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Biomedical subjects

J Jelínek

Publications and source records attributed to J Jelínek.

At least 19 recordsLinked to original sources

The role of chloride in deoxycorticosterone hypertension: selective sodium loading by diet or drinking fluid.

To evaluate the role of chloride in the pathogenesis of salt-dependent deoxycorticosterone (DOC) hypertension, we studied young Wistar rats chronically loaded with sodium bicarbonate (NaHCO(3)) or sodium chloride (NaCl) which were administered either in the diet or in the drinking fluid. Selective sodium loading (without chloride) increased blood pressure (BP) in DOC-treated animals only if NaHCO(3) was provided in the diet. In contrast, no significant blood pressure changes were induced by DOC treatment in rats drinking NaHCO(3) solution. Hypernatremia and high plasma osmolality occurred only in rats drinking NaCl or NaHCO(3) solutions. Compared to great volume expansion in NaCl-loaded DOC-treated rats, the degree of extracellular fluid volume expansion (namely of its interstitial fraction) was substantially lower in both NaHCO(3)-loaded groups in which significant hypokalemia was observed. NaHCO(3)-drinking rats without significant blood pressure response to DOC treatment represented the only experimental group in which blood volume was not expanded. In conclusion, our data confirm previous observations that NaHCO(3) loading is less potent in eliciting DOC hypertension than NaCl loading, but blood pressure rise in rats fed NaHCO(3) diet clearly demonstrated that selective sodium loading could potentiate the development of DOC hypertension if NaHCO(3) is offered within the appropriate dietary regimen. The reasons for the failure of NaHCO(3)-drinking rats to elevate blood pressure in response to chronic mineralocorticoid treatment are not obvious. However, the absence of a significant plasma volume expansion together with hypernatremia and increased plasma osmolality suggest a considerable degree of dehydration in these animals which fail to increase their fluid consumption compared to water drinking rats.

Animals↗

[Intensive therapy with paclitaxel (Taxol) and cyclophosphamide followed by administration of G-CSF as a mobilization regimen in patients with breast carcinoma and indications for autologous hematopoietic cell transplantation].

Cyclophosphamide (4 g/m2) and paclitaxel (Taxol) (175, 200 or 250 mg/m2) therapy with subsequent administration of G-CSF (10 micrograms/kg) has been used as intensification and as mobilization therapy for patients with breast cancer. This regimen was used in 19 patients, as part of adjuvant therapy in 14 and as part of therapy of metastatic disease in five. Median number of collected CD34+ cells was 17.5 x 10(6)/kg (2.9-48.1). All patients except one (94.7%) reached minimal required number of CD34+ cells (> or = 3 x 10(6)/kg). Median number of leukapheresis was two. The required number of cells (> or = 3 x 10(6)/kg) was collected in one leukapheresis in 17 out of 19 patients (89.5%) and more than five and 10 x 10(6)/kg CD34+ cells respectively were collected in 14 (73.7%) and 11 (57.9%) patients respectively. No factor significantly influencing the amount of collected cells (except the trend in favour of later year of therapy and large-volume leukapheresis) was identified. Leukopenia gr. 4 was observed in 88.9% of treated patients and febrile neutropenia developed in 46.2% patients. Although the antitumour activity of this chemotherapy was not possible to assess it seems that this intensification could be successfully used as a therapy and as very potent mobilization regimen.

Adult↗

[Congenital aplastic anemia caused by parvovirus B19 infection].

