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Biomedical subjects

Thomas Berger

Publications and source records attributed to Thomas Berger.

At least 55 records · Page 3Linked to original sources

Comparison of the specificity of implantable dual chamber defibrillator detection algorithms.

The aim of the study was to compare the specificity of dual chamber ICDs detection algorithms for correct classification of supraventricular tachyarrhythmias derived from clinical studies according to their size to detect an impact of sample size on the specificity. Furthermore, the study sought to compare the specificities of detection algorithms calculated from clinical data with the specificity calculated from simulations of tachyarrhythmias. A survey was conducted of all available sources providing data regarding the specificity of five dual chamber ICDs. The specificity was correlated with the number of patients included, number of episodes, and number of supraventricular tachyarrhythmias recorded. The simulation was performed using tachyarrhythmias recorded in the electrophysiology laboratory. The range of the number of patients included into the studies was 78-1,029, the range of the total number of episodes recorded was 362-5,788, and the range of the number of supraventricular tachyarrhythmias used for calculation of the specificity for correct detection of these arrhythmias was 100 (Biotronik) to 1662 (Medtronic). The specificity for correct detection of supraventricular tachyarrhythmias was 90% (Biotronik), 89% (ELA Medical), 89% (Guidant), 68% (Medtronic), and 76% (St. Jude Medical). There was an inverse correlation (r = -0.9, P = 0.037) between the specificity for correct classification of supraventricular tachyarrhythmias and the number of patients. The specificity for correct detection of supraventricular tachyarrhythmias calculated from the simulation after correction for the clinical prevalence of the simulated tachyarrhythmias was 95% (Biotronik), 99% (ELA Medical), 94% (Guidant), 93% (Medtronic), and 92% (St. Jude Medical). In conclusion, the specificity of ICD detection algorithms calculated from clinical studies or registries may depend on the number of patients studied. Therefore, a direct comparison between different detection algorithms based on clinical data is difficult. In contrast, simulation of supraventricular tachyarrhythmias using a uniform database may be a better tool for direct comparison of the specificity of ICD detection algorithms.

Arrhythmias, Cardiac↗

Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event.

BACKGROUND: Most patients with multiple sclerosis initially present with a clinically isolated syndrome. Despite the fact that clinically definite multiple sclerosis will develop in up to 80 percent of these patients, the course of the disease is unpredictable at its onset and requires long-term observation or repeated magnetic resonance imaging (MRI). We investigated whether the presence of serum antibodies against myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP) in patients with a clinically isolated syndrome predicts the interval to conversion to clinically definite multiple sclerosis. METHODS: A total of 103 patients with a clinically isolated syndrome, positive findings on cerebral MRI, and oligoclonal bands in the cerebrospinal fluid were studied. At base line, serum samples were collected to test for anti-MOG and anti-MBP antibodies with Western blot analysis, and the lesions detected by cerebral MRI were quantified. Neurologic examinations for relapse or disease progression (defined as conversion to clinically definite multiple sclerosis) were performed at base line and subsequently every three months. RESULTS: Patients with anti-MOG and anti-MBP antibodies had relapses more often and earlier than patients without these antibodies. Only 9 of 39 antibody-seronegative patients (23 percent) had a relapse, and the mean (+/-SD) time to relapse was 45.1+/-13.7 months. In contrast, 21 of 22 patients (95 percent) with antibodies against both MOG and MBP had a relapse within a mean of 7.5+/-4.4 months, and 35 of 42 patients (83 percent) with only anti-MOG antibodies had a relapse within 14.6+/-9.6 months (P<0.001 for both comparisons with antibody-seronegative patients). The adjusted hazard ratio for the development of clinically definite multiple sclerosis was 76.5 (95 percent confidence interval, 20.6 to 284.6) among the patients who were seropositive for both antibodies and 31.6 (95 percent confidence interval, 9.5 to 104.5) among the patients who were seropositive only for anti-MOG antibodies, as compared with the seronegative patients. CONCLUSIONS: Analysis of antibodies against MOG and MBP in patients with a clinically isolated syndrome is a rapid, inexpensive, and precise method for the prediction of early conversion to clinically definite multiple sclerosis. This finding may be important for the counseling and care of patients with a first demyelinating event suggestive of multiple sclerosis.

