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Biomedical subjects

E Hertervig

Publications and source records attributed to E Hertervig.

16 recordsLinked to original sources

Atrioventricular conduction: a determinant for the manifestation of ventricular preexcitation in patients with Wolff-Parkinson-White syndrome.

The relation between the atrioventricular conduction properties of the atrioventricular node and the anterograde conduction ability over the accessory pathway in the Wolff-Parkinson-White syndrome has never been studied. Atrioventricular nodal characteristics were studied in 285 patients with manifest and 204 with concealed accessory pathway who underwent radiofrequency ablation, and compared with 146 controls. First and second degree atrioventricular block was observed in 13 (5%) preexcitation patients after ablation, compared with none in concealed accessory pathway (P=0.001) and control patients (P=0.006). The atrial-His intervals in preexcitation patients (88 +/- 20 ms) was significantly longer than in concealed accessory pathway (76 +/- 15 ms, P<0.0001) and control patients (77 +/- 15 ms, P=0.0007), as was PR intervals (165 +/- 25 versus 149 +/- 20 and 150 +/- 21 ms, P<0.0001, respectively) even after excluding those with atrioventricular block. Significant differences in PR and atrial-His intervals were not observed between concealed accessory pathway and control patients. More preexcitation patients had ventriculoatrial dissociation than had patients in the other groups. The results indicate that atrioventricular block is not uncommon in preexcitation patients and a relatively long atrioventricular conduction time is an electrophysiological prerequisite for the manifestation of preexcitation in the Wolff-Parkinson-White syndrome.

Adult↗

Global repolarization sequence of the ventricular endocardium: monophasic action potential mapping in swine and humans.

The aim of this study was to evaluate the global sequence of repolarization over the ventricular endocardium. Disturbances in myocardial repolarization are associated with the genesis of arrhythmias. However, little is known about the global sequence of repolarization. Monophasic action potentials (MAPs) were recordedfrom 61 +/- 18 LV and/or RV sites in ten healthy pigs and from 43 +/- 15 LV or RV sites in eight patients using the CARTO system. Local activation time (AT), end-of-repolarization (EOR) time, and MAP duration were calculated and three-dimensional global maps of AT, EOR, and MAP duration constructed. LV maps were obtained from all ten pigs and RV maps from three pigs. Five RV maps and five LV maps were obtained from the eight patients. (1) EOR sequence was recognizable in 12 of 13 pig maps and in all the patient maps. (2) EOR followed the sequence of activation in 12 of 13 pig maps and 8 of 10 patient maps. (3) The longest MAPs were recorded in or near the earliest activation area, and the shortest ones in or near the latest activation area in all the pig maps and in nine often and eight often patient maps, respectively. (4) In all maps, MAP duration and AT were negatively correlated, and EOR and AT positively correlated. In conclusion, repolarization gradients exist over the pig and the human ventricular endocardium. The activation sequence is a determinant for the repolarization sequence. The magnitude of the progressive MAP shortening with progressively later activation, relative to local AT, is a critical factor governing the direction and pattern of the EOR.

Action Potentials↗

Further evidence of localized posterior interatrial conduction delay in lone paroxysmal atrial fibrillation.

AIMS: Prolongation of interatrial conduction time has been reported in patients with paroxysmal atrial fibrillation (PAF). The study objective was to localize the region of the conduction delay in patients with lone PAF. METHODS AND RESULTS: Twenty-one patients with lone PAF and 23 patients with AV nodal re-entrant tachycardia ablation without history of PAF (control group) were recruited. Endocardial recordings were made during sinus rhythm and programmed atrial stimulation. The authors measured the interatrial conduction time, the 'right-sided' conduction time between the high lateral right atrium and the proximal coronary sinus (RA-CSp), and the 'left-sided' conduction time between the proximal and the distal coronary sinus (CSp-LA). During sinus rhythm, the interatrial conduction time was longer in the PAF group (103 +/- 19 vs 86 +/- 12 ms, P<0.01) due to delay of right-sided conduction (RA-CSp was 74 +/- 20 vs 56 +/- 10 ms, P<0.01). During programmed stimulation at the distal coronary sinus, the maximal RA-CSp time was also longer in the PAF group (110 +/- 47 vs 69 +/- 16 ms, P<0.05). No differences in CSp-LA time were observed. CONCLUSION: This study supports the role of posterior septal right atrial conduction disturbances in the genesis of lone PAF.

