conditions were studied: 1) baseline, 2) 5 to 10 ppm of NO during 30 min, 3) discontinuation of NO during 30 min, 4) ALM infusion (0.5 mg/kg) during 30 min, 5) ALM infusion (0.5 mg/kg) during 30 min in combination with 5 to 10 ppm of NO. MEASUREMENT AND RESULTS: The PaO2/FIO2 ratio rose from 88 +/- 30 to 98 +/- 37 mmHg (NS) with NO alone, and from 92 +/- 25 to 130 +/- 56 mmHg (p < 0.01) with NO + ALM (p < 0.05 vs NO alone). Seven patients were considered as "NO-responders" (rise in PaO2/FIO2 ratio of 10 mmHg or more with NO); in this subgroup the PaO2/FIO2 ratio rose from 87 +/- 30 to 128 +/- 39 mmHg (p < 0.05) with NO alone, and from 93 +/- 20 to 169 +/- 51 mmHg (p < 0.01) with NO + ALM (p < 0.05 versus NO alone). MPAP decreased from 30 +/- 5 to 26 +/- 5 mmHg (p < 0.01) with NO alone, increased slightly from 28 +/- 5 to 31 +/- 5 mmHg (NS) with ALM alone and decreased to 27 +/- 5 mmHg (p < 0.05) with NO + ALM. CONCLUSIONS: NO + ALM had additive effects on gas exchange while decreasing MPAP in patients with ARDS. The effects of NO alone were small and non significant, except in a subgroup of 7 patients in whom the combination of both therapies had the more pronounced results.

Administration, Inhalation↗

Rapid isolation and serum-free expansion of human CD34+ cells.

Human CD34+ cells were isolated from bone marrow from normal volunteers and expanded under serum-free culture conditions. CD34+ cells were cultured with interleukin-3 (IL-3), IL-1, and stem cell factor and expanded in granulocyte-macrophage colony-forming units, erythroid blast-forming units, and CD34+ cell number during the first 7-14 days of incubation. By contrast, cultures maintained in fetal calf serum under identical conditions showed much reduced expansion, as measured by all of the above parameters. The level of expansion of the CD34+ cells was dependent on the combination of growth factors used during culture. The data establish the feasibility of serum-free expansion of progenitors and suggest the clinical use of this procedure for the generation of expanded progenitor cell products for transfusion after chemotherapy to minimize treatment-related cytopenias.

Adult↗

[Congenital spherocytosis in children].

The clinical course and effects of treatment of congenital spherocytosis (CS) were analyzed in 28 children. In 10 cases the disease ran a severe clinical course. Jaundice, anaemia, and splenomegaly were the most frequent clinical signs which were significantly intensified during haemolytic crises. In 14 cases splenectomy was performed, obtaining in all children a regression of jaundice and anaemia. Before the operation two children were vaccinated with Pneumo 23. In asplenic children Debecillin was prophylactically used. Serious infectious complications were observed only in one patient.

Adolescent↗

Is carbohydrate-deficient transferrin in serum useful for detecting excessive alcohol consumption in hypertensive patients?

The aim of this study was to examine the diagnostic usefulness of carbohydrate-deficient transferrin (CDT) in serum in a cross-sectional study of 439 treated hypertensive men. We related the results to alcohol intake by questionnaire and to biochemical and hemodynamic measurements known to reflect excessive alcohol consumption. The diagnostic sensitivity and the specificity for high alcohol intake (> or = 24 g/day of ethanol) were 44% and 87%, respectively. The group with reported high alcohol intake (n = 32) was characterized by hemodynamic and biochemical changes typical of alcohol abuse. The corresponding profile for the patients with increased serum CDT concentrations (n = 70) was different in several respects, indicating a considerable number of false-positive tests. We conclude that serum CDT determination had low sensitivity and specificity for excessive alcohol consumption in this group of hypertensive patients. The results illustrate the importance of evaluating new laboratory methods in unselected patient populations before drawing any conclusions about their clinical value.

Aged↗

[Preliminary evaluation of adverse effects after administration of arabinoside cytosine (Ara-C) in high doses to children with acute myelogenous leukemia].

Five children with AML were treated with high-doses of Ara-C (2 g/m2) during consolidation. After 17 cycles the toxicity was evaluated. Granulocytopenia (< 0.5 x 10(9)/l) and thrombocytopenia (< 25 x 10(9)/l) were stated after 15/17 and 13/17 cycles respectively. The nadir of bone marrow suppression appeared between day 10 and 14. In one case treatment related death during severe myelosuppression was noted. In individual cases jaundice with elevated activity of aminotransferases, paralytic ileus and pulmonary oedema were observed. All these adverse reactions were reversible. Other toxicities such as nausea/vomiting, stomatitis, diarrhea, infections and drug related fever were transient. No neurologic toxicity was seen. There is a need for developing a new way of the administration of high-dose Ara-C which could substantially reduce toxicity of the drug.

Adolescent↗