Experimental cardiac tamponade.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
Z Nagy
Publications and source records attributed to Z Nagy.
Increasing aortic permeability by atherogenic diet.
Explore the source record for details and available documents.
Animals↗
Role of lipophages in the development of rat atheroma.
Explore the source record for details and available documents.
Animals↗
Cell cycle regulatory failure in neurones: causes and consequences.
The number of Alzheimer's disease sufferers shows an alarming increase throughout the world. Therefore elucidation of the pathogenic mechanisms leading to Alzheimer's disease and the design of effective treatment, preventive or curative, became imperative. In the last few years several groups have found evidence indicating that the development of Alzheimer-type pathology and the associated excess cell death is the consequence of an aberrant re-entry of neurones into the cell division cycle. We believe that neuronal cell cycle re-entry is followed by regulatory failure that allows neurones to progress into the late stages of the cycle. At this stage, in apoptosis incompetent neurones, the active kinases lead to tau hyperphosphorylation, and the amyloid precursor protein is processed into amyloidogenic fragments. Thus the cell cycle arrest will lead to either the development of Alzheimer's type pathology or to apoptotic neuronal death. Although there are several studies aimed at the elucidation of the precise pathways and mechanisms by which the cell cycle disturbances may lead to Alzheimer's disease there is precious little known about the possible causes of the neuronal cell cycle re-entry. On the other hand we can only speculate on the mechanisms that lead to the subsequent regulatory failure.
Aging↗
Atropine-induced gastrointestinal cytoprotection dependences to the intact of vagal nerve against indomethacin-induced gastrointestinal mucosal and microvascular damage in rats.
UNLABELLED: The non-steroidal antiinflammatory drugs, such as an indomethacin (IND), cause mucosal ulceration and increase the mucosal vascular permeability in the gastrointestinal (GI) tract. Some exogenous agents, e.g. the atropine, can protect the GI mucosa against these ulcerogenic effects. The gastrointestinal functions and mucosal protection, however, are regulated by the vagal nerve. The aims of this study was to examine the dependence of atropine-induced GI cytoprotection to the vagal innervation against the development of IND-caused ulcers and microvascular damage in the mucosa of stomach and small intestine in rats. METHODS: the observations were carried out on CFY-strain rats. The mucosal damage was produced by subcutaneous administration of IND in a 20 mg/kg dose 24 h prior to the killing of animals at the same time as the start of atropine-application, which was given in a small dose (0.1 mg/kg) every 5 h. The subdiaphragmatic bilateral surgical vagotomy was done 24 h before the experiment. The vascular permeability, indicated by the microvascular endothel damage, was measured by the appearance and concentration of intravenously administered Evans blue into the GI mucosa. The number and severity of mucosal lesions and the Evans blue content of mucosa were determined in the stomach and small intestine. RESULTS: (1) The IND caused mucosal ulcers and Evans blue extravasation into the mucosa of the stomach and small intestine. (2) The IND-induced mucosal ulceration and vascular permeability significantly decreased after atropine-administration in the same parts of GI tract. (3) The extent of cytoprotective effect of atropine against the IND was decreased after bilateral surgical vagotomy. CONCLUSIONS: (1) The IND causes microvascular endothel damage in the stomach and small intestinal. (2) The atropine has a cytoprotective effect in the stomach and small intestine against the aggressive effects of IND without decrease of gastric acid secretion. (3) The intact vagal nerve is necessary to the function of cytoprotective mechanisms of atropine against the IND.
Animals↗
Changes of serum carotenoids in patients with esophageal, gastric, hepatocellular, pancreatic and colorectal cancer.
