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Biomedical subjects

K Kiss

Publications and source records attributed to K Kiss.

At least 19 recordsLinked to original sources

Role of phospholipase C-gamma in NGF-stimulated differentiation and gene induction.

The PC12 phaeochromocytoma cell line provides a useful model to study nerve growth factor-induced neuronal differentiation. The central signaling route of this process is mediated by the Ras-dependent extracellular signal-regulated kinase cascade. However, Ras-independent pathways are also stimulated by nerve growth factor and may contribute to differentiation signaling. One mediator for Ras-independent signal transduction in PC12 cells is phospholipase C-gamma that generates the second messengers diacylglycerol and inositol-trisphosphate. To probe the possible involvement of this enzyme in nerve growth factor-promoted differentiation, we used the phospholipase C inhibitor U73122 and the inositol-trisphosphate-receptor inhibitor Xestospongin C. Our results show that both chemicals block nerve growth factor-promoted neurite outgrowth, but the blockage of phospholipase C does not inhibit nerve growth factor-induced expression of c-fos, zif268 and transin genes. In addition, induction of these genes by nerve growth factor plus dibutyryl-cAMP is comparable in wild-type PC12 cells as well as in cells in which both Ras- and phospholipase C-gamma-mediated pathways are inhibited. The phospholipase C-gamma pathway thus belongs to those nerve growth factor receptor-originated signaling routes that contribute to the biological response of PC12 cells to nerve growth factor, but its gene activating potential does not have a major role in its neuritogenic effect.

Animals↗

Sodium salicylate inhibits NF-kappaB and induces apoptosis in PC12 cells.

Sodium salicylate (NaSal) is an effective analgetic and antiinflammatory drug. Beside its well-known inhibitory effect on the cyclooxigenase enzymes, it influences the activity of other signal transduction proteins including nuclear factor kappa B (NF-kappaB) transcription factor. NF-kappaB is found in the cytoplasm bound to an inhibitory protein, inhibitory kappa B (IkappaB). After its phosphorylation, IkappaB is degraded and the released NF-kappaB translocates into the nucleus. Sodium salicylate inhibits the degradation of IkappaB, thus, NF-kappaB activation cannot occur. According to previous observations, the inhibition of this activation can lead to apoptosis. The main goals of this study were to demonstrate that inhibition of NF-kappaB by sodium salicylate decreases the viability of rat phaeochromocytoma PC12 cells and to investigate the nature of cell damage and death. PC12 cells were treated with different concentrations of sodium salicylate (1-20 mM). Higher concentrations (10-20 mM) killed PC12 cells in a dose-dependent manner. The assessments were done by direct cell counting in a Burker chamber and by the WST-1 cytotoxicity assay. We also found a decreased NF-kappaB activity after sodium salicylate treatment by electrophoretic mobility shift assay (EMSA). The cells treated with sodium salicylate were undergoing apoptosis as seen on our records obtained by time-lapse videomicroscopy as well as shown by DNA fragmentation experiments. The decreased DNA binding activity of NF-kappaB indicates that the inhibition of NF-kappaB can play a role in these processes.

Animals↗

Assessment of the safety and efficacy of the novel tetrapeptide ITF-1697 on infarct size after primary PTCA in acute myocardial infarction: a randomised, placebo-controlled pilot trial.

