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Biomedical subjects

M Fiala

Publications and source records attributed to M Fiala.

At least 19 recordsLinked to original sources

The histopathology of Candida albicans invasion in neonatal rat tissues and in the human blood-brain barrier in culture revealed by light, scanning, transmission and immunoelectron microscopy.

The present studies examined the effects of Candida albicans yeast and hyphal morphologies on tissue pathologies and transmigration properties of the fungus in two experimental models: 1) an in vivo, neonatal rat model, and 2) a cell culture model of human brain microvascular endothelial cells (ECs) (BMVEC). We inoculated a hyphae-producing strain (CAI4-URA3) and a non-hyphae-producing strain (CAI4) of C. albicans into 4-10 day old rats and BMVEC cultures. Animals were inoculated by intraperitonal (i.p.), intranasal (i.n.), oral (p.o.) and intracerebral (i.c.) routes and several tissues were examined after 24-48 hrs. Rats inoculated i.p. with the hyphae-producing strain showed pathology in the kidneys, liver, spleen, and other tissues associated with inoculation tracks of the nose, and muscle and connective tissues of the abdominal wall. Few animals inoculated i.p., however, presented evidence of meningitis. The non-hyphae phase yeast produced neither tissue pathology nor meningitis. Animals inoculated i.c. with the hyphae strain after 1 and 3 hrs expressed minimal meningitis, with an increasing neutrophillic meningitis between 4 and 18 hrs after inoculation. At 18 hrs after i.c. inoculation, however, the inflammatory foci and brain pathology were extensive and demonstrated mycelia within the lateral ventricles associated with necrosis of adjacent brain tissue. Neutrophillic meningitis at this time period was pronounced. BMVEC co-cultured 1-2 hrs with both C. albicans strains showed EC phagocytosis of hyphae and blastospores into intercellular adhesion molecule-1 (ICAM-1)-labeled caveolae suggesting a transcellular role for ICAM-1 in the internalization process of C. albicans.

Animals↗

[Idiopathic premature ventricular complexes--catheter ablation as a therapeutic alternative].

UNLABELLED: Frequent isolated ventricular premature complexes (VPCs) in patients without major structural heart disease are generally associated with benign prognosis, however can lead to serious symptoms and also to the development of left ventricular dysfunction. Purpose of this study is to present mapping findings and immediate results of catheter ablation of frequent idiopathic VPCs, and evaluation of long-term clinical outcome and the role of catheter ablation in clinical practice. METHODS: Twenty-seven patients, aged 48 +/- 14 years without major structural heart disease, presenting with frequent VPCs, were investigated electrophysiologically in 28 procedures. Twenty-five patients underwent catheter ablation. RESULTS: In 19 patients, the ectopic focus was found in the right ventricular outflow tract (RVOT) and could be reached from the endocardial approach. In these patients, VPCs were successfully eliminated by the ablation. Comparison of 24-hour Holter ECG recordings showed complete elimination of the target VPCs in all the cases [18,483 +/- 12,790 (2,152-48,820)/17 +/- 10 (3-42) % VPCs before ablation vs. 94 +/- 219 (0-763)/0.01 +/- 0.2 (0-0.7) % VPCs after ablation]. In 5 patients, mapping revealed epicardial localization of the ectopic focus in the OT. Ablation endocardially from the RVOT failed in 2 of the patients, cryoablation epicardially from the venous system was partially successful in 1 patient, and no ablation was attempted in 2 patients. In another 3 patients, ectopic foci were found in other parts of the ventricles and ablation was completely successful in one case. During the 14 +/- 9 (1-34) month follow-up period, full elimination of the target VPCs and elimination or significant reduction of symptoms was achieved in 20 (74%) patients. The procedures were accomplished without complications and with fluoroscopy time of 8,2 +/- 5,9 minutes. CONCLUSION: Catheter ablation of frequent idiopathic VPCs was performed effectively and safely, particularly, if the ectopic focus was localized on the endocardial aspect of the RVOT. Efficacy of catheter ablation ofVPCs arising from the epicardium of ventricular OT or other atypical sites is limited by inaccessibility or proximity to the conduction system. Indication to more aggressive mapping and ablation methods like intrapericardial approach or ablation from inside the venous system should be always critically considered with regard to the symptoms or other clinical risk factors.