UNLABELLED: The serum levels of carotenoids (vitamin A, lutein, zeaxanthin, alfa- and beta cryptoxanthin, alfa- and beta-carotene) were measured in healthy persons (n=40) and in 98 patients with different malignant gastrointestinal diseases (44 patients with colon adenocarcinoma, 21 with gastric cancer, 15 with hepatocellular adenocarcinoma, 10 patients with pancreas adenocarcinoma and eight patients with esophagus cancer). The serum levels of carotenoids were measured with high-pressure liquid chromatography. The sera of the patients were taken at the time of the diagnosis. RESULTS: the measurements indicated that (1) the serum level of vitamin A and zeaxanthin were significantly lower in all of these groups (except of pancreas adenocarcinoma), but the extent of the A decrease was different in the patients with different types of gastrointestinal malignancy. The serum level of vitamin A was in the healthy subjects 2.072+/-0.332 mmol/l and in the case of gastrointestinal malignancies was 0.77+/-0.14 mmol/l (P<0.001) The serum level of zeaxanthin was in the healthy subjects 0.143+/-0.057 mmol/l and at the malignancies was 0.042+/-0.014 mmol/l (P<0.01). (2) There were no significant differences in the serum levels of other carotenoids in the checked groups. (3) The serum level of cholesterol, total protein, albumin and haemoglobin were in the normal range in these patients. These results indicate that the carotenoids may be responsible nutritional factors (as nutritional scavengers) in the development of different malignant diseases. This supposed role in the carcinogenesis does not depend fully on the vitamin A activity.
Carotenoids↗
Prevalence of the factor V Leiden mutation in human inflammatory bowel disease with different activity.
BACKGROUND: the developmental mechanism of inflammatory bowel disease (IBD) in patients is unknown, but it may be influenced by different environmental and genetical factors. AIMS of this study were: (1) to classify the IBD patients according the disease activity; and (2) to determine the presence of factor V Leiden mutation in IBD patients. PATIENTS AND METHODS: the observation was carried out in 49 patients with Crohn's disease (CD) and 29 patients with ulcerative colitis (UC). None of them had a history of thrombotic episodes. IBD was diagnosed by conventional clinical, endoscopic, radiological and histological criteria. The factor V Leiden mutation was detected by the polymerase chain reaction (PCR) method. Crohn's disease activity index (CDAI) was evaluated using the method of the National Cooperative Crohn's Disease Study. We determined the UC disease activity according to Truelove-Witts classification. RESULTS: The prevalence of factor V Leiden mutation was increased in both populations of the patients to compare it with healthy persons (14.28 and 27.58% vs. 5.26%, n=7/49 and 8/29 vs. 3/57). The statistical analysis did not show a significant relationship between the CDAI or the Truelove-Witts grade in UC and the presence of Leiden mutation. CONCLUSION: the presence of factor V Leiden mutation probably has a role in the development of IBD. Our results suggest a higher prevalence of this mutation in Central European patients than in Southern, Northern Europe or America, may be due to the genetical differences of these populations.
Adult↗
Leiden mutation (as genetic) and environmental (retinoids) sequences in the acute and chronic inflammatory and premalignant colon disease in human gastrointestinal tract.
BACKGROUND: Tumor, calor, dolor, pallor and functio laesa are together involved in the different acute and chronic inflammatory processes. The processes involved in the inflammation are determined by differently acquired and hereditary factors. Recently the presence of a new genetic marker (Leiden point mutation) was found in Crohn's disease and ulcerative colitis. On the other hand, the GI mucosal integrity was proven on gastrointestinal mucosal damage to be produced by different chemicals, xenobiotics, drugs. In human observations, the serum level of retinoids (vitamin A, lutein, zeaxanthin, alpha-, beta-carotene) was proven in patients with chronic gastrointestinal inflammatory bowel disease. The aims of this study were (1) to measure the prevalence of Leiden mutation; (2) to identify the changes in the serum retinoid level in patients with Helicobacter pylori infection of the stomach (n=24), hepatitis C infection (n=75), ileitis terminalis (Crohn's disease; n=49), ulcerative colitis (n=35), colon polyposis (n=59) and adenocarcinoma in colon polyps (n=9), and 57 healthy persons were used in the control group; (3) to compare the directions of the changes in the measured parameters in the acute (H. pylori and hepatitis C infections), chronic (ileitis terminalis, ulcerative colitis) GI inflammatory diseases and in colon polyposis without and with malignisation. METHODS: The Leiden mutation was measured by the method of polymerase chain reaction, the retinoid level in the patient's serum was measured by high liquid cromathografic method (HPCL). RESULTS: (1) It has been found that the prevalence of Leiden mutation increased significantly in patients with ileitis terminalis (P<0.001), ulcerative colitis (P<0.001), colon polyposis (P<0.001) and with colon polyps with malignisation (P<0.01). (2) Serum level of vitamin A and zeaxantin were decreased significantly in all group of patients except for the group with H. pylori infections. (3) alpha- and beta-carotenes were found to be practically at the same level as those in the control groups, except in patients of colon polyps with malignisation. (4) The vitamin A, lutein, zeaxantin, alpha- and beta-carotenes were decreased in patients with ileitis terminalis. CONCLUSIONS: (1) The essential role of retinoids (carotenoids) as environmental factors are suggested for keeping GI mucosal integrity in human healthy subjects and patients. (2) Leiden mutation, as a genetic marker, can be used in the screening of patients with ileitis terminalis, ulcerative colitis and colon polyposis (without and with malignisation). (3) An opposite direction can be found between the increased prevalence of Leiden mutation and decrease of serum levels of retinoids in group of patients with ileitis terminalis, ulcerative colitis and colon polyposis (without and with malignisation).
