Biomedical subjects

R Nowak

Publications and source records attributed to R Nowak.

At least 55 records · Page 3Linked to original sources

PubMed1999

Relations between IL-3-induced proliferation and in vitro cytokine secretion of bone marrow cells from AML patients.

The influence of IL-3 on the bone marrow cells of 53 patients with acute myeloid leukaemia (AML) was investigated after 72 h suspension in cultures by analysing the proliferation of blasts and the secretion of cytokines. The titres of IL-1beta IL-6, TNF-alpha and IL-3 were measured in the supernatants of these cultures with ELISA tests. Comparing the percentage of cells in S-phases of control cultures and cultures with IL-3, the leukaemias were divided into two growth pattern groups: IL-3-insensitive (n=19) and IL-3-sensitive (n=34) leukaemias. The IL-3-insensitive AML cells show a greater ability for autonomous growth, first by the increase of S-phase in the control culture compared with the S-phase in vivo (P=0.0486) and second, by the higher constitutive secretion (control culture) of IL-1beta P =0.0004), IL-6 ( P =0.0395) and TNF-alpha P=0.0005). The IL-3-induced secondary cytokine secretion is also different in the two growth pattern groups. Whereas in the IL-3-insensitive AML cells a moderate increase of IL-1beta (1.48-fold increase) was present, in the IL-3-sensitive AML cells a 4.72-fold increase of IL-1beta 2.71-fold increase of IL-6 and 11.81-fold increase of the TNF-alpha titre could be detected. Overall, the data show an inverse correlation between the ability of AML cells to respond to IL-3 with increase of an S-phase and the constitutive secretion of IL-1beta, II-6 and TNF-alpha. A further effect of IL-3 is the induction of secondary cytokine secretion in the bone marrow of IL-3-sensitive growing AML cells.

Acute Disease↗

PubMed1999

A new PCR MIMIC strategy to quantify low mdr1 mRNA levels in drug resistant cell lines and AML blast samples.

Determination of the MDR-phenotype in patients suffering from AML is an important hallmark of treatment outcome but is often complicated by technical problems in P-gp assessment. A PCR-MIMIC strategy was employed to construct PCR-fragments for a competitive and quantitative mdr1 reverse transcription-PCR-assay. Using K562 cells, which had been selected for drug resistance to the epipodophyllotoxin VP16, a stepwise increase of mdr1 levels depending on the concentration of VP16 was shown with the MIMIC technique. Comparison of mdr1 levels in drug selected K562 cells with the corresponding levels for P-gp and functional data indicated a mRNA threshold that has to be exceeded for the full expression of the MDR-phenotype. Subsequently mdr1 levels of 34 samples of de novo acute myeloid leukemia were determined with the PCR-MIMIC strategy. Ten patient samples could be identified with elevated mdr1 levels which were substantially lower than the levels observed in the MDR-cell line K 562 0.7 microM VP16. Outcome analysis revealed that eight of the ten patients had an unfavourable prognosis and did not achieve CR after induction chemotherapy. Coexpression of mdr1 and CD 34 was not associated with CR in all examined cases. Moreover all these patients had unfavourable cytogenetic aberrations. These data indicate a sensitive technique with applicability in patient material.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Flow cytometric DNA quantification in immunophenotyped cells as a sensitive method for determination of aneuploid multiple myeloma cells in peripheral blood stem cell harvests and bone marrow after therapy.

The simultaneous measurement of DNA content and myeloma-related antigens (B-B4 or CD38) by flow cytometry is proposed as a method for the detection of aneuploid plasma cells in peripheral blood stem cell (PBSC) harvests and in bone marrow after therapy. In 30 patients with initially detected aneuploid myeloma cells we evaluated the bone marrow after therapy and in eight of these patients 23 PBSC harvests were analyzed. In 13 of 23 PBSC harvests aneuploid myeloma cells were detectable (range: 0.02-0.63%). In the bone marrow of the 30 patients aneuploid plasma cells were detectable in all samples after chemotherapy (range: 0.12-35.70%) and after autologous PBSC transplantation in two of three patients (0.21% and 0.03%). Furthermore the relationship between diploid and aneuploid plasma cells can be evaluated. In the PBSC harvests the percentage of aneuploid plasma cells is significantly lower than that of diploid plasma cells (P=0.006). In contrast, in bone marrow the aneuploid plasma cells are predominant in most patients even after therapy (24 of 30 patients; P=0.0055). In the case of initially detected aneuploid myeloma cells, a contamination with malignant cells can be estimated with a simple flow cytometric method in PBSC harvests and in bone marrow after therapy.

