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Biomedical subjects

C Schmitt

Publications and source records attributed to C Schmitt.

At least 55 records · Page 3Linked to original sources

Modes of initiation of paroxysmal atrial fibrillation from analysis of spontaneously occurring episodes using a 12-lead Holter monitoring system.

Although new, possibly curative radiofrequency ablation techniques for atrial fibrillation (AF) have been developed in recent years, little is known about the mechanisms of spontaneous onset of AF episodes. Using a 12-lead 24-hour Holter monitoring system, we aimed to characterize such episodes. A total of 297 spontaneous episodes of AF in 33 patients with intermittent AF (mean age of 59 +/- 11 years) were analyzed. Two hundred seventy-six episodes (93%) were initiated by atrial premature complexes (APCs), whereas 19 episodes (6.4%) were preceded by typical atrial flutter and 2 (0.7%) by atrial tachycardia. Based on 12-lead electrocardiographic criteria, the origin of ectopic beats initiating AF was classified in 230 episodes (77.5%) as being of left atrial origin, in 6 episodes (2.0%) as being of right atrial origin and in 40 episodes (13.5%) the exact location could not be determined. In 16 of 23 patients (70%) with multiple episodes of AF, ectopic beats that initiated AF were consistently monomorphic. In the 120 seconds (6.2 APCs/min for a 30-second period) before onset of AF, frequency of ectopic beats increased from 0.8 APCs/min in AF-free intervals to 4.1/min (6.2 APCs/min for a 30-second period), (p = 0.003 and p = 0.016, respectively). In 209 of 254 episodes (82%), AF onset occurred during normal sinus rate (60 to 100 beats/min). Thus, paroxysmal AF is triggered most frequently by monomorphic left APCs. In most AF episodes, the increase in the number of ectopic beats that initiated episodes of AF occurred at a normal sinus rate.

Adult↗

Value of programmed ventricular stimulation for prophylactic internal cardioverter-defibrillator implantation in postinfarction patients preselected by noninvasive risk stratifiers.

OBJECTIVES: The aim of this prospective study was to evaluate the role of programmed ventricular stimulation (PVS) after noninvasive risk stratification to identify a subgroup of acute myocardial infarction (AMI) survivors considered at risk for ventricular arrhythmias and whether these patients could benefit from internal cardioverter-defibrillators (ICDs). BACKGROUND: The predictive value of noninvasive and invasive risk stratifiers after AMI has been questioned. The question of whether the group of patients with inducible monomorphic ventricular tachycardia (VT) after AMI could profit from ICD implantation is unanswered. METHODS: A consecutive series of 1,436 AMI survivors was screened noninvasively by Holter monitoring, heart rate variability, ventricular late potentials, and ejection fraction. A subgroup of 248 patients (17.3%) were identified as high-risk patients and scheduled for PVS. Due to the study design, 54 patients >75 years were excluded; thus, 194 patients were eligible for PVS. Triple extrastimuli at two paced cycle lengths (600 ms and 400 ms) were applied. RESULTS: In a subgroup of 98 (51%) high-risk patients, PVS was performed; 21 patients had an abnormal response, and in 20 patients an ICD was implanted. During a mean follow-up of 607 days the arrhythmic event rate (sudden cardiac death, symptomatic VT, cardiac arrest) was 33% with a positive electrophysiological test versus 2.6% (p < 0.0001) with a negative electrophysiological test. A subgroup of 96 high-risk patients declined electrophysiological study. In this nonconsent group, cardiac mortality (combined sudden and nonsudden) was significantly higher (log-rank chi-square 9.38, p = 0.0022, relative risk 4.7, 1.6 to 13.9) compared to the group guided by electrophysiological testing and consecutive ICD implantation. CONCLUSIONS: After a two-step risk stratification, PVS is helpful in selecting a subgroup of AMI survivors without spontaneous ventricular arrhythmias who benefit from prophylactic ICD implantation.

Defibrillators, Implantable↗

Src homology 2 domain-containing inositol 5-phosphatase 1 mediates cell cycle arrest by FcgammaRIIB.

