Intraperitoneally administered IgG from patients with amyotrophic lateral sclerosis or from an immune-mediated goat model increase the levels of TNF-α, IL-6, and IL-10 in the spinal cord and serum of mice.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that involves the selective loss of the upper and lower motor neurons (MNs). Neuroinflammation has been implicated in the pathogenesis of the sporadic form of the disease. We earlier developed immune-mediated animal models of ALS and demonstrated humoral and cellular immune reactions in the nervous system and in the sera of patients and animals. The accumulation of immunoglobulin G (IgG), an elevated intracellular level of calcium, ultrastructural alterations in the MNs, and activation of the microglia were noted in the spinal cord of ALS patients. Similar alterations developed in mice inoculated intraperitoneally with IgG from ALS patients or from an immune-mediated goat model. METHODS: We have now examined whether the intraperitoneal injection of mice with IgG from sporadic ALS patients or from immunized goats with the homogenate of the anterior horn of the bovine spinal cord is associated with changes in the pro-inflammatory (TNF-α and IL-6) and anti-inflammatory (IL-10) cytokines in the spinal cord and serum of the mice. The levels of cytokines were measured by ELISA. RESULTS: Intraperitoneally administered IgG from the ALS patients induced subclinical signs of MN disease, while the injection of IgG from immunized goats resulted in a severe respiratory dysfunction and limb paralysis 24 h after the injections. Significantly increased levels of TNF-α and IL-10 were detected in the spinal cord of the mice injected with the human ALS IgG. The level of IL-6 increased primarily in the serum. The IgG from the immunized goats induced highly significant increases in the levels of all three cytokines in the serum and the spinal cord of mice. CONCLUSIONS: Our earlier experiments had proved that when ALS IgG or IgG from immune-mediated animal models was inoculated into mice, it was taken up in the MNs and had the ability to initiate damage in them. The pathological process was paralleled by microglia recruitment and activation in the spinal cord. The present experiment revealed that these forms of IgG cause significant increases in certain cytokine levels locally in the spinal cord and in the serum of the inoculated mice. These results suggest that IgG directed to the MNs may be an initial element in the damage to the MNs both in human ALS and in its immune-mediated animal models.

Role of triggering pulmonary veins in the maintenance of sustained paroxysmal atrial fibrillation.

BACKGROUND: Triggers from thoracic veins have been implicated not only in the initiation, but also in the perpetuation of paroxysmal atrial fibrillation (PAF). To investigate their role we studied the distribution and stability of dominant frequencies (DFs) during PAF and the response to isolation of the triggering pulmonary vein (PV). METHODS AND RESULTS: Triggering structures inducing PAF were identified during isoproterenol challenge in 26 patients (15 males, 55 ± 8.5 years). During sustained PAF, sequential recordings were made with a decapolar circular mapping catheter from each PV and the left atrial posterior wall (LAPW), together with coronary sinus (CS) and right atrium (RA) recordings. DF was determined using fast Fourier transformation. Recordings were repeated after ≥15 minutes of PAF. Radiofrequency ablation was directed first at the triggering PVs. PAF initiated from the PVs in 24 patients and from RA in two. There was a significant frequency gradient from the triggering structure to the PVs, CS, LAPW, and RA (P < 0.0001). During the second recording, DF decreased at all sites (P < 0.02), but the frequency gradient remained unchanged. Despite isolation of the triggering PV, PAF continued in 53% of patients, although DF measured in the CS was lower. AF termination occurred with contralateral PV isolation in half of the remaining patients and further AF slowing was noted in the rest. CONCLUSIONS: Triggering structures harbor the fastest activity during sustained PAF pointing to their leading role in arrhythmia perpetuation. However, nontriggering PVs also seem to contribute to PAF maintenance.

Reimplantation and long-term mortality after transvenous lead extraction in a high-risk, single-center cohort.

