Biomedical subjects

H Novotná

Publications and source records attributed to H Novotná.

At least 19 recordsLinked to original sources

PubMed2006

International Staging System required standardization of biochemical laboratory testing in multiple myeloma.

The standardization of biochemical measurement procedures in multiple myeloma is necessary for reliable prognostic stratification of patients in multicentric trials. The new prognostic index International Staging System for multiple myeloma uses only two laboratory markers, albumin and beta-2 microglobulin. Our study compared results of albumin, beta-2 microglobulin and monoclonal immunoglobulin measurements from six centers which provide treatment for multiple myeloma in the Czech Republic and attempted to standardize the analytic procedures. We have found that the measurement of albumin is well standardized and the results from all laboratories were comparable. The measurement of beta-2 microglobulin achieved comparability only after a partial unification of analytical methods. The determination of monoclonal immunoglobulin concentration provided comparable results for concentrations higher than 20 g/l with higher variability for lower values.

Antibodies, Monoclonal↗

PubMed2004

[Comparison of diagnostic validity of carbohydrate-deficient transferrin and other laboratory markers in chronic ethanol abuse].

BACKGROUND: Carbohydrate-deficient transferrin (CDT) has been reported to be the best laboratory marker of the chronic alcohol abuse, but there are conflicting data on its accuracy and sensitivity ranging from 19% to 96% in various studies. The aim of this study was to compare the diagnostic efficiency of CDT with the other markers of alcohol abuse used in clinical practice with respect to possible sex differences. METHODS AND RESULTS: The serum CDT (using the method of anion-exchange chromatography and TIA), mean corpuscular volume (MCV), gamma-glutamyl-transferase (GMT) values and platelet count were evaluated in 50 alcohol-dependent patients admitted to the Center of Detoxification and in the reference group of 85 healthy teetotallers. The cut-off values for %CDT where established in the level of 2.2% and 2.5% for men and women respectively. In men we proved a comparatively high diagnostic efficiency of CDT (AUC 0.94, sensitivity 82.6%, specificity 96.7%) and GMT, MCV seem to be less accurate marker of chronic alcohol abuse. In contrast there was a lower diagnostic validity of CDT in women in comparison with common markers (AUC 0.83, sensitivity 60%, specificity 88%). CONCLUSIONS: The laboratory diagnosis of chronic alcohol consumption can be improved by using a combination of several markers. The specificity and also the cumulative sensitivity of such a battery of laboratory markers can be elevated by CDT evaluation. In a part of patients, CDT can be the only detectable abnormality.

Adult↗

PubMed2003

[Diagnostic value of carbohydrate-deficient transferrin, gamma-glutamyltransferase and mean erythrocyte volume as laboratory markers of chronic alcohol abuse].

INTRODUCTION: Our research aimed at finding out values of carbohydrate-deficient transferin (CDT), gamma-glutamyltransferase (GGT) and mean corpuscular volume (MCV) for the purposes of future etiological diagnostics of alcohol neuropathy in thin fibres. METHODS: We examined the serum of 80 control subjects (50 women and 30 men), and the serum of 33 alcoholics (20 men and 13 women) with the daily consumption of more than 60 g alcohol in the course of the last four weeks. CDT was determined with the use of microcolumn separation after iron saturation followed by turbidimetric immunoassay (ChronoAlcoI. D., Sangui Biotech, Inc.) on Cobas-Mira analyser. CDT is expressed as a percentage of the total transferin. Senzitivity, specificity, positive likelihood ration (+LR), ROC and the area under the ROC curve were determined using statistical program MedCalc. RESULTS: The senzitivity, specificity and positive likelihood ratio (+LR) for CDT-%, respectively, were 82.6, 96.7 and 24.8 for men (cut off 2.2%), and 60.0, 88.0 and 5.0 for women (cut off 2.5%). The respective values for GMT were 95.7, 90.0 and 9.6 for men (cut off 0.64 mu kat/l), and 90.0, 80.0 and 4.5 for women (cut off 0.38 mu kat/l); for MCV 82.6, 96.7 and 24.8 for men (cut off 95.0 fL), and 80.0, 100.0 and 20.0 for women (cut off 97.2 fL). The area under the ROC curve for CDT-%, GMT and MCV, respectively, were 0.940, 0.964 and 0.896 for men, and 0.829, 0.917 and 0.906 for women. CONCLUSION: In men, CDT-% and MCV showed the same values of the statistical parameters studied. GGT was more sensitive and less specific. In women, all the parameters studied presented a lesser diagnostic value, except for MCV with 100% specificity and +LR 20.0.

