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Biomedical subjects

B Balint

Publications and source records attributed to B Balint.

At least 19 recordsLinked to original sources

Increased nitric oxide metabolites in exhaled breath condensate after exposure to tobacco smoke.

BACKGROUND: Cigarette smoking reduces the level of exhaled nitric oxide (NO) in healthy subjects, although the mechanism is unclear. NO is a highly reactive molecule which can be oxidised or complexed with other biomolecules, depending on the microenvironment. The stable oxidation end products of NO metabolism are nitrite and nitrate. This study investigated the effect of smoking on NO metabolites in exhaled breath condensate. METHODS: Fifteen healthy current smokers were recruited together with 14 healthy non-smokers. Measurement of exhaled NO, lung function, and collection of exhaled breath condensate were performed. Nitrite, nitrite + nitrate, S-nitrosothiols, and nitrotyrosine levels were measured. The effect of inhaling two cigarettes in smokers was also evaluated. The mean level of exhaled NO in smokers was significantly lower than in non-smokers (4.3 (0.3) ppb v 5.5 (0.5) ppb, p<0.05). RESULTS: There was no difference in the levels of nitrite, nitrite + nitrate, S-nitrosothiols, and nitrotyrosine in the exhaled breath condensate at the baseline visit between smokers and non-smokers. After smoking, nitrite + nitrate levels were significantly but transiently increased (from 20.2 (2.8) microM to 29.8 (3.4) microM, p<0.05). There was no significant change in the levels of exhaled NO, nitrite, S-nitrosothiols, or nitrotyrosine 30 and 90 minutes after smoking. CONCLUSIONS: These findings suggest that acute smoking can increase the level of nitrate, but not nitrite, S-nitrosothiols, or nitrotyrosine in breath condensate. The deleterious effect of oxidant radicals induced by smoking may contribute to the epithelial damage of airways seen in smokers.

Adult↗

Increased nitrotyrosine in exhaled breath condensate in cystic fibrosis.

Exhaled nitric oxide (ENO), a marker of inflammation in airway diseases is decreased in cystic fibrosis (CF) patients, perhaps because nitric oxide (NO) is metabolized to oxidative end-products. A stable product, 3-nitrotyrosine, may indicate local formation of reactive nitrogen species. Whether NO metabolites in exhaled breath condensate may be increased in CF patients was investigated. The fractional concentration of ENO (Feno), nitrotyrosine and oxides of nitrogen in exhaled breath condensate from 36 stable CF patients were compared to 14 normal subjects using an enzyme immunoassay and fluorescence assay. Nitrotyrosine levels in breath condensate were increased significantly in stable CF patients, compared with normal subjects (25.3 +/- 1.5 versus 6.3 +/- 0.8 ng x mL(-1), p<0.0001). There was an inverse correlation between the levels of nitrotyrosine and the severity of lung disease. Feno levels were significantly lower in CF patients than in normal subjects (4.4 +/- 0.3 versus 5.6 +/- 0.4 (parts per billion), p<0.05). No correlation was found between nitrotyrosine and Feno levels in CF. There was no significant difference in the levels of nitrite and nitrate between CF patients and normals. The elevation in nitrotyrosine may reflect increased formation of reactive nitrogen species such as peroxynitrite or direct nitration by granulocyte peroxidases, indicating increased oxidative stress in airways of cystic fibrosis patients.

Adult↗

The cryopreservation protocol optimal for progenitor recovery is not optimal for preservation of marrow repopulating ability.

The efficiency of five different cryopreservation protocols (our original controlled-rate and noncontrolled-rate protocols) was evaluated on the basis of the recovery after thawing of very primitive pluripotent hemopoietic stem cells (MRA(CFU-GM), pluripotent progenitors (CFU-Sd12) and committed granulocyte-monocyte progenitors (CFU-GM) in mouse bone marrow. Although the nucleated cell recovery and viability determined immediately after the thawing and washing of the cells were found to be similar, whether controlled-rate or noncontrolled-rate cryopreservation protocols were used, the recovery of MRA(CFU-GM), CFU-Sd12 and CFU-GM varied depending on the type of protocol and the cryoprotector (DMSO) concentrations used. It was shown that the controlled-rate protocol was more efficient, enabling better MRA(CFU-GM), CFU-Sd12 and CFU-GM recovery from frozen samples. The most efficient was the controlled-rate protocol of cryopreservation designed to compensate for the release of fusion heat, which enabled a better survival of CFU-Sd12 and CFU-GM when combined with a lower (5%) DMSO concentration. On the contrary, a satisfactory survival rate of very primitive stem cells (MRA(CFU-GM)) was achieved only when 10% DMSO was included with a five-step protocol of cryopreservation. These results point to adequately used controlled-rate freezing as essential for a highly efficient cryopreservation of some of the categories of hematopoietic stem and progenitor cells. At the same time, it was obvious that a higher DMSO concentration was necessary for the cryopreservation of very primitive stem cells, but not, however, for more mature progenitor cells (CFU-S, CFU-GM). These results imply the existence of a mechanism that decreases the intracellular concentration of DMSO in primitive MRA cells, which is not the case for less primitive progenitors.