Human parvovirus B19 causes the fifth disease (erythema infectiosum) in childhood. Intrauterine infection by parvovirus in immunocompromised fetus can lead to the severe congenital aplastic anemia. Here we report the case of 2.5-year-old girl with congenital infection with parvovirus B19. The girl was born as a pre-term baby with hydrops, congenital aplastic anemia, and low level of immunoglobulins IgG and IgM. She depended on the repeated blood transfusions and she did not respond to erythropoietin therapy. The parvovirus B19 infection in bone marrow was detected by polymerase chain reaction and its therapy started with intravenous administration of immunoglobulins. Hemoglobin reached normal level one year later, but low levels of parvovirus B19 were detectable for another 6 months. Immunoglobulin treatment was finished when the virus could not be detected in the circulation. However, one-month later parvovirus B19 DNA was detected again. The two months course of immunoglobulin treatment was repeated, and the DNA analysis of blood cells for parvovirus B19 has been negative since then. Five months after the final withdrawal of the immunoglobulin therapy the girl is in a good shape and all lab tests, except for the decreased levels of IgM, are within the normal range. The PCR monitoring of the presence of parvovirus B19 DNA in blood and bone marrow cells during and after the treatment of congenital aplastic anemia caused by parvovirus B19 chronic infection becomes the necessity for the rational therapy.

DNA, Viral↗

Function of the isolated perfused kidneys from young or adult rats with post-DOCA-salt hypertension.

The function of isolated perfused kidneys in post-DOCA phase of DOCA-salt hypertension was evaluated in rats subjected to DOCA-salt treatment either from youth or only in adulthood. Post-DOCA-salt hypertension was more severe in young than in adult animals. Kidneys isolated from young post-DOCA-salt hypertensive rats had higher renal vascular resistance when compared to adult ones. Perfusion of isolated kidneys over a wide range of perfusion pressure (110-170 mm Hg) has shown similar decrease of glomerular filtration, filtration fraction, diuresis and natriuresis in both age groups of DOCA-salt treated groups. Perfusion pressure-sodium excretion curves had reduced slope and were shifted to the right in both hypertensive groups, indicating huge glomerular damage. Nevertheless, the relative difference in glomerular filtration and sodium excretion between hypertensive rats and age-matched normotensive controls was always greater in younger animals. These results suggest that the more pronounced changes in glomerular hemodynamics and filtration could be involved in higher blood pressure-response of young animals to DOCA-salt treatment.

Aging↗

[Interferon alpha--the drug of choice for patients with chronic myeloid leukemia].

BACKGROUND: The conventional, or standard, treatment of chronic myeloid leukaemia (CML) with hydroxyurea and busulfan has no marked influence on its course or duration. Interferon (IFN) alpha administration has, on the other hand, been shown to induce not only a haematological but also cytogenetic response, i.e. partial or complete bone marrow repopulation by Ph-negative cells. This has triggered studies comparing IFN and conventional chemotherapy. The present work had the purpose to gain experience with IFN alpha treatment and compare the results with hydroxyurea and busulfan treatment, in the chronic phase of CML. METHODS AND RESULTS: Therapeutic results obtained in 30 patients given IFN alpha and 30 others given conventional chemotherapy were evaluated retrospectively. In spite of the short time of IFN administration (4-27 months), significantly more complete haematological responses (83%) were observed in this than the conventional chemotherapy group (57%). Cytogenetic responses were achieved in 36%, complete cytogenetic remission in 20% of IFN-treated patients. Conventional chemotherapy produced no cytogenetic effect. CONCLUSION: The results obtained confirm the value and efficacy of IFN-alpha treatment in CML patients, especially if it is started early and the dose is effective. Regular cytogenetic monitoring is necessary. Longer follow-up of the patients will be necessary for evaluation of the IFN effect on the length of their survival.

Adult↗

Three cases of near-tetraploid acute myeloid leukemias originating in pluripotent myeloid progenitors.

We report three cases of acute myeloid leukemia (AML) with a near-tetraploid karyotype in most metaphases while lacking chromosomal abnormalities typical for AML. All patients, 63, 72 and 81 years old, were female. In two cases, AML was diagnosed 5-7 months after a cytopenic period while the third patient had a secondary AML after therapy for a pleural tumor. Leukemic blasts were classified as AML M0, AML M1 and AML without further specification. Two patients died on the 18th and 52nd day after the start of cytotoxic chemotherapy, the third patient refused chemotherapy and died 22 days after the diagnosis. The three patients may represent a distinct AML category with the following features: (1) the near-tetraploid karyotype in most bone marrow metaphases examined at diagnosis of AML; (2) the presence of very large myeloid blasts in the bone marrow and dysplastic changes in erythroid and/or megakaryocytic lineages pointing to the origin of AML in pluripotent myeloid progenitor cells; (3) the expression of the CD34 antigen; (4) the low growth of granulocyte-macrophage colony forming cells in culture; and (5) the presence of a preleukemic phase, a higher age and a poor prognosis.

