[Centenary of the birth of Imre Haynal, M. D].
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Biomedical subjects
Publications and source records attributed to J Fehér.
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The methods of the multivariate mathematics have been applied in several studies to increase the diagnostic reliability of medical decision support system. In the recent years some new algorithms for decision support (fuzzy logic) and for pattern recognition (neural nets), both specified by nonlinearity, were developed. This paper provides results for the application of this methods in the area of quantitative cytology and the comparison with the traditional classifiers. 21 normal, 15 dysplastic, 23 malignant, Feulgen stained gastric imprint smears were analysed on a Leitz Miamed DNA equipment. The determination of mean DNA content, the 2c deviation index (2cDI), 5c Exceeding rate (RcER), G1,S,G2 phase fraction ratios, cell nucleus area, form factor was performed. The discriminant analysis classified correctly the 95.6% of malignant cases, 86.7% of dysplasias, and 80.7% normal cases. Our diagnostic system using fuzzy logic made the diagnostic borders fine tuneable, and reliable. The back propagation neural net could classify all three diagnostic groups above 95% correctly. The application of nonlinear computational methods made the diagnostic system more reliable. The application of these algorithms are encouraged.
The authors applied regularly the hydrogen (H2) breath test during the medical investigations in patients with gastrointestinal symptoms. On the basis of the repeated examinations the hydrogen (H2) breath test is a sensitive, well repeatable method. After analysing of 108 examinations the authors have observed in 51.8% lactose intolerance, in 17.8% small intestinal bacterial overgrowth syndrome, in 46.4% motility disorders. The proportion of "low hydrogen producers" was 14.3%. Only 1/5 of patients with new diagnosed lactose intolerance had knowledge about the intolerance, and 10% was asymptomatic. In case of small intestinal bacterial overgrowth syndrome the repeated hydrogen (H2) test may indicate the effectivity of applied antibiotic therapy. The mean orocaecal transit time was 99 minutes and the normal range was 66-132 minutes, counted on the basis of mean +/- 2 SD. The authors suggest that the results support the important role of hydrogen (H2) breath test in the modern gastroenterological diagnostics.
Quantitative morpho- and densitometric analysis of Feulgen stained breast aspiration smears were performed by absorption cytophotometer and a TV image analyser. The DNA Index, and the ratio of G1-S-G2 phase fraction ratio yielded by the quantitative DNA analysis, showed significant differences between benign and malignant alterations. Based on the 13 morphometric and 5 densitometric parameters the TV-image analyser could classify the examined smears 80% correctly by cluster analysis. Groups of the cytological Grade I.-III. were also differentiable by this method. The application of TV image analyser system in the diagnosis of aspiration cytological smears could be suggested. The complex quantitative morpho- and densitometric analysis could contribute to the correct classification of diploid tumours.
The authors studied the function of human fetal liver cell--on level of DNA and gene regulation--by methods of molecular biology. Experiments were done under strict observation of the ethical guidelines of the 1975 Declaration of Helsinki Human Research Committee. They conclude that human fetal liver culture may serve as a suitable in vitro modell for study of the liver specific gene expressions. They found that cultured human fetal liver cells from second trimester express albumin and AFP. They demonstrate that fetal hepatocytes--like adult hepatocytes--respond to the inflammatory mediators, IL-1, IL-6 and TNF, by induction of CRP and alpha-1-Ach expression and regression of albumin synthesis proving the ability of fetal hepatocytes to produce an acute phase response.
This study was performed to examine the pattern of superoxide (O2-.) generation from leukocytes using the O2-. specific chemiluminescence (CL) method. Cypridina luciferin analog, 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo [1,2-alpha]pyrazin-3-one (MCLA) was used as a CL probe. The appropriate conditions of the MCLA method was first determined for the evaluation of the time course of O2-. generation by leukocytes. The time course of O2-. generation obtained by the MCLA-CL system was compared with that by the luminol-dependent CL, electron spin resonance (ESR)/spin trapping, and cytochrome c systems. Following stimulation by three different stimulants (PMA, OZ, FMLP), leukocytes continuously generated O2-. for up to 5 h in the MCLA-CL system, irrespective of the kind of stimulation. The curves obtained by generation ceased more rapidly in the luminol-CL, ESR/spin trapping, and cytochrome c systems. A 50% activity of the initial value was observed at 70 min in the MCLA-CL system, but 30, 10 and 35 min in the other systems, respectively. The CL or O2-. generation value decreased to less than 1% (possible termination) at 300, 90, 120 and 180 min, respectively. With the exception of ESR studies with OZ, the cell viability was not significantly affected in any of the trials. These results indicate that leukocytes can generate O2-. much longer than previously estimated and that the MCLA-CL-system is the most suitable system for the measurement of the O2-. generation by leukocytes.
