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Biomedical subjects

L Pajor

Publications and source records attributed to L Pajor.

At least 37 records · Page 2Linked to original sources

[Parvovirus B19 infection in hydrops fetalis].

In a retrospective study from 210 foetal autopsies carried out in a period between 1992 and 1999 fifteen hydropic foetuses were found. The cause of the hydrops was shown to be Rh incompatibility in one case only. The cause of hydrops was not discernible in one case. In the others pathological examination clarified the cause and pathomechanism of non-immune hydrops. One isolated cystic hygroma, one monochorionic twin pregnancy with twin to twin transfusion, one case of sacrococcygeal teratoma and 4 cases of congenital heart diseases were reported. Postmortem interphase cytogenetic examination showed X0 monosomy in 2 cases. In further 4 foetuses pathognomic viral inclusions in the proerythroblasts raised the probability of parvovirus B19 infection what was confirmed by immunohistochemistry and electronmicroscopic examination. The occurrence of the parvovirus B19 associated cases of foetal hydrops was shown to be higher (4/15) in this series than in the literature. The accumulation of cases in 1998 is suggestive of an outbreak. The prenatal diagnostic implications and the attempts on further management are also discussed.

Adult↗

[Incidence and distribution of t(12;21) in prognostic groups of pediatric acute lymphoblastic leukemia].

The authors investigated by reverse transcription-polymerase chain reaction the incidence of the t(12;21)(p13;q22) translocation among 130 pediatric acute lymphoblastic leukemia registered by the Hungarian Pediatric Oncology Workgroup. The distribution of this translocation was analysed in the ploidy categories as defined by the flow cytometric DNA analysis and interphase cytogenetics. The incidence of the translocation proved to 19%, the positive patients' age ranged between 2 and 14 with an average of 5.8 years. Ninety percent of the leukemic patients harbouring the t(12;21) exhibited the precursor B-cell phenotype, 10% coexpressed myeloid markers. Coexistence of the t(12;21) with the m-bcr type of Philadelphia translocation was not observed. Ninety five percent of the t(12;21) positive children was diploid by flow cytometry whereas the same figure proved to be 58% using interphase cytogenetics. This difference was due to the hypo- and pseudodiploidy undetectable by flow cytometry but revealed by interphase cytogenetics. The authors conclude that the t(12;21) positive patients which seemed to be homogeneous at gross DNA level were markedly heterogeneous with interphase cytogenetics and this might explain the inconsistent data in the literature in connection with prognostic significance of the t(12;21).

Adolescent↗

[Clinical experience with rhenium-188 HEDP therapy for metastatic bone pain].

Rhenium-188 hydroxyethylidene diphosphonate (Re-188 HEDP) is a new radiopharmaceutical for treatment of metastatic bone pain. Re-188 is a generator-produced radionuclide emitting high energy beta and gamma rays and having a relative short physical half-life makes it of especially interesting for therapeutic purpose. Seven patients (pts) with multiple painful bone metastases were treated with Re-188 HEDP. Five pts with prostate cancer and 2 pts with breast cancer received a fixed activity of 3000 MBq of Re-188 HEDP intravenously in two steps. Complete blood counts were determined, blood chemistry examinations and urine-analysis were performed before and 1, 2, 3, 4, 6, 8, 12 weeks following the treatment. A visual analogue score, a verbal rating scale, the Spitzer index and the Karnofsky score were used to assess pain and performance status. Three hours after Re-188 HEDP administration at 1 m from the anterior mid-trunk of the pts gamma and at the patient body surface beta-radiation dose measurements were made, together with urine radioactivity measurements. Three pts become pain-free, 2 pts exhibited partial pain improvement and 1 patient gave no response to the Re-188 HEDP therapy. In 1 patient due to central nervous system metastasis the modification of the pain intensity could not be evaluated. Three pts displayed a flare reaction within 1 week after the treatment. Transient decreases in platelet and white blood cell counts were observed. There were no significant changes in the liver and renal functions. Radiation dose rate values of 6.3 +/- 1.0 microSv/h for gamma, and of 183 +/- 40 s-1 for beta-radiation were found. 25-32% of the administered dose was eliminated via the urinary tract in the first three hours. The preliminary data suggests that Re-188 HEDP is an effective radiopharmaceutical in treatment for metastatic bone pain. An administered activity of 3000 MBq can bring about a pain reduction without causing any clinically significant bone marrow toxicity.

Alkaline Phosphatase↗

Silent Philadelphia chromosome: a distinct developmental stage in a philadelphia chromosome-positive chronic myeloproliferation?