Aneuploidy↗

PubMed1999

[Functional assessment after operative treatment of femoral shaft fracture].

The paper presents results of treatment in 135 patients (aged 16-77 years) with fracture of the femoral shaft treated with one of the four techniques: open intramedullary Küntcher nailing, Zespol fixation, AO plating and closed locked and unlocked intramedullary nailing. The assessment has been based on authors' own 4-grade, 35-points scale involving 7 parameters. Closed intramedullary nailing proved to the most efficient. No reoperation in this group occurred. The percentage of excellent and good results was the highest--96.4% and such was the score--32.6 points. Open methods (Küntcher nailing, Zespol fixation, AO plating) rendered 88.2%, 31.7 points and 59% excellent and good results, 26.2 points in group without complication and reoperated one respectively.

Adolescent↗

PubMed1999

[Ender nails in the stabilization of trochanteric fractures of the femur in the elderly].

Results of treatment for trochanteric fracture of the femur in 50 patients aged 25-91 (mean 71 years) are presented. In all cases reviewed the fracture has been stabilized with 3 or 4 Ender nails. In majority of cases bony union has been achieved. Short operating time, small incision remote from fracture site, early weight bearing constitute unquestionable advantages of the method. Most frequent complications as shortening of the extremity involved, excessive external rotation, pain related to migration of the nails, varus deformity at the fracture site were usually found in patients with marked osteoporotic changes.

Adult↗

PubMed1998

Late complications after postoperative radiotherapy in endometrial cancer: analysis of 317 consecutive cases with application of linear-quadratic model.

PURPOSE: To evaluate the incidence and risk factors for late complications after postoperative radiotherapy in endometrial cancer patients. METHODS AND MATERIAL: We performed a detailed retrospective analysis of 317 endometrial cancer patients given postoperative radiotherapy. A total of 247 patients (78%) received both intracavitary (BRT) and external beam irradiation (XRT); 49 patients (15%) received only BRT, and 21 (7%) only XRT. BRT included radium (Ra) and cesium (Cs). The mean dose rate for both isotopes at 0.5 cm from the applicator surface was 0.47 +/- 0.06 and 1.42 +/- 0.41 Gy/h, and the mean total dose was 50.5 +/- 10.3 and 48.4 +/- 15.0 Gy, respectively. Mean BRT dose at 0.5 cm was 50.1 +/- 11.7 Gy (range 14.5-71.0). Mean XRT dose in the International Commission on Radiation Units and Measurements (ICRU) reference point was 49.0 +/- 3.7 Gy (range 22.0-66.0) given in fractions of 1.54-2.49 Gy (mean 2.0 +/- 0.17) with a two- or four-field technique. Follow-up ranged from 4 to 21 years (median 7.3). Normalized total dose (NTD) including XRT and BRT doses was calculated based on a linear quadratic equation. RESULTS: Five-year overall survival rate was 75%, and 5-year disease-free survival (censored for noncancer deaths) was 81%. Late radiotherapy complications of any grade occurred in 158 patients (51%), including bowel complications in 41% and urinary bladder complications in 21%. A total of 37 grade 3 or 4 complications were observed in 33 patients (11%), of whom 32 were treated with both XRT and BRT. Severe bowel and/or urinary bladder complications occurred in 24 patients: in 14 of 72 patients (19.4%) who received XRT and Cs BRT, and in 10 of 172 patients (6.0%) applied XRT and Ra BRT. The higher proportion of severe bowel and/or bladder complications in the former group was due to the particularly frequent rate of these events (30.0%) in a subset of 47 patients who received XRT combined with Cs BRT at the dose rate of 1.7 Gy/h and the total BRT dose of 60 Gy. Higher NTD, XRT fraction dose, BRT dose rate, Cs BRT, two-field XRT technique, short overall radiotherapy time, and older age were correlated with increased late-event risk in univariate analysis. Multivariate Cox analysis demonstrated that the independent risk factors for late bowel complications were NTD (p = 0.000) and BRT dose rate (p = 0.036), whereas for bladder complications they were BRT dose rate (p = 0.005) and XRT fraction dose (p = 0.041). Neither clinical factor (age, parity, prior abdominal surgery, FIGO stage, diabetes mellitus, or hypertension) nor the surgery-to-radiotherapy interval, nor overall radiotherapy time was independently associated with the risk of late bladder or bowel complications. CONCLUSIONS: The risk of late complications after postoperative radiotherapy in endometrial cancer depends mainly on treatment-related factors: NTD, BRT dose rate, and XRT fraction dose. The use of combined XRT and BRT increases the risk of late effects. NTD calculations including BRT dose rate and XRT fraction dose enable estimation of radiobiologically equivalent dose and can decrease the risk of mistakes when the radiotherapy regimen is changed.

