Search PubMed⌕ Search

Biomedical subjects

M Frick

Publications and source records attributed to M Frick.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of transient apical ballooning with cardiac magnetic resonance imaging and 31-phosphorous magnetic resonance spectroscopy.

Apical ballooning is an increasingly reported transient cardiomyopathy with yet unknown origin. In this study 2 cases of apical ballooning are described in whom we used a combined approach of cardiac magnetic resonance imaging (CMR) and 31-Phosphorous magnetic resonance spectroscopy (31P MRS). Electrocardiogram showed ST abnormalities and cardiac serum markers were mildly elevated, but CAG demonstrated smooth coronary arteries. Cine-CMR revealed severe apical akinesia and significantly decreased ejection fraction. Furthermore we detected reduced myocardial phosphocreatine to beta-ATP (PCr/b-ATP) ratios during the first week of acute disease. After 1 week we observed an improvement of PCr/b-ATP ratios by 68% and 34%, which was associated with an increase in left ventricular function. Our data suggest that 31P MRS might be a valuable tool in the evaluation of apical ballooning, but larger cohorts are needed to improve the understanding of metabolic changes during transient apical ballooning.

Aged↗
PubMed2006

Perceived heart rhythm in relation to ECG findings after direct current cardioversion of atrial fibrillation.

OBJECTIVE: To investigate the agreement between perceived heart rhythm and the ECG-registered heart rhythm, as well as between symptoms and the ECG after direct current (DC) cardioversion of atrial fibrillation (AF). METHODS: Consecutive patients with symptomatic AF subjected to DC cardioversion were interviewed about perceived heart rhythm and symptoms one week after restoration of sinus rhythm (SR). An ECG was obtained after the interview. A chance-corrected measure of agreement was calculated by using Cohen's kappa test. RESULTS: 356 patients were enrolled. One week after successful cardioversion 160 patients considered their rhythm to be regular and 222 ECGs showed SR. 130 patients considered their heart rhythm to be regular in agreement with ECG in SR (kappa = 0.34, 95% confidence interval (CI) 0.24 to 0.44), indicating a fair agreement. At the same time 59 patients perceived AF and 134 ECGs showed AF. Thirty eight patients perceived AF, in agreement with AF found on their ECG (kappa = 0.13, 95% CI 0.02 to 0.25), a poor agreement. 141 of 356 patients reported improvement of symptoms in agreement with SR on their ECG (kappa = 0.26, 95% CI 0.15 to 0.36), indicating fair agreement. Perceived SR and improvement of symptoms were strongly associated (n = 129; p < 0.001). CONCLUSION: Agreement between perceived heart rhythm and ECG, as well as between improvement of symptoms and SR recorded on the ECG, is no more than poor to fair after successful cardioversion of patients with persistent AF. The association between perceived SR and improvement of symptoms is strong. These findings support the need for objective criteria to select patients who would benefit most from rhythm control. They also support the need for further studies on quality of life of patients with AF, with due attention paid to patients' perception of their cardiac rhythm.

Aged↗
PubMed2006

A fluorescent microplate assay for exocytosis in alveolar type II cells.

The authors describe a simple, reliable, and quantitative assay to monitor exocytotic fusion of lamellar bodies (LBs) in adherent rat alveolar type II (AT II) cells. The assay is based on fluorescence measurements of LB-plasma membrane (PM) fusions modified for the use in multiwell culture plates to obtain a high-sample throughput. In particular, it is based on the presence of a highly light-absorbing dye in the cell supernatants to increase the specificity of fluorescence signals and to yield pseudo-confocal information from the cells. When the assay was tested with agonist-(ATP) and phorbolester-induced stimulation of LB-PM fusions, the authors found a good correlation with direct microscopic investigations based on single cell recordings. To further validate the assay, they used Curosurf at 10 mg/ml. However, it influenced neither the basal nor the ATP-stimulated rate of LB-PM fusions. This was corroborated by the fact that Curosurf had no effect on resting Ca (2+) levels nor the ATP induced Ca (2+) signals. The results cast new light on previous findings that surfactant phospholipids decrease the rate of secretion in AT II cells in a dose-dependent way. The authors conclude that the inhibitory effect exerted by phospholipids might be due to action on a later step in exocytosis, probably associated with exocytotic fusion pore expansion and content release out of fused vesicles.