PURPOSE: The use of cardiac implantable electronic devices (CIEDs) has increased significantly over the last decades. With the development of transvenous lead extraction (TLE), procedural success rates also improved; however, data regarding long-term outcomes are still limited. The aim of our study was to analyze the outcomes after TLE, including reimplantation data, all-cause and cause-specific mortality. METHODS: Data from consecutive patients undergoing TLE in our institution between 2012 and 2020 were retrospectively analyzed. Periprocedural, 30-day, long-term, and cause-specific mortalities were calculated. We examined the original and the revised CIED indications and survival rate of patients with or without reimplantation. RESULTS: A total of 150 patients (age 66 ± 14 years) with 308 leads (dwelling time 7.8 ± 6.3 years) underwent TLE due to pocket infection (n = 105, 70%), endocarditis (n = 35, 23%), or non-infectious indications (n = 10, 7%). All-cause mortality data were available for all patients, detailed reimplantation data in 98 cases. Procedural death rate was 2% (n = 3), 30-day mortality rate 2.6% (n = 4). During the 3.5 ± 2.4 years of follow-up, 44 patients died. Arrhythmia, as the direct cause of death, was absent. Cardiovascular cause was responsible for mortality in 25%. There was no significant survival difference between groups with or without reimplantation (p = 0.136). CONCLUSIONS: Despite the high number of pocket and systemic infection and long dwelling times in our cohort, the short- and long-term mortality after TLE proved to be favorable. Moreover, survival without a new device was not worse compared to patients who underwent a reimplantation procedure. Our study underlines the importance of individual reassessment of the original CIED indication, to avoid unnecessary reimplantation.

Randomized trial of intracardiac echocardiography during cavotricuspid isthmus ablation.

UNLABELLED: Randomized Trial of ICE During CTI Ablation. INTRODUCTION: Despite a high success rate, radio-frequency ablation (RFA) of the cavotricuspid isthmus (CTI) can be unusually challenging in some cases. We postulated that visualization of the CTI with intracardiac echocardiography (ICE) could maximize the success rate, decrease the procedure and ablation time, and minimize the radiation exposure. METHODS AND RESULTS: In our prospective, randomized study, we included 102 patients scheduled for CTI ablation. We randomized patients in 2 groups: guided only by fluoroscopy (n = 52) or ICE-guided (n =50) group. Procedure time, fluoroscopy time, and the time spent for RFA were significantly shorter, radiation exposure (dose-area product-DAP) and the sum of delivered radio frequency energy were significantly lower in the ICE-group (68.06 ± 15.09 minutes vs 105.94 ± 36.51 minutes, P < 0.001, 5.54 ± 3.77 minutes vs 18.63 ± 10.60 minutes, P <0.001, 482.80 ± 534.12 seconds vs 779.76 ± 620.82 seconds, P = 0.001 and 397.62 ± 380.81 cGycm(2) vs 1,312.92 ± 1,129.28 cGycm(2) , P < 0.001, 10,866.84 ± 6,930.84 Ws vs 16,393.56 ± 13,995.78 Ws, P = 0.048, respectively). Seven patients (13%) from the fluoroscopy-only group crossed over to ICE-guidance because of prolonged unsuccessful RFA and were all treated successfully. Four vascular complications and 2 recurrences were equally distributed between the 2 groups. CONCLUSIONS: ICE-guided ablation of the CTI significantly shortens the procedure and fluoroscopy time, markedly decreases radiation exposure, and time spent for ablation in comparison with fluoroscopy-only procedures. At the same time, visualization with ICE allowed successful ablation in challenging cases. (J Cardiovasc Electrophysiol, Vol. 23, pp. 996-1000, September 2012).

Electrogram analysis at the His bundle region and the proximal coronary sinus as a tool to predict left atrial origin of focal atrial tachycardias.