We previously found that low affinity receptors for the Fc portion of IgG, FcgammaRIIB, which are widely expressed by hematopoietic cells, can negatively regulate receptor tyrosine kinase-dependent cell proliferation. We investigated here the mechanisms of this inhibition. We used as experimental models wild-type mast cells, which constitutively express the stem cell factor receptor Kit and FcgammaRIIB, FcgammaRIIB-deficient mast cells reconstituted with wild-type or mutated FcgammaRIIB, and Src homology 2 domain-containing inositol polyphosphate 5-phosphatase 1 (SHIP1)-deficient mast cells. We found that, upon coaggregation with Kit, FcgammaRIIB are tyrosyl-phosphorylated, recruit SHIP1, but not SHIP2, SH2 domain-containing protein tyrosine phosphatase-1 or -2, abrogate Akt phosphorylation, shorten the duration of the activation of mitogen-activated protein kinases of the Ras and Rac pathways, abrogate cyclin induction, prevent cells from entering the cell cycle, and block thymidine incorporation. FcgammaRIIB-mediated inhibition of Kit-dependent cell proliferation was reduced in SHIP1-deficient mast cells, whereas inhibition of IgE-induced responses was abrogated. Cell proliferation was, however, inhibited by coaggregating Kit with FcgammaRIIB whose intracytoplasmic domain was replaced with the catalytic domain of SHIP1. These results demonstrate that FcgammaRIIB use SHIP1 to inhibit pathways shared by receptor tyrosine kinases and immunoreceptors to trigger cell proliferation and cell activation, respectively, but that, in the absence of SHIP1, FcgammaRIIB can use other effectors that specifically inhibit cell proliferation.

Animals↗

Online reference database of European Y-chromosomal short tandem repeat (STR) haplotypes.

The reference database of highly informative Y-chromosomal short tandem repeat (STR) haplotypes (YHRD), available online at http://ystr.charite.de, represents the largest collection of male-specific genetic profiles currently available for European populations. By September 2000, YHRD contained 4688 9-locus (so-called "minimal") haplotypes, 40% of which have been extended further to include two additional loci. Establishment of YHRD has been facilitated by the joint efforts of 31 forensic and anthropological institutions. All contributing laboratories have agreed to standardize their Y-STR haplotyping protocols and to participate in a quality assurance exercise prior to the inclusion of any data. In view of its collaborative character, and in order to put YHRD to its intended use, viz. the support of forensic caseworkers in their routine decision-making process, the database has been made publicly available via the Internet in February 2000. Online searches for complete or partial Y-STR haplotypes from evidentiary or non-probative material can be performed on a non-commercial basis, and yield observed haplotype counts as well as extrapolated population frequency estimates. In addition, the YHRD website provides information about the quality control test, genotyping protocols, haplotype formats and informativity, population genetic analysis, literature references, and a list of contact addresses of the contributing laboratories.

Databases, Factual↗

Testicular disease in childhood B-cell non-Hodgkin's lymphoma: the French Society of Pediatric Oncology experience.

PURPOSE: To investigate whether testicular disease in childhood B-cell lymphoma should continue to be considered a sanctuary site, as it is with other lymphoid malignancies such as acute lymphoblastic leukemia. PATIENTS AND METHODS: Seven hundred forty-two children with B-cell non-Hodgkin's lymphoma were included in the LMB protocols of the French Society of Pediatric Oncology from February 1981 to May 1994. Thirty patients (5.3%) had testicular involvement at diagnosis. We describe the clinical presentation and outcome of these 30 patients, who were treated without local radiation therapy. RESULTS: Five patients underwent diagnostic orchidectomy. The median patient age was 8.5 years (range, 2 to 14 years), and their cancers were stage III (18 patients), stage IV (five patients), and B-cell acute lymphoblastic leukemia (seven patients). Five patients had central nervous system involvement. Twenty-eight patients (95%) achieved complete remission. Twenty-six patients are alive without progressive disease (median follow-up, 6.5 years). CONCLUSION: Testicular disease does not seem to confer a poor prognosis, and it is curable with intensive combination chemotherapy alone. Local treatment (surgery or radiation) is avoidable; therefore, gonadal function can be preserved.

Adolescent↗

Restenosis after coronary placement of various stent types.