Animals↗

The use of therapeutic plasma exchange for treatment of acute polyradiculoneuropathy.

The rationale for therapeutic plasma exchange (TPE) in acute polyradiculoneuropathy (APRN) is based on the presence of circulating antibodies which cause demyelination of the peripheral nerves. This study included 24 patients, most having a neurological defect of grade 4, classified into groups A and B. Group A was treated with immunosuppressive drugs only, while group B was treated by a combination of immunosuppressive drugs and TPE. The average volume of plasma removed during a single TPE procedure was 2.95 L, and totalled 21 L overall. The efficacy of the TPE treatment was assessed on the basis of changes in the neurological deficit grade, and in electrophysiological parameters. It was shown that improvements were significantly better and faster in patients treated by a combination of immunosuppressive drugs and TPE, and when TPE was started within the first 7 days after the onset of the disease.

Acute Disease↗

Application of therapeutic plasma exchange in hematology.

Therapeutic plasma exchange (TPE) was used in 146 patients with hematologic disorders: hyperviscosity syndrome, 74; cryoglobulinemia, 53; porphyria, 9; immune complex disease, 3; cold agglutinin disease, 1; hemolytic uremic syndrome, 1; autoimmune hemolytic anemia, 1; autoimmune thrombocytopenia, 1; autoimmune neutropenia, 1; Clq deficiency, 1; and secondary immunodeficiency, 1. It was shown that TPE applied in patients with hyperviscosity syndrome resulted in rapid reduction of paraprotein concentrations, and normalization or significant decrease of serum viscosity associated with marked clinical improvement (regression of neurologic, renal, hematologic, visual and other disturbances). Application of TPE in patients with cryoglobulinemia resulted in plasma cryoglobulin reduction and clear clinical effects (blood flow improvement, skin ulcer healing, reversal of impaired renal function and disappearance of purpura and other abnormalities). Very good results were obtained in patients with porphyria (decreased sensitivity to sunlight) and also in patients with Clq deficiency. Satisfactory clinical improvement and better laboratory findings were also seen in patients with immune complex disease, autoimmune hemolytic anemia, autoimmune thrombocytopenia and hemolytic uremic syndrome.

Evaluation Studies as Topic↗

Therapeutic leukapheresis.

For the majority of leukemic patients, leukapheresis represents emergency treatment aimed at reducing the number of white blood cells and producing an immediate improvement in the clinical picture. We have shown that leukapheresis procedures performed for the therapy of leukocytosis in 4 patients with acute leukemia (2 myelocytic; 1 lymphocytic; 1 monoblastic) resulted in marked reduction in the white blood cell count and a considerable reduction in symptomatology. Repeat removal of white blood cells applied in 20 instances for patients with chronic myelocytic leukemia also produced a significant decrease in the cell count and relief of symptoms such as sweating, malaise, and pain due to splenomegaly. In chronic lymphocytic leukemia (31 patients), intensive and frequent leukapheresis procedures were followed by a marked fall in white blood cell count, regression of splenomegaly/lymphadenopathy and resolution of many symptoms and signs induced by the large number of cells.

Adolescent↗

Evaluation of cryopreserved murine and human hematopoietic stem and progenitor cells designated for transplantation.