Adolescent↗

Distinct time pattern of complement activation and cytotoxic T cell response in Guillain-Barré syndrome.

Humoural and cellular immune mechanisms are involved in the pathogenesis of Guillain-Barré syndrome (GBS). While activation of complement has been implicated in the initiation of myelin damage, we provide data here on the role of cellular cytotoxicity in GBS. Archival autopsy tissues including spinal roots, dorsal root ganglia and peripheral nerve were examined from 11 subjects who died 1 day to 8 weeks after onset of symptoms from GBS exhibiting a primary demyelinating pathology. In order to study the extent of humoural and cellular immune processes with regard to disease duration, a broad panel of antibodies to immunological and cellular markers was used to visualize the stage of demyelination, the deposition of complement components and expression of CD59, and to characterize cell infiltrates. Deposits of C9neo antigen on degenerating myelin sheaths were predominantly detected in acute cases. Expression of CD59 was upregulated on demyelinating fibres, but did not correlate with the presence of C9neo antigen or duration of disease. Quantitative analysis of endoneurial T cells showed a correlation between the density of CD3+ T cells per square unit and the degree of demyelination, but not with the duration of disease. The ratio of CD8+ to CD3+ T cells, however, was significantly increased in cases of GBS with a subacute course. Granzyme B positive lymphocytes and upregulation of MHC class I molecules on Schwann cells and myelin sheaths were detected in cases with more than 4 weeks disease duration. These findings implicate an important role of cytotoxic T cell responses for myelin damage in subacute stages of GBS.

Adult↗

Hyperpolarization-activated current Ih disconnects somatic and dendritic spike initiation zones in layer V pyramidal neurons.

Layer V pyramidal cells of the somatosensory cortex operate with two spike initiation zones. Subthreshold depolarizations are strongly attenuated along the apical dendrite linking the somatic and distal dendritic spike initiation zones. Sodium action potentials, on the other hand, are actively back-propagating from the axon hillock into the apical tuft. There they can interact with local excitatory input leading to the generation of calcium action potentials. We investigated if and how back-propagating sodium action potentials alone, without concomitant excitatory dendritic input, can initiate calcium action potentials in the distal dendrite. In acute slices of the rat somatosensory cortex, layer V pyramidal cells were studied under current-clamp with simultaneous recordings from the soma and the apical dendrite. A train of four somatic action potentials had to reach high frequencies to induce calcium action potentials in the dendrite ("critical frequency," CF approximately 100 Hz). Depolarization in the dendrite reduced the CF, while hyperpolarization increased it. The CF depended on the presence of the hyperpolarization-activated current Ih: blockade with 20 microM 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride (ZD7288) reduced the CF to 68% of control. If the neurons were stimulated with noisy current injections, leading to in-vivo-like irregular spiking, no calcium action potentials were induced in the dendrite. However, after Ih channel blockade, calcium action potentials were frequently seen. These data suggest that Ih prevents initiation of the dendritic calcium action potential by proximal input alone. Dendritic calcium action potentials may therefore represent a unique signature for coincident somatic and dendritic activation.

Action Potentials↗

Neonatal kyphectomy in the patient with myelomeningocele.

STUDY DESIGN: A retrospective cohort study was used to investigate a group of neonates with myelomeningocele who had a kyphectomy performed in conjunction with dural sac closure during the first few days of life. OBJECTIVES: To assess the effectiveness of operative intervention in the neonatal period to correct the kyphotic deformity in the patient with myelomeningocele and to monitor its long-term results. SUMMARY OF BACKGROUND DATA: Orthopedic management originally focused on the immediate treatment of the kyphotic deformity in the infant with myelomeningocele. However, there has been a movement toward postponing surgical treatment of the kyphos until a later age. This study included the longest follow-up of the largest group of neonates that a single surgeon has managed surgically since the treatment of this condition was originally described. METHODS: The radiographic and clinical results for all neonates treated with a kyphectomy at the time of myelomeningocele closure between 1980 and 2000 were analyzed. RESULTS: Neonatal kyphectomy was performed on nine males and two females. The average preoperative kyphotic angle measured 67 degrees. The average initial correction was 77 degrees, and the average loss of correction at follow-up assessment was 55 degrees. There were no serious complications, and wound closure was successful in all patients. One patient required a repeat kyphectomy and posterior spinal fusion at the age of 9 years and 2 months. The average follow-up period was 7 years and 4 months (range 44-174 months). CONCLUSIONS: Kyphectomy performed at the time of dural sac closure in the neonate is a safe procedure with excellent initial correction. Eventual recurrence is expected despite the procedure. However, it occurs in the form of a longer, more rounded deformity that is less technically demanding.