AIMS: Early activation at the His bundle (HB) region or proximal coronary sinus (CS) during focal atrial tachycardias (FATs) often necessitates biatrial mapping. Analysis of CS electrograms (EGMs) consisting of a near-field (N) component from CS musculature and a far-field (F) component from left atrial (LA) myocardium can uncover LA activation preceding right atrial (RA) activation. A similar pattern might be observed at the HB. METHODS AND RESULTS: Eight patients underwent RA and LA pacing testing the hypothesis that N and F components originating from the RA and LA septum are present in the HB atrial EGM (Pacing group). In this group N preceded F (N-F sequence) in all, while F preceded N (F-N sequence) in seven of eight patients during RA and LA pacing, respectively. Twenty-seven patients with FAT demonstrating earliest activation at the HB or proximal CS during limited RA mapping were also studied (FAT group). Two observers analysed the EGMs at the earliest site during FAT. They found an N-F sequence in 17 (94%) and 16 (89%) of 18 RA FAT and an F-N sequence in seven (78%) and eight (89%) of nine LA FAT, respectively. The F-N sequence predicted the need for LA access with a sensitivity of 78 and 89% and a specificity of 94 and 89%. CONCLUSION: Near-field and F components from RA and LA activation can be identified in the HB atrial EGM. Earliest atrial EGM analysis at the HB or CS can predict the need for LA access during FAT ablation.

Polymorphisms of the ApoE, HSD3B1, IL-1beta and p53 genes are associated with the development of early uremic complications in diabetic patients: results of a DNA resequencing array study.

Genetic polymorphisms of the genes involved in angiogenesis, the inflammatory cascade or apoptosis control can influence the chronic complications of diabetic patients. Parallel evaluation of multiple genetic polymorphisms became available with the development of DNA resequencing arrays. We aimed to develop a 16-gene, 18,859-nucleotide resequencing array to analyze the genetic background of uremic and gastrointestinal complications. DNA was isolated from 10 ml of peripheral blood of 41 non-uremic and 37 uremic patients with type II diabetes mellitus (DM); 32 suffering from gastric erosion complications. An Affymetrix Customseq Resequencing array was developed containing a total of 37 PCR products of selected genes. Confirmatory analysis was performed for 5 known polymorphisms by RFLP and for 4 others by capillary sequencing. Statistical analysis was performed using the Fisher's exact test. Correlations between the DNA resequencing array and the confirmatory methods were 96% for RFLP and 99.4% for capillary sequencing. The genetic polymorphisms of the ApoE, HSD3B1, IL-1beta and p53 genes were found to be significantly different (p<0.05) between the uremic and non-uremic diabetes group. In regards to the gastric erosion complications of the diabetic uremic patients, the A17708T polymorphism of the p53 intron 10 was found to have a statistically significant (p<0.05) role. In conclusion, DNA sequencing arrays can contribute to a multiparameter genetic analysis yielding highly correlating results using a single method in patients suffering type II DM.

Association between dissociated firing in isolated pulmonary veins and the initiation and maintenance of atrial fibrillation.

