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Biomedical subjects

C Baumgartner

Publications and source records attributed to C Baumgartner.

At least 19 recordsLinked to original sources

Association of an ABCB1 gene haplotype with pharmacoresistance in temporal lobe epilepsy.

The multidrug transporter P-glycoprotein is suspected of contributing to pharmacoresistance in temporal lobe epilepsy (TLE). To assess the role of functional variations in its coding gene (ABCB1) the authors genotyped 210 patients with TLE who were stratified according to their degree of drug resistance. They identified a common haplotype that when present in the homozygous state significantly increased the risk for pharmacoresistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Postictal paresis in focal epilepsies--incidence, duration, and causes: a video-EEG monitoring study.

BACKGROUND: Although familiar to every neurologist, postictal paresis (PP) has only rarely been analyzed systematically. OBJECTIVE: To describe the frequency and duration of PP in patients undergoing video-EEG monitoring, the semiology characteristics of seizures preceding PP, and the pattern of associated symptoms and signs. METHODS: The records of 513 consecutive patients who underwent prolonged video-EEG monitoring during presurgical epilepsy evaluation were reviewed for postictal motor deficit. Three hundred twenty-eight patients fulfilled the inclusion criteria. The videotapes of patients with PP were subsequently analyzed with a careful analysis of ictal motor phenomena at the side of the PP. RESULTS: PP was found in 44 patients (13.4%). PP was always unilateral and always contralateral to the seizure focus and had a median duration of 173.5 seconds (range 11 seconds to 22 minutes). Of all seizures with PP, 77.8% were accompanied by evident and 9.7% by very slight ictal motor phenomena ipsilateral to the side of PP, whereas 9.7% of the seizures showed no motor signs (two seizures [2.8%] could not be evaluated for motor phenomena). The most common ictal lateralizing sign was unilateral clonic activity in 55.6% of all seizures. Concomitant dystonic posturing was found in 47.9% and ictal limb immobility in 24.6% of the seizures. PP was of longer duration if ictal clonic activity was present and after tonic-clonic seizures. CONCLUSIONS: PP is relatively frequent (13.4%), is easy to detect, and has a high lateralizing value. The high incidences of dystonic posturing and of ictal limb immobility in our patients with PP may indicate that an active inhibitory process is involved in its pathogenesis.

Adolescent↗

Supervised machine learning techniques for the classification of metabolic disorders in newborns.

MOTIVATION: During the Bavarian newborn screening programme all newborns have been tested for about 20 inherited metabolic disorders. Owing to the amount and complexity of the generated experimental data, machine learning techniques provide a promising approach to investigate novel patterns in high-dimensional metabolic data which form the source for constructing classification rules with high discriminatory power. RESULTS: Six machine learning techniques have been investigated for their classification accuracy focusing on two metabolic disorders, phenylketo nuria (PKU) and medium-chain acyl-CoA dehydrogenase deficiency (MCADD). Logistic regression analysis led to superior classification rules (sensitivity >96.8%, specificity >99.98%) compared to all investigated algorithms. Including novel constellations of metabolites into the models, the positive predictive value could be strongly increased (PKU 71.9% versus 16.2%, MCADD 88.4% versus 54.6% compared to the established diagnostic markers). Our results clearly prove that the mined data confirm the known and indicate some novel metabolic patterns which may contribute to a better understanding of newborn metabolism.

Algorithms↗

Vestibular processing in human paramedian precuneus as shown by electrical cortical stimulation.

The authors describe a 16-year-old patient with recurrent episodes of epileptic linear self-motion perception and occasional body tilts. Intracranial seizure monitoring located the seizure onset, caused by a circumscribed ependymoma, in the right paramedian precuneus. Electrical cortical stimulation of this area could reproduce the same vestibular sensations, which ceased after lesionectomy. The findings implicate the paramedian area of the precuneus in the processing of static and dynamic vestibular, probably otolithic, information.

Adolescent↗

Anaesthesia with midazolam/medetomidine/fentanyl in chinchillas (Chinchilla lanigera) compared to anaesthesia with xylazine/ketamine and medetomidine/ketamine.