In this paper, a patient is described who presented with peripheral blood and bone marrow features uncharacteristic of chronic granulocytic leukemia, which proved to be Philadelphia (Ph) chromosome-positive by metaphase and interphase cytogenetic analyses but lacked the p210 type of BCR/ABL fusion gene mRNA product by two different sensitive RT-PCR assays. In the course of the 32-month follow-up with a termination into a myeloblastic crisis, molecular investigations were performed four times. They indicated a constantly high rate of Ph positive cells and lack of BCR/ABL mRNA expression, except in the second investigation, when the patient showed reverse transcription polymerase chain reaction positivity with b3/a2 type of chimera, fusion gene mRNA expression, and a striking change in the bone marrow histology. Our findings might indicate that the dormant Ph chromosome state may exist not only at the primitive progenitor, but also at the entire peripheral blood cell compartment level.

Base Sequence↗

[Competitive polymerase chain reaction: a new method for measuring N-myc amplification].

The highly variable biological behaviour of neuroblastoma, a neoplasm which belongs to the family of primitive neuroectodermal tumours, is determined by its molecular pathological characteristics. Among them amplification of the N-myc gene is the most important factor in both therapeutic and prognostic points of view. Value of the amplification can be determined by different methods. The latest of them is the competitive polymerase chain reaction (PCR), essence of which is the parallel reaction of the target N-myc gene (exon 3.) and the endogen competitor CF gene (exon 3.) in the same reaction solution. The authors applied the method on 11 neuroblastoma cases diagnosed between 1994 and january of 1999. In three cases the amplification was determined also by fluorescens in situ hybridization (FISH). Six of the 11 cases were detected to have more than 10-fold, two of the six about 100-fold N-myc amplification. Results of the PCR and FISH correlated well. The two methods applied by the authors complete each other and are appropriate for determining the gene amplification which gives valuable prognostic and therapeutic information about the examined tumour.

Genes, myc↗

New human Dirofilarioses in Hungary.

About ten cases of filariosis have recently been recorded in the Hungarian medical literature, six of them caused by Dirofilaria repens. Dirofilaria repensis a mosquito-transmitted filaroid worm in the subcutaneous tissue of dogs and cats in the temperate areas of the Old World. It accidentally infects man, too, and can remain unidentified due to physicians, poor knowledge of the parasite. In the last two years six new Dirofilaria repensinfections have been found in various parts of the country: five localised dermally and one in the deep tissues. Two of the cases might have been acquired in Italy during summer travels. Four patients, however, have never been abroad, these cases must be considered autochtonous infections. The thickness of the multilayered cuticle of the worm, diameter of the body and the size, form and number of the longitudinal ridges on its surface are used in the histological diagnosis of the the parasite.

Adult↗

Cytogenetic profile of primary pituitary germinoma.

We present a case of a germinoma in the sellar region of a 10-year-old female patient who presented with a history of polydipsia, polyuria and visual disturbances. The tumor was resected and histologically analyzed. Interphase cytogenetics was performed using chromosome specific (peri)-centromeric DNA probes for all the somatic and X chromosomes on fresh frozen tissues. Fluorescent in situ cell hybridization demonstrated accumulated cytogenetic abnormalities involving significant alterations of chromosome 1, 4, 5/19 and 15. The child was treated postoperatively by radiation and now appears well with only minor neurological deficits. At 3-year follow-up no recurrent tumor mass could be demonstrated.

Child↗

The existence of lymphoid lineage restricted Philadelphia chromosome-positive acute lymphoblastic leukemia with heterogeneous bcr-abl rearrangement.

Analysis of lineage involvement was performed in 17 Philadelphia chromosome-positive acute lymphoblastic leukemia patients with no history of chronic myeloproliferative disorder. The percentage of blastic cells as defined by flow cytometry matched that of the Ph-positive cells in 14 out of 17 patients. The bcr-abl rearrangement was investigated by fluorescent in situ hybridization in morphologically identified blastic cells, myeloid elements, lymphocytes and erythroblasts using a combined light and fluorescent microscopical imaging. Lymphoid lineage restriction could be determined in all but three of the patients. These 14 patients exhibited heterogeneity in terms of m-bcr and M-bcr types of translocation as revealed by reverse transcription polymerase chain reaction. The three patients with multilineage involvement and M-bcr type of translocation reverted to chronic phase and the percentage of Ph-positive cells remained high. Thus, we could identify an uncommitted stem cell origin among Ph-positive ALLs only in those patients whose disease subsequently proved to be a lymphoid blastic crisis with clinically silent chronic phase.

Adult↗

Repair of traumatic urethral fistula and huge tissue defect with Lehoczky's island flap.