Selenium (Se) status of Hungarian rock-soil systems has been poorly investigated. The goal of this study was to get general information on the main features of Se geochemistry, and to have a brief look into the human Se status in Hungary, developing an appropriate method for a forthcoming systematic regional investigation. A multistage program was applied: 1. stream sediment sampling; 2. investigation of rock-soil profiles typical in Hungary; and 3. extraction of mobile Se fractions from soils. Human serum samples from apparently healthy blood donors residing in both urban and rural areas were collected from three districts in Hungary. It was concluded that Hungarian rock-soil systems, especially the acid igneous rocks and the widely distributed young sediments (loess and sand formations) with most of the agricultural activity, are low in Se, and the mean serum Se level of the blood samples were also low.
A 50-year-old man is described who had a 15-year history of Raynaud's phenomenon with severe and frequent vasospastic attacks in his fingers and toes during the past years. Exacerbation of his digital symptoms, which started about 4 years ago, was accompanied by signs of thyroid deficiency, such as tiredness, memory impairment, decreased libido, constipation, dryness of skin and bradycardia. Hormonal evaluation revealed primary hypothyroidism and the patient began substitution therapy with L-thyroxine. After 2 months of treatment not only did he become euthyroid but the digital symptoms also disappeared. The patient may thus represent one of the very few cases whose thyroid replacement therapy proved to be highly effective in treating both hypothyroidism and Raynaud's phenomenon.
The distribution and the possible source of somatostatin- and substance P-immunoreactive nerve fibers were studied in the liver of the cat by immunocytochemical techniques. Abundant substance P-immunoreactive and a moderate number of somatostatin-immunoreactive nerve fibers were found running around the blood vessels in the perilobular connective tissue. Some somatostatin-immunoreactive nerve cell bodies were also observed in the liver. A moderate number of somatostatin-immunoreactive nerve profiles were found inside the hepatic lobules along the sinusoid endothelial cells and the hepatocytes. The interspace between the axon and hepatocyte and endothelial cells membranes was about 20 nm. Cutting the extrinsic hepatic nerves resulted in marked reduction of substance P-immunoreactive nerves but only a slight reduction of somatostatin-immunoreactive nerves in the liver. These findings provide a morphological basis for the possibility that somatostatin and substance P may act as transmitters or neuromodulators on the neighboring smooth muscle cells of vessels and may regulate the function of the hepatocytes. It is also possible that some of these fibers serve sensory function along the blood vessels.
The aim of the study was to investigate the pathological role of free radicals during myocardial reperfusion. Low (0.5 mg/kg body weight) and high doses (5 mg/kg) of superoxide dismutase (SOD) were infused into the left atrium of mongrel dogs for 4 min starting 29 min after ligation and 1 min before reperfusion of the left anterior descending coronary artery (LAD). Arterial blood pressure, heart rate, electrocardiogram, and the regional contractile force of the left ventricle were monitored throughout the ligation (30 min) and reperfusion periods (20 min). Concentrations of creatine kinase (CK) and malondialdehyde (MDA) in the coronary sinus blood were determined before (0 min) and during ligation (15 and 25 min) and during reperfusion of the LAD (2, 7, and 20 min). In other groups of dogs, the effect of the two doses of SOD on epicardial blood flow was investigated during ligation and reperfusion by the measurement of epicardial temperature using a thermocardiograph. Experimental subjects were mongrel dogs of either sex (n = 25), weight 10-35 kg. Compared to controls (mean +/- SEM, 43.1 +/- 1.2; n = 7), the number of ventricular extrasystoles during the first 5 min of reperfusion was significantly (p < .001) decreased in dogs treated with the high dose (15.01 +/- 2.14; n = 5), but not in those receiving the low dose of the drug (34.6 +/- 5.66; n = 5). The concentrations of CK increased gradually until the end of reperfusion without differences among the different groups. Plasma MDA was the highest in control dogs 7 min after reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Congenital coronary arteriovenous fistulae are commonly associated with complications which include congestive heart failure, bacterial endocarditis, angina pectoris, secondary to "coronary steal" phenomenon and fistula rupture. Conventional treatment of large coronary arteriovenous fistulae is surgical ligation. In this report we describe the data and therapeutic approach of a patient with a severe coronary stenosis in a large diagonal branch in whom PTCA was successfully conducted, while, in this opportunity no embolization of the fistula was performed.