The influence of five different cryopreservation protocols on the quality and/or quantity of frozen cells was investigated on mouse bone marrow cells and human peripheral blood mononuclear cells (MNC). The efficiency of the protocols was evaluated on the basis of the recovery of very primitive pluripotent hematopoietic stem cells (MRA), pluripotent progenitors (CFU-Sd12), committed granulocyte-monocyte progenitors (CFU-GM) of mouse cells after thawing. The recovery of MRA, CFU-Sd12 and CFU-GM varied depending on the type of freezing procedure and cryoprotector (DMSO) concentrations used. It was shown that the controlled-rate protocol was more efficient, enabling better recovery of all categories of progenitor cells in frozen samples. The most efficient was the controlled-rate protocol of the cryopreservation designed to compensate for the release of fusion heat, which enabled the best recovery of CFU-GM (73.0 +/- 8.8%) and CFU-Sd12 (90.0 +/- 15.9%) when combined with 5% DMSO concentration (protocol 4). On the contrary, a better recovery (79.8 +/- 13.5%) of very primitive stem cells (MRA) was achieved only when the higher concentration (10%) DMSO was used in combination with a five-step protocol of cryopreservation (protocol 1). These results pointed out the adequately used controlled-rate freezing to be essential for a highly efficient cryopreservation of some of the categories of hematopoietic stem and progenitor cells. At the same time, it was obvious that a higher DMSO concentration was necessary for the cryopreservation of MRA, but not for more mature progenitor cells (CFU-S, CFU-GM). These results imply the existence of a mechanism that decreases the intracellular concentration of DMSO in MRA cells, which is not the case in less primitive progenitors. For human MNC, the recovery and viability of the cells, as well as the engraftment potential of cryopreserved cells after thawing were investigated. Cryopreservation protocol 1 resulted in better MNC recovery (82.7 +/- 10.4%) than protocol 3 (49.9 +/- 15.1%). The mean recovery of MNCs (collected from patients for autologous transplantation) was 78.5 +/- 7.3% (protocol 1) and 53.1 +/- 26.2% (protocol 3). The obtained favorable recovery of thawed cells and rapid reconstitution of hematopoiesis (on the day 11th following the transplantation) in patients confirmed that the controlled-rate freezing in combination with optimal DMSO concentration was able to obtain sufficient progenitor cryoprotection.

Adult↗

Plasma exchange in myasthenia gravis and multiple sclerosis.

During the last twenty-year period therapeutic plasma exchange (TPE) was used in the treatment of 68 patients with myasthenia gravis and 61 patients with multiple sclerosis. The therapeutic effects were evaluated on the basis of neurologic deficit changes, electrophysiological findings, necessary laboratory analyses and patient's general conditions. It was shown that the therapeutic effects mosty depended on the nature and stage of the basic disease, adequate selection of the patients and timely applied therapeutic procedure. Significant positive effects of the TPE treatment applied with the anti-inflammatory and immunosuppressive therapy were observed in patients with myasthenia gravis and multiple sclerosis upon clinical findings and some paraclinical tests.

Adolescent↗

[Blood transfusion therapy at the Military Medicine Academy--present possibilities].

Blood component therapy refers to the transfusion of the specific part of blood that a patient needs, as opposed to the routine transfusion of whole blood (WB) in the past. This not only maintains blood resources, but also provides the optimal method of transfusing patients who require large amounts of a specific blood component. Since this concept have been accepted, the Institute of Transfusiology of Military Medical Academy (MMA) possess appropriate equipment for blood collection and processing of WB in components. Mainly, all kind (except frozen) of packed red cells (RBCs), platelet concentrates (random-donor buffy coat or apheresis donation), single-donor (apheresis) or random-donor (buffy coats) granulocytes, fresh frozen plasma (FFP), single-donor cryoprecipitate are prepared. Recently, fibrin glue (obtained by recycled cryoprecipitation from single-donor or autologous plasma), and some of new generation of blood components: hematopoietic stem and progenitor cells (fresh or cryopreserved), collected from bone marrow or harvested from peripheral blood after mobilization and donor-specific mononuclear cells for cell therapy, i.e. immunomodulation during relapse of leukemia after bone marrow transplantation, have become the routine. Analysis of blood component therapy done at the MMA during the past 11 years (1989-1999) showed that: a) participation of WB transfusion in the group of surgical clinics was permanently decreased (from 59.60% in 1989 to 0.37% in 1999); b) WB transfusion (in the last few years) practically was not used in the group of internal medicine clinics (0.82% in 1993 and 0.45% in 1999); c) overall WB transfusion in MMA is extremely rare (0.37%).

Blood Component Removal↗

[Biochemical changes in thrombocyte concentrates stored for 5 days].