Age Factors↗

Energy transfer on the MgO surface, monitored by UV-induced H2 chemisorption.

Surface anions on edges (4-coordinated = 4C) and on corners (3-coordinated = 3C) of cubic MgO nanoparticles exhibit UV resonance absorptions around 5.5 and 4.6 eV, respectively. After monochromatic excitation of either site the electron paramagnetic resonance (EPR) spectrum exhibits exclusively signal components related to 3-coordinated O- radicals (O-(3C), electron hole centers), which are perfectly bleached by H(2) addition. The disappearance of the O-(3C) EPR signal components is paralleled by a depletion of the UV resonance absorption of the 3-coordinated O(2-) only and the appearance of one single band in the OH stretching region of the IR spectrum. Obviously the sites of UV excitation and subsequent UV induced surface reaction with H(2) are not the same. This may coherently be explained in terms of mobility of the exciton (O(2-)(4C)* or--after ionization--of the corresponding electron hole O-(4C) along the edge where it was created. Finally the mobile state is trapped at a corner site where the O(3C)H group is formed.

Journal Article↗

Serum and cerebrospinal fluid antibodies to Nogo-A in patients with multiple sclerosis and acute neurological disorders.

Nogo-A is a protein associated with central nervous system (CNS) myelin thought to impair regenerative responses and to suppress sprouting and plastic changes of synaptic terminals. In this study, we report that serum IgM autoantibodies to the recombinant large N-terminal inhibitory domain of Nogo-A are a frequent finding in multiple sclerosis (MS) and acute inflammatory (IND) and non-inflammatory neurological diseases (OND), but not in neurodegenerative diseases (ND), systemic inflammatory disease and healthy controls. Furthermore, we demonstrate intrathecal production of anti-Nogo-A antibodies measured by increased IgG indices. Intrathecal anti-Nogo antibodies were significantly more frequent in patients with relapsing-remitting as compared to chronic progressive (CP) MS. We also found a highly significant negative correlation of these antibody responses with age indicating that they are more frequent in younger patients. We finally demonstrate that human anti-Nogo-A antibodies recognize native Nogo-A in brain extracts, oligodendrocytes and cells expressing human Nogo-A.

Acute Disease↗

Serial contrast-enhanced magnetic resonance imaging and spectroscopic imaging of acute multiple sclerosis lesions under high-dose methylprednisolone therapy.

To evaluate biochemical changes in contrast-enhancing multiple sclerosis (MS) lesions, we examined 14 patients with relapsing-remitting MS at acute clinical exacerbation with the help of contrast-enhanced magnetic resonance imaging (MRI) and 1H magnetic resonance spectroscopic imaging (1H MRSI). Using a 1.5-tesla MR system (Magnetom Vision, Siemens, Germany), we followed 29 contrast-enhancing and 24 nonenhancing MS lesions as well as normal-appearing white matter (NAWM) before and during high-dose methylprednisolone (HDMP) therapy. Metabolite ratios of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate (Lac) were calculated. A transient decrease in contrast enhancement under HDMP therapy was observed. Both groups of MS lesions showed significantly decreased NAA to Cr ratios compared to NAWM with no changes in time. Baseline 1H MRSI revealed significantly increased Cho to Cr ratios in the contrast-enhancing MS lesions (1.13 +/- 0.25) compared to the nonenhancing MS lesions (0.85 +/- 0.26, P < 0.001) and NAWM (0.97 +/- 0.22, P = 0.015). Both the contrast-enhancing and the nonenhancing MS lesions exhibited a significant increase in Cho to Cr ratios from the second to the third 1H MRSI. We identified resonances of lactate in both groups of MS lesions and NAWM without any significant group differences or changes over time. 1H MRSI provides additional information that help to estimate macrophages' activity, cell membrane activation, and neuronal impairment within MS lesions. We believe that combined contrast-enhanced MRI and 1H MRSI may help to further investigate inflammatory processes within active MS lesions and should be employed more frequently to the research on therapy effects in MS.