Adult↗

PubMed2002

Age-related extracellular to total body water volume ratio (Ecv/TBW)--can it be used for "dry weight" determination in dialysis patients? Application of multifrequency bioimpedance measurement.

The article suggests a novel method for quantitative determination of optimal dry weight in dialysis patient based on their extracellular volume (ECV) to total body water (TBW) ratio and its relation to age. Values of ECV and TBW are evaluated by means of whole body multifrequency bioimpedometry. In an effort to find a suitable marker of hydration status in an individual from bioimpedance data, significant correlation has been found between ECV/TBW ratio and age in health. Assuming that all excess fluid in dialysis patients is stored exclusively in ECV and that distribution of their TBW at the state of optimal dry weight corresponds to that of a healthy person of the same age, the pre-dialysis ECV/TBW could be used for quantitative determination of optimal dry weight and/or of the ultrafiltration to reach this weight. Practical bioimpedance measurement of ECV/TBW in a group of dialysis patients both pre- and post-dialysis confirmed both above assumptions, i.e. nearly exclusively extracellular origin of ultrafiltration as well as normalisation of the ECV/TBW ratio towards the end of dialysis. Supporting evidence of increasing ECV/TBW value with age was also found in literature. Although the suggested method needs detailed analysis of possible disturbing factors (ethnic "specificity" of the reference ECV/TBW vs. age characteristics in health, possible difference in "biological" and "physical" age of dialysis patient and others), the article is published at this early stage to enable wider testing of the proposed novel method by different investigators.

Adolescent↗

PubMed2001

[Cystatin C in estimates of glomerular filtration in patients with renal disease--initial experience].

Cystatin is reported in the literature with increasing frequency as a new reliable parameter for estimates of glomerular filtration. The authors examined cystatin C by the PET method of DAKO Co. in 151 patients from the nephrological out-patient clinic. 91 patients had normal renal functions, 60 suffered from renal insufficiency of different severity. Between cystatin C and glomerular filtration assessed by creatinine clearance was a close correlation, R = -0.787 according to Pearson. The authors evaluated separately a group of 36 patients with glomerulonephritis, 34 diabetic patients with diabetic nephropathy, 38 patients with tubulointerstitial nephritis and 43 subjects with other kidney diseases. The groups did not differ significantly when compared with the whole group nor mutually (p = n.s.). The authors of the study confirmed that a good correlation of cystatin with creatinine filtration is not influenced by the type of basic nephrological disease. The effect of administration of insulin, antihypertensive drugs, cyclosporin A and glucocorticoids was not proved in the investigated group. The published method is accurate, not demanding from the technical aspect. The examined subject is not restricted by conditions ensuring the accuracy of assessment and seems thus useful and perspective for nephrological patients.

Adult↗

PubMed1999

Expression of genes for microphthalmia isoforms, Pax3 and MSG1, in human melanomas.