The purpose was to evaluate biochemical and functional changes in platelet concentrates prepared from buffy-coat (PC-BC), stored up to five days at temperature of 20 +/- 2 degrees C. Forty-two PC-BC units from random blood donors were examined. In order to determine the biochemical changes we studied the release of lactate dehidrogenase (LDH), changes in pH value, pCO2, pO2, glucose and lactate concentrations. In addition, the aggregation of platelets with adenosine diphosphate (ADP), and hypotonic shock response were examined. The concentration of LDH markedly increased from 138.8 IU/l (day 1st) up to 234 IU/l (day 5th). The lactate concentration increased significantly (p < 0.001) from 2.1 to 8.6 mmol/l, and consequently pH decrease was observed (from 7.31 to 7.13). The level of glucose decreased gradually from 22.8 to 19.4 mmol/l. The pCO2 decreased progressively from 36.8 mmHg to 24 mmHg during first two days of storage and after that gradually to 20 mmHg. In contrast, pO2 fluctuated between 108 and 133 mmHg during five day of storage. Recovery of hypotonic shock response was 70% on day 1st and 35.7% on day 5th, respectively (p < 0.001). Platelet aggregation using ADP showed significant increase from 6.6 sec (day 1st), to 11.2 sec (day 4th) and 14.6 sec (day 5th), too. Significant differences in biochemical parameters and platelet functions, with confirmed relationship between changes obtained during five days stored PC-BC did not affect the efficacy of applied platelets.

Blood Platelets↗

[Significance of blood transfusion in the development of cytotoxic antibodies in patients on hemodialysis].

The aim was to evaluate the influence of red blood cells (RBC) transfusion on the development of cytotoxic antibodies (C-Ab) in patients subjected to hemodialyses (HD) and planned for the kidney transplantation. The group of 71 HD patients, of mean age 42 years (19-65), 48 males and 23 females, planned for the kidney information was examined. Out of 71 HD patients, only 42 (59.19%) HD patients (group I) received subcutaneously recombinant human erythropoietin--rhuEPO (Eprex--epoetin-alpha or Recormon SE--epoetin-beta in dosage of 4,000 IU during every HD; i.e. one to three times a week) and they were not treated by RBC transfusion. The other 29 (40.85%) HD patients (group II) received RBC transfusion: 18 (62.07%) HD patients received < 10 units 18 of RBC, 8 (27.59%) HD patients received 10-20 units of RBC; 3 (10.35%) HD patients received > 20 units of RBC. Testing of C-Ab was done in all patients every three months by standard lymphocytotoxicity test on the panel from 20 different lymphocyte donors with definite class I phenotype of antigen HLA. C-Ab was not found in HD patients who were not treated by RBC transfusion. Out of 18 HD patients who received < 10 units of RBC only 3 (16.67%) HD patients developed C-Ab; out of 8 HD patients who received 10-20 units of RBC, in 4 (50%) patients was proved C-Ab; and C-Ab was proved in all 3 HD patients who received > 20 units of RBC. RhuEPO administration is very important for the transfusiologic treatment of HD patients; especially those who are planned for the kidney transplantation. Development of C-Ab is in direct correlation with the number of transfunded units of RBC. HD patients who received 10 or more units of RBC were at great risk to develop C-Ab.

Adult↗

[Treatment of Hodgkin's disease with high-dose chemotherapy and autologous stem cell transplantation].

High dose chemotherapy (HDC) with autologous stem cell transplantation (SCT) was applied for the treatment of 13 patients (pts) with Hodgkin's disease (HD) (10 with relapsed form and 3 with conventional chemotherapy resistant form) in the Clinic for Hematology, Military Medical Academy, from May 1997 to October 1999. After the initial treatment for the reduction of tumor, burden stem cells were mobilized by cyclophosphamide 2.5-7.0 g/m2 with G-CSF 5-12 micrograms/kg body mass (BM). The average number of colected mobilized mononuclear cells (MNC) was 2.99 (1.66-5.9) x 10(8)/kg BM by the apheresis large volume from peripheral blood. All patients received BEAM (BCNU, etoposide, Cyto-Ara, and melfalan) conditioning regimen with adequate supportive therapy. Good engraftment (100%) was observed at postransplantation period: number of polymorphonuclear cells was > 0.5 x 10(9)/l, on day 13th (10-21) and number of platelets > 20 x 10(9)/l, on day 17th (11-28). One patient (7.6%) died due to infective complications at day 98th after transplantation, 9 (69.2%) patients achieved complete and 3 (23.1%) patients partial remission of the disease. Out of three patients with partial remission, one relapsed, seven months after autologous SCT, with conventional chemotherapy resistant form and two, after the applied conventional locoregional radiotherapy reached remission. One patient (7.6%) developed secondary malignancy of acute myeloid leukemia form with threelinage displasy 27 months after autologous SCT. HDC with autologous SCT contributes to more successful treatment of early relapsed and standard chemotherapy resistant forms of HD and gives the opportunity for successful quality of living for those patients.

Adolescent↗