BACKGROUND: Whether dissociated firing (DiFi) in isolated pulmonary veins (PVs) implies arrhythmogenicity of the particular PVand, therefore, a better outcome of PV isolation (PVI) for paroxysmal atrial fibrillation (PAF) is debated. METHODS: Thirty-one patients undergoing their first PVI for PAF were studied. Isoproterenol was infused for induction, and the triggering PV was identified. During sustained PAF, sequential recordings were made with a decapolar circular mapping catheter from each PV. The dominant frequency (DF) was determined using fast Fourier transformation. Spontaneous DiFi was monitored for 30 min after PVI. RESULTS: PAF was triggered by the PVs in all patients. Fourteen (45 %) patients had DiFi after PVI in at least one PV. It was recorded most commonly from the left upper (84 %) and lower (67 %), less commonly from the right upper (31 %) PV. Out of the 23 PVs with DiFi, 13 (57 %) showed sporadic ectopic beats while 10 (44 %) had sustained ectopic rhythm or isolated tachycardia. There was no difference in size between PVs with or without DiFi (5.9±1.2 vs. 5.6±1.0 cm ostial perimeter, p=0.40). Triggering PVs more commonly showed any DiFi, compared to nontriggering PVs (68 vs. 27 %, p=0.003) and more commonly had sustained DiFi (53 vs. 0 %, p<0.001). During PAF PVs with any DiFi showed faster maximal DF compared to PVs without DiFi (7.1±1.3 vs. 5.9±1.1 Hz, p=0.001). Higher maximal DF was recorded in PVs with sustained versus sporadic DiFi versus PVs without DiFi (7.5 ±0.9 vs. 6.8±1.6 vs. 5.9±1.1 Hz, respectively, p=0.002). Patients with DiFi after PVI had a longer mean time to recurrent PAF compared to those without DiFi (52 vs. 32 months, p=0.048). CONCLUSIONS: Dissociated firing in isolated PVs is associated with their role in the initiation and maintenance of PAF.

Should the Aortic Root Be the Preferred Route for Ablation of Focal Atrial Tachycardia Around the AV Node?: Support From Intracardiac Echocardiography.

OBJECTIVES: The purpose of this study was to determine the optimal approach to focal atrial tachycardia originating from around the atrioventricular node. BACKGROUND: Focal atrial tachycardia (FAT) demonstrating earliest activation around the atrioventricular (AV) node during right atrial (RA) mapping has been eliminated by ablation at the RA para-Hisian region, from the left atrium (LA) or the noncoronary aortic cusp (NCC). However the optimal approach has not been determined. METHODS: We conducted a retrospective analysis of a consecutive series of 148 patients undergoing catheter ablation for FAT between 2006 and 2014 in our institution. RESULTS: Earliest activation was recorded in the peri-AV nodal region during RA mapping in 34 patients (23%). Of these, 7 patients (20.5%) had successful ablation at the RA septum, using either radiofrequency (n = 4) or cryoenergy (n = 3). Seven FATs (20.5%) were ablated from the LA at the region of the aortomitral continuity, and 20 patients (59%) had successful ablation in the NCC, including 1 patient with a recurrence after a temporarily successful cryoablation from the RA. The proportion of the 3 approaches in this series showed a significant temporal evolution and overall frequency favoring ablation in the NCC (p = 0.011 for time trend and 0.013 for actual vs. expected frequencies). Intracardiac echocardiography proved superior catheter stability with the NCC approach. There were 2 cases of atrioventricular block and 1 recurrence after RA ablation versus no complications or recurrent FAT with NCC and LA approaches. CONCLUSIONS: Most peri-AV nodal FATs can be safely and effectively ablated from the NCC. The strategy of preferential NCC approach avoids RA para-Hisian ablation with the accompanying risk of AV block.

Impaired adaptation to left atrial pressure increase in patients with atrial fibrillation.

