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Biomedical subjects

J Zentner

Publications and source records attributed to J Zentner.

At least 19 recordsLinked to original sources
PubMed2003

Evidence for strychnine-sensitive glycine receptors in human amygdala.

Recent studies suggested the existence of strychnine-sensitive glycine-receptors in mammalian amygdala. In the present study, we investigated the amino acid concentrations as well as immunocytochemical and pharmacological properties of glycine-receptors in fresh human amygdala tissue obtained from epilepsy surgery. High pressure liquid chromatography revealed a considerable amount of glycine and its precursors and glycine-receptors agonists L-serine and taurine in this tissue. Immunohistochemistry using the monoclonal antibody mAb4a, recognizing an epitope common to all alpha-subunit variants of glycine receptors, displayed a specific labeling at the soma and on proximal dendrites of mostly tripolar, large-sized neurons of irregular distribution and arrangement. To elucidate the pharmacological properties of the glycine-receptors found slices of human amygdala were preloaded with [(3)H]-choline and superfused. Glycine induced an overflow of [(3)H]-acetylcholine, which was inhibited by strychnine in a concentration-dependent manner. Furthermore, the glycine-induced release of [(3)H]-acetylcholine was significantly inhibited by furosemide, indicating glycine-induced actions to be attributed to chloride channels. These actions of glycine were not influenced by MK-801, D-CP-Pene or bicuculline. Thus, the effects of glycine did not seem to be mediated through NMDA or GABA receptors. These observations indicate that strychnine-sensitive, chloride-conducting glycine receptors, which elicit the release of [(3)H]-acetylcholine, are present at the soma and on proximal dendrites of neurons in human amygdala. It is hypothesized that glycine may display a regulatory role in amygdaloid functions, probably via cholinergic interneurons.

Acetylcholine↗
PubMed2003

Modulation of electrically evoked acetylcholine release through cannabinoid CB1 receptors: evidence for an endocannabinoid tone in the human neocortex.

Cannabinoids are known to inhibit neurotransmitter release in the CNS through CB1 receptors. The present study compares the effects of synthetic cannabinoids on acetylcholine (ACh) release in human and mice neocortex. We further investigated a possible endocannabinoid tone on CB1 receptors in human neocortex caused by endogenous agonists like anandamide or 2-arachidonylglycerol. Brain slices, incubated with [3H]-choline, were superfused and stimulated electrically under autoinhibition-free conditions to evoke tritium overflow assumed to represent ACh release. The first series of experiments was performed with 26 pulses, 60 mA, at 0.1 Hz. In mice neocortical slices, the cannabinoid receptor agonist WIN55212-2 decreased ACh release (pIC50=6.68, I(max)=67%). In the human neocortex the concentration-response curve of WIN55212-2 was bell-shaped and flat (I(max observed) approximately 30%). The estimated maximum possible inhibition, however, was much larger: I(max derived)=79%. Lec, the negative logarithm (lg) of the biophase concentration of endocannabinoids in 'WIN55212-2 units,' was -6.52, the pKd of WIN55212-2 was 7.47. The CB1 receptor antagonist/inverse agonist SR141716 enhanced ACh release in the human neocortex (by 38%) and prevented the inhibitory effect of WIN55212-2. The concentration-response curve of WIN55212-2 was changed in its shape including a shift to the right due to the presence of SR141716. A pA2 of this antagonist between 11.60 and 11.18 was obtained. SR141716 alone had no effect in mice neocortical slices. A partial agonist without inverse agonistic activity, O-1184, enhanced ACh release in the human neocortex. The endocannabinoid uptake-inhibitor AM404 decreased ACh release in human, but not in mice, neocortical slices. Change of the stimulation parameters (eight trains of pseudo-one-pulse bursts (4 pulses, 76 mA, 100 Hz), spaced by 45 s intervals) led to a stronger inhibitory effect of WIN55212-2, and abolished the disinhibitory effect of SR141716 and O-1184. The results show that activation of CB1 cannabinoid receptors leads to inhibition of ACh release in the human and mouse neocortex. The endocannabinoid tone is high in the human, but not in the mouse neocortex and is dependent on neuronal activity. SR141716 acts as a competitive CB1 receptor antagonist.

Acetylcholine↗
PubMed2003

Shutting down operating theater ventilation when the theater is not in use: infection control and environmental aspects.