Acid Phosphatase↗

Antitumor action of bovine seminal ribonuclease. Cytostatic effect on human melanoma and mouse seminoma.

This paper reports on the antitumor activity of BS RNase on human melanoma and mouse seminoma. Human melanoma cells established in culture were extremely susceptible to BS RNase, administered in concentrations ranging from 1-100 microg/ml. Concentrations of BS RNase over 10 microg/ml caused complete inhibition of cell growth. Bovine pancreatic ribonuclease (RNase A), a prototype of the ribonuclease superfamily, did not exert any effect under these conditions. Based on our previous results, athymic mice bearing human melanoma or mouse seminoma were treated with intratumoral administration of BS RNase (12.5 mg/kg b.w.). This dose was injected for five consecutive days excluding weekends. The intratumoral administration of BS RNase to nude mice bearing human melanoma showed a significant antitumor effect. There were no tumors seen in eighty percent of mice treated for three weeks, and tumors in the other mice diminished significantly. After some delay the tumors started to regrow. Prolonging of the treatment to five weeks had a similar effect. The effect of BS RNase on mouse seminoma was well pronounced. Five to seven doses of BS RNase were sufficient to eliminate tumors in all treated mice. However, as in the previous experiment, the growth of tumor tissue later reappeared.

Animals↗

A comparison of three preinduction cervical priming methods: prostaglandin E2 gel, Dilapan S rods and Estradiol gel.

The aim of the study was to evaluate the efficacy of three cervical priming methods. From January 1, 1994 to December 31, 1996 247 patients presenting an indication for induction of labor with an unripe cervix were randomly assigned to one of the following preinduction protocols: 0.5 mg of Prostaglandin E2 gel administered intracervically (n = 83), four hygroscopic Dilapan S rods applied intracervically (n = 82), and 150 mg of Estradiol gel administered intravaginally (n = 82). The inclusion criteria were the patient's informed consent, singleton pregnancy of more than 36 weeks, cephalic presentation, Bishop score < 5 points and reactive non-stress test. If the cervical maturation (Bishop score > or = 5, and/or Bishop score augmentation by 2 points) did not occur after 14 hours of priming, the case was considered a failure. In the opposite case the patient was induced by means of extraamniotic PGE2 administration. The mean gain in the Bishop score was 3.7 points in the PGE2 group 3.9 points in the Dilapan S group, and 2.8 points in the Estradiol group. 71 patients (85.5%) were successfully preinduced in the PGE2 group, 73 (89.0%) in the Dilapan S group, and 63 (76.8%) in the Estradiol group. Labor was induced by preinduction only in 23 patients (31.3%) of the PGE2 group in 17 (20.7%) of the Dilapan S group, and in 14 (17.1%) of the Estradiol group. The mean induction to delivery interval was 7 h 27 min in PGE2 group, 7 h 49 min in the Dilapan S group and 9 h 15 min in the Estradiol group. The Caesarean section rate was 24.4% in the PGE2 group, 10.5% in the Dilapan S group, and 24.4% in the Estradiol group. PGE2 gel and Dilapan S rods proved higher efficacy than Estradiol gel. The highest frequency of labor induced by preinduction only was in the PGE2 group. There were shorter induction to delivery intervals in the PGE2, and Dilapan S groups. The lowest Caesarean section rate was in the Dilapan S group. Neither serious side effects nor negative neonatal outcome were noted in either group.

Adult↗

[Mixed myelodysplastic and myeloproliferative syndromes].