Microphthalmia (MITF) gene product, a transcription factor of the basic-helix-loop-helix type, is thought to play a role in the regulation of genes encoding the enzymes necessary for melanogenesis. These include tyrosinase, TRP-1 and TRP-2. Melanocyte-specific isoform of microphthalmia, MITF-M, is expressed in normal and malignant melanocytes. The presence of two other isoforms of microphthalmia, MITF-A and MITF-H, which differ from MITF-M in the amino-terminus, was demonstrated also in some non-melanocytic lineages. Here we have analyzed the presence of all three known isoforms of MITF mRNA in a panel of 17 human melanoma cell lines by a reverse transcriptase-polymerase chain reaction using isoform-specific primers. While, as expected, the predominant form in melanoma cell lines was MITF-M, low amounts of MITF-A mRNA was found in almost all melanomas, as well as in most of 20 tumor cell lines of the non-melanocyte origin (lung and colon carcinomas, osteosarcomas and neuroblastomas). The expression of MITF-H was not detected, with a few exceptions, in the tested cell lines. Pax3 transcription factor was reported earlier to regulate positively the melanocyte-specific promoter of the MITF gene. We found here that the Pax 3 mRNA was expressed in all melanoma cell lines, even in those that had repressed the MITF-M and were amelanotic. This suggests that additional factors, besides Pax3, are required for the MITF expression. The MSG1 (melanocyte-specific gene 1), a gene originally isolated from melanocytes and containing a strong transcription activation domain, was also found expressed in all melanomas and most non-melanocyte tumor cell lines. Together, these data indicate that the MITF-M isoform is the major type of MITF mRNA present in human melanoma cell lines and show that the expression of the isoform MITF-A and the MSG1 is not restricted to malignant melanocytes and occurs in a wide range of tumor cell lines.

DNA-Binding Proteins↗

PubMed1997

Expression of the aromatic L-amino acid decarboxylase mRNA in human tumour cell lines of neuroendocrine and neuroectodermal origin.

Neuroendocrine differentiation of lung tumours is characterised by the expression of several neuroendocrine markers and is confined mostly to specific histological subtypes, i.e. small cell carcinomas and carcinoids. One of the markers seen in neuroendocrine tumours, high activity of the aromatic L-amino acid decarboxylase (AADC), is helpful in distinguishing the classic and variant small cell lung tumour subtypes. Here, we have analysed the expression and quantified the level of mRNA coding for AADC in human tumour cell lines by use of the reverse transcription and polymerase chain reaction (RT-PCR). High amounts of mRNA were detected in classic small cell lung carcinomas and a neuroblastoma cell line. Other cell lines (melanomas, non-small cell lung carcinomas and osteosarcoma) also showed AADC expression, but the levels were 2-3 orders lower. Also, the tissue-specific (neuronal versus liver-specific) mRNA type has been estimated. Small cell lung carcinomas, neuroblastoma and melanoma expressed messenger RNA specific for neuronal tissues. Importantly, the non-small cell lung carcinoma cell lines expressed either liver-specific (non-neuronal) mRNA (cell line A549) or predominantly the neuronal (cell line NCI-H520) AADC message. These data indicate that a range of tumour cell lines transcribe the AADC gene and that two distinct types of AADC mRNA which reflect the embryonal (neuronal or non-neuronal) origin of the tumour may be produced in non-small cell lung cancer cells.

Adenocarcinoma↗

PubMed1995

[Pleural effusion in plasmacytic leukemia].

Multiple myeloma affects predominantly osseous spaces and the close vicinity of bones. A plasmacellular exudate is rare. The authors describe the course of plasmacellular leukaemia in a 68-year-old female patient where the first symptom of the disease was anaemia and a dextrolateral pleural exudate with a cytological finding of plasma cells. The exudate disappeared after the first cycle of chemotherapy and intrapleural administration of cytostatic. After the third cycle of chemotherapy remission of the disease was recorded which was, however, short. After three months' remission (six months after establishment of the diagnosis) the disease exacerbated violently, the dextrolateral exudate reappeared and gradually the insufficiency of the infiltrated bone marrow increased. The patient died one month after the relapse of the disease. The finding of a plasmacellular exudate must be considered the sign of a very poor prognosis and in that case very aggressive treatment is indicated.

Aged↗

PubMed1995

Mutations of K-ras oncogene and absence of H-ras mutations in squamous cell carcinomas of the lung.