A 20-years-old male patient suffered pelvic bone fracture and a penetrating urethral injury through the perineum due to a car accident. The injury and the unsuccessful reconstruction resulted in a large perineal tissue defect, urethral fistula, and dislocation of the anus close to the fistula. The authors performed a successful reconstruction; closure of the urethral fistula, sinking of the anus to its proper place, and substitution of the missing skin and subcutaneous tissue with Lehoczky's flap. The flap with its good blood supply and mass of tissue repaired the defect and promoted the rapid, functionally and cosmetically excellent result.

Adult↗

[Two cases of malignant and benign systemic mastocytosis].

The authors give a short account about the clinical histories of two patients: one with malignant systemic mastocytosis resulting in acute myeloid leukaemia, the other with indolent systemic mastocytosis. A brief review is reported about the physiological and pathophysiological role of mastocyte system. Benign and malignant types, classification of mastocyte proliferation are detailed, several distinct characteristics of clinical appearance, main aspects of diagnosis, therapy and prognosis in patients with different forms of systemic mastocytosis are briefly discussed.

Adult↗

Biclonal chromosomal aberrations in a child with myelodysplastic syndrome.

Hematological malignancies and premalignant diseases are generally of monoclonal origin. The prognostic and therapeutic significance of finding two genetically independent clones remains to be determined. We followed a case of childhood myelodysplastic syndrome showing biclonal chromosomal abnormalities (+8, -7) by conventional cytogenetic examination and double target fluorescence in situ hybridization (FISH). A 7-year-old girl presented with Plaut-Vincent angina and leukopenia. The cytogenetic aberration of +8 was the first sign to suggest MDS. Serial bone marrow controls, prompted by a progressive clinical course detected myelodysplastic changes and a new clonal aberration (-7). The presence of -7 and +8 in two independent clones was verified by double-target FISH. While at diagnosis and during cytokine treatment more cells showed +8, after successful all-trans retinoic acid (ATRA) therapy, the clone with -7 predominated. Following allogeneic bone marrow transplantation the patient displayed donor-derived hematopoesis. Our data stress the significance of cytogenetic and FISH examinations in detecting specific genetic abnormalities and progressive clonal changes as an indicator and guideline for therapy. Different cell clones characterized by different genetic changes might be associated with different biologic features reflected in their response to treatment.

Angina Pectoris↗

Sporadic p53 mutations and absence of ras mutations in glioblastomas.

As concerns human adult brain neoplasms, the biological behaviour of glioblastoma, a high-grade neuro-ectodermal tumour, is among the most disadvantageous. Glioblastoma may develop either as a primary tumour without clinical and histological evidence of a prior precursor lesion, or as the final stage of malignant transformation of a low-grade or anaplastic astrocytoma. There are conflicting reports in connection with the association of the p53 tumour suppressor gene mutation with the clinical and histological progression of gliomas. Previous studies likewise led to contradictory results concerning the significance of ras oncogenes in different histological malignancies, and especially in neuro-epithelial tumours. The possible roles of p53 and ras gene alterations in the development of "primary" and "transformed" glioblastomas were studied in this work. Eighteen tumours were investigated by means of immunohistochemistry and polymerase chain reaction-assisted-single strand conformation polymorphism (PCR-SSCP) sequence analysis in a search for molecular genetic differences between primary and transformed glioblastomas. An increased incidence of p53-immunopositive cells was observed in both types of glioblastomas but there was no significant difference between the transformed tumours and the primary form. All samples were screened for point mutation in codons 12 and 61 of the H-, K-, and N-ras oncogenes and exons 5-8 of the p53 gene. No aberrant band or mutation was found in the H-, K- and N-ras oncogenes. Aberrant bands were seen in only 2 (11%) of the 18 tumours in the SSCP analyses of exons 6 and 8. Sequence analysis of the 2 abnormal cases revealed G --> C transmission in the second nucleotide of codon 280 on exon 8, which resulted in a change in the encoded amino acid from arginine to threonine (case 15). A ttagtct --> ttggtct transmission on intron 5 (case 8) was also found. No genetic difference could be identified between the primary and the transformed glioblastoma forms as concerns their p53 and ras oncogenes. There are two possible explanations for these findings: (a) The p53 and ras gene mutations were not primary events in the morphological transformations. Alterations in these genes may therefore take place at an early stage in glioma progression. (b) The different genetic changes may accumulate during glioblastoma development. These specific genetic events may additionally play a role in multistep tumourigenesis.

Adult↗

High mitotic index associated with poor prognosis in gastrointestinal autonomic nerve tumour.