OBJECTIVE: In hospital operating rooms (ORs), specially conditioned air is supplied to protect patients from airborne agents that may cause infections. This study investigated whether it is hygienically safe to shut down the air supply at night if measures are taken to ensure a timely restart before surgery is performed. DESIGN: Experimental study. SETTING: Neurosurgical OR of a German university hospital. METHODS: The ventilation system was switched off and restarted after 10 hours. Particles suspended in the air near the operating table were counted, OR temperature was measured, and settle plates were exposed and incubated. RESULTS: In 13 investigations, a median of 1.3 x 10(4) particles 0.5 microm/m3 or greater (range, 5.8 x 10(3) to 1.1 x 10(5)) were documented immediately after restart in the morning. After 10 minutes and subsequently, no test showed a particle count exceeding the threshold limit of 1.0 x 10(4) particles 0.5 microm/m3 or greater recommended by the German Society of Hygiene and Microbiology. Only a few colony-forming units (CFU) were detected per settle plate (median, 0 CFU/60 cm2; range, 0 to 8) and OR temperatures quickly reached normal levels. CONCLUSIONS: Shutting down OR ventilation during off-duty periods does not appear to result in an unacceptably high particle count or microbial contamination of the OR air shortly after the system is restarted. Because substantial energy and cost savings are likely, this should be considered in hygienically safe heating, ventilation, and air conditioning systems. However, normal ventilation should be established at least 30 minutes before surgical activity.

Academic Medical Centers↗
PubMed2002

MR arthrography: pharmacology, efficacy and safety in clinical trials.

OBJECTIVE: A meta-analysis was carried out of clinical trials published between 1987 and 2001 in respect of the clinical pharmacology and safety as well as the diagnostic efficacy of gadolinium-DTPA (Gd-DTPA) for direct intra-articular injection before MRI examination. DESIGN: Scientific papers (clinical, postmortem and experimental studies) and information from the manufacturer regarding intra-articular injection of Gd-DTPA that addressed questions of mode of action, optimal concentration and dose, elimination and safety were reviewed. Clinical studies were classified according to their study design. The sensitivity, specificity and accuracy of MR arthrography (MRA) were compared with a "gold standard" (arthroscopy, arthrotomy) and other radiological evidence for different joints. RESULTS: Fifty-two clinical studies of the overall 112 studies addressed aspects of diagnostic efficacy of MRA in patients or in healthy volunteers. The shoulder was the most assessed joint (29 of 52 studies). Good (>80%) or even excellent (90-100%) sensitivity, specificity and accuracy were found for MRA in most indications, especially for the shoulder and knee joints and induced extension of rotator cuff lesions, labrum abnormalities and postoperative meniscal tears. Two millimoles per liter has proven to be the best concentration for intra-articular administration of Gd-DTPA. After passive complete diffusion from the joint within 6-24 h, complete and rapid renal elimination takes place after intra-articular injection. Local safety proved to be excellent after intra-articular administration of Gd-DTPA. Regarding systemic tolerance almost no side effects have been reported, but the same safety considerations apply for intra-articular administration of Gd-DTPA as for intravenous injection. CONCLUSIONS: The diagnostic efficacy of intra-articular MRA in most clinical conditions affecting major joints is greater than that of plain MRI. In some diagnostic problems MRA achieves almost the same sensitivity and specificity as the surgical gold standard. Given a sterile application, the intra-articular administration of Gd-DTPA in a concentration of 2 mmol/l prior to MRI is a safe procedure.

Arthrography↗
PubMed2002

Surgical treatment of epilepsies.

Epilepsy is characterized by recurrent epileptic seizures. Surgical interventions represent a reasonable alternative to long-term antiepileptic drug treatment in those patients destined to achieve incomplete seizure control. The presurgical work-up aims at identifying appropriate surgical candidates. Surgical options with a curative goal include temporal and extratemporal resections and hemispherectomy. With these procedures complete seizure control can be achieved in approximately 2/3 of patients. With palliative procedures such as callosotomy, multiple subpial transections, and vagal nerve stimulation, approximately half of the patients will significantly improve after surgery. In all, epilepsy surgery has proven to be a highly effective treatment option. Major problems include the definition of the epileptogenic area with respect to optimal seizure control and minimum neurological and neuropsychological impairment after surgery.

Brain Diseases↗
PubMed2002

Effect of skin disinfection with octenidine dihydrochloride on insertion site colonization of intravascular catheters.

BACKGROUND: We investigated the efficacy of two commercially available, alcohol-based antiseptic solutions in decontaminating the insertion site of central lines. One solution contained the bispyridine octenidine dihydrochloride. PATIENTS AND METHODS: Inpatients receiving either a central venous catheter (CVC) or a peripherally inserted central catheter (PICC) were alternately assigned to different skin disinfection regimens at the insertion site: (A) 0.1% octendine dihydrochloride with 30% 1-propanol and 45% 2-propanol, (B) 74% ethanol with 10% 2-propanol. Quantitative skin cultures were obtained from the insertion site at predetermined intervals. RESULTS: A total of 60 patients received 12 CVCs and 47 PICCs (no significant difference with respect to gender, age and catheter type). In total, 90 cultures were assessed in each group. The median colony-forming unit (cfu) counts per 24 cm(2) (group A vs B) were 2,270 vs 2,950 before, 20 vs 40 following and 860 vs 1,210 24 h after catheter insertion, respectively. A statistically significant difference in the efficacy of skin decontamination was seen between groups in culture set (3) and in the difference between culture sets (2) and (3) (Wilcoxon rank sum test). CONCLUSION: Octenidine/propanol appears to be more effective than alcohol (ethanol/propanol) alone in reducing microflora of the skin at the PICC/CVC insertion site over a 24-h period.