Adult↗

[Tachycardia-induced cardiomypathy: less usual causes, less usual treatment: 3 case-reports].

Tachycardia-induced cardiomypathy is a potentially reversible form of left ventricular dysfunction and heart failure that is often neglected in clinical practice. Three case-reports of tachycardia-induced cardiomyopathy associated with three different tachyarrhythmias, cured by catheter ablation, are presented. All cases were characterized by specific clinical conditions. Potential consequences of inadequate clinical analysis and treatment are discussed.

Cardiomyopathy, Dilated↗

[Sustained monomorphic ventricular tachycardia in patients with structural heart disease. Different arrhythmogenic substrates, different options of palliative and curative treatment in the era of three-dimensional mapping].

UNLABELLED: Results of catheter ablation of sustained monomorphic ventricular tachycardia (SMVT) in patients with structural heart disease are presented. METHODS: Catheter ablation was performed in 34 patients (5 females), aged 63 +/- 11 years. One (3%) patient had a permanent SMVT resistant to electric cardioversion, 13 (38%) patients had incessant SMVT, 4 (12%) patients had SMVT at least once a day, 9 (26%) patients at least once a week, and 7 (21%) patients at least once a month. Twenty-nine (85%) patients were treated with amiodarone. Twenty-seven (79%) patients had a history of remote myocardial infarction, 2 (6%) patients presented with dilated cardimyopathy, 4 (12%) patients had arrhythmogenic right ventricular cardimyopathy, and 1 (3%) patient was after surgery for tetralogy of Fallot. Left ventricular ejection fraction was 35 +/- 13%. Ablation was mostly performed as a palliative approach with the purpose to eliminate clinically significant forms of SMVT leading to frequent ICD discharges, respectively to the worsening of heart failure. Less frequently, ablation was accomplished as a curative therapy. For the SMVT ablation, electroanatomic mapping was used, and, target or substrate mapping and ablation or their combinations were employed. RESULTS: Clinical form of SMVT was successfully eliminated in 33 (97%) patients, all inducible ventricular tachyarrhythmias were eliminated in 14 (41%) patients. Any ventricular tachycardia did not recur in 29 (85%) patients during 22 +/- 17 months follow-up. Twenty-three (68 %) patients had eventually implanted ICD. Ablation was performed as a curative procedure in 11 (32 %) patients. Average procedure duration was 213 +/- 56 minutes, fluoroscopy time was 18 +/- 9 minutes, and number of radiofrequency applications was 23 +/- 13. CONCLUSION: Catheter ablation in patients with structural heart disease offers a highly effective method in elimination of clinical forms of SMVT. In long-term perspective, it is associated with low recurrence of any ventricular tachyarrhythmia. Efficacy of the ablation in elimination of all inducible forms of ventricular tachyarrhythmia is lower and therefore it should be mostly viewed as a palliative method, particularly in patients with left ventricular dysfunction and incomplete revascularization.

Aged↗

Psychosocial factors at the workplace--do they affect substance use? Evidence from the Tyrolean workplace study.

BACKGROUND: To determine the prevalence of drug consumption and the impact of workplace demands and burdens for substance use, we conducted a survey in a representative sample of Tyrolean employees. METHODS: This analysis was restricted to the 700 respondents (395 male, 305 female; age 18-60 years) in the year 2001 by telephone interview who hold a full-time or part-time job during the 6 months preceding the interview. We studied the use of antidepressants, benzodiazepines, analgetics. stimulants and phytotherapeutics. RESULTS: Of the whole sample, 5.6% employees (4.8% male, 6.6% female) stated that they take some kind of pills to cope with job demands. There was no statistically significant difference between males and females. Substance use depended to a great extent on the work atmosphere and job satisfaction. The prevalence of drug consumption increased from 3.7% (good atmosphere at work) and 3.3% (high job satisfaction) to 12.6% (bad atmosphere at work) and 42.9% (low job satisfaction ) (p = 0.019 and p = 0.001). The feeling of being a victim of bullying at work appears to be particularly destructive for the individuals' well-being. Only 4.1% of the employees who were not victims of bullying took drugs because of job problems, as compared with 20% of the bullying victims. DISCUSSION: Our results indicate that drug consumption as the consequence of workplace burdens is a frequent and serious problem with negative consequences for the life quality of the individuals and for the individuals' efficiency. Therefore, occupational medicine and employers should direct their attention to ensure the best possible work place structure and occupational conditions.