Role of free-radical reactions is most significant in toxic liver injuries. Two traditional groups of liver injuries induced by drugs and chemicals are distinguished, 1. direct toxic type and 2. idiosyncratic type. Liver injury of direct toxic type is generally developed following toxin exposure, it is dose dependent, incubation period is short, and the injury often affects other organs (e.g. kidney). Direct toxins frequently cause typical zonal necrosis usually without concomitant signs of hypersensitivity. It is typical of idiosyncratic reaction that it appears only in a shorter period of exposure, it cannot be predicted, it is not dose-dependent, its incubation period varies and sometimes (in one-fourth of cases) it is accompanied by extrahepatic symptoms of hypersensitivity (fever, leukocytosis, eosinophilia, rashes), its morphologic picture shows great variety. A part of direct toxins is toxic itself, in the other part the basic compound is not toxic but it changes into toxic metabolites in the liver. Liver is well-protected against free-radicals developing in the organism: it is one of our best antioxidant supplied organs. It is probably due to the one of the important tasks of liver, namely detoxication of drugs, chemicals and toxic materials, with subsequent release of free-radicals. It is proved by the fact that in normal bile peroxidized lipids produced by free-radical chain reactions can also be detected. The pathologic free-radical reactions and one of their sequelae, peroxidation of lipids (LPO) do not necessarily cause cell and tissue damage. Antioxidant protection of cells and tissues is able to prevent free-radical injury and it enables, that the already developed damages become reversible. According to recent investigations, the lipid peroxidation, caused by free-radical reactions, or covalent binding of radical products to biomolecules does not lead directly to cellular destruction, only via further reactions. Such intermediary steps can be the phospholipase A2 activation, accumulation of lysophosphatides, poly-ADP-ribose polymerase repair enzyme activation, following oxidative damage of DNA, with subsequent NAD and ATP depletion. Its significance may be that the irreversible cellular and tissue damage can be prevented perhaps not only by administration of antioxidants, but also by compounds (e.g. phospholipase A2 inhibitors) affecting the above-mentioned biochemical mechanisms.
Oxygen-centered radicals, such as superoxide (O2-) and hydroxyl radicals (.OH) generated by phagocytes have been suggested to be involved in the pathogenesis of chronic inflammations of the bowel, such as Crohn's disease and colitis ulcerosa. Recently, sulfasalazine (SASP) and its metabolites have been reported to exert their effects as a direct scavenger of oxygen-centered radicals in the bowel. To scavenge oxygen-centered radicals in vivo, however, SASP and its metabolites have to react with O2- and/or .OH in vitro very rapidly, furthermore they have to reach an appropriate (possible millimolar) concentration range at the site of inflammation. To test this possibility, we investigated the direct O2- and .OH scavenging activity of SASP and its metabolites using the specific electron paramagnetic resonance/spin trapping method, and we compared the 50% inhibition rates of SASP and its metabolites with their known concentrations in the bowel and in the human plasma. It was found that SASP and its metabolites, such as 5-amino-salicylic acid (5-ASA), and acetyl-5-amino-salicylic acid (AC-5-ASA), but not sulfapyridine (SP) and acetyl-sulfapyridine (Ac-SP) have a direct O2- and .OH scavenging activity in vitro systems. Among the compounds, SASP and 5-ASA can reach a concentration which is appropriate to scavenge oxygen-centered radicals in the bowel but not in the human plasma. It was concluded that the in vivo antiinflammatory effects of SASP and its metabolites are, at least partly, due to the direct oxygen-centered scavenging activity of these drugs.