BACKGROUND: An injury to the hemopoietic stem cell may lead to the aplasia of hemopoiesis, myelodysplasia and to an unregulated myeloproliferation. There is not a strict demarcation of them, so that mixed syndromes can develop as are hypoplastic syndromes on one side and mixed myelodysplastic and myeloproliferative syndromes (MDS-MPS) on the other side. METHODS AND RESULTS: Among our 616 pts with MDS we looked for those cases, who had beside myelodysplasia signs of myeloproliferation with increased number of blood cells. They were examined in detail including bone-marrow histology, bone marrow cultivation, cytogenetics and bcr-abl gen. Signs of MDS-MPS were found in 22 patients at the first contact with the patient (13 patients had thrombocytemia and 9 patients had leukocytosis). Further 7 patients were diagnosed as MDS, proliferative syndrome developed after several months (MDS-MPS in evolution). The level of thrombocytemia was relatively stable, the number of leukocytes was progressive. All subtypes of MDS were found. All subjects had variable degree of anemia. Ring-sideroblasts and myelofibrosis were frequent finding in MDS-MPS. Men prevailed in patients with leukocytosis. Cytogenetic and cultivation findings were similar to MDS cases, deletion of long arm of chromosome 20 was present in 3 patients. Five patients transformed to acute myeloid leukemia. CONCLUSIONS: Sings of myelodysplasia and myeloproliferation were found in 4% of our MDS patients, designated as mixed myelodysplastic and myeloproliferative syndrome (MDS-MPS). In this syndrome beside evident signs of myelodysplasia thrombocythemia or leukocytosis with the release of bone marrow precursors are present. In only one case polycythemia was encountered.

Adult↗

[Will transfer of cytostatic drug resistance genes increase hematopoiesis resistance in the treatment of malignant tumors?].

The aim of aggressive antitumor chemotherapy is to kill the tumor with the largest possible dose of a cytotoxic drug. The maximum dose tolerated by the patient is limited by the toxicity to normal tissue, hematopoiesis being frequently the most sensitive system. Transfer of drug resistance genes to hematopoietic cells could protect them against chemotherapy-related toxicity and thus could be a way of gene therapy in cancer. Methylating and chloroethylating derivatives of nitrosourea are effective anticancer drugs, however, acute hematopoietic toxicity and late risk of leukemia are serious side effects. The major lesion responsible for toxic and mutagenic effects of alkylnitrosoureas is O6-alkylation of guanine in DNA. This lesion is specifically repaired by O6-alkylguanine-DNA-alkyltransferase and hematopoietic cells can be protected against toxic and mutagenic effect of nitrosoureas by alkyltransferase gene transfer. Endogenous alkyltransferase in tumor tissue could be inactivated by administration of O6-benzylguanine, while hematopoietic cells could still be chemoprotected by inhibitor-resistant alkyltransferase gene transfer. This approach could increase the therapeutic efficacy of nitrosoureas in gene therapy augmented cancer treatment.

Antineoplastic Agents↗

Human remains from the Moravian Gravettian: the Dolní Vĕstonice 3 postcrania.

To add to our knowledge of European earlier Upper Paleolithic (especially Pavlovian) human biology, the postcranial skeleton of the Dolní Vĕstonic 3 partial skeleton was excavated and reassembled. It represents the remains of an adult female, who was buried in a tightly flexed position with the ventral side down and turned slightly to the left. Subsequent compaction led to extensive damage to the axial skeleton and long bone epiphyses. It nonetheless retains the C1 and C2, fragments of the C5 to S3, portions of the pelvis, most of the long bone diaphyses, and a number of manual and pedal remains. Dolní Vĕstonice 3 was a relatively gracile individual in terms of diaphyseal robusticity and especially muscular attachment rugosity, despite the strong development of femoral and tibial diaphyseal structural buttresses. Upper limb asymmetry is slight and variable. She is similar to other earlier Upper Paleolithic remains in having warm temperate to tropical body proportions but is at the lower limit of Gravettian variation in body size indicators. There is no evidence of significant antemortem lesions on the preserved postcrania.

Adult↗

[Hemostasis using vasopressin analogs during conization of the uterine cervix and minor vaginal operations].