OBJECTIVE AND DESIGN: ITF-1697 is a chemically modified LYS-Pro tetrapeptide that corresponds to sequence 113-116 of C-reactive protein. Previous studies have demonstrated significant anti-ischaemic and antithrombotic activity of this tetrapeptide. The aim of this prospective, randomised, double-blind study in patients with acute myocardial infarction undergoing coronary revascularisation was to investigate the safety and efficacy of prolonged intravenous (i.v.) infusion of ITF-1697 at different doses on reduction of infarct size, as assessed by radionuclide imaging. PATIENTS AND METHODS: Injection of technetium-99m (Tc99m) was followed by injection of ITF-1697 or placebo bolus and 24-hour infusion in patients with acute myocardial infarction. Percutaneous transluminal coronary angioplasty (PTCA) was performed and succeeded by radionuclide imaging. A second Tc99m injection and radionuclide imaging was performed 7 days after the PTCA or at hospital discharge. The primary efficacy variable was set as the ratio between the myocardial salvage (size of the initial perfusion defect minus the final size of the infarct) and the initial area at risk (myocardial salvage index). Twenty-three patients were included in the study protocol, of whom nine were randomised to the ITF-1967 dose 1 group (loading dose 55 microg/kg i.v., infusion 0.5 microg/kg/min for 24 hours), a further nine to the ITF-1697 dose 2 group (loading dose 110 microg/kg i.v., infusion 1.0 microg/kg/min for 24 hours), and the remaining five to the placebo group. RESULTS: The defined safety variables (adverse events, laboratory parameters, vital signs and clinical outcome) exhibited no relationship to the application of ITF-1697. Comparison of myocardial salvage index revealed no statistical difference within the three groups (p = 0.65). Hypothesis testing on the myocardial salvage as well as the empirical and bias-correct confidence intervals (CIs) revealed significant differences between the ITF-1697 dose 2 group and the placebo group (95% CI 2.75, 18.07). CONCLUSION: The application of the tetrapeptide ITF-1697 during acute myocardial infarction to reduce infarct size was found to be feasible and safe in this pilot trial.

Adult↗

Molecular pathogenesis of Coxiella burnetii in a genomics era.

The agent of acute and chronic Q fever, Coxiella burnetii, occupies a unique niche among intracellular pathogens. The mechanisms the organism employs to cause disease are unclear but involve persistence in a parasitophorous vacuole and the subsequent host response. Studies designed to model molecular mechanisms of pathogenesis have relied upon indirect evidence for testing the role of virulence factors since methods for generation of defined mutations have not been developed. Evidence suggests replication involving a developmental lifecycle is critical for intra- and extracellular survival but this cycle is incompletely defined. It has been proposed that survival in the phagolysosomal-like parasitophorous vacuole requires specific iron uptake systems, secretion of enzymes to detoxify the compartment (catalase and SOD), and down-regulation of an oxidative burst (acid phosphatase). Studies to test these potential virulence mechanisms can be accelerated with the recent development of the complete genome sequence for the prototype acute disease isolate, Nine Mile. Proteins differentially expressed during the developmental cycle can more readily be identified with MALDI-TOF description of proteomic profiles. Genes encoding secreted Cu/Zn SOD, catalase, and acid phosphatase are predicted and can be tested for function and expression. An iron regulon is predicted based upon Fur-regulated open reading frames. The specific role the iron-regulated genes play in iron acquisition can be tested. Confirmation of the iron regulon and others can be tested using microarrays based upon the genomic ORF predictions. These are examples of how we are rapidly changing the experimental approaches used to investigate C. burnetii to improve our understanding of the biology of this unusual and highly adapted organism.

Coxiella burnetii↗

Gender differences in panic disorder symptoms and illicit drug use among young people in Hungary.

The authors have investigated the frequency of illicit drug use, and spontaneous and drug-provoked panic disorder symptoms in Hungarian youths. A semi-structured self-reporting questionnaire (with questions about drug usage and the persistence of some DSM-IV panic disorder symptoms) was filled out in discos/nightclubs, secondary schools and universities. Almost 17% of the total sample (n = 1298) reported on illicit drug-use at least once in their life, and this rate was significantly higher among males. Regardless of the illegal drug use 14.6% of the total sample reported on four or more DSM-IV symptoms of panic disorder, and this rate was significantly higher among females. Analyzing the panic disorder symptoms only among drug-users (n = 219), the frequency of persons with four or more anxiety symptoms was 14.1% before drug use, and it increased to 30.6% during the period of drug use (P < 0.001). The findings support previous results showing (i) higher prevalence of anxiety symptoms among females; (ii) higher rate of illicit drug use among males; and (iii) a possible anxiety-provoking effect of illicit drugs.

Adult↗

Increase of chlamydial LPS antibodies in patients with acute coronary syndrome without detection of chlamydial DNA in atherectomy samples.