Acute Disease↗
Comparison of different hypo-osmotic swelling solutions to select viable immotile spermatozoa for potential use in intracytoplasmic sperm injection.
The hypo-osmotic swelling test, originally developed as a diagnostic sperm test, is used to discriminate viable from non-viable spermatozoa for intracytoplasmic sperm injection (ICSI) in cases of complete asthenozoospermia. In the present study, three hypo-osmotic solutions were compared, i.e. (A) Jeyendran solution containing sodium citrate and fructose; (B) a mixture of 50% culture medium and 50% milli-Q water; and (C) milli-Q water. While both the percentage of swelling and vitality assessed by eosin Y remained unchanged after 5-30 min of sperm exposure to solutions A and B, incubation in water for only 5 min was in itself detrimental. Ten frozen-thawed donor samples and 10 asthenozoospermic patient samples were exposed to the three solutions for given periods of time. Percentages of swelling and the results of the eosin Y test were well correlated for solutions B and C, but only weakly correlated for solution A. Percentage viability was further assessed by eosin Y and motility of spermatozoa after 2 h and 24 h exposure to the three solutions was compared with unexposed control spermatozoa. While a significant decrease in both parameters was observed for all three solutions in comparison with the control, sperm quality was significantly higher after exposure to solution B than after exposure to solutions A and C. It may be concluded that solution B (composed of 50% culture medium and 50% water) is to be preferred for the selection of viable immotile spermatozoa for ICSI.
Cell Survival↗
Impaired vasoreactivity of the basilar artery system in patients with brainstem lacunar infarcts.
BACKGROUND AND PURPOSE: Diminished vasoreactivity (VR) has been evidenced in patients with hemispheric small vessel disease, however, there is no data regarding vertebrobasilar (VB) territory VR changes in patients with subcortical vascular encephalopathy located in the brainstem. Therefore, we compared the cerebral blood flow velocity (CBFV) responses of the VB system during different vasoregulatory challenges in healthy volunteers to those in patients with brainstem lacunar infarcts. METHODS: In 20 patients with brainstem lacunar infarcts and in 10 healthy volunteers the VR of the VB system was measured by analyzing the CBFV changes during different stimulation paradigms (ventilation, tilting and acetazolamide tests). During transcranial Doppler registration the systemic blood pressure and the expiratory partial CO2 pressure were monitored. RESULTS: During hypercapnia the VR was significantly higher in the control group than in the patient group (10.1 +/- 4.9 vs. 3.4 +/- 5.0 cm/s/kPa, p = 0.0025). In a subgroup of patients with mean baseline CBFV <25 cm/s the VR was 1.5 +/- 2.4 cm/ s/kPa, while patients with mean baseline CBFV >25 cm/s showed a significantly higher value (7.8 +/- 6.9 cm/s/kPa). Furthermore, in patients with mean baseline CBFV <25 cm/s the pulsatility index was significantly higher than in patients with mean baseline CBFV >25 cm/s (1.11 +/- 0.26 vs. 0.86 +/- 0.19, p = 0.0325), reflecting significantly higher vascular resistance in the former group. Although CBFV measurements during tilting and acetazolamide tests tended to support these findings, they showed no significant differences between patients and controls. CONCLUSION: Patients with cerebral microangiopathy involving the brainstem showed impaired VR in the VB flow territory in association with baseline CBFV.