Authors describe a new mathematical approach based on mixture decomposition and maximum likelihood method for the determination of subpopulations and G1-S-G2 phase fraction ratios in aneuploid, multiploid DNA histograms. A special computer routine was developed for this purpose (DAHSY). The present study relates to DNA histograms obtained by a Leitz Miamed DNA TV image analyser system. Altogether 23 normal, 14 dysplastic and 28 tumours Feulgen stained gastric imprint smears were measured. In addition to determination of subpopulations and G1-S-G2 phase fraction ratios, the authors also performed a morphometric analysis of Feulgen stained nuclei and determined the values of 5c exceeding rate (5cER) and the 2c deviation index (2cDI). More than one subpopulation were found only in tumours. The usual G1-S-G2 phase fraction rates in normal gastric smears were 85.5%, 9.04%, 4.9%, in dysplastic cases 74%, 15.4%, 10.2% and in tumours 53.8%, 22.9%, 18.8%. Significance of the differences were calculated by the T-test. The G1 phase fraction ratio clearly discriminates the malignant lesions from all others. The S+G2 phase fraction ratio, however, distinguishes the normal cases from the dysplastic ones. The 2cDi and 5cEr could support a multivariate diagnostic system. The cell nucleus area was found also to be of diagnostic value.
The DNASK is a PC-based image analysis module for quantitative cytological and histological examinations on Feulgen-Schiff preparations. The module consists of a frame grabber, a CCD black and white video camera and the DNASK software package which can be incorporated in an IBM compatible PC-AT joining to a standard pathological research photo microscope. The use of 386 IBM AT systems leads to significant decrease of the measurement's time. Mono- or color VGA graphics card should be used. The resolution of the images is 512 x 512 pixels and 256 gray values. The image caption is made in less than 0.5 second, the measurement of a cell nuclei (18 parameters) takes less, than 5 seconds (IBM AT 286). The camera is a standard CCD one. The microscope should be a good quality, modern microscope with built-in light source, however, the application of voltage stabiliser is strongly recommended. The software is able to measure the parameters mostly used and suggested in the international literature: 15 morpho- and densitometric parameters of the cell nuclei 6 DNA histogram parameters of the measured case, like DNA Index, 2c deviation Index, 5c exceeding rate, G1-S-G2 phase fraction ratio. The system supports the grouping of the measured cases and at the end of a study results of the single measurements can be collected and summarized in an ASCII file, which is readable by major statistical programpackages. The DNASK has a special graphical user interface for the control of the program.
The new nonsurgical methods of treating gallstone disease in gallbladder rely on fragmentation with extracorporeal shock wave lithotripsy (ESWL) and on dissolution of stones with ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA). Fragmentation alone is usually insufficient for gallbladder stones, and dissolution is only possible for cholesterol stones. Although oral dissolution with or without ESWL is an attractive alternative of surgery, only 25 percent of the patients are candidates for this therapy. Dissolution of the gallbladder stones by topical application of methyl-tertbutyl ether (MTBE) is an other option whose safety is still open to question. Therefore, cholecystectomy will remain the principal treatment for symptomatic gallbladder stones.
The production of different cytokines, namely interleukin-2, interleukin-1 and tumor necrosis factor-alpha produced by peripheral immunocompetent cells was evaluated in patients with systemic lupus erythematosus in active and inactive stage of the disease. The results obtained were compared to healthy controls. It has been found that lymphocytes from both groups of SLE patients produced similarly less interleukin-2 activity. Interleukin-1 activity of monocytes was significantly reduced only in patients with active stage of the disease, whereas tumor necrosis factor-alpha production was diminished even in cases of inactive SLE. The simultaneous detection of the above mentioned cytokines may indicate further details concerning immunoregulatory disturbances of systemic lupus erythematosus.
After definition in the group of the non ulcer dyspepsia (NUD) can be counted all those patients at whom beside the dyspeptical complaints, the radiological and endoscopical examinations didn't show ulcerative changes. The authors made biopsy 550 times on the occasion of 1390 gastroscopical examination (39.5% of the cases). The histological examination showed chronic gastritis in 372 cases (26.7% of all the examinations, 67.6% of the histological examinations). At this group of patients the dyspeptical complaints gave the principal indication of gastroscopical examination. Also it was examined the presence of dysplasia and intestinal metaplasia beside the different severity grade of chronic gastritis. The presence of Helicobacter pylori (Hp) was examined by histological methods. Hp positivity was noticed in 16.4% in the upper group. The authors made Hydrogen-breath examinations in 34 cases between patients with NUD. The results of Hydrogen-breath examinations also raise the multifactorial nature of the NUD. On the basis of examinations chronic gastritis and CP infection can form subdivisions in the heterogenic group of patients with NUD. For exacter judgement of Hp pathogenicity are needed further and wide-spread examinations. The authors would like to call the attention to the indispensability of the biopsy during the gastroscopical examination.