Actuarial Analysis↗

PubMed1998

The incidence of DNA aneuploidy in multiple myeloma does not correlate with stage of disease.

The bone marrow of 47 patients with multiple myeloma (MM), 2 patients with plasma cell leukemia, and 11 patients with monoclonal gammopathy of undetermined significance (MGUS) was analyzed by flow cytometry for the detection of DNA aneuploidy. The question to be addressed was whether a correlation exists between the incidence of DNA aneuploidy and the stage of disease. With one-parameter analysis of DNA staining, a DNA aneuploidy was detectable in 17 of 60 patients. The detection rate for DNA aneuploidies could be increased to 37 of 60 patients with the second method, the simultaneous measurement of DNA content in additional immunophenotyped cells (CD38 or B-B4). In MGUS and the early stages of MM, the discrepancy between both methods was higher than in stage III MM. There were no statistical differences in the incidence of DNA aneuploidy between MGUS or the early stages of MM and stage III MM (21/32 patients vs 16/26 patients). The CD56 expression in plasma cells was significantly higher in cases of DNA aneuploidy (mean +/- SD, 64.7% +/- 33.65% vs 39.3% +/- 36.69%; P = .028). Comparing the ratio of diploid to DNA aneuploid with that of CD56+ to CD56- plasma cells, a correlation was found in MGUS (r = 0.7320) in the early stages of MM, I and II (r = 0.8023), but not in stage III MM. Based on these data, the dual-staining method for DNA content in immunophenotyped cells is preferred for the detection of DNA aneuploidy, especially in the early stages of MM and in MGUS. The clinical importance of a classification of DNA aneuploidy and CD56 antigen expression together is proposed for testing.

ADP-ribosyl Cyclase↗

PubMed1997

Sensitivity of combined DNA/immunophenotype flow cytometry for the detection of low levels of aneuploid lymphoblastic leukemia cells in bone marrow.

By simultaneous DNA staining and immunophenotyping, the aneuploid blasts of acute lymphoblastic leukemia (ALL) can be quantitated by flow cytometry. The present study evaluates the application of this method for the detection of minimal residual disease (MRD). For this purpose leukemia cells with known aneuploidy were serially diluted with diploid bone marrow cells obtained after chemotherapy. These mixed samples were immunophenotyped using antibodies CD34, CD10, or CD19 and processed for DNA staining with propidium iodide. Fifty thousand cells were measured for each experiment and the results were compared with the analysis of control sample without added aneuploid cells. Aneuploid cells diluted to 1% were not detectable in 6/15 cases when DNA content analysis was used alone, and in dilutions of < 1%, these cells were not detectable. When DNA content and immunophenotype were simultaneously measured, aneuploidy was detectable in 15/15 cases at 1.00%, 6/6 at 0.50%, 16/16 at 0.10%, and 16/17 at 0.05%. Therefore this method may be useful for the detection of minimal residual disease in cases of aneuploid lymphoblastic leukemia.

Aneuploidy↗

PubMed1997

Development of a preferential relationship with the mother by the newborn lamb: importance of the sucking activity.