Coronary stent implantation is being performed in an increasing number of patients with a wide spectrum of clinical and lesion characteristics. A variety of stent designs are now available and continuous efforts are being made to improve the stent placement procedure. The objective of this study was to perform a comprehensive analysis of the relation between clinical, lesion, and procedural factors, and restenosis after intracoronary stenting in a large and unselected population of patients. A consecutive series of 4,510 patients with coronary stent placement was analyzed. Exclusion criteria were only a failed procedure and an adverse outcome within the first month after the intervention. Follow-up angiography was performed in 80% of patients at 6 months. Clinical, lesion, and procedural data from all 3,370 patients (4,229 stented lesions) with follow-up angiography were analyzed in a logistic regression model for restenosis (> or =50% diameter stenosis). Clinical factors contributed to the predictive power of the model much less than lesion and procedural factors. The strongest risk factor for restenosis was a small vessel size, with a 79% increase in the risk for a vessel of 2.7 mm versus a vessel of 3.4 mm in diameter. Stent design was the second strongest factor; the incidence of restenosis ranged from 20.0% to 50.3% depending on the stent type implanted. In conclusion, this study demonstrates the predominant role of lesion and procedural factors in determining the occurrence of restenosis after coronary stent placement. Among these factors, stent design appears to play a particularly important role in the hyperplastic response of the vessel wall.

Analysis of Variance↗

Study of the infection of human blood derived monocyte/macrophages with hepatitis C virus in vitro.

Hepatitis C virus (HCV) is essentially hepatotropic, but clinical observations based on quasispecies composition in different compartments or on viral RNA detection in cells suggest that the virus is able to infect and persist in cells other than liver cells. It was shown previously that peripheral blood mononuclear cells (PBMCs) are permissive to HCV replication in vitro but at a very low rate. Since different viruses associated with chronic infections are known to persist in monocyte/macrophages, it is important to determine whether these mononuclear blood cells are susceptible preferentially to HCV. In order to study HCV interaction with monocytes/macrophages, these cells were isolated from the blood of healthy donors and incubated with HCV genotype 1b positive sera. The detection by RT-PCR of the positive- and negative-strand RNA in the cells at different times and the increase in the amount of intracellular viral RNA measured by the branched DNA assay suggest that monocyte/macrophages can support HCV RNA replication. The rate, however, is very low. The analysis of hypervariable region 1 (HVR-1) nucleotide sequences indicated that some minor variant present in the inoculum might display a specific tropism for the monocytes/macrophages. These results provide evidence that human monocytes/macrophages might represent a reservoir for HCV. This cell tropism may be a crucial factor in the pathogenesis of hepatitis C.

Base Sequence↗

The effects of scrambling on Spanish and Korean agrammatic interpretation: why linear models fail and structural models survive.

Several models of comprehension deficits in agrammatic aphasia rely heavily on linear considerations in the assignment of thematic roles to structural positions (e.g., the Trace-Deletion Hypothesis, the Mapping Hypothesis, and the Argument-Linking Hypothesis). These accounts predict that constructions in languages with rules that affect syntactic structure but preserve relative linear order should be unimpaired. Other models [e.g., the Double-Dependency Hypothesis, (DDH)] do not resort to linearity but are purely structural in conception and therefore should be immune to word-order effects. We tested linear and nonlinear accounts with scrambling structures in Korean and topicalization structures in Spanish. The results are very clear. The (nonlinear) DDH is entirely compatible with the evidence, but the linear accounts are not.

Adult↗

Reentry circuit location and left atrial three-dimensional activation patterns in left atrial flutter.

We report the case of a patient with left atrial flutter (LAF) in whom the reentry circuit location was mapped with a 64-electrode basket catheter deployed in the left atrium. Left atrial three-dimensional activation patterns were constructed with a software program and presented as color-coded isochrones. The reentrant activation traveled preferentially around the mitral annulus in a clockwise direction. It consisted of a single reentry confined anteriorly by the mitral annulus and posteriorly by an anatomic-functional barrier composed of a functional conduction block extending between pulmonary veins and surrounding a part of the posterior wall of the left atrium. The lower portion of the posterior wall and the anterior wall in close proximity to mitral annulus were preferentially used by the reentrant impulse.

Atrial Flutter↗

Heterophoria measured with white, dark-grey and dark-red Maddox rods.