BACKGROUND OR PURPOSE: Episodes of left atrial (LA) pressure increase predispose to atrial fibrillation (AF). The adaptation of LA mechanical function and electrophysiology to pressure elevation in healthy adults, and in patients with AF, is largely unknown. METHODS: Eleven patients with left-sided accessory pathway (controls) and 16 patients with paroxysmal AF undergoing catheter ablation were studied. LA pressure (LAP) was recorded through transseptal catheterization, while speckle tracking-derived peak LA longitudinal strain (PALS) was measured using transthoracic echocardiography. Stiffness index (SI) was calculated as mean LAP/PALS. Effective refractory period (ERP) of the LA was determined during simultaneous atrioventricular (AV) pacing and during atrial pacing. RESULTS: At baseline, AF patients had higher LA pressure (mean LAP 8.3 ± 4.7 vs. 5.1 ± 3.1 mmHg, p = 0.048), reduced LA mechanical function (PALS 15.1 ± 5.1 vs. 21.6 ± 6.2 %, p = 0.006, SI 0.69 ± 0.75 vs. 0.28 ± 0.22, p = 0.015), and longer LA ERP (242.3 ± 33.4 vs. 211.7 ± 15.6 ms, p = 0.017). Mean LAP was increased to the same extent by AV pacing in controls and AF patients (mean change 12.6 ± 7.4 vs. 12.6 ± 7.5 mmHg, p = 0.980). At the same time PALS decreased (from 15.1 ± 5.1 to 11.6 ± 3.3 %, p = 0.008), SI increased (from 0.69 ± 0.75 to 1.29 ± 1.17, p < 0.001) and ERP shortened (from 242.3 ± 33.4 to 215.9 ± 26.3 ms, p = 0.003) in AF patients, while they remained unchanged in controls. CONCLUSIONS: The stiffened LA in patients with AF responds to acute pressure elevation with an exaggerated increase in wall tension and decrease in ERP, which is not seen in the normal LA. This may underlie the propensity for AF during episodes of atrial stretch in these patients.

Effects of Helicobacter pylori infection on gastric inflammation and local cytokine production in histamine-deficient (histidine decarboxylase knock-out) mice.

UNLABELLED: Helicobacter pylori infection in humans causes gastritis. The infection elicits a complex immune response in which the activation of mast cells and histamine release is of particular importance. Histamine further promotes the immune response and stimulates gastric acid secretion. The inflammatory effects of H. pylori can be studied in intragastrically infected mice. The aim of this study was to compare the local cytokine responses of histamine-deficient, histidine decarboxylase knock-out (HDC KO) and wild-type (WT) mice following H. pylori infection. METHODS: H. pylori was administered intragastrically to HDC KO and WT mice. The animals were infected three times in a 1-week-period and were sacrificed 8 weeks after the first intervention. The local TNF-alpha, IL-6 and IL-10 cytokine levels in gastric mucosal specimens were determined by ELISA. Gastric mucosa sections were also analysed for histological signs of inflammation. To investigate the antibody response following H. pylori infection, the total anti-H. pylori IgG and the ratio of IgG1/IgG2a isotypes were determined in the serum by ELISA. RESULTS: H. pylori induced considerable cytokine production in the infected groups. The TNF-alpha and IL-6 levels were significantly higher in the WT mice than in the HDC KO mice, whereas the IL-10 levels did not differ between the groups. Anti-H. pylori IgG was detected only in the infected groups and the titre was higher in the WT mice. A higher IgG1/IgG2a ratio was observed in the H. pylori infected HDC KO group. Histological analysis revealed that the grades of inflammation were less severe in the infected HDC KO animals. CONCLUSIONS: The results suggest that H. pylori induces lower TNF-alpha and IL-6 secretion in the gastric mucosa in the HDC KO mice than in the WT animals, while the levels of induction of IL-10 were similar. The imbalance between Th1/Th2 is less pronounced in the HDC KO mice, which might explain the milder inflammation in the gastric mucosa. These results provide further information on the role of histamine in the pathomechanism of H. pylori-induced gastritis.

Inhibitory action of a new proton pump inhibitor, trifluoromethyl ketone derivative, against the motility of clarithromycin-susceptible and-resistant Helicobacter pylori.

We previously reported that a trifluoromethyl ketone derivative, 1-(2-benzoxazolyl)-3,3,3-trifluoro-2-propanone (TF18), exhibited the potent antibacterial activity against Helicobacter pylori, but had no urease activity. In order to clarify the mechanism of anti-H. pylori action of TF18, we evaluated the growth and motility of TF18 on clarithromycin-susceptible H. pylori (CSHP) and -resistant H. pylori (CRHP). An effective proton pump inhibitor (TF18) had remarkable dose-dependent antibacterial activity and was able to inhibit the flagellar motor of both CSHP and CRHP isolates. The antimotility effect of TF18 was more pronounced at subinhibitory concentration in CRHP than in CSHP. The swimming (the forward motion) was more sensitive to the inhibition than the tumbling. Based on the results, it is supposed that TF18 works as an uncoupler similar to the 'clutch' in a biological motor, in which counterclockwise rotation is more sensitive to the effect of TF18 than the clockwise rotation.