BACKGROUND: Chlamydia pneumoniae, a respiratory pathogen, has been connected with the pathogenesis of coronary artery disease (CAD). Previous studies indicated a correlation between antibodies to chlamydial LPS and the risk of cardiovascular disease. The aim of this study was to determine whether C. pneumoniae plays a direct role in the pathology of acute coronary syndromes (ACS). METHODS AND RESULTS: Twenty-five consecutive patients (median age 56 years) with ACS (17 acute myocardial infarction, 8 unstable angina) were included in the study and underwent directional coronary atherectomy. Tissue and blood samples were subjected to conventional and real time polymerase chain reaction (PCR) for C. pneumoniae. Antichlamydial immunoglobulin A (IgA) and IgG were examined by LPS enzyme immunoassay (EIA) and microimmunofluorescence (MIF) at intervention and on days 20, 45 and 180 thereafter. DNA of C. pneumoniae was detected neither in atherectomy samples nor in peripheral blood. Serologic results with LPS EIA showed a rapid and significant increase in specific IgA and IgG within 20 days including seroconversion in six cases (4 IgA, 2 IgG). Positive IgA and IgG MIF levels (30% and 87%) remained stable throughout the observation period. CONCLUSIONS: We conclude that negative detection of chlamydial DNA excludes a direct role of chlamydia in ACS. Our findings of rapid LPS antibody increase suggest a role of chlamydial LPS antigen which appears to be released during the acute event e.g. from damaged tissue, indicating a renewed accessibility to the immune system. An indirect role of chlamydia in the further aetiologic process of CAD seems possible.

Acute Disease↗

An iatrogenic coronary arteriovenous fistula causing a steal phenomenon: an intracoronary Doppler study.

We present the case of a 67-year-old man in whom a guidewire broke at rotablation of the right coronary artery, creating an iatrogenic aneurysmal arteriovenous fistula to the coronary sinus. Successful Doppler wire-guided fistula occlusion by percutaneous coil embolization lead to normalization of coronary blood flow and relief of the patient's symptoms. Myocardial ischemia in this patient may have been due to a steal phenomenon caused by coronary artery fistulae, as suggested by blood flow velocity data obtained before and after fistula occlusion.

Aged↗

Anxiety disorders comorbidity in bipolar I, bipolar II and unipolar major depression: results from a population-based study in Hungary.

BACKGROUND: The aim of this study was to analyze the lifetime comorbidity between DSM-III-R anxiety disorders in separate subgroups of patients with major depression, bipolar II and bipolar I disorder in a community sample of a Hungarian population. METHODS: Randomly selected subjects (aged between 18 and 64 years, N=2953) were interviewed by the Diagnostic Interview Schedule (DIS) which generated DSM-III-R diagnoses. RESULTS: The prevalence of generalized anxiety disorder, agoraphobia and simple phobia was the highest among bipolar II patients (20.8, 37.5 and 16.7%, respectively), social phobia was most prevalent in (nonbipolar) major depression (17.6%), while the rate of panic disorder was the same in the (nonbipolar) major depressive and bipolar II subgroups (12.4 and 12.5%, respectively). Bipolar I patients showed a relatively low rate of comorbidity. CONCLUSIONS: The findings support previous results on the particularly high rate of lifetime comorbidity between anxiety disorders and unipolar major depression and particularly bipolar II illness. LIMITATIONS: Underestimation of the prevalence of bipolar II disorder by the diagnostic methodology used, resulting in a small number of bipolar II cases, lack of analysis of data by gender, no data on obsessive-compulsive disorder.

Adolescent↗

Adaptive remodeling of the infarct-related artery is associated with recurrent ischemic events after thrombolysis in acute myocardial infarction.