Adenosine Triphosphate↗
PubMed2004

Tracing surfactant transformation from cellular release to insertion into an air-liquid interface.

Pulmonary surfactant is secreted by alveolar type II cells as lipid-rich, densely packed lamellar body-like particles (LBPs). The particulate nature of released LBPs might be the result of structural and/or thermodynamic forces. Thus mechanisms must exist that promote their transformation into functional units. To further define these mechanisms, we developed methods to follow LBPs from their release by cultured cells to insertion in an air-liquid interface. When released, LBPs underwent structural transformation, but did not disperse, and typically preserved a spherical appearance for days. Nevertheless, they were able to modify surface tension and exhibited high surface activity when measured with a capillary surfactometer. When LBPs inserted in an air-liquid interface were analyzed by fluorescence imaging microscopy, they showed remarkable structural transformations. These events were instantaneous but came to a halt when the interface was already occupied by previously transformed material or when surface tension was already low. These results suggest that the driving force for LBP transformation is determined by cohesive and tensile forces acting on these particles. They further suggest that transformation of LBPs is a self-regulated interfacial process that most likely does not require structural intermediates or enzymatic activation.

Air↗
PubMed2004

Open, randomized study to compare the immunogenicity and reactogenicity of an influenza split vaccine with an MF59-adjuvanted subunit vaccine and a virosome-based subunit vaccine in elderly.

BACKGROUND: An open, randomized, multicenter study was carried out in elderly to compare the immunogenicity and reactogenicity of a conventional influenza split vaccine (SpV) with an MF59-adjuvanted subunit vaccine (aSuV) and a virosome-based subunit vaccine (vSuV) since earlier studies reported better immunogenicity for adjuvanted and virosome-based vaccines. PATIENTS AND METHODS: A total of 840 subjects, aged 60 years or more, who had not been vaccinated or diagnosed with influenza in the preceding season were investigated. Hemagglutination-inhibition antibody titers were measured, and signs and symptoms recorded. RESULTS: The three vaccines exceeded EU efficacy requirements for subjects aged older than 60 years and seroprotective levels (titers > 1:40) were equally maintained with the three vaccines during 8 months post vaccination. SpV was as immunogenic as aSuV for the A/H3N2 strain (p < 0.0001) and significantly more immunogenic than aSuV for A/H1N1 strain (p = 0.0006). SpV was as immunogenic as vSuV for all three strains and significantly more immunogenic than vSuV for the A/H1N1 strain (p < 0.0001). In terms of reactogenicity, aSuV showed a higher rate of solicited local signs and symptoms than SpV (p = 0.021) and vSuV (p = 0.046), respectively. Incidence of solicited general symptoms was comparable on all treatments. No serious adverse event related to vaccination was reported. CONCLUSION: These findings suggest that all three vaccines are highly immunogenic with an acceptable reactogenicity profile and that they are appropriate for use in elderly.

Adjuvants, Immunologic↗
PubMed2003

Duration of warfarin sodium therapy prior to electrical cardioversion of atrial fibrillation.

OBJECTIVES: To evaluate the duration of anticoagulation treatment with warfarin sodium before elective DC-cardioversion and to identify clinical variables predicting short-term versus long-term waiting times. DESIGN: Retrospective. SUBJECTS: Patients with a known start date for warfarin sodium, a known duration of atrial fibrillation (AF) and who underwent DC-cardioversion were included. MAIN OUTCOME MEASURES: Duration of treatment with warfarin sodium prior to DC-cardioversion. METHODS: The hospital records of 288 consecutive patients with AF scheduled for elective cardioversion at two hospitals in Stockholm were reviewed. Only patients with a known start date for warfarin sodium and known duration of AF were included in the study. RESULTS: The median age was 70 (26-85) years and the duration of AF at time of cardioversion were 18 weeks (5-273) weeks. The median treatment duration prior to cardioversion with warfarin sodium was 12 weeks. Sinus rhythm was established in 224 (78%) patients of which 90 (40%) remained in sinus rhythm 1 month after cardioversion. In multivariate analysis, the only independent predictor of short waiting times for cardioversion (8 vs. 15 weeks) was if a cardiologist instituted the treatment with warfarin sodium (P < 0.001, 95% CI 5.0-9.0). CONCLUSION: The average waiting time from start of warfarin sodium treatment to elective cardioversion exceeds by far the recommended 3-4 weeks on therapeutic international normalized ratio (INR). In order to minimize the time period until cardioversion significant changes in the out-of-hospital care logistics has to be undertaken.