Acute Disease↗

The influence of high versus normal impedance ventricular leads on pacemaker generator longevity.

As pacemaker generator longevity is dependent on current consumption and resistance of the pacing lead, the use of a high impedance pacing lead theoretically results in an extension of battery longevity. Therefore, the effect of high versus standard impedance ventricular leads on generator longevity was studied. In 40 patients (21 women, age 73 +/- 13 years) with a standard dual chamber pacemaker indication, a bipolar standard impedance ventricular lead was implanted in 20 patients, the remaining patients received a bipolar high impedance lead in a randomized fashion. All patients received identical pacemaker generators and atrial leads. The estimated longevity of the generator was calculated automatically by a programmed pacemaker algorithm. After a mean follow-up of 39 +/- 4.8 months, no significant differences were observed with respect to mean pacing and sensing thresholds of the atrial and ventricular leads in both groups. However, the high impedance leads displayed a significantly higher impedance and a significantly lower current drain as compared to standard impedance leads (1,044 +/- 139 vs 585 +/- 90 Omega, and 2.2 +/- 0.4 vs 4.3 +/- 1.1 mA). The extrapolated generator longevity was significantly longer in the high impedance lead group, as compared to the standard impedance lead group (107.3 +/- 8.5 vs 97.6 +/- 9.0 months; P = 0.02). In conclusion, implantation of a high impedance lead for ventricular pacing results in a clinically relevant extension of generator longevity.

Aged↗

Atrial noninvasive activation mapping of paced rhythm data.

INTRODUCTION: Atrial arrhythmias have emerged as a topic of great interest for clinical electrophysiologists. Noninvasive imaging of electrical function in humans may be useful for computer-aided diagnosis and treatment of cardiac arrhythmias, which can be accomplished by the fusion of data from ECG mapping and magnetic resonance imaging (MRI). METHODS AND RESULTS: In this study, a bidomain-theory-based surface heart model activation time (AT) imaging approach was applied to paced rhythm data from four patients. Pacing sites were the right superior pulmonary vein, left inferior pulmonary vein, left superior pulmonary vein, coronary sinus, posterior wall of right atrium, and high right atrium. For coronary sinus pacing, the AT pattern of the right atrium was compared with a CARTO map. The root mean square error between CARTO geometry (85 nodal points) and the surface model of the right atrium was 8.6 mm. The correlation coefficient of the noninvasively obtained AT map of the right atrium and the CARTO map was 0.76. All pulmonary vein pacing sites were identified. The reconstructed pacing site of right posterior atrial pacing correlates with the invasively determined pacing catheter position with a localization distance of 4 mm. CONCLUSION: The individual anatomic model of the atria of each patient enables accurate noninvasive AT imaging within the atria, resulting in a localization error for the pacing sites within 10 mm. Our findings may have implications for imaging of atrial activity in patients with focal arrhythmias or focal triggers.

Adult↗

A new paraclinical CSF marker for hypoxia-like tissue damage in multiple sclerosis lesions.

Recent studies on the immunopathology of multiple sclerosis revealed a heterogeneity in the patterns of demyelination, suggesting interindividual differences in the mechanism responsible for myelin destruction. One of these patterns of demyelination, characterized by oligodendrocyte dystrophy and apoptosis, closely mimics myelin destruction in acute white matter ischaemia. In the course of a systematic screening for virus antigen expression in multiple sclerosis brains, we identified a monoclonal antibody against canine distemper virus, which detects a cross-reactive endogenous brain epitope, highly expressed in this specific subtype of actively demyelinating multiple sclerosis lesions with little or no immunoreactivity in other active multiple sclerosis cases. The respective epitope, which is a phosphorylation-dependent sequence of one or more proteins of 50, 70 and 115 kDa, is also expressed in a subset of active lesions of different virus-induced inflammatory brain diseases, but is present most prominently and consistently in acute lesions of white matter ischaemia. Its presence is significantly associated with nuclear expression of hypoxia-inducible factor-1 alpha within the lesions of both inflammatory and ischaemic brain diseases. The respective epitope is liberated into the CSF and, thus, may become a useful diagnostic tool to identify clinically a defined multiple sclerosis subtype.