We studied four different drug regimes for anaesthetic management in chinchillas and evaluated and compared their cardiovascular and respiratory effects. In this randomized, cross-over experimental study, seven adult chinchillas, five females, two males [515 +/- 70 (SD) g] were randomly assigned to one of the following groups: group 1 [midazolam, medetomidine and fentanyl (MMF), flumazenil, atipamezole and naloxone (FAN); MMF-FAN] received 1.0 mg/kg midazolam, 0.05 mg/kg medetomidine and 0.02 mg/kg fentanyl i.m., and for reversal 0.1 mg/kg flumazenil, 0.5 mg/kg atipamezole and 0.05 mg/kg naloxone s.c. after 45 min; group 2 (MMF) 1.0 mg/kg midazolam, 0.05 mg/kg medetomidine and 0.02 mg/kg fentanyl i.m.; group 3 [xylazine/ketamine (X/K)] 2.0 mg/kg xylazine and 40.0 mg/kg ketamine i.m.; and group 4 [medetomidine/ketamine (M/K)] 0.06 mg/kg medetomidine and 5.0 mg/kg ketamine i.m. Reflexes were judged to determine anaesthetic stages and planes. Anaesthesia with X/K and M/K was associated with a prolonged surgical tolerance and recovery period. By reversing MMF, recovery period was significantly shortened (5 +/- 1.3 min versus 40 +/- 10.3 min in MMF without FAN, 73 +/- 15.0 min in X/K, and 31 +/- 8.5 min in M/K). Without reversal, MMF produced anaesthesia lasting 109 +/- 16.3 min. All combinations decreased respiratory and heart rate but compared with X/K and M/K, respiratory and cardiovascular complications were less in the MMF groups. Focussing on the clinical relevance of the tested combinations, completely reversible anaesthesia showed two major advantages: anaesthesia can be antagonized in case of emergency and routinely shortens recovery. In small animals particularly these advantages lead to less complications and discomfort and thus often can be lifesaving. As all analgesic components (medetomidine and fentanyl) are reversed, postoperative analgesia should be provided before reversal of anaesthesia.

Anesthesia↗

Preserved memory traces within diencephalic amnesia.

A male patient with bilateral thalamic lesions (medio-ventral nuclei) was investigated. Despite explicit memory impairments his lexical ability was normal. We recorded magnetic field changes (magnetoencephalography, MEG) during the performance of an animate/inanimate discrimination task in which some words where repeated after long delays. Normally, repeated items are classified significantly faster than their first presentations which is accomplished by an unconscious process called priming. The patient did not show any behavioural evidence of priming but the physiological data indicated preservation of this robust form of memory. Brain activation associated with repetitions was attenuated at early stages. The activity difference was posteriorly distributed which is consistent with previous reports about repetition priming. The present study indicated that the bilateral thalamic lesions of our patient disconnected the information processing stream between the primed information and the behavioural response.

Amnesia↗

Pulmonary hypertension induced in dogs by hypoxia at different high-altitude levels.

Chronic natural hypoxia at 2300 m altitude induces mild pulmonary hypertension (PH) in healthy dogs. The influence of more severe hypoxia on the same group of dogs was evaluated by re-examining such dogs at 3500 m, after they had regularly exercised at this altitude level for half a year. Despite severe hypoxaemia at 3500 m (PaO2 52+/-5 mmHg), none of the dogs developed erythrocytosis, and their PCV at 3500 m (48% +/- 4%) did not differ from that at 2300 m (49% +/- 4%). There was a tendency towards an elevated systemic BP, with a significant increase in diastolic BP (105 +/- 13 mmHg at 3500 m versus 98 +/- 17 at 2300 m). Tricuspid regurgitation (TR) was detected in 7 dogs at 3500 m compared to 8 dogs at 2300 m. The mean TR Vmax was significantly higher at 3500 m, and all 7 dogs had systolic PH at 3500 m (33.6-54.8 mmHg), when PH was defined as TR Vmax > or = 2.8 m/s, i.e. a peak pressure gradient > 30 mmHg. Hence, in dogs, increasing altitude and the concomitant hypoxia result in a progressively more pronounced PH and an elevated systemic BP. Intermittent severe hypoxaemia of around 50 mmHg may not cause erythrocytosis in healthy dogs, even over a prolonged period.

Altitude↗

[Congenital cardiac diseases in dogs: a retrospective analysis].