BACKGROUND: Recurrent ischemic events occur during the hospital stay of 7-32% of patients after successful thrombolytic treatment of acute myocardial infarction (AMI). OBJECTIVE: To define the association between postinfarction angina pectoris and the clinical, angiographic, and intravascular ultrasound (IVUS) parameters of the infarct-related artery for consecutive prospectively included patients. METHODS: Clinical, qualitative, and quantitative angiographic and IVUS data for 64 patients (56 men, aged 53+/-12 years) with thrombolysis of AMI were analyzed. All patients underwent coronary angiography and pre-interventional IVUS measurement electively within 1 month of AMI or at the time of the occurrence of postinfarction angina pectoris. Classification as adaptive or constrictive remodeling was according to whether the cross-sectional area of a vessel was larger or smaller than that of the proximal or distal reference segment. RESULTS: Nineteen of the 64 patients (29.7%) suffered from recurrence of ischemic events (group 1), whereas 45 patients (60.3%, group 2) remained free from symptoms. In univariate analyses, multivessel disease (42 versus 24%, P= 0.0236) and adaptive remodeling (63 versus 24%, P= 0.0032) were found to occur more commonly among patients in group 1. The patients in group 1 exhibited larger total vessel cross-sectional areas than did the patients in group 2 (17.5+/-4.2 versus 14.9+/-6.1 mm2, P = 0.0556). In multivariate regression analysis, adaptive remodeling proved to be a significant predictor (P = 0.0145) of the recurrence of ischemic events after thrombolysis of AMI. CONCLUSIONS: Adaptive remodeling of the infarct-related artery is associated with early postinfarction angina pectoris after thrombolysis of AMI.

Adult↗

Directional coronary atherectomy: the Vienna experience.

BACKGROUND: Several multicenter trials have shown excellent results for directional coronary atherectomy (DCA) in a selected patient cohort. To prove the applicability of this method in daily clinical routine and a nonselected patient cohort, we analyzed 46 consecutive cases performed at our catheterization lab. METHODS: DCA was performed as a routine procedure in 45 suitable patients. Balloon dilatation or stent implantation postprocedure was accomplished only in case of unsatisfactory results. Quantitative coronary angiography was achieved pre- and postprocedure as well as at 6-month follow-up. RESULTS: Optimal atherectomy < 20% residual stenosis was reached in 24 (52%) of 46 target lesions and a residual stenosis < 50% in 46 (100%) lesions. Procedure-related complications occurred in three (6%) patients (one major complication, death, < 24 hours, 2%; two minor complications, pseudoaneurysm, 4%). The 6-month angiographic follow-up revealed a binary restenosis rate of 29% (n = 11). Ten out of 11 restenotic lesions required revascularization. When patients were stratified in two groups according to their preprocedural minimal lumen diameter (MLD), this parameter proved to be a very strong predictor of outcome. The percentage of restenosis was significantly higher in patients with an MLD > 1.60 mm compared to patients with a smaller MLD (54% vs 19.3%; P < 0.0001). Reference vessel diameter preprocedure did not differ significantly. CONCLUSIONS: Our study demonstrated that DCA is a suitable technique for the daily clinical routine, as the rates of complications and restenosis were similar to that in a highly selective patient cohort. Additionally, our study showed that patient selection should include preprocedural analysis of MLD in order to achieve optimal results. Therefore, atherectomy yielded comparable results to other conventional techniques and may be used instead of or in combination with them.

Aged↗

Ultra-short pulse (femtosecond) laser surgery: initial use in LASIK flap creation.

The highly localized tissue effects of low energy femtosecond duration (ultrashort) laser pulses may be used to create three-dimensional intrastromal resections with micron precision and minimized collateral tissue damage. A surgical laser system that produces and delivers such pulses has been developed and tested clinically for creation of a corneal flap in LASIK. Expanded evaluation of this technology in this and additional keratorefractive applications is currently underway.

Corneal Stroma↗

Building capacity for awareness and risk factor identification in the community: the blood pressure assessment program of the Calgary Fire Department.

In 1995, the Calgary Fire Department developed a program to assess blood pressure in community fire stations, selected businesses and public venues. The program has gradually expanded. Currently, all 30 fire stations across Calgary, Alberta assess blood pressures for the public seven days per week throughout the year. Since 1995, there have been 10,883 measurements in 3477 people. Most people (2106) assessed had hypertensive readings, and 72 had readings greater than 220 mmHg systolic or greater than 120 mmHg diastolic, and were referred for immediate medical assessment. The program has been recently integrated into a more global vision for the prevention and control of cardiovascular disease in Calgary. Future plans include offering lipid assessments, assisting other communities to adopt the program and using the program to provide physical measures (of blood pressure, glucose, total and high density lipoprotein cholesterol, height and weight) to an ongoing questionnaire that surveys the health of Calgarians. The history of the program, its training methods, quality control, preliminary results and future plans are presented in detail to provide an example of a community-based program that could aid in the detection, monitoring and awareness of hypertension.