Local and peripheral cytokine response and CagA status of Helicobacter pylori-positive patients with duodenal ulcer.

The mucosal production of TNF-alpha, IL-6, IL-8, IL-10 and nitrotyrosine was investigated in H. pylori-positive patients with duodenal ulcer (DU). The concentrations of these cytokines in gastric antrum mucosal specimens from patients infected with H. pylori (n = 40) were determined by ELISA and compared with data on mucosal specimens from H. pylori-negative patients (n = 12). Nitrotyrosine was determined by ECL Western blotting. It was additionally investigated whether the tissue levels of the cytokines correlated with the peripheral cytokine levels, and the CagA status of the patients. The local TNF-a, IL-6 and IL-8 concentrations in the antral biopsy samples were significantly higher (p < 0.001) in the patients infected with H. pylori than in the samples from the H. pylori-negative subjects. There was a negative correlation between the TNF-alpha and IL-10 concentrations. Further more, in 23 of the 40 biopsy specimens, considerable nitrotyrosine production was detected by ECL Western blotting. There was no significant difference in peripheral TNF-a and IL-6 production between the DU patients and healthy blood donors (n = 100; 58% of whom were also H. pylori-positive). Only the in vitro IL-8-producing capacity was higher in the peripheral blood of the DU group after ex vivo induction with H. pylori. CagA positivity was demonstrated in 39 (97.5%) of the 40 patients with DU, and in 41 (70.7%) of the 58 H. pylori-positive, healthy blood donors. This study suggests that besides the bacterial virulence factor, the host response, with an increased mucosal production of inflammatory cytokines and reactive oxygen and nitrogen species could be relevant to the gastric pathophysiology in H. pylori-induced DU. There is no generalized cytokine overproduction in these DU patients, but the moderate increase in in vitro IL-8 production might be of pathophysiological importance.

Genetic polymorphism of interleukin-8 (IL-8) is associated with Helicobacter pylori-induced duodenal ulcer.

BACKGROUND AND AIMS: Helicobacter pylori infection almost invariably causes chronic gastritis, but only a proportion of the infected subjects develop peptic ulcers. The local inflammation associated with H. pylori infection is characterized by an increased production of the proinflammatory cytokines IL-1-B, IL-6, IL-8 and TNF-alpha. Since such cytokine production is often determined by the genetic polymorphism of regions regulating cytokine gene expression, we investigated the relationship between TNF-alpha and IL-8 polymorphisms and the development of duodenal ulcer disease. We also sought a correlation between the promoter polymorphism of the lipopolysaccharide (LPS) receptor CD14 and the formation of peptic ulcer, because CD14 plays a crucial role in the initiation of the cytokine cascade. METHODS: Genomic DNA extracted from the peripheral blood of 69 patients with H. pylori-positive duodenal ulcer disease and 47 H. pylori-positive healthy controls was analyzed for TNF-alpha -308 promoter polymorphism by RFLP, and for IL-8 -251 polymorphism by ARMS. Genetic polymorphism within the promoter of the CD14 gene was identified using the LightCycler instrument via melting point analysis. RESULTS: No significant correlation could be revealed between the TNF-alpha and CD14 promoter polymorphisms and the clinical outcome of H. pylori infection. The IL-8 A/T heterozygote mutant variant was detected with a significantly higher frequency (65.22%) among the ulcer patients than among the healthy, H. pylori-positive blood donors (36.17%), while the frequency of the normal allelic genotype (TT) was significantly higher in the control group (44.6% vs 15.9%). CONCLUSION: Analysis of the genetic predisposition to enhanced cytokine production revealed a significant association only for the IL-8 polymorphism. This observation draws attention to the possible importance of IL-8 polymorphism as a genetic predisposing factor in the pathomechanism of H. pylori-induced duodenal ulcer disease, and to the relative protection from duodenal ulcer disease that is associated with the TT genotype.