Adolescent↗

[Endothelial injury and activation of the coagulation cascade during radiofrequency catheter ablation].

GOAL OF STUDY: To identify the extent of systemic activation of the coagulation cascade and to evaluate thrombogenic effect of the radiofrequency catheter ablation. METHODS AND RESULTS: Markers of activation of the coagulation cascade (D-dimers [DD]), markers of activation of the fibrinolytic system (tissue plasminogen activator [t-PA] and its inhibitor [PAI-1]), and markers of endothelial damage (von Willebrand factor [vWf]) were monitored in 50 patients undergoing catheter ablation. Levels of these substances were identified in time T0--at the beginning of the examination, T1--after finishing diagnostic part of the electrophysiological study, T2--after finishing all applications of radiofrequency energy, and T3--24 hours after T2. Levels of vWf were significantly elevated in time T1 compared to values in T0 (p < 0.001) and were further elevating after finishing the procedure in time T2 (p < 0.05). Levels of t-PA were also elevated in time T1, however after application of the radiofrequency energy, further increase in T2 was nonsignificant. Concentrations of PAI-1 were in time T2 significantly lower compared to T1 values (p < 0.001). Levels of DD were significantly elevated during entire procedure and elevated levels persisted even 24 hours later (p < 0.001). Levels of vWf a t-PA in time T2 correlated with total time of application of radiofrequency energy. Significantly higher activation of the coagulation cascade was identified, in patients undergoing isolation of pulmonary veins compared to patients undergoing catheter ablation of other arrhythmias. In the subgroup of patients treated with anticoagulation before the intervention elevation of DD levels in times T1 and T2 was lower compared to patients who did not undergo any treatment (p < 0.05). CONCLUSION: The radiofrequency catheter ablations activate the coagulation cascade. Moreover, application of the radio frequency energy increases systemic thrombogenic state and this effect "depends on the dose". A risk group make patients undergoing catheter isolation of pulmonary veins.

Blood Coagulation↗

Therapeutic outcome of adjustable gastric banding in morbid obese patients.

We examined 77 obese patients treated with bariatric surgery in order to analyse treatment success, and compare those with a good or a poor outcome. The subjects, who were recruited one year after undergoing adjustable gastric banding, were asked questions concerning their sociodemographic status, postoperative course, past and present weight status, eating behaviours and difficulties in changing eating habits. Furthermore, we also used two body image questionnaires, and considered the patients' evaluations of positive and negative changes, as well as their wishes for the future. There were no preoperative differences between the 71% of patients in the good outcome group and the 29% in the poor outcome group. With regard to the postoperative course, the poor outcome group had more problems in adapting to new eating behaviours, experienced significantly more post-surgical complications, and had a persistently negative body evaluation. Both groups were satisfied with their achieved weight loss achieved, and their improved self-esteem and mobility. Adjustable gastric banding seems to be successful in inducing weight loss and allowing a better quality of life. However, factors such as postoperative complications, the ability and willingness to adopt new eating attitudes, and an improved body image seem to be crucial for therapeutic outcome.

Adaptation, Psychological↗

Neuroendocrine-immune surveillance of osteosarcoma: emerging hypothesis.