Adult↗

Dispersion of atrial repolarization in patients with paroxysmal atrial fibrillation.

UNLABELLED: To study the role of the dispersion of atrial repolarization (DAR) in the genesis of atrial fibrillation (AF), monophasic action potentials (MAP) were recorded simultaneously from a catheter at the high lateral right atrium (HLRA) and a catheter moving around the high, middle and low lateral right atrium (RA) the high, anterior and posterior septal RA and the RA appendage in 15 patients with paroxysmal AF and 15 patients with atrioventricular nodal re-entry tachycardia (AVNRT) or concealed Wolff-Parkinson-White syndrome (WPW) without history of AF. After recordings during sinus rhythm (SR), MAPs were recorded during programmed stimulation (PS) via the HLRA catheter at a drive cycle length (CL) of 500 ms. Thus, MAPs were recorded simultaneously from 2 sites at a time and sequentially from 4 to 12 sites during SR, drive pacing and PS. Taking the MAP at the HLRA as reference, the dispersion of repolarization time (dispersion of RT) and its two components, the dispersions of activation time (dispersion of AT) and MAP duration (dispersion of MAP duration) among the 4 to 12 sites were calculated and taken as parameters of DAR. RESULTS: During SR and PS, the maximal dispersion of RT was significantly greater in AF than in control patients, 113+/-49 ms vs 50+/-28 ms (P<0.001) and 114+/-56 vs 70+/-43 ms (P<0.05) respectively. The increased dispersion of RT in the AF group was caused by increases in both dispersion of MAP duration and dispersion of AT. CONCLUSION: During SR and PS, DAR increased in patients with paroxysmal AF due to increases in dispersion of MAP duration and dispersion of AT, which suggests the involvement of both repolarization and conduction disturbances in the development of paroxysmal AF.

Action Potentials↗

Gender and atrioventricular conduction properties of patients with symptomatic atrioventricular nodal reentrant tachycardia and Wolff-Parkinson-White syndrome.

The objective of this study was to delineate the sex distribution and atrioventricular conduction properties in patients with manifest or concealed Wolff-Parkinson-White syndrome (WPW) and atrioventricular nodal reentrant tachycardia (AVNRT). The study comprised 328 patients with AVNRT, 347 with manifest, and 220 with concealed WPW who underwent radiofrequency ablation. A male preponderance was observed in patients with manifest WPW (69%), but not in those with concealed WPW (52%) and female preponderance in AVNRT patients (67%). The PR (166 +/- 25 ms) and AH (88 +/- 20 ms) intervals obtained 30 minutes after ablation in manifest WPW patients were significantly longer than in concealed WPW patients (149 +/- 20, 76 +/- 15 ms, P <.0001). The PR (146 +/- 20 ms) and AH intervals (75 +/- 15 ms) measured before ablation in AVNRT patients were shorter than those obtained before ablation in concealed WPW patients (154 +/- 21, 80 +/- 17 ms, P <.05) and after ablation in manifest WPW patients (P <.0001). The PR interval in AVNRT patients was also shorter than those measured during follow-up in concealed (153 +/- 21 ms, P <.05) and manifest WPW patients (165 +/- 23 ms, P <.0001). The ventriculoatrial block cycle length in AVNRT patients was significantly shorter than in manifest and concealed WPW patients. When age-matched patients were assigned to each group, significant differences in PR interval were observed between men and women (159 +/- 22 vs. 151 +/- 22 ms, P <.0001). Differences in sex distribution exist among patients with manifest and concealed WPW and AVNRT. The atrioventricular conduction properties required for the manifestation of pre-excitation and induction of AVNRT and gender differences in atrioventricular conduction may account for the differences in sex distribution.

Adult↗

Familial occurrence of microscopic colitis: a report on five families.

BACKGROUND: The etiology and pathogenesis of microscopic colitis is unknown. Whether genetic predisposition is of importance, as in many other gastrointestinal diseases, is unknown. Familial occurrence of collagenous colitis has earlier been reported only in two families. METHODS: Familial occurrence of microscopic colitis was searched for in a Swedish national microscopic colitis register. RESULTS: Familial occurrence of microscopic colitis was identified in five families. In all families a sister-sister relationship was found. Two sisters with collagenous colitis had been living apart in different Nordic countries for many years before developing the disease. In one pair, the smoking sister had collagenous colitis and the never smoking sister had lymphocytic colitis. CONCLUSIONS: Considering the relative rarity of microscopic colitis, these findings indicate that a genetic predisposition may be of importance.