Aged↗
PubMed2001

Fusion pore expansion is a slow, discontinuous, and Ca2+-dependent process regulating secretion from alveolar type II cells.

In alveolar type II cells, the release of surfactant is considerably delayed after the formation of exocytotic fusion pores, suggesting that content dispersal may be limited by fusion pore diameter and subject to regulation at a postfusion level. To address this issue, we used confocal FRAP and N-(3-triethylammoniumpropyl)-4-(4-[dibutylamino]styryl) pyridinium dibromide (FM 1-43), a dye yielding intense localized fluorescence of surfactant when entering the vesicle lumen through the fusion pore (Haller, T., J. Ortmayr, F. Friedrich, H. Volkl, and P. Dietl. 1998. Proc. Natl. Acad. Sci. USA. 95:1579-1584). Thus, we have been able to monitor the dynamics of individual fusion pores up to hours in intact cells, and to calculate pore diameters using a diffusion model derived from Fick's law. After formation, fusion pores were arrested in a state impeding the release of vesicle contents, and expanded at irregular times thereafter. The expansion rate of initial pores and the probability of late expansions were increased by elevation of the cytoplasmic Ca2+ concentration. Consistently, content release correlated with the occurrence of Ca2+ oscillations in ATP-treated cells, and expanded fusion pores were detectable by EM. This study supports a new concept in exocytosis, implicating fusion pores in the regulation of content release for extended periods after initial formation.

Adenosine Triphosphate↗
PubMed2001

Inhibition of ATP-induced surfactant exocytosis by dihydropyridine (DHP) derivatives: a non-stereospecific, photoactivated effect and independent of L-type Ca2+ channels.

Purinergic stimulation of surfactant secretion via exocytosis of lamellar bodies is mediated by an elevation of the intracellular Ca2+ concentration ([Ca2+](i)). We tested the dihydropyridine (DHP) analogues isradipine (+/-enantiomers), nifedipine and Bay K 8644 (racemic forms) on ATP-induced surfactant secretion and [Ca2+](i) in single type II cells, using FM1-43 and fura-2 fluorescence. None of the DHPs (2 microM) had an effect on ATP-induced surfactant secretion in the dark. They did, however, inhibit secretion in a concentration-dependent manner during illumination, particularly with UV light. This effect was not stereospecific, because it was mimicked by (-)-isradipine. In addition, (+)- or (-)-isradipine, but not nifedipine or Bay K 8644, elicited a slow increase of [Ca2+](i) during illumination with UV light, which was reversible by exposure to dark. None of the DHPs inhibited the ATP-induced Ca2+ signal. In perforated patch clamp experiments, depolarizing voltage steps did not induce L-type Ca2+ (Sr(2+)) currents, even in the presence of the agonist Bay K 8644 (1 microM). We conclude that impairment of ATP-induced surfactant secretion by all tested DHPs and alterations of Ca2+ homeostasis by isradipine are photoactivated effects, independent of L-type Ca2+ channels.

Adenosine Triphosphate↗
PubMed2001

Factors predicting success rate and recurrence of atrial fibrillation after first electrical cardioversion in patients with persistent atrial fibrillation.