Osteosarcoma is a bone-forming cancer predominantly found in children and adolescents more often than in adults. Osteosarcoma of the gnathic apparatus is relatively rare in the young population, and this condition becomes a concern of clinical dentists for predominantly the middle-aged and aging patient groups. Osteosarcomas are invaded by lymphocytes, which exhibit signs of activation. The immune processes that are engaged within the malignant bone matrix involve the production of cytokines, which regulate the process of apoptotic programmed cell death. This paper discusses the mechanisms by which apoptosis of osteosarcoma cells is modulated by the neuroendocrine-immune system, and potential physiological implications.

Adolescent↗

[Treatment of atrioventricular accessory pathways using catheter ablation: analysis of immediate and long-term results at the end of the learning curve period].

UNLABELLED: Immediate and long-term results of catheter ablation of atrioventricular accessory pathways (AP) are presented. METHOD: One hundred and seventy-one patients aged 41.8 +/- 14.4 years underwent catheter ablation of 179 AP. Right and left AP occurred simultaneously in 3 patients; thus 65 ablation procedures for 57 rights AP in 57 patients were compared with 125 ablation procedures for 122 left AP in 117 patients. RESULTS: Including repeated procedures ablation was successful in 116 (99%) patients with left AP and in 57 (100%) patients with right AP. First catheter ablation failed in 4 (7%) patients with right AP and in 4 (3.4%) patients with left AP (p = NS). Two of these patients with left AP and all 4 pts with right AP had successful reablation. AP conduction recurred after successful ablation in 7 (12.3%) patients with right AP and in u 5 (4.1%) patients with left AP (p = 0.1). Three patients with right AP did not undergo another ablation, other 9 patients with AP recurrence had successful reablation. Procedure time during left AP ablation was shorter (159.6 +/- 70.7 vs. 183.4 +/- 75.6 min.; p = 0.02) and number of RF current deliveries was lower during left AP ablation (9.3 +/- 8.5 vs. 13.3 +/- 11.8; p = 0.008) compared to right AP ablation. Fluoroscopy time during left AP ablation (22.4 +/- 19.1 min.) did not significantly differ from that during right AP ablation (20.9 +/- 17.1 min.). Concealed AP was present in 13 (22.8%) patients with right AP and in 59 (48.4%) patients with left AP (p = 0.002). Anatomico-functional variant of AP occurred in 5 (8.8%) patients with right AP and in 4 (3.3%) patients with left AP (p = NS). Atrial fibrillation complicated ablation procedure in 9 (15.8%) patients with right AP and in 7 (5.7%) patients with left AP (p = NS). During 30.3 +/- 17 (2-60) months follow-up period tachyarrhythmia associated with the presence of an AP occurred in 3 patients with right AP and in 1 patient with unsuccessful ablation of left AP. None of these patients underwent repeated ablation. CONCLUSION: Successful ablation of AP can be achieved successfully in 100%. Catheter ablation of right AP is generally more difficult and primary ablation failure and AP conduction recurrence is nonsignificantly more often. Irregularity of the tricuspid annulus, instability of the ablation catheter, presence of the conduction system, higher occurrence of anatomico-functional AP variants and sustained atrial fibrillation during the ablation procedure represent the main causes of this finding.

Adolescent↗

Cyclooxygenase-2-positive macrophages infiltrate the Alzheimer's disease brain and damage the blood-brain barrier.