Adult↗

Localization of the initial fibrillatory cycle in patients with paroxysmal atrial fibrillation.

BACKGROUND: Recent reports suggest the presence of conduction delay in the posterior septal region during sinus rhythm in patients with lone paroxysmal atrial fibrillation (AF). OBJECTIVE: To explore the location of intra-atrial conduction delay associated with initiation of AF. DESIGN: In 8 lone AF patients (51 +/- 10 years), 20 AF paroxysms were induced during electrophysiological examination. Bipolar electrograms were acquired from a 10-polar catheter in the coronary sinus (CS), a 4-polar His bundle catheter, and a 20-polar Halo catheter in the right atrium. RESULTS: Induced AF paroxysms showed earliest registered atrial activity in interatrial septum (IAS) or proximal CS in 17 cases (85%). Conduction delay at the posterior IAS or proximal CS accompanied induction of 18 AF paroxysms (6 patients). Atrial activation sequence at the beginning of the AF paroxysms was stable and reproducible in six repeatedly induced AF episodes (3 patients). CONCLUSION: In lone AF patients, induction of AF is associated with conduction disturbances in the IAS and proximal CS regions.

Adult↗

Recording monophasic action potentials using a platinum-electrode ablation catheter.

AIMS: The monophasic action potential (MAP) is conventionally recorded using Ag-AgCl electrodes which are not suitable for delivering radiofrequency currents. To be able to use the sharp MAP upstroke for identifying the local activation, as a step towards the development of a MAP-guided catheter ablation technique, the possibility of recording MAP via platinum electrodes of an ordinary ablation catheter was explored. METHODS AND RESULTS: One hundred and forty-two MAP recordings from the endocardium were obtained via an ablation catheter in 40 patients undergoing electrophysiological study/catheter ablation. During sinus rhythm and pacing, 90% of the ventricular and 100% of the atrial MAPs had stable baselines. The amplitudes were 13 +/- 4.2 mV for ventricular and 2.4 +/- 0.8 mV for atrial MAPs. During mapping and ablation, MAPs and uni- and bipolar electrograms were recorded simultaneously using the same tip electrode in eight patients. The MAPs provided more distinct local activation than the electrograms. During 17 MAP recordings, additional MAPs were recorded simultaneously using an Ag-AgCl electrode catheter in the immediate vicinity of the ablation catheter. The MAPs taken with the ablation catheter had characteristics consistent with those taken with the Ag-AgCl catheter. CONCLUSIONS: (1) Platinum electrodes can be used for timely recording of MAPs in patients. (2) It is feasible to record MAPs and deliver radiofrequency currents via the same platinum-tip electrode. These findings suggest that MAP-guided catheter ablation is technically possible.

Action Potentials↗

[Atrial fibrillation--new knowledge yields new therapeutic possibilities].

Atrial fibrillation (AF) is the most common cardiac arrhythmia prompting treatment. Advances in our knowledge of the pathophysiology of AF provide the basis for new and improved treatment modalities. Thus, focal excitation and localised impulse conduction defects are possible trigger factors which can be counteracted by focal ablation and pacing synchronisation, respectively. Perpetuation of AF, caused by continuous multisite re-entry, is promoted by successive shortening of repolarisation. Internal defibrillation and anatomical limitation of re-entry are treatments that counteract perpetuation of the arrhythmia. Current knowledge of AF and the application of new treatments are discussed by the Lund AF research group.

Atrial Fibrillation↗

Familial adenomatous polyposis is associated with a marked decrease in alkaline sphingomyelinase activity: a key factor to the unrestrained cell proliferation?