Adult↗

Pre-existing arterial remodeling is associated with in-hospital and late adverse cardiac events after coronary interventions in patients with stable angina pectoris.

OBJECTIVES: The goal of this study was to investigate the association between the atherosclerotic arterial remodeling and the incidence of cardiac events after coronary interventions in patients with stable angina. BACKGROUND: The local mode of de novo atherosclerotic remodeling is associated with plaque vulnerability and clinical symptoms. It may, therefore, reflect plaque morphology influencing the long-term outcome after coronary interventions. METHODS: Quantitative angiography and intravascular ultrasound were obtained in 244 patients with stable angina before and after single-vessel revascularization. On the basis of the lesion and the reference segment vessel size, patients were categorized into three groups (adaptive [AR], constrictive [CR] and intermediate [IR] remodeling). The lesion was analyzed for lumen, total vessel and plaque areas. Clinical follow-up was obtained at a mean period of 7.7+/-3.7 months. RESULTS: Patients with CR had a higher rate of in-hospital complications (10.9% vs. 2.9% and 2.7% in group CR vs. AR and IR, p = 0.035). In contrast, patients with AR had the highest rate of major adverse cardiac events (MACE) (44.3% vs. 25.5% in IR and 28.1% in CR, p = 0.024) with a predominance of revascularization at follow-up. Both target lesion restenosis (p = 0.036) and nontarget lesion de novo stenosis (p = 0.007) occurred more frequently in this group. Adaptive remodeling was a significant predictor of MACE in multivariate analysis. CONCLUSIONS: Adaptive remodeling is associated with a higher rate of MACE, target lesion restenosis and nontarget de novo stenosis. This finding may be due to differential responses of the adaptively remodeled vessel to revascularization and a generally accelerated course of systemic atherosclerosis.

Aged↗

Successful emergency percutaneous cardiopulmonary support during coronary intervention in an 80-year old patient.

In an 80-year old patient with acute coronary syndrome emergency institution of stand-by percutaneous cardiopulmonary support (PCPS; Bio-Medicus; Medtronic Inc, Minneapolis MN) for hemodynamic collapse in the cardiac catheterization laboratory resulted in successful hemodynamic stabilization and enabled safe performance of a complex coronary intervention. Weaning from PCPS was effectuated after 4 hours total extracorporal circulation time. Despite development of a systemic inflammatory response syndrome and prolonged weaning from mechanical ventilation the patient could be discharged from the intensive care unit after 14 days and eventually from hospital another 28 days later with favorable outcome. Although an increased complication rate with prolonged rehabilitation has to be taken into account percutaneous cardiopulmonary support may constitute a live-saving option even in selected elderly patients.

Aged↗

Enteropathic arthritis in the sacroiliac joint. Imaging and differential diagnosis.

OBJECTIVES: A new high resolution computed tomography (HRCT) scoring system of sacroiliac joint (SIJ) involvement in enteropathic arthritis is introduced. PATIENTS AND METHODS: SIJ's of 100 patients were studied. A total of 25 patients presented with pain syndrome, 25 with suspicious seronegative spondylarthritis, 25 with inflammatory bowel diseases and 25 without joint or bowel diseases, as a control group. HRCT was carried out in all 100 patients. For comparison, a plain film radiography (PFR), conventional CT (slices of 10 mm) and bone scan were used. RESULTS: Quantitative differences: In the pain syndrome group, there were no erosions identified neither intraarticular calcifications. Disc degeneration was seen in 12/25 cases. In 4/25 patients, vacuum phenomena appeared in the SIJ. In 3/25 patients, ventral capsular calcification occurred in the ventral sacroiliac ligament (anterior capsule complex). In the seronegative spondylarthritis group, 16/25 patients had positive findings, while PFR documented erosions only in 3/25 cases. In the bowel diseases group, erosions were detected in 17/25 cases with HRCT, while the plain film was positive only in three cases and in seven cases the findings were questionable. Intraarticular calcification with erosion was documented in three cases and in seven cases without erosion. The bone scan was positive in 7/25 of this cases, but in 5/7 there was mismatching with HRCT. Important new finding was the HRCT detected erosion which was not detected on BS but was obvious on Anti-Granulocyte-Antibody scintigraphy. In the control group, only degenerative changes were seen in 4/25 cases and no erosions. CONCLUSION: HRCT is: (1) the reliable imaging of definitive (often 'cold stage') sacroileitis; (2) gives optimal detection of erosion; and (3) appears to be the only method in the documentation of calcifications in the posterior ligamental portion of the SIJ.

