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Biomedical subjects

M Hrubisko

Publications and source records attributed to M Hrubisko.

At least 19 recordsLinked to original sources

Suitability of cisplatin solutions for 14-day continuous infusion by ambulatory pump.

The stability of cisplatin (DDP) solutions (1 and 1.6 mg/ml in saline-mannitol) in plastic infusion bags was studied for up to 14 days at 25 degrees C, 37 degrees C and 60 degrees C. Small changes in the solution were observed, but no evidence of any decomposition product was seen. Some precipitation of DDP was seen in the 1.6-mg/ml solution at the lower temperatures. Fluid loss from the bags was significant at the higher temperatures.

Chromatography, High Pressure Liquid

[Results of detection of hepatitis C virus antibodies (anti-HCV) in blood donors and selected patients].

The authors examined 509 donors for potential carriership of the virus of hepatitis C (HCV), using kits for the detection of anti-HCV. Concurrently they examined also 110 hameatological patients who had a major transfusion of blood, plasma and its derivatives. They found that in the so-called healthy population anti-HCV is present in 0.39%. In haematological patients, i.e. patients with frequent haemotherapy they detected 29 positive cases, i.e. 26.36%. The largest number of anti-HCV positive patients was in the group of haemocoagulopathies. The investigation confirmed the close association between haemotherapy and the transmission of HCV. The authors draw attention to the need to introduce anti-HCV examinations in the transfusion service as an important preventive provision.

Blood Donors

[Respiratory changes in rabbits during metabolic acidemia].

The authors investigated the hyperventilation reaction during acute metabolic acidaemia in anaesthetized rabbits with preserved vagi and after vagotomy. They assessed the respiratory pattern, partial CO2 pressure and pH of arterial blood [PaCO2, pHa]. The value of the minute ventilation [VE] did not differ in animals with intact vagi and those after vagotomy. In rabbits after vagotomy the VE was more effective, as apparent from pHa values. The protraction of the period of expiration [Te] by extension of the expiratory break in vagotomized animals suggests a facilitating action of the vagal pulmonary feedback on the expiration--inspiration activity [inspirium on-switch system].

Animals

[Side-effects of continuous and discontinuous cytapheresis].

The authors evaluate the incidence of complications in 767 cytapreheses made on two types of blood cell separators. Complications, incl. technical problems before cytapheresis proper, were encountered more frequently during work with the discontinuous blood cell separators Haemonetics model 30 (27.%) than during work with the continuous automatic blood cell separator Fenwal CS 3000 (13.2%). Most frequently collapse and symptoms of hypocalcaemia were involved. Serious reactions account only for 7.6 and 4.4% of all reactions. The authors discuss the causes and possible prevention of complications during cytapheresis. With regard to the assessed results cytaprehesis by means of a separator can be considered a safe method in blood donors.

Cytapheresis

Cross resistance studies with L1210 leukemia subline single and double resistant to cisplatin and iproplatin (CHIP).

Resistance to cisplatin (DDP) and/or iproplatin (CHIP) was induced in vitro in murine L1210 leukemia cells. Double-resistant sublines with combined resistance to both drugs were also developed. Cross resistance investigations with DDP, CHIP, oxoplatinum (OXO), carboplatin (CBDCA) and its quadrivalent derivative OXOCBDCA were performed in these resistant sublines. Lack of cross resistance between DDP and CHIP was found. A higher resistance to CHIP in the double-resistant sublines was observed. A multistep process in the development of resistance to this compound is supposed. The importance of the aminoligand and the role of different pharmacokinetics in the cross resistance are discussed.

Animals

Electrophoretic analysis of DNA modifications induced by cis- and trans-diamminedichloroplatinum (II) during heat-denaturation of conformation isomers of pBR322 DNA.