Acute Disease↗

Timing and precision of spike initiation in layer V pyramidal cells of the rat somatosensory cortex.

The timing and location of action potential initiation in layer V pyramidal cells of the rat somatosensory cortex depends on different ligand-gated and intrinsic conductances. In order to assess the shunting effect of GABA(A) receptor activation and I(h) on the summative properties of these neurons, we recorded simultaneously from their somata and dendrites and induced combined excitatory and inhibitory postsynaptic potentials using extracellular stimulation. Three major consequences of GABA(A) receptor activation on the integration properties were found: (i) the action potential could be initiated in the distal apical dendrite, if GABA(A) receptors were simultaneously activated in the soma; (ii) GABA(A) receptor activation narrowed the time window for suprathreshold summation of two coincident excitatory synaptic inputs by a factor of 3.4; and (iii) uneven weights of the GABAergic components between two inputs could lead to unbalanced shunting and consequently to a time shift in the peak of the coincidence detection window. Blockade of I(h) practically abolished coincidence detection within a time window of 30 ms. Location of spike initiation and summation of coincident inputs in pyramidal cells is determined by at least two shunting mechanisms: activation of the presynaptic inhibitory network and modulation of I(h) as a function of the postsynaptic membrane potential.

Action Potentials↗

Cutaneous melanoma metastasizing to the iris and choroid: a case report.

BACKGROUND: Cutaneous melanoma is a primary tumour that rarely produces intraocular metastases. We report on a 47-year-old woman who was referred to our outpatient department because of anisocoria. METHODS: A cutaneous melanoma of the upper left arm had been excised 21 months ago with subsequent polychemotherapy for lymph node involvement. Visual acuity and intraocular tension were normal. The left iris showed a brownish, parapupillary, prominent nodule. In both eyes, multiple circumscribed whitish choroidal sub-pigment epithelial tumours were observed. RESULTS: General metastasis to lymph nodes, pleura, lungs, mucosa and skin was diagnosed. The patient died 2 months later. CONCLUSION: Metastases of cutaneous melanoma to the iris are extremely rare. The ophthalmologist may be helpful in monitoring treatment by quantitative documentation at follow-up.

Choroid Neoplasms↗

Angiotensin II influences the hyperpolarization-activated current Ih in neurones of the rat paraventricular nucleus.

The hypothalamic paraventricular nucleus (PVN) consists of mainly two types of neurones (type I and type II), according to their characteristic electrophysiological properties. An excitatory influence of angiotensin II (Ang II) on PVN neurones has been shown to be mediated by the AT(1) receptor. We investigated the underlying mechanism of the Ang II effect on PVN neurones with patch-clamp experiments. Using current-clamp mode, we identified a sag in 59% of only type II neurones due to a hyperpolarization-activated current I(h). Voltage-clamp measurements revealed that Ang II (1 microM) provokes a shift of the I(h) activation curve to more depolarized values by 8.1 mV, an effect reduced by the additional application of the AT(1) receptor antagonist Losartan (10 microM). These findings suggest that the excitatory effect of Ang II in type II neurones is at least partially due to an increased population of active I(h) channels.

Angiotensin II↗

Antibody response to myelin oligodendrocyte glycoprotein and myelin basic protein depend on familial background and are partially associated with human leukocyte antigen alleles in multiplex families and sporadic multiple sclerosis.

We investigated the association of the antibody response to myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP) with human leukocyte antigen (HLA) class II alleles in 41 patients with sporadic multiple sclerosis (MS) and 12 multiplex MS families. We found significantly increased antibody response to MOG and MBP in MS patients without any difference to asymptomatic relatives. HLA DRB1*04 was associated with IgM reactivity to MOG in MS patients, and DRB1*15 and DRB5 with anti-MOG IgA among asymptomatic relatives. We conclude that antibody responses to MOG and MBP depend on familial background. Moreover, the humoral immune reactivity against MOG is partially under control of certain HLA class II alleles.

Adult↗