AIMS: Three gastrointestinal autonomic nerve tumours (GANT) were characterized by immunohistochemistry and flow cytometry. Two of the three cases occurred in the small intestine, while the third was found in the stomach. Besides the immunohistochemical and ultrastructural description, the aim of this study was to examine the relation between the known and accepted predictive factors (ploidy data, the S-phase fraction, the mitotic and MIB-1 index and the size of the tumour) and the survival of the patients. METHODS AND RESULTS: The immune profile showed that 3/3 cases were vimentin and NSE, 2/3 were synaptophysin and PGP 9.5 positive, while 1/3 also showed S100 positivity. Ultrastructurally, all the cases had dense core granules, one of them contained skenoid fibres. The flow cytometry revealed diploid DNA in all cases, however, significant differences could be seen in the proliferative activity of the individual neoplasms. CONCLUSIONS: In spite of the published data of gastrointestinal stromal tumours (GIST) generally, neither the MIB-1 index and the ploidy data nor the size of the primary tumour helped to predict the clinical progression of the examined GANTs. However, the high proliferative activity (57 mitoses/10 HPF) and the elevated S-phase fraction (24%) was associated with advanced, metastatic and recurring disease in case 3. On the basis of these three cases, high mitotic activity is the most reliable factor in predicting aggressive clinical behaviour.

Adult↗

[Interphase cytogenetics in oncologic diagnosis].

Nowadays, the detection of specific DNA sequences on interphase nuclei of cytological and paraffin slide preparations by in situ hybridization, the interphase cytogenetics became an established technology in the pathological diagnostics. A historical overview on the development of the technique is presented, the theoretical basis of the detection of numerical and structural chromosomal aberrations is demonstrated and the applications are exemplified on different types of malignant lymphomas, leukaemias as well as epithelial tumors. Combined use of the interphase cytogenetics, light microscopy and immunohistochemistry with the digital imaging techniques can provide us with morphological, immunophenotypic and genotypic informations of the same cellular object which might be a milestone in the pathomorphological diagnostics.

Base Sequence↗

[Advantages of CD45 vs. side scatter based gating in the course of flow cytometric immuno-phenotyping in malignant hematologic diseases].

The application of the CD45 vs. side scatter gating in the flow cytometric immunophenotyping of malignant haematological disorders was investigated. In the course of the conventional double labeling the light scatter based gating is the method of choice, which allows the immunophenotypic characterization of the subpopulations of interest. Using this gating strategy one can separate the lymphocytes, monocytes, neutrophil granulocytes, eosinophils and platelets as distinct cell populations in normal blood samples. The blastic cells present in different malignant hematological disorders might, however, represent an overlapping population with the lymphocytes, NK-cells, monocytes, and nucleated erytroid elements on the FSC vs. SSC histogram, making it difficult or impossible to separate them from the residual reactive cells. This will impart false mixed immunophenotypic property to the blastic cells. The authors found definitive advantages of CD45 vs. SSC gating in contrast to the FSC vs. SSC analysis due to the reliable separation of lymphoblasts, myeloblasts, nucleated erytroblasts as well as the debris from the reactive cell populations. The most plausible application of this method is shown in the course of three-color labeling, applying CD45 as a constant marker. Furthermore, the authors demonstrated that the CD45 vs. SSC gating strategy will result in considerable increase in resolution of blastic population also in the course of the most conventional dual-color labeling method.

Flow Cytometry↗

Combined metaphase, interphase cytogenetic, and flow cytometric analysis of DNA content of pediatric acute lymphoblastic leukemia.

Eleven pediatric acute lymphoid leukemia patients were investigated for chromosomal aneuploidy by interphase cytogenetics using chromosome specific (peri)centromeric probes for all the somatic and sex chromosomes. Results were compared with metaphase cytogenetic and flow cytometric derived DNA aneuploidy data. Experiments performed on normal human cells using chromosome specific (peri)centromeric probes indicated that disomy could be recognized in a range of 89.1+/-2.7% (12.9)-96.8+/-0.2% (0.9) for the somatic chromosomes and in 98.1+/-0.4% (1.3) for the sex chromosomes. Using the cutoff level of the mean false monosomy and trisomy in the control cells +2 S.D., chromosome loss or gain for the somatic chromosomes could be revealed beyond a clonal ratio of 3.6-13.2% and 1.1-6.8%, respectively. The same value for the sex chromosomes was 3.5% and 0%, respectively. In 5 of 11 patients the leukemic cells proved to be diploid with all three methods at both gross DNA and chromosome levels. Interphase cytogenetics revealed chromosome loss or gain in all of the remaining six patients, however, the metaphase analysis indicated numerical aberration in only two patients. In one of them only the increased chromosome number could have been detected without identifying the chromosomes involved and in the other one the two methods indicated trisomy for a different chromosome. Flow cytometric data showed aneuploidy in three of the six aneuploid leukemia patients. The results suggest that interphase cytogenetics might be more accurate compared with flow cytometry and metaphase analysis to reveal aneuploidy.

Adolescent↗