BACKGROUND: Heterophoria is defined as a deviation from orthovergence position when no fusional contours are provided. It has been suggested that darkening one eye effects the phoric angle between the two eyes. We tested this assumption by comparing the phoric angles with white, dark-grey and dark-red Maddox rods. METHODS: In a first group of 14 subjects horizontal heterophoria was measured with white, dark-grey and dark-red Maddox rods. In a second group of 43 different subjects horizontal heterophoria was measured with white and dark-red Maddox rods. Subjects were asked to continually correct any perceived deviation, using Herschel prisms. Readings were taken after 1 min. RESULTS: Group 1 (n=14): No significant difference between white, dark-grey and dark-red Maddox rods (Friedmann test). Correlation between white and dark-grey Maddox rods r=0.97 (P<0.0001), slope of regression line 0.92 (95% confidence interval 0.78-1.06). Correlation between white and dark-red Maddox rods r=0.94 (P<0.0001), slope of regression line 0.67 (95% confidence interval 0.53-0.82). Group 2 (n=43): No significant difference between white and dark-red Maddox rods (Wilcoxon signed rank tests). Correlation r=0.96 (P<0.0001), slope of regression line 0.95 (95% confidence interval 0.87-1.03). CONCLUSION: Our study revealed no significant difference and a high correlation among the phoric angles obtained with white, dark-grey and dark-red Maddox rods. The close match suggests that darkening one eye does not effect the phoric angle between the two eyes.

Diagnostic Techniques, Ophthalmological↗

The Freiburg Stereoacuity Test: automatic measurement of stereo threshold.

BACKGROUND: There is a need for a stereotest with the following properties: (1) Natural viewing conditions, i.e. stimulus contours visible for each eye alone, but no or hardly any cue for monocular detection, and (2) suitability for threshold determination over a wide range of disparities. To comply with these requirements, we developed the Freiburg Stereoacuity Test. METHOD: The stimulus configuration is shown on a visual display unit (VDU) using phase-difference haploscopy with ferromagnetic liquid crystal shutters. The stereo target consists of a vertical bar that can be presented "in front of' or "behind" a frame. The sizes of the bar and the frame are kept constant relative to the stereo disparity. Anti-aliasing allows for disparities finer than the pixel raster. To mask monocular cues the bar is displaced randomly to the right or left. The stereo threshold was determined in two observers with normal eyes, using first the method of constant stimuli and then the best PEST. Both procedures were repeated with observers wearing scatter transparencies that reduced their visual acuity to about 1/10. In addition, the two observers with insight into the test design and two strabismic patients performed the best PEST procedure with one eye only. RESULTS: With constant stimuli both observers achieved a stereoacuity of 2.6 arcsec and 3.1 arcsec, respectively, taking a hit rate of 75% as the threshold. The best PEST revealed a stereoacuity of 2.5 arcsec and 3.0 arcsec, respectively. The scatter transparencies raised the threshold to 261 and 257, respectively. With one eye only, the two observers with insight into the test design exploited the subtle position cue and reached a coarse pseudostereopsis. The two strabismic patients did not utilise the position cue. CONCLUSION: The Freiburg Stereoacuity Test allows determination of stereoacuity over a wide range of disparities (1-1000 arcsec). Although the stimuli can be seen with each eye alone, monocular depth cues are sufficiently masked. The Freiburg Stereoacuity Test is available at http://www.ukl.uni-freiburg.de/aug/bach/fst/.

Adolescent↗

Electrophysiologic characteristics of paroxysmal and chronic atrial fibrillation in human right atrium.

OBJECTIVES: The aim of the study was to analyze the electrophysiologic characteristics of paroxysmal (PAF) and chronic (CAF) atrial fibrillation (AF) in the human right atrium (RA). BACKGROUND: Differences that exist between PAF and CAF and the mechanisms of self-sustenance of these arrhythmias are incompletely understood. METHODS: A total of 53 patients with PAF (25 patients, mean age 59 +/- 6.1 years, 3 women) and CAF (28 patients, mean age 59 +/- 13 years, 7 women) underwent multisite mapping of the RA during ongoing AF using a 64-electrode basket catheter. Quantitative evaluation and three-dimensional activation patterns were performed using a computerized system. RESULTS: Patients with PAF, as compared with patients with CAF, had significantly longer AF cycle length, shorter time intervals with type III AF throughout the RA and a smaller number of endocardial breakthroughs (mean 51 +/- 19 vs. 104 +/- 40, p < 0.001). The majority of endocardial breakthrough points (88% in PAF patients and 98% in CAF patients) were located in the septal region and coincided anatomically with major interatrial connection routes. Coexistence of re-entrant and apparently focal activation determined maintenance of AF in the RA in PAF, whereas random re-entry was documented more frequently in patients with CAF. In patients with CAF, the duration of arrhythmia (in years) correlated strongly with the percentage of time during which type III AF was observed in the lateral wall of the RA (r = 0.71). CONCLUSIONS: Clinical PAF and CAF, as recorded in the RA, have, at least quantitatively, distinct electrophysiologic features and different mechanisms of maintenance.