In a time period of 6 years, 158 congenital cardiac defects were diagnosed in 146 dogs at the Clinic for Small Animal Medicine University of Zurich. In respect to all dogs with cardiac disease, these were 23.5% of the cases. Most common defects were subaortic stenosis (SAS, 31.5%), pulmonic stenosis (PS, 23.3%), ventricular septal defect (VSD, 14.4%), patent ductus arteriosus (PDA, 13.7%) and tricuspid dysplasia (TD, 7.5%). Complex defects were found in 8.2% of the dogs. Although single dogs per breed were affected by various defects, some breed-related tendencies could be observed. We found PS more numerously in boxers and Jack Russell Terriers whereas SAS, VSD and TD were also found in breeds reported to be predisposed. Congenital cardiac defects are an important clinical entity, and knowledge of prevalence is helpful when considering the differential diagnosis and for making a tentative diagnosis in an individual case.

Animals↗

[Cardiac tamponade due to pericardial mesothelioma in an 11-year-old dog: diagnosis, medical and interventional treatments].

In a dog presenting with the clinical signs of exercise intolerance and ascites, cardiac tamponade due to suspected idiopathic pericarditis was diagnosed based on thoracic radiographs, electrocardiogram (EKG) and cardiac ultrasound. Pericardial effusion recurred soon after pericardiocenteses, prescription of colchizine and again after balloon pericardiotomy. After partial pericardectomy by thoracoscopy and after obtaining a histological diagnosis of mesothelioma adjuvant intracavitary chemotherapy using cisplatin was performed. Already one week later the dog developed marked dyspnea due to severe pleural effusion. The dog was maintained at acceptable life quality judged based on playfulness and appetite using repeated pleuro-centeses for an additional two months, when the dog was euthanized due to uncontrollable pleural effusion. Despite extensive treatments life span from initial presentation to euthanasia was only 5 months. Necropsy revealed extensive mesothelioma metastases covering the whole pleura, epicardium and remaining pericardium. Diagnostic and therapeutic aspects of (recurrent) pericardial effusion are discussed based on this case.

Animals↗

[Possibilities of minimal invasive cardiac catheter interventions in the dog].

The therapeutic possibilities in veterinary cardiology have developed rapidly in the past few years. Whereas until recently cardiac intervention in dogs could only be performed by thoracotomy, new minimally invasive techniques are adopted. Procedures like balloondilatation of pulmonic stenosis, coil embolisation of patent ductus arteriosus, pacemaker implantation in symptomatic bradyarrhyhtmia, and palliative balloon pericardiotomy are becoming more and more established. These alternative interventional methods are attractive, because no postsurgical pain and no complications potentially associated with thoracotomy ensue. The knowledge of such new treatment modalities and particularly the indications for an intervention are prerequisites to apply them optimally and broadly.

Animals↗

Effects of two Gbetagamma-binding proteins--N-terminally truncated phosducin and beta-adrenergic receptor kinase C terminus (betaARKct)--in heart failure.

Myocardial overexpression of the C-terminus of beta-adrenergic receptor kinase (betaARKct) has been shown to result in a positive inotropic effect or an improvement of survival in heart failure. However, it is not clear whether this beneficial effect is mainly because of dominant-negative inhibition of betaARK1, and a consecutive resensitization of beta-adrenergic receptors (betaAR), or rather due to inhibition of other Gbetagamma-mediated effects. In this study, we tested whether overexpression of N-terminally truncated phosducin (nt-del-phosducin), another Gbetagamma-binding protein that does not resensitize betaARs owing to simultaneous inhibition of GDP release from Galpha subunits, shows the same effects as betaARKct. Adenoviral gene transfer was used to express nt-del-phosducin and betaARKct in isolated ventricular cardiomyocytes and in myocardium of rabbits, which suffered from heart failure because of rapid ventricular pacing. BetaAR-stimulated cAMP formation was increased by betaARKct, but not by nt-del-phosducin, whereas both proteins inhibited Gbetagamma-mediated effects. Both transgenes also increased contractility of normal and failing isolated cardiomyocytes and improved contractility in rabbits with heart failure after gene transfer in vivo. In conclusion, overexpression of nt-del-phosducin enhances the contractility of cardiomyocytes to the same extent as betaARKct, suggesting that the effects of betaARKct might be owing to inhibition of Gbetagamma rather than to betaAR resensitization.

Adenoviridae↗

Asymmetric ending of secondarily generalized seizures: a lateralizing sign in TLE.