Acetazolamide↗
Assessment of the pathological stages of Alzheimer's disease in thin paraffin sections: a comparative study.
The staging method proposed by Braak and Braak allows the objective and reliable assessment of Alzheimer-related neurofibrillary pathology. Originally the method was designed for 100-microm thick sections. However, the use of thick sections proved to present difficulties in a routine neuropathology laboratory. In order to adapt the staging method for thin paraffin-embedded sections, we performed an inter- and intrarater study analysing the reliability of the staging method in thin sections. Statistical analysis of the data provided by six independent examiners in two rating sessions reveal kappa values of 0.6-0.8 for both the interrater and the intrarater reliability. The average rate of mistake of the examiners was rarely bigger than a half stage. We conclude that the adapted staging method in thin sections is strongly reliable and we recommend it for staging purposes in institutions where the preparation of thick sections would be difficult.
Alzheimer Disease↗
Accuracy of clinical operational diagnostic criteria for Alzheimer's disease in relation to different pathological diagnostic protocols.
In this study we analysed the accuracy of two sets of clinical diagnostic criteria, the NINCDS/ADRDA and DSM-III-R, in relation to the currently used pathological diagnostic criteria for Alzheimer's disease (AD), the Khachaturian criteria, the Tierney A3 criteria and the CERAD protocol. The sensitivity of the individual clinical diagnostic criteria, NINCDS/ADRDA and DSM-III-R, is poor (34-58%) irrespective of the pathological diagnostic criteria applied for the definite diagnosis of AD. The combination of the NINCDS/ ADRDA 'possible' and 'probable dementia of the Alzheimer type' (DAT) categories has a high sensitivity (91-98%). However the combination resulted in very poor specificity (40-61 %). Thus, none of the clinical diagnostic criteria is satisfactory. We found similar results when we analysed the predictive value of these clinical diagnostic criteria. The positive predictive value of NINCDS 'probable DAT' category and that of the DAT diagnosis by DSM-III-R is very high (89-100%). This makes the use of these categories suitable for research purposes. However, the negative predictive value of both diagnoses is poor (33-63%), making these criteria unsuitable for diagnostic purposes in clinical practice.
Aged↗
Relationship between clinical and radiological diagnostic criteria for Alzheimer's disease and the extent of neuropathology as reflected by 'stages': a prospective study.
The distribution of pathology related to Alzheimer's disease (AD) is not uniform throughout the brain. Sites which have a predilection for the development of Alzheimer-type pathology are the limbic regions and neocortical association areas. The changes in these areas of the brain develop gradually, following a well-determined sequence that allows a pathological staging of the disease process. According to the staging hypothesis, the first pathological alterations develop in the transentorhinal and entorhinal regions. The neurofibrillary pathology then spreads into the hippocampus, but not until the final stages does it affect the neocortex. In this study we analyse the relationship between the pathological stages of AD, according ot the staging hypothesis, and the clinical diagnosis in a prospectively assessed patient group. Prediction of any given pathological stage from the clinical diagnosis was found to be poor. This may be partly due to the fact that additional pathologies can alter the clinical picture and severity of dementia in patients who are only in the initial stages of AD. Nevertheless, the NINCDS-ADRDA clinical criteria had a high sensitivity for detection of AD-related pathology: the 'probable AD' category included 22/38 (57.9%) of those in the late isocortical stage, while the 'possible AD' category included 19/23 (82.6%) of those in the limbic stage. Using proposed neuro-imaging protocols for improved identification of patients with AD-related pathology, we largely identified subjects in whom the extent of pathology had spread to the neocortex.
Aged↗
The progression of Alzheimer's disease from limbic regions to the neocortex: clinical, radiological and pathological relationships.
Alzheimer's disease (AD) is characterised by the gradual accumulation of neurofibrillary pathology in selected regions of the brain. Earlier studies indicate that the accumulation of neurofibrillary tangles is associated both with decline in patient's cognitive performance as well as with medial temporal lobe atrophy on CT scans. There are also indications that progression through the pathological stages of AD is associated with decline in cognitive functions. The results of this study indicate that progression of disease, especially beyond the boundaries of the limbic regions, is associated with marked decline in the cognitive performance of patients suffering from AD. However the clinical manifestations of early pathological stages are not so well defined. We also found that the atrophy of the medial temporal lobe on CT scans is related to the progression of pathology. Atrophy is most apparent when the disease reaches its isocortical stages and is not marked in the limbic stages of the disease. The additive effect of pathologies co-existing with AD is apparent in reduced cognitive scores, while the atrophy of limbic structures, as measured on CT scans, seems to be mainly attributable to AD-related pathology.