Lambs develop a preferential relationship with their mothers within 24 h after birth. In a first experiment, we attempted to determine whether neonatal sucking was a potent reinforcer in the establishment of this preference by temporarily covering the udders of ewes after parturition. Lambs were assigned to one of three treatments: they had free access to the udder (group 1) or were prevented from sucking either between birth and 6 h afterward (group 2) or between 12 and 18 h after birth (group 3). Measurements of cholecystokinin plasma levels at birth and at 6 and 18 h showed that all lambs ingested some colostrum when the udder was made accessible. When tested in a two-choice test situation at 24 h of age, lambs from group 1 spent significantly more time near their mothers than near the alien ewes, those from group 2 did not show any discrimination, and lambs from group 3 clearly preferred the alien ewes. At 2 days of age, lambs from groups 1 and 3 showed a strong preference for their mothers, whereas those from group 2 still displayed no preference. In a second experiment, we attempted to determine whether sucking also had a reinforcing value in the maintenance of this preference. Lambs were assigned to one of three treatments: they had free access to the udder (group 1) or were prevented from sucking for 6 h either at birth (group 2) or at the age of 3 days (group 3). Lambs from group 2 did not discriminate between their own and alien dams when tested at 24 h of age, unlike those of groups 1 and 3. When a second test was performed at 4 days of age, all the lambs showed a strong preference for their dams. We concluded that sucking has strong rewarding properties in the establishment of a preferential relationship with the mother by the lamb. On the other hand, the maintenance of this preference does not rely on sucking as strongly.

Animals↗

PubMed1997

Cholecystokinin receptors mediate the development of a preference for the mother by newly born lambs.

The aim of this study was to investigate the effect of selective cholecystokinin (CCK) antagonists on the development of a preference for the mother by newly born lambs. At birth lambs received an injection of the CCK-A antagonist devazepide (0.01 or 0.1 mg/kg), the CCK-B antagonist PD135158 (0.01 or 0.1 mg/kg), or saline for the controls (1 ml/kg). No major side effects were observed in the first 4 postnatal hours except that lambs receiving PD135158 displayed more exploratory behavior towards the maternal body than lambs from the other groups. When tested in a 2-choice test situation at 24 hr of age, lambs treated with PD135158 or saline spent significantly more time near their dams than near the alien ewes, whereas lambs treated with devazepide did not show any discrimination. The effect of devazepide persisted at 48 hr of age. The use of a CCK-A antagonist, but not a CCK-B antagonist, was concluded to prevent the formation of a preferential relationship between the lamb and its mother, most probably by impairing neonatal learning.

Animals↗

PubMed1997

Discrimination between shepherds by lambs reared under artificial conditions.

We studied the ability of 32 lambs reared artificially in groups of four to discriminate between their shepherd and an unknown shepherd. Half of the lambs were bottle fed in isolation by one shepherd during the first 3 wk. The other half was fed alternately by three shepherds. Lambs had no visual contact with humans for the next 3 wk. Lambs were weaned at 6 wk of age and reared together with the minimum human contact necessary for rearing management. Lambs were tested at 3, 6, and 14 wk of age, investigating the effect of the rearing conditions on the response to isolation and to reunion with the known or an unknown shepherd. During tests, lambs were observed 1) in isolation for 1 min, 2) in the presence of a shepherd who entered and squatted at one end of the pen for 1 min, trying to touch the lambs if they approached, 3) again in isolation for 1 min. Early rearing management (one vs three shepherds) had no significant effect on any criteria studied. Lambs vocalized and moved less when in the presence of the shepherd than when isolated. They vocalized less, moved less, approached more quickly, and interacted more with the known than with an unknown shepherd. The difference persisted after 3 wk spent without visual human contact. However, no difference was evident at 14 wk of age. The effect of shepherd knowledge is clearly demonstrated by this experiment after an intensive early period of contact.

Aging↗

PubMed1997

[Pathomechanics of spinal and rib cage deformity in idiopathic scoliosis].

Idiopathic scoliosis is a triplanar deformity associated with a rib hump. The quantitative assessment of the principal elements of spinal and rib cage deformity based on the chosen parameters measured on a-p radiographs and CT scans was done in a group of 89 children with idiopathic scoliosis. The average Cobb angle was 63 degrees. In regression and correlation analysis the statistically significant correlation among spinal lateral curve, axial rotation and kyphosis/lordosis index was found. Significant correlation between the elements of spinal deformity and the size of the rib hump were also found. The rib cage may play an important role in the pathogenesis of idiopathic scoliosis.

Adolescent↗

PubMed1997

[Database for assessment of treatment results in patients with multiple trauma].

Data base for assessment of results of treatment of politrauma patients is presented. It was created on the basis of Abbreviated Injury Scale, Injury Severity Score and Revised Trauma Score. Examination was supplemented with TRISS method inclusive of graphic assessment PRE-CHART and statistic Z and M. The software was created on the basis of Excel 7.0 and Windows 95.

Computer Graphics↗

PubMed1996

Alternative polyadenylation of the gene transcripts encoding a rat DNA polymerase beta.