BACKGROUND: Monocyte/macrophages are known to infiltrate the brain of patients with HIV-1 encephalitis (HIVE). In Alzheimer's disease brain, the origin of activated microglia has not been determined. MATERIALS AND METHODS: We employed the antigen retrieval technique, immunocytochemistry, immunofluorescense, and confocal microscopy to identify macrophages and microglia in relation to amyloid-beta plaques and the blood-brain barrier in autopsy brain tissues from patients with Alzheimer's disease (AD) and HIVE. RESULTS: In both conditions, cyclooxygenase-2 positive macrophages and, to a lesser degree, T and B cells infiltrate brain perivascular spaces and neuropil. The macrophages are distinguishable from ramified microglia, and decorate the vessels at the sites of apparent of endothelial tight junction protein ZO-1 disruption. The macrophages also infiltrate amyloid-beta plaques, display intracellular amyloid-beta and are surrounded by amyloid-beta-free lacunae. Furthermore, the macrophages partially encircle the walls of amyloid-beta-containing vessels in amyloid angiopathy, and exhibit intracellular amyloid-beta but not paracellular lacunae. Significantly larger zones of fibrinogen leakage surround the microvessels in HIVE brain tissues compared with AD tissues (P = 0.034), and AD tissues have significantly greater leakage than control tissues (P = 0.0339). The AD group differs from a normal control age-matched group with respect to both the area occupied by CD68 (P = 0.03) and cyclooxygenase-2 immunoreactive cells (P = 0.004). CONCLUSION: In both HIVE and AD, blood-borne activated monocyte/macrophages and lymphocytes appear to migrate through a disrupted blood-brain barrier. The lacunae around macrophages in amyloid-beta plaques but not in vessel walls are consistent with the ability of macrophages to phagocytize and clear amyloid-beta deposits in vitro.

AIDS Dementia Complex↗

[Determination of the end-point of the radiofrequency linear lesion in the subeustachian isthmus and its relation to treatment of atrial flutter and fibrillation. Acute and long-term results in 90 patients].

UNLABELLED: Complete subeustachian isthmus (isthmus) block created with radiofrequency (RF) linear lesion eliminates type I. atrial flutter (AFL). The end-point of the procedure is measurable. PATIENTS AND METHOD: Ninety patients (21 F) aged 57.6 +/- 12.5 years underwent RF catheter ablation for AFL. Twenty patients had significant structural heart disease (SHD). Atrial fibrillation (AF) was previously documented in 34 (37.8%) patients. Complete isthmus block served as the end-point of the procedure. RESULTS: Following the first ablation procedure complete isthmus block was achieved in 81 (90%) patients and incomplete isthmus block in 7 (7.8%) patients. First procedure failed in 2 (2.2%) patients. AFL recurred in 6 (6.8%) patients, in 4 (4.9%) out of 81 patients with complete isthmus block and in 2 (28.5%) out of 7 patients with incomplete isthmus block. After repeated successful ablation and creation of complete isthmus block in these 6 patients and in 1 patient with previous ablation failure, complete isthmus block was achieved in 84 (93.3%) patients, incomplete isthmus block in 5 (5.6%) patients and ablation was unsuccessful in 1 patient. During 21 +/- 10.6 (6-45) month follow-up since the last ablation AFL did not recur in any of 89 (98.9%) patients with complete or advanced incomplete isthmus block. AF occurred in 39 (43.3%) patients. Incidence of AF was significantly higher in patients without SHD and with AF previously documented or induced (group 2) (25/43; 58.1%) compared to patients without SHD and no AF documented or induced (group 1) (6/27; 22.2%) (p < 0.01). AF occurred in 40% patients with SHD (group 3), which did not significantly differ from any of the former two groups of patients. In this group AF occurred in 10 out of 12 (83.3%) patients with AF documented prior to ablation, which was significantly more compared to 1 (12.5%) patient out of 8 without documented AF (p < 0.01). CONCLUSION: Complete conduction block over the subeustachian isthmus during catheter ablation has a clearly measurable end-point and represents effective method in permanent cure of AFL. Clinical benefit is reduced by AF, particularly in patients, in whom the arrhythmia was documented prior to ablation. In these patients catheter ablation of AFL can be considered a first step to combined treatment with previously ineffective antiarrhythmic drugs and with other ablation strategies.

Adolescent↗

Cocaine activates redox-regulated transcription factors and induces TNF-alpha expression in human brain endothelial cells.