Aged↗

Decreased plasma concentration of brain natriuretic peptide as a potential indicator of cardiac recovery in patients supported by mechanical circulatory assist systems.

OBJECTIVES: We sought to investigate the relationship between the plasma concentration of brain natriuretic peptide (BNP), echocardiographic findings and the clinical outcome of patients supported with ventricular assist devices (VADs) to determine the role of BNP as a predictor for cardiac recovery. BACKGROUND: Ventricular unloading in patients with end-stage heart failure supported by VADs may lead to myocardial recovery. The BNP is produced in the myocardium in response to chronic volume overload, but the effects on it of ventricular unloading by VADs are largely unknown. METHODS: Twenty-one patients diagnosed with nonischemic cardiomyopathy and supported by VADs were evaluated for echocardiographic data and blood chemistry including BNP. They were divided into patients who died while on mechanical support (group I; n = 9), patients who were transplanted (group II; n = 8) and patients who were successfully weaned off the system and did not require transplantation (group III; n = 4). RESULTS: Brain natriuretic peptide plasma concentrations decreased significantly after initiation of mechanical circulatory support (p = 0.017). Furthermore, the changes in BNP plasma concentrations showed a faster decrease to normal levels within the first week after implantation of the VAD in patients who were weaned off the system (group III) compared to patients in group I and group II. CONCLUSIONS: This study shows that ventricular unloading with VADs decreases BNP plasma concentrations in patients who suffer from end-stage heart failure. Furthermore, we hypothesize that an early decrease of BNP plasma concentration may be indicative of recovery of ventricular function during mechanical circulatory support.

Adolescent↗

Study of beta-lactoglobulin/acacia gum complex coacervation by diffusing-wave spectroscopy and confocal scanning laser microscopy.

Complex coacervation has been investigated on mixtures of beta-lactoglobulin (beta-lg) and acacia gum (AG) at pH 4.2 where these two macromolecules interact electrostatically. Changes in beta-lg/AG complex coacervation induced by the presence of beta-lg aggregates were considered. The nature and structure of particles resulting from complex coacervation were determined by using confocal scanning laser microscopy (CSLM). CSLM revealed fundamental differences in the structure of each of the studied dispersions (at 1 wt.% total concentration). Spherical vesicular coacervates and precipitates (based on beta-lg aggregates) were the hallmark of BLG/AG dispersions (beta-lg dispersion containing insoluble aggregates). Only coacervates were visible in AF-BLG/AG dispersions (beta-lg dispersion free of insoluble aggregates). The latter were characterised by the presence of large foam-like coacervates induced by partial coalescence of single coacervates, especially at the 2:1 protein to polysaccharide (Pr:Ps) ratio. Diffusing wave spectroscopy (DWS) was used to study the stability of dispersions as a function of time. Depending on the Pr:Ps ratio and the presence of beta-lg aggregates, the intensity correlation function (g(2)(t)) shifted to lower correlation times rapidly after mixing of both macromolecules. This revealed the formation of a large number of small particles, characterised by faster Brownian motion. At 1 and 5 wt.% total concentration, the 8:1 Pr:Ps ratio exhibited a rapid decrease of the backscattered intensity in time, both for BLG/AG and AF-BLG/AG mixtures, revealing rapid sedimentation/coalescence of particles. This precluded the achievement of a stable correlation function. For the 2:1 Pr:Ps ratio, mixtures exhibited both coalescence and sedimentation phenomena as confirmed by shifts in the g(2)(t) towards larger correlation times and the decrease of the initial value of g(2)(t) with time. Mixtures obtained for the 1:1 Pr:Ps ratio were characterised by small variations in the DWS signal, emphasising the stability of produced particles. The increase of the total biopolymer concentration reduced the effect of both Pr:Ps ratio and presence of protein aggregates. From CSLM and DWS observations, possible differences in the complex coacervation mechanism in both types of mixtures were highlighted. The use of protein aggregates to control complex coacervation was underlined.