Arthritis↗

Human immunodeficiency virus-associated malignant lymphoma in eastern Denmark diagnosed from 1990-1996: clinical features, histopathology, and association with Epstein-Barr virus and human herpesvirus-8.

The clinicopathological features of human immunodeficiency virus (HIV)-associated lymphoma were investigated in a retrospective study of 85 adult patients in eastern Denmark diagnosed during the period 1990-1996. The possible pathogenetic role of Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) in these tumours was also studied. Seventy patients (82%) presented with extranodal disease and 26 (31%) had CNS involvement at diagnosis. Diffuse large cell B-cell lymphoma was the most frequent histological subtype, comprising 65 of 79 cases available for microscopic re-evaluation (82%) and including 20 of 23 evaluable patients with CNS lymphoma (87%). EBV RNA was demonstrated by in situ hybridization in 51 of 65 evaluable tumours (79%) and in 14 of 16 cases (88%) with CNS-lymphoma. Three cases showed a T-cell phenotype. The presence of HHV-8 DNA was analysed by PCR in 32 cases. A strong band consistent with tumour cell infection was detected in only one case, weaker bands being seen in 4 cases. None of these patients had primary effusion lymphomas. In conclusion, Danish AIDS-related lymphomas are of predominantly high-grade B-cell type with extranodal localization and atypical presentation. Our results provide further evidence that EBV plays a major role in the pathogenesis of large cell AIDS-related lymphoma, whereas HHV-8 does not appear to contribute significantly to the development of solid lymphomas in this group of patients.

Adult↗

[Magnesium in coronary artery disease--is there evidence?].

The role of magnesium in coronary artery disease has been evaluated extensively during the last three decades. The intravenous application of magnesium in acute coronary syndromes is of major importance, the beneficial effects of magnesium in acute myocardial infarction have been underlined in several studies. The promising results of LIMIT-2 could not be confirmed by the data of ISIS-4. A world-wide, multicenter trial (MAGIC) has been set up in order to evaluate the optimal patient cohort as well as the ideal dose regimen for the application of intravenous magnesium in patients with acute MI. Furthermore, magnesium is of significance in the pathomechanism of reperfusion injury and reduction of malign arrhythmia in the critical acute phase of MI, if applied intravenously. In stable coronary artery disease oral magnesium therapy has proven beneficial effects too.

Arrhythmias, Cardiac↗

[Significance of magnesium in cardiac arrhythmias].

Magnesium is of great importance in cardiac arrhythmias. It increases the ventricular threshold for fibrillation. Sinus node refractoriness and conduction in the AV node are both prolonged. Main indications for intravenous application of magnesium are Torsade de pointes tachycardias, digitalis toxicity induced tachyarrhythmias and multifocal atrial tachycardias. Additionally, patients with ventricular arrhythmias due to overdoses of neuroleptics or tricyclic antidepressants may profit from i.v. magnesium. Monomorphic ventricular tachycardias and ventricular arrhythmias refractory to class III antiarrhythmics have been shown to respond to i.v. magnesium. Recent publications have documented that perioperative use of magnesium can reduce the incidence of arrhythmic events on the atrial and ventricular level. Oral magnesium has been used for many years in patients with symptomatic extrasystoles. Studies show that the incidence of extrasystoles as well as patients' symptoms are reduced during oral magnesium therapy.

Administration, Oral↗