Mutations of the K-ras gene have been implicated in the pathogenesis of human lung adenocarcinomas. In most studies published so far, squamous cell lung cancers harbored ras mutations only exceptionally or no mutations were detected at all. We have examined 141 lung tumor DNA samples for mutations in codons 12, 13, and 61 of K-ras and H-ras oncogenes. A large panel of 118 squamous cell carcinomas was included in the study. For K-ras codon 12, we used a sensitive two-step PCR-restriction fragment length polymorphism method which detects <1% of mutated DNA in the sample. K-ras mutations were found in 17 tumors (12%; 14 in codon 12 and 3 in codon 13). Among 19 adenocarcinomas, mutation was revealed in 7 samples (37%). Of these, one sample harbored two point mutations in codon 12. Nine mutational events were found in squamous cell carcinomas (8%, one adenosquamous carcinoma included, all in codon 12). Of four large cell carcinomas, one contained a mutation. Mutant-enriched PCR products harboring mutations were directly sequenced. Fifteen mutational events were G-->T transversions or G-->A transitions, one was a G-->C transition, and one sample revealed a frameshift deletion of one G from codon 12. Similar mutational spectrum was found in both squamous cell carcinomas and adenocarcinomas, suggesting similar carcinogenic pathways in both histological types of the tumor. The presence of mutations did not correlate with the stage of the disease. Moreover, we analyzed all samples for mutations in codons 12, 13, and 61 of the H-ras gene. We found only one mutation in codon 12. Thus, H-ras mutations apparently play an inferior role in lung carcinogenesis. We conclude that mutations of the K-ras oncogene can play a role in the development of not only lung adenocarcinomas but also of a subset (about 8%) of squamous cell carcinomas.

Adenocarcinoma↗

PubMed1994

Hypomethylation of CCGG sites in the 3' region of H-ras protooncogene is frequent and is associated with H-ras allele loss in non-small cell lung cancer.

The methylation of MspI/HpaII sites flanking a variable tandem repeat in the 3' region of the c-Ha-ras protooncogene was analyzed in 74 DNA samples of non-small cell lung carcinomas and control lung tissues. Of 39 informative samples, 7 allelic deletions (18%) were found at the c-Ha-ras locus and of these, five (71%) showed hypomethylation of the nondeleted allele. Heterozygous DNA samples without allele loss revealed hypomethylation in 37% (12 of 32). Among 35 homozygotes, 9 showed hypomethylation (26%). We also analyzed c-Ha-ras mutations at codons 12, 13, and 61 by polymerase chain reaction and designed restriction fragment length polymorphism and found no mutation. Thus, c-Ha-ras mutations are not associated with the development of the detected abnormalities. We conclude that hypomethylation at specific sites in the 3' region is associated with loss of heterozygosity for the c-Ha-ras gene in non-small cell lung cancer. The finding that, in informative samples, hypomethylation occurs 2-3 times more frequently than allelic loss suggests that it might be a change contributing or predisposing to a genetic instability that can ultimately lead to c-Ha-ras allelic deletions found in tumor DNA.

Alleles↗

PubMed1994

Treatment of refractory multiple myeloma with vincristine, adriamycin, dexamethasone, and with repeated application of cyclophosphamide (C-VAD).

The quick reduction of differentiated myeloma cells by VAD chemotherapy (vincristine, adriamycin, dexamethasone) causes, according to the investigation by Bell et al., the acceleration of the proliferation of myeloma stem cells. In 1990 Bell demonstrated that this proliferation could be stopped by administering 500 mg of cyclophosphamide in 1-week intervals. We therefore modified the classical VAD scheme to the following "C-VAD" scheme:vincristine 0.5 mg/day in continuous infusion on the first to the 4th day, adriamycin 9 mg/m2/day in continual infusion on the 1st to the 4th day, dexamethasone 40 mg p.o. or i.v. always on 4 days starting with the 1st, 10th and 20th days, cyclophosphamide 600 mg i.v. on the 5th, 10th and 20th days). A further cycle follows on the 28th day. In the present paper the effect and the tolerance of this C-VAD scheme is evaluated: In the group of 21 patients with refractory myeloma 9 remissions were achieved, 5 partial remissions, in 6 patients the disease progressed, 1 patient died after the 2nd cycle without the possibility of evaluating the therapeutic response. The mean remission length was 10.2 months. The tolerance of chemotherapy was satisfactory, C-VAD chemotherapy did not cause any serious drop in the number of leucocytes and thrombocytes. Echocardiographically lower adriamycin cardiotoxicity was demonstrated in continual administration in comparison with the bolus administration. The C-VAD scheme is considered to be suitable for comparison with the VAD chemotherapy in a randomized study.