Journal Article↗

Ultrastructural observations in hepatitis C virus-infected lymphoid cells.

It is currently unclear whether the hepatocellular damage in chronic hepatitis C virus (HCV) infection is produced through the intrahepatic action of the anti-HCV immune response or through a direct cytopathic effect. In order to investigate the features of HCV replication (morphogenesis and cytopathic effect), we studied the infection of a permissive lymphocytic B cell line, Daudi cells, which were infected with sera of HCV-positive patients, and were examined after various time points under electron microscope. Viral genomic RNA was detected by in situ hybridization, and apoptosis with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. The amount of viral genomic RNA was observed to increase during infection. HCV replicated rapidly, since characteristics of viral morphogenesis resembling those of yellow fever virus in a hepatoma cell line could be found 2 days after infection. These included the following: a) several viral particles identical in size (about 42 nm) and structure (a spherical 30-nm-sized electron-dense nucleocapsid surrounded by a membrane) to yellow fever virus were present in the cytoplasm of cells displaying already typical signs of the early stage of apoptosis; b) numerous membrane-bound organelles and in particular the endoplasmic reticulum and vacuoles were observed; c) proliferation of membranes was apparent; and d) intracytoplasmic electron-dense inclusion bodies which have been demonstrated to correspond to nucleocapsids for other flaviviruses were detected. Several cells presented electron-dense areas in the endoplasmic reticulum displaying 30-nm circular structures lying among an amorphous material. Striking cytopathic features with ballooning, extremely enlarged vacuoles and signs of apoptosis were found in cells often containing sequestered aggregates of virus-like particles. By in situ hybridization we found that such enlarged cells contained HCV RNA. Our results thus indicate that the ultrastructural features of HCV viral particles and their morphogenesis resemble that of yellow fever virus and dengue virus. In Daudi cells, HCV infection seems to rapidly trigger apoptotic cell death, and efficient release of viral particles does not seem to take place.

Apoptosis↗

Lithuanian haemophilia A and B registry comprising phenotypic and genotypic data.

Haemophilia represents the most common hereditary severe bleeding disorder in humans. About 100 families with this condition live in Lithuania, one of the Baltic states with a population of 3.7 million. Haemophilia care and genetic counselling are still rendered difficult owing to limited availability of clotting factor concentrate and molecular genetic diagnosis. In the present study, a haemophilia registry, comprising phenotypic and genotypic data of the majority of Lithuanian haemophilia A and B patients, was established. The phenotype includes the degree of severity, factor VIII:C, factor VIII:Ag, factor IX:C, von Willebrand factor and antigen (VWF:RiCoF, vWF:Ag) and inhibitor status. Genotyping of the factor VIII and IX genes was performed using mutation screening methods and direct sequencing. In 61 out of 63 patients with haemophilia A (96.8%) and all eight patients with haemophilia B (100%), the causative mutations could be detected. Nineteen of the factor VIII gene defects and two of the factor IX gene mutations are reported for the first time. Identified mutations allowed direct carrier diagnosis in 83 female relatives revealing 44 carriers, 38 non-carriers and one somatic mosaicism. The information provided by this registry will be helpful for monitoring the treatment of Lithuanian haemophilia patients and also for reliable genetic counselling of the affected families in the future.

Factor IX↗

Diamond colour centres as a nanoscopic light source for scanning near-field optical microscopy.

Recently it was shown that a single molecule at cryogenic temperatures could be used as a local light source for illumination of a sample in the near field. Conventional light-emitting systems such as dye molecules and semiconductor quantum dots could also be used for this purpose, but they suffer from lack of photostability. However, colour centres in diamond have been found to be remarkably stable against bleaching and blinking effects. Here we present the first SNOM images taken with nanoscopic diamond crystals as a light source.

Journal Article↗