Peroperative haemorrhage is a frequent complication of conization of the portio uteri by surgery-by a "cold knife" scalpel or another method (LEEP, laser, etc.). In a clinical study comprising 41 patients with the diagnosis CIN I-III or laceration of the portio uteri classical conization by means of a scalpel was made with concurrent haemostasis with terlipressin (TLP) by paracervical administration (400 micrograms-REMESTYP 2 amp.). Concurrently the blood loss in ml was followed, the Hb level and other effects of the preparation. From the results ensues that side-effects after local administration of TLP were observed only in 12.2%. Peroperative blood losses were on average under 15 ml. Local paracervical TLP administration appears effective from the clinical aspect with regard to the low frequency of side-effects and the favourable haemostatic effect.

Blood Loss, Surgical↗

Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase.

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony-forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.

Animals↗

Mixed myelodysplastic and myeloproliferative syndromes.

Aplastic anemia, myelodysplastic syndromes (MDS) and chronic myeloproliferative diseases (MPD) are stem cell disorders. There is no clear-cut demarcation of them. Hypoplastic MDS displays features of aplastic anemia and MDS, on the other side mixed myelodysplastic and myeloproliferative syndromes (MDS-MPS) develop. In our collection of 566 MDS patients, features of myelodysplasia as well as myeloproliferation, MDS-MPS, were present in 25 patients (4.4%). Twelve patients had at the time of diagnosis megakaryocytic proliferation and thrombocythemia beside signs of MDS, and seven had myelodysplasia with granulocytic proliferation and leukocytosis. In another six patients, MDS was the first diagnosis and the proliferative phase developed later during the course of the disease. These patients can be characterized as MDS-MPS in evolution. All subjects had a variable degree of anemia. While the level of thrombocythemia has been relatively stable, the number of leukocytes has been progressive, but rarely extended beyond 100 x 10(9)/l. Ring-sideroblasts and myelofibrosis were frequent findings. Two more homogeneous MDS-MPS groups emerged in our analysis: sideroblastic anemia with thrombocythemia and a group fulfilling the criteria of Philadelphia chromosome negative and bcr-abl negative "atypical chronic myeloid leukemia (aCML)'. One patient with thrombocythemia and three with leukocytosis (23%) transformed to acute myeloid leukemia (AML). Men prevailed (12/13) in patients with leukocytosis and MDS-MPS in evolution. Of the 46% MDS-MPS patients with chromosomal aberrations, del(20)(q) is of interest.

Adult↗

Derivative (6)t(1;6)(q22;p21) revealed in bone marrow cells by FISH 9 months before diagnosis of acute T-lymphoblastic leukemia.

A chromosomal clone with unbalanced translocation resulting in partial trisomy of segment 1q22-qter and partial monosomy of segment 6p21-pter was revealed by fluorescence in situ hybridization (FISH) using a panel of different whole chromosome painting probes. The pathologic clone appeared after sequential chemotherapy treatment for AML-M5 when the patient was in complete remission before development of T-ALL. However, this clone was present during the whole period of treatment for T-ALL. The clone remained the only chromosomal aberration found. Breakpoints were detected more easily and more precisely with the use of the FISH technique than with G-banding only.

Bone Marrow↗

[Induction of cervix ripening with hydrophilic Dilapan rods in pregnancy at term].

During the period between July 1, 1993 and July 31, 1994 the authors preinduced 52 pregnant women in term using the cervical dilatator Dilapan. The group comprised patients with single pregnancies > 38 weeks, vertex presentation, cervical score < 5 and reactive NST. They introduced into the cervical canal 4 Dilapan rods for 12-18 hours and after extraction of the rods, depending on the finding, the patients were induced with Prostaglandin e.a. or oxytocin i.v. The preinduction was successful in 46 patients (88.5 per cent), in 16 patients (30.8 per cent) uterine contractions were induced by Dilapan alone. Forceps delivery was performed 4 times (7.7 per cent) and Caesarean section 12 times (23.1 per cent). Apart from pain in the hypograstrium resembling menstruation pain, no side-effects were recorded. There were no irregularities such as the length of labour stages, blood loss due to injury during labour and the incidence of neonatal hypoxia. Based on the described experience Dilapan can be recommended as a preinduction method for maturation of the portio uteri.

Adult↗