Administration, Oral↗

PubMed1994

[Lower cardiotoxicity of adriamycin during continuous administration in patients with refractory multiple myeloma treated with cyclophosphamide, vincristine, adriamycin and dexamethasone (C-VAD)].

Standard treatment of refractory myeloma is combined VAD treatment (vincristine, adriamycin and dexamethasone). In recent years adriamycin was sometimes replaced by mitoxanthrone which caused greater myelotoxicity. As a positive feature of the exchange of adriamycin for mitoxanthrone, authors using it, report its lower cardiotoxicity. In the literature there are, however, occasional reports on a lower cardiotoxicity of adriamycin when administered in a continuous infusion. In the submitted work the authors sought answers to two questions. 1. Is the cardiotoxicity of adriamycin administered in a continuous infusion lower than the cardiotoxicity of adriamycin administered as a bolus? 2. Is it possible to add to VAD chemotherapy cyclophosphamide without increasing the toxicity excessively? After echocardiographic evaluation of the diastolic and systolic function following a cumulative dose of 200 mg the authors observed smaller changes of the above functions in the group treated with adriamycin a in a continuous infusion (patients with multiple myeloma) than in the group with bolus therapy (patients with non-Hodgkin lymphomas and acute leukaemia). Addition of 600 mg cyclophosphamide on the 5th, 10th and 20th day to the classical VAD pattern made treatment more intensive without causing a deteriorated tolerance of this treatment.

Aged↗

PubMed1994

[Difficulties in the therapy of primary amyloidosis].

The therapy of primary amyloidosis is still unsatisfactory. The response rate after the cytostatics, dimethylsulphoxide, colchicin and vitamin E is usually low. None of these treatment modalities prolongs significantly the survival in majority of treated patients. The success of interferon alpha in the maintenance therapy of follicular non-Hodgkin's lymphoma and in the remission of multiple myeloma, as well as successful treatment of primary cryoglobulinaemia, brought us to the idea to test interferon alpha in the therapy of primary amyloidosis. Interferon alpha-2b was administered to the patient with three years history of primary amyloidosis. Interferon alpha was used in the dose of 3 x 10(6) daily for the treatment period of 10 weeks. The evaluation of the response was based on the weekly assessment of the light chain lambda concentration in the morning spot of urine. No significant decrease of the light chain concentration during the course of the therapy was observed. The administration of interferon alpha-2b was interrupted in the 10th week of the therapy because of manic psychosis. The question is, whether a higher dose than 3 x 10(6) IU daily would be able to decrease the light chain production, or if this disease is resistant to interferon alpha therapy. Because of the low incidence of primary amyloidosis, the experiences will be collected on the base of small groups of case reports.

Amyloidosis↗

PubMed1993

[Determination of beta 2-microglobulin in the serum and cerebrospinal fluid using radial immunodiffusion (comparison with the Elisa Pharmacia method)].

The authors elaborated a method of radial immunodiffusion for assessment of beta 2-microglobulin serum and cerebrospinal fluid levels in patients. The method is based on a modified procedure of staining and decolouration. The antibody produced by USOL Co. which was used for the purpose was not modified. Comparison of 90 sera and 27 cerebrospinal fluid samples where also the reference method ELISA Pharmacia was used revealed almost absolute agreement, the correlation coefficient was 0.98. The method is used for clinical monitoring in patients with myelomas and renal insufficiencies.

Adult↗

PubMed1987