The hydrolysis of sphingomyelin generates key molecules regulating cell growth and inducing apoptosis. Data from animal cancer models support an inhibitory role for this pathway in the malignant transformation of the colonic mucosa. In the intestinal tract, a sphingomyelinase with an optimum alkaline pH has been identified. We recently found that the activity of alkaline sphingomyelinase is significantly decreased in colorectal adenocarcinomas, indicating a potential anticarcinogenic role of this enzyme. To further examine whether the reduction of sphingomyelinase is present already in the premalignant state of neoplastic transformation, we measured sphingomyelinase activities in patients with familial adenomatous polyposis (FAP) and in sporadic colorectal tubulovillous adenomas. Tissue samples were taken from adenomas and surrounding macroscopically normal mucosa from 11 FAP patients operated with ileorectal anastomosis, from three FAP patients with intact colon, from 13 patients with sporadic colorectal adenomas and from 12 controls. Activities of acid, neutral and alkaline sphingomyelinase were measured together with alkaline phosphatase. In FAP adenoma tissue, alkaline sphingomyelinase activity was reduced by 90% compared to controls (P < 0.0001), acid sphingomyelinase by 66% (P < 0.01) and neutral sphingomyelinase by 54% (P < 0.05). Similar reductions were found in the surrounding mucosa. In sporadic adenoma tissue, only alkaline sphingomyelinase was reduced significantly, by 57% (P < 0.05). Alkaline phosphatase was not changed in FAP adenomas, but decreased in the sporadic adenomas. We conclude that the markedly reduced levels of alkaline sphingomyelinase activities in FAP adenomas and in the surrounding mucosa may be a pathogenic factor that can lead to unrestrained cell proliferation and neoplastic transformation.

Adenoma↗

Alkaline sphingomyelinase activity is decreased in human colorectal carcinoma.

BACKGROUND: The metabolism of sphingomyelin generates important signals regulating cell proliferation and apoptosis. Previous studies found that the administration of colon carcinoma carcinogen was associated with an accumulation of membrane sphingomyelin, and that dietary sphingomyelin inhibited promotion of experimental colon carcinoma in mice, indicating that the abnormal metabolism of sphingomyelin is linked to colon carcinoma development. However, the changes in sphingomyelinase (SMase) activity in colon carcinoma have not been directly studied. The authors identified, specifically in the intestine, a distinctive alkaline SMase that differs from the known acidic and neutral SMases. The functions and clinical implications of the enzyme are unknown. This study examined the changes in all three SMase activities in human colorectal carcinoma. METHODS: Tissue samples were taken from colorectal carcinoma and normal mucosa from 18 patients. After homogenization, the activities of acidic, neutral, and alkaline SMase, as well as ceramidase and alkaline phosphatase, were determined. The enzyme activities in cancer tissue were compared with normal tissue from the same patients. RESULTS: In the normal tissue, there is an activity gradient from the ascending colon to the rectum for neutral and alkaline SMases but not for acidic SMase. In colorectal carcinoma, alkaline SMase activity was preferentially decreased by 75%, whereas acidic and neutral SMase activity decreased by 30% and 50%, respectively. No changes could be found for either ceramidase or alkaline phosphatase activity. CONCLUSIONS: Alkaline SMase activity preferentially decreases in human colorectal carcinoma, suggesting a regulatory role of the enzyme in colon mucosa cell proliferation.

Adult↗

Distribution of alkaline sphingomyelinase activity in human beings and animals. Tissue and species differences.

The alkaline sphingomyelinase (SMase) was first found in rat intestinal brush border. The important roles of this enzyme in digestion of sphingomyelin and in mucosal cell proliferation have been suggested. In the present work, the distribution of the alkaline SMase in the tissues of human beings and animals have been studied. By assaying the enzyme activity in human biopsy samples, we found that the alkaline SMase activity was absent in the stomach, increased in the duodenum, present at high levels in the small intestine, and slightly declined in the colon and rectum. High activities were found similarly in the intestinal contents of the healthy adults and infants. The activities were also found in the intestinal mucosa of rats, normal and germ-free mice, and hamsters with the same distribution pattern as in humans, but not in the intestinal mucosa of guinea pigs. Apart from the intestinal tract, a SMase activity preferring alkaline pH was identified in human and guinea pig bile, but not in the bile of rat, pig, sheep, and cow. No activity was found in either pancreatic tissue or pancreatic juice in all species tested, and none was detected in human urine and milk. In conclusion, alkaline SMase exists predominantly in the digestive system with considerable tissue and species differences.

Adult↗

Anti-neutrophil cytoplasmic antibodies in chronic inflammatory bowel disease. Prevalence and diagnostic role.

BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA), originally found to be associated with vasculitis, have been reported to be present in chronic inflammatory bowel disease. Most often the ANCA staining pattern is of the perinuclear type (p-ANCA), although nuclear and cytoplasmic stainings are seen. Single studies have shown some of the antibodies to react with lactoferrin or cathepsin G; however, most studies have not been able to determine a main antigenic specificity. We studied the prevalence of ANCA in sera from 155 patients with ulcerative colitis, 128 patients with Crohn's disease, and 51 patients with coeliac disease. The presence of ANCA was correlated to disease activity, extent, and age of onset of the diseases. Furthermore, we tried to characterize the antigen specificity by enzyme-linked immunosorbent assay (ELISA), using elastase, lactoferrin, myeloperoxidase, proteinase 3, and cathepsin G as antigens. METHODS: The sera were screened for ANCA by indirect immunofluorescence. Anti-nuclear antibodies (ANA) were analysed on HEp2 cells, and ELISA for specific ANCA was performed using the antigens mentioned. RESULTS: Most of the sera with positive immunofluorescence had the p-ANCA type of pattern. Seventy-eight of 155 (50.3%) of the patients with ulcerative colitis were ANCA-positive, compared with 31 of 128 (24.2%) of patients with Crohn's disease (p < 0.001). However, in the subgroup with Crohn's colitis, 16 of 44 (36.4%) were ANCA-positive. Only 4 of 51 patients (7.7%) with coeliac disease showed positive immunofluorescence (p < 0.001 compared with ulcerative colitis). Less than 10% of the samples were positive in the specific ELISA assays; thus other than the most well known granule proteins can be the target for ANCA in ulcerative colitis. CONCLUSION: ANCA occur significantly more often in ulcerative colitis than in Crohn's disease. However, the prevalence of ANCA is rather high in Crohn's colitis. ANCA are thus of limited value in differentiating Crohn's colitis from ulcerative colitis. ANCA found in inflammatory bowel disease are different from those associated with vasculitis. The antigen(s) responsible remain to be determined.

Adult↗

The expression of glutathione transferase mu in patients with inflammatory bowel disease.

BACKGROUND: Glutathione transferases (GST) are a group of multifunctional enzymes important in the detoxification of many electrophiles and, in addition, fatty acid hydroperoxides, thus limiting tissue damage from oxidative free radical attack. Of the four classes of GST (alpha, mu, pi, and theta), a class mu isoenzyme, GST mu, is dominantly inherited and is expressed in approximately half of the population. GST mu expression was examined in patients with inflammatory bowel disease and correlated to clinical course, extension, and age of onset of the diseases. METHODS: GST mu can be measured as GST activity against trans-stilbene oxide. This GST activity was measured in whole blood in 179 patients with ulcerative colitis, 109 patients with Crohn's disease, and 449 age-matched controls. RESULTS: Frequencies of GST mu expression were as follows: controls (n = 449, 51.2%), mild ulcerative colitis (n = 76, 47.3%), moderate ulcerative colitis (n = 43, 46.5%), and severe ulcerative colitis (characterized by colectomy) (n = 60, 36.7%). This trend was, however, not significant (p = 0.094). Patients with onset of the colitis before the age of 30 years (n = 91) had a lower frequency of GST mu expression (35.2%) than patients with a later onset (n = 88, 52.3%) (p < 0.05). This difference was more pronounced among the colectomized patients (19.4% versus 55.2%) (p < 0.01). In Crohn's disease, patients with colitis had a lower frequency of GST mu expression (n = 29, 31.0%) than controls; however, this was not statistically significant (p = 0.055). No difference was found with regard to age of onset. CONCLUSION: We conclude that in patients with ulcerative colitis, lack of GST mu is related to early age of onset and a more severe clinical course leading to colectomy.

Adult↗

Activation of neutral sphingomyelinase participates in ethanol-induced apoptosis in Hep G2 cells.

The mechanism underlying ethanol-induced apoptosis in liver cells is not clear. Sphingomyelin (SM) metabolism is a novel signal transduction pathway that has an impact on apoptosis in many cell types. We investigated whether the SM pathway is involved in ethanol-induced apoptosis in the liver. Hep G2 cells were treated with ethanol followed by assaying apoptosis, sphingomyelinase (SMase) activity, caspase-3 activity, and the changes of SM content in the cells. We found that ethanol dose-dependently increased apoptosis and the effect was accompanied by increases of caspase-3 activity and neutral SMase activity. At concentrations of 80 and 160 mM, ethanol significantly increased caspase-3 activity by 120% and neutral SMase activity by 24%. The activity of acid SMase was only slightly increased without statistical significance. C(2)-ceramide, the exogenous SM metabolite, mimicked the effects of ethanol on apoptosis and caspase-3 activation. When the SM content was determined 24 h after treatment with ethanol, its level was 15% lower than that of controls. The results indicate that metabolism of SM triggered by neutral SMase participates in ethanol-induced apoptosis in Hep G2 cells and activation of caspase-3 is involved in the apoptotic pathway.

Apoptosis↗