Cocaine abuse is frequently associated with cerebrovascular pathology. Although the cellular and molecular mechanisms of these alterations are not fully understood, they may involve oxidative injury or dysfunction of brain microvascular endothelial cells. To test this hypothesis, total glutathione levels, activation of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), as well as induction of the TNF-alpha gene expression were determined in human brain microvascular endothelial cells (HBMEC) exposed to cocaine. Exposure of HBMEC to cocaine resulted in a dose-dependent depletion of total glutathione levels. In addition, cocaine markedly activated redox-regulated transcription factors, NF-kappaB and AP-1. Activation of these transcription factors was accompanied by induction of AP-1- or NF-kappaB-dependent transcription, as measured by dual luciferase assay in HBMEC transfected with the AP-1- or NF-kappaB-responsive reporter constructs. Furthermore, HBMEC treatment with cocaine induced a dose-dependent expression of the tumor necrosis factor-alpha (TNF-alpha) gene. These results indicate that exposure to cocaine can trigger inflammatory pathways via activation of redox-sensitive transcription factors and induction of expression of the inflammatory genes in HBMEC. These events may contribute to the cerebrovascular insults observed in cocaine-abused patients.

Brain Chemistry↗

Essential role of HIV type 1-infected and cyclooxygenase 2-activated macrophages and T cells in HIV type 1 myocarditis.

HIV-1 cardiomyopathy has become a major cause of death in AIDS patients, but its pathogenesis is unclear. We used an antigen retrieval technique and immunostaining to investigate the hearts of 15 AIDS patients, of whom 3 had dilated cardiomyopathy. Immunocytochemistry shows infiltration of the left ventricular myocardium with mononuclear cells, ranging from minimal to diagnostic of myocarditis. The infiltrates include macrophages and CD3(+) and CD8(+) T cells. The tight junction protein ZO-1 is disrupted at the site of monocyte-macrophage vascular penetration and the coronary vessels show fibrinogen leakage in the hearts of AIDS patients, but not in the normal heart. A subset of infiltrating macrophages is doubly positive for cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase. HIV-1 peptides gp120 and Nef are expressed in macrophages and T cells, but not in cardiomyocytes. COX-2 is expressed by both gp120-positive and gp120-negative macrophages. The hearts of AIDS patients separate into those showing minimal infiltrates with low COX-2 expression and those with dense infiltrates and high COX-2; all failing hearts are in the latter group. These data suggest that COX-2-activated and HIV-1-infected monocyte-macrophages and T cells play a crucial role in the progression of HIV-1 myocarditis to HIV-1 cardiomyopathy.

Brain↗

Actions of endotoxin and morphine.

In summary, our current studies show that treatment with a bacterial endotoxin, lipopolysaccharide (LPS), induces the expression of mu opioid receptors in the rat mesentery. This induction may be mediated through IL-1's actions on mu opioid receptors. Morphine stimulates the expression of adhesion molecules in human brain microvascular endothelial cells (HBMEC) isolated from pathological tissues. Under pathological conditions, mu opioid receptor-dependent pathways may be modulated through the induction of mu opioid receptors, especially in endothelial cells. Treatment with morphine increases [14C]-inulin permeability of an in vitro microvascular endothelial cell barrier, and decreases endothelial cell viability. Morphine pre-treatment potentiates the effects of LPS on endothelial cell viability, and on LPS induction of IL-1beta secretion from 1alpha, 25-dihydroxy-vitamin D3-treated HL-60 human leukemia cells. Previously, it was suggested that an opioid-dependent pathway may be involved in the recovery from endotoxin shock (D'Amato and Holaday, 1984). Induction of mu opioid receptors by treatment with high doses of endotoxin suggests that mu opioid receptor-dependent pathways may be involved in mediating the response to endotoxins. Taken together, these data provide valid evidence for an association between endotoxins and opioid actions. These studies suggest that opioid-dependent pathways in disease or in endotoxin exposure may be modified by cytokine-induced expression of opioid receptors in endothelial cells. In a pathological condition, an alteration of the opioid-dependent pathway may be expected. When morphine is used for its therapeutic values, it may, indeed, potentiate LPS' effects in an adverse manner. From a clinical perspective, these data indicate that morphine and an endotoxin, such as LPS, may interact in a positive 'feedback type of reaction, and thereby modulate the body's immune responses with unexpected and detrimental results.

Animals↗