Characterization of a novel multifunctional resveratrol derivative for the treatment of atrial fibrillation.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk for stroke, heart failure and cardiovascular-related mortality. Candidate targets for anti-AF drugs include a potassium channel K(v)1.5, and the ionic currents I(KACh) and late I(Na), along with increased oxidative stress and activation of NFAT-mediated gene transcription. As pharmacological management of AF is currently suboptimal, we have designed and characterized a multifunctional small molecule, compound 1 (C1), to target these ion channels and pathways. EXPERIMENTAL APPROACH: We made whole-cell patch-clamp recordings of recombinant ion channels, human atrial I(Kur), rat atrial I(KACh), cellular recordings of contractility and calcium transient measurements in tsA201 cells, human atrial samples and rat myocytes. We also used a model of inducible AF in dogs. KEY RESULTS: C1 inhibited human peak and late K(v)1.5 currents, frequency-dependently, with IC50 of 0.36 and 0.11 µmol·L(-1) respectively. C1 inhibited I(KACh)(IC50 of 1.9 µmol·L(-1)) and the Na(v)1.5 sodium channel current (IC50s of 3 and 1 µmol·L(-1) for peak and late components respectively). C1 (1 µmol·L(-1)) significantly delayed contractile and calcium dysfunction in rat ventricular myocytes treated with 3 nmol·L(-1) sea anemone toxin (ATX-II). C1 weakly inhibited the hERG channel and maintained antioxidant and NFAT-inhibitory properties comparable to the parent molecule, resveratrol. In a model of inducible AF in conscious dogs, C1 (1 mg·kg(-1)) reduced the average and total AF duration. CONCLUSION AND IMPLICATIONS: C1 behaved as a promising multifunctional small molecule targeting a number of key pathways involved in AF.

Surgical technique and the mechanism of atrial tachycardia late after open heart surgery.

INTRODUCTION: Diverse atrial tachycardias (ATs) can develop after open heart surgery. The aim of our study was to examine the determinants of the mechanism of postoperative AT. METHODS AND RESULTS: One hundred patients with AT occurring at least 3 months after open heart surgery were studied. Patients were grouped according to the atrial incision applied at the time of surgery. During 127 electrophysiology procedures, 151 ATs were studied. Eighty-eight patients had cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL), 49 patients had at least one non-CTI-dependent AFL and 11 patients had focal AT. While CTI-dependent AFL was equally prevalent across groups, the finding of a non-CTI-dependent AFL was progressively more common as more extensive atriotomy was applied (p < 0.001). Among patients who had right atrial (RA) operations, RA incisional tachycardia was the most common non-CTI-dependent circuit, while the finding of perimitral or left atrial (LA) roof-dependent AFL was associated with LA atriotomy (p = 0.002 and p = 0.041, respectively). After adjustment for possible confounders, surgical group remained independent predictor of non-CTI-dependent AFLs (p < 0.001). No predictor was identified for focal AT, which originated from typical predilection sites and in 36% from the vicinity of surgical scar. Radiofrequency ablation was highly effective for all ATs, but the recurrence rate of AFL and atrial fibrillation was high at 22% and 27%, respectively, during 19 ± 15 months of follow-up. CONCLUSION: While CTI-dependent AFL is the most common AT late after open heart surgery, atypical AFL becomes progressively more common with more extensive atriotomy. Right atrial incisional tachycardia is the dominant non-CTI-dependent AFL after opening of the RA, while a perimitral or roof-dependent LA circuit can be expected after LA operations.