The use of conformation isomers of pBR322 DNA in the study of interactions of Pt complexes with DNA provided for a good monitoring of induced changes in the structure of DNA by gel electrophoresis. On the basis of characteristic changes in the gel electrophoretic mobility of platinated isomers of pBR322 DNA we detected the presence of Pt-DNA adducts representing both intra- and interstrand bifunctional binding of Pt complexes to DNA. Also, this method made it possible to distinguish between DNA modifications induced by the therapeutically active cis-diamminedichloroplatinum (II) (cis-DDP) alone, and those induced by its therapeutically inactive trans-isomer (trans-DDP). The electrophoretically detected DNA modifications were more effective if the interaction of the Pt complex took place with heat-denatured DNA. This process, as compared to that performed with native DNA, ran 100 times faster.

Cisplatin

[40 years of the Czechoslovak transfusion service].

The authors analyze the development and creation of the concept of a uniformly organized blood transfusion service in the CSSR from its beginning to the present time. For the needs of the Czechoslovak socialist health services it proved expedient to integrate haemotherapeutic care in a common department of haematology and transfusiology, in a network of common sections of haematology and blood transfusion and to focus the transfusion service on clinical work. On average there is one common department for a population of 135,000 which ensures blood transfusions as well as haematological work and there is one doctor specialized in haematology and transfusiology per 48,000 population. Blood donorship in the CSSR for basic needs of the transfusion service is not paid; it is organized by the Czechoslovak Red Cross. On average 35,000 units of blood per 1 million inhabitants are collected per year. Component haemotherapy predominates; only 20-25% of the production is used for transfusions of whole blood. The ratio of whole blood transfusions to erythrocytes is 35:65%. The annual number of blood transfusions per hospital bed is 5 on average. The incidence of undesirable posttransfusion reactions, mainly febrile and allergic, is low, it varies between 0.2 and 0.4%. Serious haemolytic reactions are rare and occur in recent years in one patient per 100,000 transfusions. The achievement of the standard of the Czechoslovak blood transfusion service is due to the care of the two national ministries of health, the good training of workers and the clinical orientation of the performed work.

Blood Transfusion

[Further development of the transfusion service in Czechoslovakia].

The blood transfusion service in the CSSR must react in its future activities not only to recent advances in the discipline but also to the present adverse position as regards the spread of AIDS and other virus diseases. Therefore the further development in the CSSR is focused above all on the prevention of transmission of virus infections, incl. organized development of autologous transfusions. To this end the training of new specialists in the discipline must be focused, i. e. on training of clinical transfusiologists. As the basis the concept is used that haematology and blood transfusion in Czechoslovakia is a specialization of internal medicine or paediatrics. In the development of laboratory diagnosis attention is focused on the use of micromethods with the possibility of automation of examinations as well as economy of diagnostic procedures and staff.

Blood Transfusion

[Blood group Du].

When examining blood group D, sensitive methods must be used which will detect false Du as D positive. When these methods are used the incidence of true Du is low, 1-2 pro mille. Moreover Du positive erythrocytes are practically not immunogenic, they may only be able to stimulate a secondary immune response, as easily revealed during antibody screening and during cross-matching. Their immunoreactivity is also low, a passively administered anti-D antibody does not eliminate them from the circulation. The clinical impact of true Du is therefore doubtful. There are also doubts as to the practical value of examination of Du. The authors submit their views on different clinical situations which concern donors and recipients of blood transfusions, pregnant women and neonates.

Blood Grouping and Crossmatching

[Genetic linkage of the autosomal dominant form of Charcot-Marie-Tooth amyotrophy and 3 genetic markers on chromosome 1].

In a large pedigree with the autosomal dominant form of Charcot-Marie-Tooth neuropathy type I (CMT 1) segregating in four generations, genetic linkage was studied between this disease and three genetic markers from the centromere region of chromosome 1: Duffy blood group (Fy), salivary and pancreatic isoamylases (AMY 1, AMY 2), and DNA polymorphism at the antithrombin III locus, detected with the probe pAT3c. The lod-scores found do not support linkage between CMT 1 and both Fy and AT 3, since they are negative for all recombination frequencies. Very close linkage could have been excluded. For the AMY polymorphism, the pedigree was not linkage-informative. In agreement with the data from literature, these results support the notion of genetic heterogeneity of CMT 1: in the pedigree under study, the responsible locus is probably not in the centromeric region of the chromosome 1, where it was shown to map to in several other pedigrees. Thus, there seem to exist at least two loci responsible for this type of CMT disease.