The authors investigated whether asymmetric ending of the clonic phase of secondarily generalized tonic clonic seizures (SGTCS) has lateralizing value concerning the hemisphere of seizure onset. They studied 70 patients with mesial temporal lobe epilepsy who underwent epilepsy surgery. Asymmetric ending of the clonic phase occurred in 43% of patients. The last clonic movement appeared on the upper extremity ipsilateral to the hemisphere of seizure onset in 83%.

Chi-Square Distribution↗

Altered expression of voltage-dependent calcium channel alpha(1) subunits in temporal lobe epilepsy with Ammon's horn sclerosis.

Voltage-dependent calcium channels, the initial components in the calcium signalling cascade, are increasingly being recognised as relevant factors in the pathology of epilepsy. To further characterise their role in temporal lobe epilepsy associated with Ammon's horn sclerosis, we investigated the immunohistochemical distribution of five different voltage-dependent calcium channel alpha(1) subunits (alpha(1A), alpha(1B), alpha(1C), alpha(1D), alpha(1E)) in 14 hippocampal specimens of patients with Ammon's horn sclerosis in comparison with eight autopsy control cases. In epilepsy specimens an increased immunoreactivity was observed for alpha(1A), alpha(1B), alpha(1D) and alpha(1E) in the neuropil of the dentate gyrus molecular layer. Dentate gyrus granule cells and residual CA3 pyramidal neurones showed enhanced immunoreactivity for alpha(1A), while labelling of these neurones was decreased for alpha(1C). Astrocytes in Ammon's horn sclerosis specimens were strongly immunoreactive for the alpha(1C) subunit contrasting with an absent astrocytic alpha(1C) labelling in controls. Our results suggest that the expression of calcium channels in neurones and glial cells is dynamically regulated in temporal lobe epilepsy, supporting the relevance of calcium signalling pathways for this disease.

Adolescent↗

Plasticity of Y1 and Y2 receptors and neuropeptide Y fibers in patients with temporal lobe epilepsy.

Marked expression of neuropeptide Y (NPY) and its Y2 receptors in hippocampal mossy fibers has been reported in animal models of epilepsy. Because NPY can suppress glutamate release by activating presynaptic Y2 receptors, these changes have been proposed as an endogenous protective mechanism. Therefore, we investigated whether similar changes in the NPY system may also take place in human epilepsy. We investigated Y1 and Y2 receptor binding and NPY immunoreactivity in hippocampal specimens that were obtained at surgery from patients with temporal lobe epilepsy and in autopsy controls. Significant increases in Y2 receptor binding (by 43-48%) were observed in the dentate hilus, sectors CA1 to CA3, and subiculum of specimens with, but not in those without, hippocampal sclerosis. On the other hand, Y1 receptor binding was significantly reduced (by 62%) in the dentate molecular layer of sclerotic specimens. In the same patients, the total lengths of NPY immunoreactive (NPY-IR) fibers was markedly increased (by 115-958%) in the dentate molecular layer and hilus, in the stratum lucidum of CA3, and throughout sectors CA1 to CA3 and the subiculum, as compared with autopsies. In nonsclerotic specimens, increases in lengths of NPY-IR fibers were more moderate and statistically not significant. NPY mRNA was increased threefold in hilar interneurons of sclerotic and nonsclerotic specimens. It is suggested that abundant sprouting of NPY fibers, concomitant upregulation of Y2 receptors, and downregulation of Y1 receptors in the hippocampus of patients with Ammon's horn sclerosis may be endogenous anticonvulsant mechanisms.

Adolescent↗

Chromogranins as markers of altered hippocampal circuitry in temporal lobe epilepsy.