Intracardiac echocardiography in a case with previous failed cavotricuspid isthmus ablation.

The Eustachian ridge (ER) can present an obstacle to cavotricuspid isthmus (CTI) ablation. We describe a case, where intracardiac echocardiography revealed a prominent ER as a likely reason for a previous failed CTI ablation and guided the looping of the ablation catheter around the ER, resulting in an ultimately successful ablation.

T-251A polymorphism of IL-8 relating to the development of histological gastritis and G-308A polymorphism of TNF-alpha relating to the development of macroscopic erosion.

OBJECTIVES: Genetic variations of the inflammatory IL-8 and TNF-alpha genes can influence the outcome of gastric alterations. Our aims were to determine the prevalence and effect of the T-251A functional polymorphism of IL-8 and the G-308A polymorphism of TNF-alpha in histological and macroscopic gastric diseases related to Helicobacter pylori infection. METHODS: Genomic DNA was extracted from biopsy samples from patients with gastritis (n=86, H. pylori positive=41), atrophy (n=32, H. pylori positive=13), intestinal metaplasia (IM) (n=43, H. pylori positive=22) and from histologically negative patients (n=57). The samples were divided by macroscopic diagnosis into erosion and negative groups. The T-251A polymorphism was examined with the amplification refractory mutation system method; the G-308A polymorphism was determined by the polymerase chain reaction-restriction fragment length polymorphism method. For statistical evaluation, Fischer's exact test was used. RESULTS: In the case of T-251A of IL-8, the frequency of the A/A genotype was significantly increased in gastritis (P=0.049) and IM (P=0.038) groups as compared with the histologically negative ones. No relationship was found between macroscopic erosions and H. pylori infection. In the case of G-308A, the G/G genotype frequency was statistically increased in erosions as compared with negative groups (P=0.035). No difference in the distribution of G-308A genotypes in relation to histological alterations and the H. pylori infection was observed. CONCLUSIONS: The effect of the polymorphism of IL-8 seems to be relevant in the pathogenesis of histological gastritis and IM, and the effect of the polymorphism of TNF-alpha is relevant in the pathogenesis of macroscopic erosive gastritis.

Polymorphism of the heat-shock protein gene Hsp70-2, but not polymorphisms of the IL-10 and CD14 genes, is associated with the outcome of Crohn's disease.

OBJECTIVE: In Crohn's disease (CD) a Th-1 dominant immune reaction is induced, which could be associated with genetic predisposition. Several previous studies have investigated the roles of CD14, heat-shock protein (Hsp)70 and IL-10 gene polymorphisms in the development of the disease. The results are contradictory and inter-racial differences are implicated. Therefore, this phenomenon was evaluated in well-documented Caucasian patients with CD in order to verify the clinical importance of these polymorphisms. MATERIAL AND METHODS: The genomic DNA of 133 patients with CD and that of 75 healthy controls were examined. CD was divided into subgroups according to the Vienna classification. An arbitrary classification system based on disease severity was also applied, which was determined according to the therapeutic intervention. The CD14 (-159 C-->T) promoter gene polymorphism was investigated by melting-point analysis. The IL-10 (-1082 G-->A) and Hsp70-2 (1267 A-->G) gene polymorphisms were detected by RFLP (restriction fragment length polymorphism). RESULTS: None of the allele frequencies of the examined polymorphisms differed significantly between the patient and control populations. Neither the CD14 nor the IL-10 polymorphisms exhibited any correlation with the development or with the progression of the disease. With regard to Hsp70-2 gene polymorphism, those patients who carry at least one A allele have a significantly lower probability of the need for surgical intervention. CONCLUSIONS: Allele A of the Hsp70-2 gene may be associated with a less severe form of CD, suggesting the clinical value of the genotype assessment. The genetic determination of the defense mechanisms in CD appears to be associated with the polymorphism of the Hsp70-2 gene rather than that of the CD14 or IL-10 genes.