BACKGROUND: The recurrence rate of atrial fibrillation (AF) after elective cardioversion is high. HYPOTHESIS: The study aimed to identify clinical predictors for successful electrical cardioversion and maintenance of sinus rhythm after a first electrical cardioversion in patients with persistent AF without concomitant antiarrhythmic drugs of class I and III. METHODS: Consecutive outpatients (n = 166) with persistent AF for > 1 month, scheduled for elective cardioversion, were prospectively included in the study. A clinical investigation, echocardiographic assay, and Holter electrocardiogram (ECG) before and ECG 4 weeks after cardioversion, were performed in all patients. RESULTS: The mean age of the patients was 68 years (range 45-83) and duration of AF was 5 (1-48) months. Sinus rhythm was established in 124 (75%) patients. In multivariate analysis, only duration of AF < 6 months (p < 0.04, odds ratio [OR] 2.2, 95% confidence interval [CI] 1.1 to 4.7) and patients weight (p < 0.03, OR 2.3, 95% CI 1.1 to 4.8 for weight < 80 kg) were identified as independent predictors of successful cardioversion. At 4 weeks after cardioversion, only 46 (37%) of 124 patients maintained sinus rhythm. Independent factors for maintenance of sinus rhythm, in multivariate analysis, were AF <3 months (p < 0.04, OR 2.5, 95% CI 1.1 to 5.6), treatment with beta blockers (p < 0.00001, OR 7.0, 95% CI 3.0 to 16.3) or verapamil/diltiazem (p < 0.04, OR 3.6, 95% CI 1.1 to 12.1), and right atrial dimension < 37 mm (p < 0.02, OR 5.9, 95% CI 1.4 to 25.4). CONCLUSIONS: In patients with persistent AF, the patient's weight and the duration of AF are independent predictors for a successful cardioversion. Short duration of AF, treatment with beta blockers or verapamil/diltiazem, and right atrial area/dimension are independent predictors for maintenance of sinus rhythm.

Adult↗
PubMed2001

Asymptomatic versus symptomatic persistent atrial fibrillation: clinical and noninvasive characteristics.

OBJECTIVE: This prospective study was designed to investigate the differences between asymptomatic versus symptomatic arrhythmia as well as left ventricular dysfunction in a consecutive population of patients with persistent atrial fibrillation. DESIGN: A total of 282 consecutive outpatients referred with persistent atrial fibrillation formed the study population. A structured medical history was obtained. A two-dimensional transthoracic echocardiography to assess the left ventricular function and a 24-h electrocardiogram (ECG) recording were performed. Irregularity of the heart rhythm was analysed with heart rate variability (HRV) in the time domain as well as maximum and minimum heart rate and the longest pause. SETTING: Three university hospitals. RESULTS: The mean age of the patients was 69 years and the mean duration of atrial fibrillation was 7 months. The prevalence of symptomatic patients was 68%, while 32% had no symptoms from atrial fibrillation, left ventricular dysfunction was observed in 20%. Asymptomatic subjects had more often lone atrial fibrillation than those with symptoms. Valvular heart disease was an independent predictor of symptoms while male gender, ischaemic heart disease and a high heart rate were independent predictors of impaired left ventricular function. CONCLUSION: Valvular heart disease is related to symptoms in persistent atrial fibrillation. Ischaemic heart disease, male gender and a high heart rate are more common in patients with impaired left ventricular function. Compromised left ventricular function does, occur also in asymptomatic subjects underlining the importance of a careful investigation including echocardiography in all subjects with persistent atrial fibrillation.

Adult↗
PubMed2001

Spontaneous delayed recovery of perfusion after thrombolyzed acute myocardial infarction: is it predictable before discharge?

In patients with thrombolyzed acute myocardial infarction, early assessment of the final infarct size is difficult because spontaneous recovery of perfusion and function of the left ventricle may be delayed. This study was undertaken to evaluate the ability of predischarge low-dose dobutamine echocardiography to predict late spontaneous recovery of perfusion assessed by single-photon emission computed tomography after acute myocardial infarction. We prospectively studied 53 consecutive patients with myocardial infarction treated with thrombolysis. Low-dose dobutamine echocardiography and resting (99m)Tc-sestamibi single-photon emission computed tomography (MIBI SPECT) were performed 4 +/- 2 days after infarction. A follow-up SPECT study was carried out in 45 patients after 6 months. Myocardial recovery was defined as a reduction of SPECT defect size by more than 10% at follow-up compared with the early study. In 25 of the 45 patients, the size of the left ventricular perfusion defect decreased significantly from 42% +/- 16% to 27% +/- 10% (group 1), whereas in the remaining 20 patients it showed no significant change (group 2). Predischarge low-dose dobutamine echocardiography showed a significant improvement in wall motion score index compared with baseline in group 1, from 1.62 +/- 0.28 to 1.41 +/- 0.24, P <.001, whereas in group 2 this index remained without significant change. Predischarge low-dose dobutamine echocardiography is an accurate tool for prediction of late recovery of myocardial perfusion after acute myocardial infarction treated with thrombolysis.