Rat cells produce two different transcripts of DNA polymerase beta (beta-Pol). The low-molecular-weight transcript (1.4 kb) was already sequenced. We report here the cloning and sequencing of the full-length cDNA, corresponding to the high-molecular-weight (HMW) transcript (4.0 kb) of beta-Pol. Sequence data strongly suggest that both transcripts are produced from a single gene by alternative polyadenylation. The HMW transcript contains the entire 1.4 kb transcript sequence and additional 2.2 kb on the 3' end. The 3' UTR of the HMW transcript contains some regulatory sequences which are not present in the 1.4-kb transcript. The A + U-rich fragment and (GU)21 sequence are believed to influence the stability of the mRNA. The functional significance of the A-rich region locally destabilizing double-stranded secondary structure remains unknown.

Alternative Splicing↗

PubMed1996

Alternative splicing of DNA polymerase beta mRNA is not tumor-specific.

Mammalian DNA polymerase beta is a crucial enzyme in cell genomic maintenance. Its structure is highly conserved. Some splice variants of beta-pol mRNA were observed. One alternative splice DNA polymerase beta mRNA, generated by 87 nt deletion (exon 11) in the catalytic domain of this enzyme, was suggested to be responsible for genomic instability in tumorigenesis and in genetic disorder (Werner syndrome). Here, we show that exon-11-deleted beta-pol mRNA is present in all examined normal and tumor tissues as well as in resting or PHA-stimulated peripheral-blood mononuclear cells. This finding proves that the presence of the exon-11 alternative splicing variant of beta-pol mRNA is not tumor-specific.

Alternative Splicing↗

PubMed1996

[Therapy of chronic myeloid leukemia with interferon-alpha. A decade of experiences].

PATIENTS AND RESULTS: One hundred and fifty-nine patients with chronic myelogenous leukemia have been treated in six studies during 10 years at Hannover Medical School University Center. The prognosis of 111 patients without pretreatment has been improved compared to conventional therapy with a median survival of 5.7 years. Cytogenetic remissions have been induced in all studies followed for a longer time. The most pronounced improvement of prognosis has been observed in these patients. CONCLUSIONS: Several conclusions can be drawn on the basis of the results on the different treatment concepts: 1. Patients with pretreatment have an unfavourable response to interferon. 2. There is a likely effect of the dose of Interferon alpha on the frequency of cytogenetic remissions. 3. The combination of Interferon alpha and interferon gamma has been toxic and ineffective in a pilot study. 4. The combination of interferon and cytosine arabinoside has a positive impact on the frequency of cytogenetic remissions. A continuous parallel application of both drugs seems to be most effective in this respect. An ongoing trial has been initiated to compare a fixed combination of Interferon alpha and cytosine arabinoside and with hydroxyurea respectively. Additionally the feasibility of autologous peripheral blood stem cell transplantation will be studied in patients with insufficient response to the interferon treatment.

Antineoplastic Agents↗

PubMed1996

[Unrecognized carbon monoxide poisoning--the importance of subsequent studies in death with undetermined cause].

The author reports a case of an old man and his wife, who were found dead in the bedroom of their apartment with signs of putrifaction. The physician certified an internal cause of death respectively death by an overdosage of drugs. But toxicological investigations induced by a forensic scientist proved, that death was due to poisoning with carbon monoxide. Blood saturation levels were 70 and 66 per cent. The origin of the intoxication was a malfunctioning gas geyser in the kitchen. The heater had been installed many years previously and had not been checked by competent authorities in the last 6 years. If the poisoning had not been detected, other people might come into the risk of a fatal accident too.

Aged↗

PubMed1996

Complex cytogenetic and immunophenotypic aberrations in a patient with Sezary syndrome.

Sezary syndrome is defined as the leukemic variation of cutaneous T-cell lymphomas. Here we describe the cytogenetic pattern of peripheral T-cells of a 50-year-old male patient suffering from this disease. We used Giemsa-banding (G-banding) technique and a fluorescence in situ hybridization (FISH) assay to determine cytogenetic changes affecting 15 different chromosomes. The cells displayed an abnormal hypodiploid karyotype with a prominent insertion located at the short arm of chromosome 1. Unbalanced translocations were observed involving chromosomes 4 and 14. Besides other abnormalities we detected a 6q- deletion. These multiple genetic changes may reflect the high aggressivity of the neoplastically transformed T-cell population and the poor response to chemotherapeutic treatment.

Aneuploidy↗