Chromogranins are polypeptides which are widely expressed in the central nervous system. They are stored in dense core vesicles of nerve terminals, from where they are released upon stimulation. Using immunocytochemistry, we investigated the distribution of chromogranin A, chromogranin B, secretoneurin, and, for comparison, dynorphin in hippocampal specimens removed at routine surgery from patients with drug-resistant mesial temporal lobe epilepsy and in autopsy tissues from nonneurologically deceased subjects. In post mortem controls (n = 21), immunoreactivity for all 4 peptides (most prominently for chromogranin B and dynorphin) was observed in the terminal field of mossy fibers. For chromogranins, staining was observed also in sectors CA1 to CA3 and in the subiculum. Chromogranin B immunoreactivity was found in the inner molecular layer of the dentate gyrus, the area of terminating associational-commissural fibers. Secretoneurin and dynorphin immunoreactivity labeled the outer molecular layer and the stratum lacunosum moleculare of sectors CA1 to CA3, where projections from the entorhinal cortex terminate. In specimens with Ammon's horn sclerosis (n = 25), staining for all 3 chromogranins and for dynorphin was reduced in the hilus of the dentate gyrus. Instead, intense staining was observed in the inner molecular layer, presumably delineating terminals of sprouted mossy fibers. Specimens obtained from temporal lobe epilepsy patients without Ammon's horn sclerosis (n = 4) lacked this pronounced rearrangement of mossy fibers. In the stratum lacunosum moleculare of sector CA1, secretoneurin and dynorphin immunoreactivity was reduced in sclerotic, but not in nonsclerotic, specimens, paralleling the partial loss of fibers arising from the entorhinal cortex. Instead, presumably sprouted secretoneurin-immunoreactive fibers were found in the outer dentate molecular layer in sclerotic specimens. These changes in staining patterns for chromogranins and dynorphin mark profound plastic and functional rearrangement of hippocampal circuitry in temporal lobe epilepsy.

Adult↗

The predictive value of MDR1, CYP2C9, and CYP2C19 polymorphisms for phenytoin plasma levels.

Phenytoin, an anticonvulsant, exhibits nonlinear pharmacokinetics with large interindividual differences. Because of its small therapeutic range with the risk of therapeutic failure or adverse drug effects in susceptible persons, therapeutic drug monitoring is frequently applied. The interindividual differences in dose response can partially be explained by known genetic polymorphisms in the metabolic enzyme CYP2C9 but a large deal of individual variability remains still unexplained. Part of this variability might be accounted for by variable uptake of phenytoin, which is a substrate of p-glycoprotein, encoded by the human MDR1 gene. We evaluated, whether phenytoin plasma levels correlate with a polymorphism in the MDR1 gene, C3435T, which is associated with intestinal PGP activity. Genotyping and analyses of plasma levels of phenytoin and metabolites in 96 healthy Turkish volunteers showed that the MDR1C > T3435 polymorphism affects phenytoin plasma levels (P = 0.064) and the metabolic ratio of p-HPPH vs phenytoin (MDR1*TT genotype, P = 0.026). The MDR1*CC genotype is more common in volunteers with low phenytoin levels (P < or = 0.001, chi2 test). A combined analysis of variable alleles of CYP2C9, 2C19 and MDR1 revealed that the number of mutant CYP2C9 alleles is a major determinant, the number of MDR1*T alleles further contributes to the prediction of phenytoin plasma levels and CYP2C19*2 does not explain individual variability. The regression equation that fitted the data best included the number of mutant CYP2C9 and MDR*T alleles as predictory variables and explained 15.4% of the variability of phenytoin data (r2 = 0.154, P = 0.0002). Furthermore, analysis of CYP2C9 and MDR1 genotypes in 35 phenytoin-treated patients recruited from therapeutic drug monitoring showed that combined CYP2C9 and MDR1 analysis has some predictive value not only in the controlled settings of a clinical trial, but also in the daily clinical practice.

Adolescent↗

Nuclear medicine in the preoperative evaluation of epilepsy.

The clinical usefulness of nuclear medicine in the preoperative evaluation of epilepsy is highlighted with regard to non-lesional temporal lobe epilepsy, extratemporal epilepsy, bitemporal interictal epileptiform discharges (IEDs) and in dual pathology and cortical dysgenesis. Ictal single photon emission computed tomography (SPECT) shows good sensitivities in the correct lateralization of an electroencephalogram-defined epileptic focus in lesional and, to a lesser extent, non-lesional epilepsy. Positron emission tomography (PET) using 18F-fluorodeoxyglucose or 11C-flumazenil gives a good detection rate of the seizure onset zone in non-lesional cases and extratemporal epilepsy. The investigation of patients with bitemporal IEDs can confirm the existence of bitemporal seizure onset. For patients with a dual pathology or cortical dysgenesis nuclear medicine offers the opportunity to delineate the existence or extension of abnormalities possibly responsible for the seizure disorder.

Epilepsy↗