Antithrombin III

Antitumor activity and cross-resistance studies with Pt-ascorbato complexes.

Two ascorbatoplatinum complexes, cis-diammineascorbatoplatinum(II) (AMA) and cis-bis(ascorbato)-trans-diaminocyclohexaneplatinum(II) (CHA), were tested for antitumor activity in vivo on P388 leukemia and in vitro in suspension culture and soft agar assay. Sensitive line of L1210 and sublines with resistance induced against cis-diamminedichloroplatinum(II) (DDP) and two derivatives of trans-1,2-diaminocyclohexane (DACH) were used for the in vitro tests. DNA synthesis inhibition in both sensitive and resistant cells was tested. The results are compared with DDP and DACH-Pt(II)-4-carboxyphtalate (TMA). Both tested complexes proved their antitumor activity in our experimental systems. The CHA complex was more effective than AMA and its effectiveness is comparable with that of DDP and TMA. Cross-resistance was found between DDP and AMA as well as TMA and CHA. There was no cross-resistance between DDP versus CHA, and TMA versus AMA.

Animals

Growth, flow cytometric, and karyological characterization of L1210 cell sublines resistant to various Pt derivatives.

Growth, flow cytometric, and karyological characteristics were analyzed with respect to differences between sensitive L1210 cells and eight sublines resistant to cisplatin (DDP), 1,2-diaminocyclohexane(DACH)-Pt(II) citrate, DACH-Pt(II) glucarate, cis-dichloro-bis-(isopropylamine)-trans-dihydroxyplatinum (IV) (CHIP, iproplatin), and methotrexate (MTX). No great differences were found in growth properties. The sensitive and a majority of resistant sublines displayed similar flow cytometric and karyological characteristics, major differences were found only in the sublines resistant to CHIP. The relationship between the mechanism(s) of resistance and different pharmacokinetics of the drugs is discussed with special reference to DNA content and chromosome structure.

Animals

Fibrinolytic activity disturbances in malignant blood diseases.

Repeated investigation of 105 patients suffering from different blood disorders demonstrated a more frequent occurrence of disturbances in fibrinolysis (66% as in blood clotting tests (40%) indicating a compensated or decompensated intravascular blood clotting. In the group of patients with thrombocythaemia the disturbance of fibrinolysis as much as in 83% was present, and always in sense of insufficiency. In myeloproliferative diseases without proliferation of megakaryocytes the antithrombotic treatment improved both the fibrinolysis as well as the clotting disturbances. In thrombocythaemia the long-termed treatment with anti-platelet drugs, eventually with other antithrombotics favourably influenced the blood clotting parameters as well as the symptomatology from vascular occlusion, however the euglobulin lysis remained unchanged. In sense of the idea on the ineffective megakaryocytopoiesis in primary and other myeloproliferative diseases accompanying thrombocythaemia attention is called to the specificity of the fibrinolytic insufficiency in thrombocythaemia in comparison with other myeloproliferative diseases without thrombocythaemia.

Anemia

Results and further perspectives of plasmocytoma chemotherapy.

Polychemotherapy has improved prognostic parameters of survival in patients with plasmocytoma. The mean survival in patients given long-time prednisone and melphalan treatment is 20 months, in those given polychemotherapy over 30 months. In patients with a slow disease progression the combinations COPP and VMCP give satisfactory results in about 40%, but in a majority of patients more effective treatment is necessary. The authors compare the 5-year survival of two polychemotherapy groups with the prednisone and melphalan group. The mean survival after prednisone and melphalan was 33 months, after polychemotherapy (groups COPP, VMCP) 46 months and 57 months (VMCP + M2), respectively. Survival time was influenced by the clinical stage.

Antineoplastic Combined Chemotherapy Protocols