Adrenergic beta-Agonists↗
PubMed2001

Mechanisms of surfactant exocytosis in alveolar type II cells in vitro and in vivo.

Surfactant secretion must be regulated to maintain a low surface tension in the lung during various conditions such as exercise. In vitro studies reveal a slow, unique exocytotic process at the interface of stimulated and constitutive exocytosis. The exocytotic mechanisms and sites of regulation in vivo, however, are still poorly understood.

Animals↗
PubMed2001

Secretion in alveolar type II cells at the interface of constitutive and regulated exocytosis.

Long-term, simultaneous, measurements of cytoplasmic free Ca(2+) concentrations and single exocytotic fusion events in surfactant-secreting type II cells were performed. All fusion (constitutive, phorbol ester-induced, and agonist-induced) was Ca(2+)-dependent. Kinetic analysis revealed that agonist (adenosine triphosphate [ATP])-induced fusion exhibited a kinetic pattern that correlated well with the Ca(2+) signal. The effects of Ca(2+) release from intracellular stores (early) and Ca(2+) entry (late) could be demonstrated for the first time by dissecting the slow (10-to-15-min) fusion response to ATP into these two components. Bath Ba(2+) or Sr(2+) could replace Ca(2+) to elicit a fusion response in thapsigargin-pretreated cells lacking ATP-induced Ca(2+) release from stores. Although the late response was partially inhibited by interrupting the phospholipase D-protein kinase C axis, a high Ca(2+) dependence of the entire secretory course was demonstrated by a significant correlation between the integrated Ca(2+) signal and the fusion response. There was also a highly significant correlation between constitutive and ATP-stimulated fusion activity in individual cells. We propose a common mechanistic model for all types of fusion in this slow secretory cell, in which constitutive and regulated forms of exocytosis are subject to the same principles of regulation.

Adenosine Triphosphate↗
PubMed2001

Clinical utility of monitoring tacrolimus blood concentrations in liver transplant patients.

The relationship between the dose of tacrolimus, trough tacrolimus blood concentration, and selected clinical endpoints (acute rejection, nephrotoxicity, and other toxicities) were examined in a prospective, multicenter clinical trial to validate the use of an enzyme-linked immunosorbent assay (ELISA) for monitoring whole-blood concentrations of tacrolimus in liver transplant patients. A total of 111 subjects from six transplant centers were evaluated over 12 weeks posttransplantation. In addition to trough tacrolimus blood concentrations, hematocrit, ALT, AST, GGTP, alkaline phosphatase, total bilirubin, serum creatinine, BUN, serum potassium, serum magnesium, blood glucose, and serum albumin were also measured. The relationship between trough tacrolimus blood concentrations and clinical endpoints was analyzed using both a logistic regression model and a Cox proportional hazard model. By logistic regression analysis, a statistically significant (p = 0.0465) relationship between increasing trough tacrolimus blood concentrations and decreasing risk of acute rejection was demonstrated over a 7-day time window. Nephrotoxicity and other toxicities also demonstrated statistically significant relationships with trough tacrolimus blood concentrations. The results of the Cox analysis were consistent with the logistic regression analysis. Using receiver operator characteristic curves, trough tacrolimus concentrations as measured by the ELISA method were able to differentiate the occurrence of nephrotoxicity and toxicity from nonevents. To minimize nephrotoxicity of tacrolimus, it is necessary to maintain trough blood concentrations below 15 ng/ml. This study demonstrates that the ELISA method used to measure tacrolimus blood concentrations in this study provides information of predictive value for managing the risk of nephrotoxicity, other toxicity, and rejection in liver transplant patients.

Administration, Oral↗