Aged↗
Diagnosing dementia: interrater reliability assessment and accuracy of the NINCDS/ADRDA criteria versus CERAD histopathological criteria for Alzheimer's disease.
We investigated the interrater reliability and accuracy of two independent medical doctors in using NINCDS/ADRDA criteria to classify 82 elderly subjects enrolled in OPTIMA, a longitudinal study investigating dementia. Kappa statistics revealed moderate agreement (0.5) in overall classification of dementia type, and almost perfect agreement (0.9) on the absence or presence of dementia. Combining NINCDS/ADRDA 'possible' and 'probable' Alzheimer's disease (AD) categories produced substantial agreement (0.7). Comparison with CERAD histopathological criteria for AD showed that combining 'possible' and 'probable' AD resulted in a high sensitivity and accuracy, but a low specificity. To increase specificity, the NINCDS/ADRDA 'probable AD' category should be used alone. An important finding was that the accuracy of diagnoses of AD made from the case notes alone was not different from the diagnoses obtained following active involvement with participants.
Aged↗
Constructional apraxia in Alzheimer's disease: association with occipital lobe pathology and accelerated cognitive decline.
The functional impact and progression of occipital lobe pathology in sporadic late onset Alzheimer's disease (AD) is barely explored. It is accepted that the primary and association visual areas are affected relatively late, in the neocortical stages of AD. We analysed 60 prospectively assessed AD patients in whom global cognitive deterioration and constructional apraxia were evaluated longitudinally using the CAMDEX. Radioactive immunohistochemistry was used to assess the amount of AD-related pathology in Brodmann areas 18 and 17. Braak staging of each case was also carried out. This study showed that in AD patients constructional apraxia is associated with higher expression of hyperphosphorylated tau. Additionally our findings indicate that early constructional apraxia is a predictor of accelerated cognitive decline in AD.
Age Factors↗
Staging of Alzheimer-type pathology: an interrater-intrarater study.
The staging method proposed by Braak and Braak is based on the sequential accumulation of neurofibrillary pathology in the cerebral cortex. Unlike the currently used diagnostic criteria for Alzheimer's disease (AD) it does not take into consideration the age of the patients and whether they were demented or not for the establishment of the pathological stage of the disease. To examine the interobserver reliability of the method we performed an inter- and intrarater study using the Braak staging method in 41 brains. The agreement between the examiners and between the diagnoses of the same examiner at different times was almost perfect, the kappa statistics reaching values above 0.90. These findings indicate that the staging, relying on the differential distribution of neuritic pathology in the brain in AD, is a reliable and reproducible method for the description of AD-related pathology. This makes it suitable for brain-banking and research purposes.
Aged↗
Hippocampal pathology reflects memory deficit and brain imaging measurements in Alzheimer's disease: clinicopathologic correlations using three sets of pathologic diagnostic criteria.
Neurofibrillary tangles (NFT), neuritic plaques and amyloid load were quantified in sections of the hippocampus at the level of the lateral geniculate body in 41 consecutive cases fulfilling pathological criteria for diagnosis of Alzheimer's disease (AD) and coming to autopsy after longitudinal study during life. A strong correlation was found between NFT density in the hippocampus and cognitive impairment scores obtained shortly before death, particularly with scores of memory impairment. Weaker and less consistent correlations were found for hippocampal neuritic plaques and amyloid load with cognitive/memory deficits. No significant correlations were found between hippocampal pathology and either age of onset or disease duration. All three measures of hippocampal pathology were inversely correlated with the minimum medial temporal lobe (MTL) width, a measure of the MTL atrophy made from temporal-lobe-oriented X-ray computed tomography scans performed during life; the strongest correlation being between atrophy of the MTL and NFT density in the hippocampus.
Alzheimer Disease↗