1-Propanol↗
PubMed2002

Error analysis in cranial neuronavigation.

Neuronavigation systems are now an important component of many modern neurosurgical treatment strategies. Their support facilities intraoperative orientation and makes neurosurgical operations more precise and less traumatic. Computer-aided neurosurgery is definitively not a temporary fashionable phenomenon, the concept of neuronavigation is here to stay. This report summarizes a ten-years-long experience and presents an error analysis of 108 failures (12.4 %) in a total of 874 image-guided cranial neurosurgical procedures with an arm-linked (mechanical) system and two different infrared-light emitting (optical) systems. The application of neuronavigation incurs multiple reasons for pitfalls because of the complex man-machine interface. Principally, we have to differentiate two types of errors: "machine made errors" due to soft- or hardware failure and "man made errors" generally, due to inadequate handling of the navigation system. The error analysis demonstrated that the so-called human interface plays the main role causing a high error rate.

Bias↗
PubMed2002

Calvarial sclerosing osteomyelitis.

We report a 15-year-old boy who suffered from calvarial sclerosing osteomyelitis and presented with painful head swelling. X-rays of the skull revealed areas of irregular radiolucency. MR imaging and CT showed a well-demarcated intradiploic lesion with thickening of the skull extending from the frontal to the parietal calvarium with a low signal on T1-weighted images, strong but heterogeneous enhancement after gadolinium application and a mixed signal on T2-weighted images. Computer-navigated neurosurgery was planned, and the craniotomy defect was reconstructed by a preformed titanium implant. Sclerosing osteomyelitis of the calvarium has to be included in the differential diagnosis of osteolytic and sclerosing lesions of the skull coinciding with persistent swelling of the head.

Adolescent↗
PubMed2001

Modulation of K+-evoked [3H]-noradrenaline release from rat and human brain slices by gabapentin: involvement of KATP channels.

To elucidate the mechanism of action of the anticonvulsant gabapentin (GBP), we compared its effects on K+-evoked [3H]-noradrenaline ([3H]-NA) release from rat hippocampal and human neocortical slices with those of the KATP channel opener pinacidil and the Na+ channel blockers phenytoin, carbamazepine and lamotrigine. Rat hippocampal and human neocortical slices were loaded with [3H]-NA and superfused. [3H]-NA release was evoked by increasing the extracellular [K+] from 3 to 15 mM. GBP decreased [3H]-NA release from rat hippocampal with a pIC50 of 5.59 and a maximum inhibition of 44%. Concentration-dependent inhibition was also seen in human neocortical slices (39% inhibition with 100 microM GBP). These inhibitory effects were antagonized by the KATP channel antagonist glibenclamide, yielding a pA2 of 7.50 in the rat. The KATP channel opener pinacidil (10 microM), like GBP, decreased [3H]-NA release from rat hippocampal slices by 27% and this effect was also antagonized by glibenclamide. In human neocortical slices the inhibition by pinacidil (10 microM) was 31%. Although phenytoin (10 microM), carbamazepine (100 microM) and lamotrigine (10 microM) also decreased [3H]-NA release (by 25%, 57% and 22%, respectively), glibenclamide did not antagonize the effects of these classical Na+ channel blockers. These findings suggest that GBP inhibits K+-evoked [3H]-NA release through activation of KATP channels. To establish whether the KATP channels under investigation were located on noradrenergic nerve terminals or on other neuronal elements, the effects of GBP were compared in the absence and in the presence of tetrodotoxin (TTX 0.32 microM) throughout superfusion. Since the functional elimination of the perikarya of interneurons by TTX reduced the inhibitory effect of GBP, the KATP channels mediating the effect of GBP may be located on nerve terminals, probably on both noradrenergic and glutamatergic nerve endings.

Acetates↗
PubMed2001

Cortical current density reconstruction of interictal epileptiform activity in temporal lobe epilepsy.

OBJECTIVE: To investigate the value of cortical current density (CCD) reconstruction in localizing intracranial generators of interictal epileptiform activity in mesial and lateral temporal lobe epilepsy (TLE). METHODS: Non-linear minimum L(1)-norm CCD reconstruction (with current sources restricted to the individual cortical surface and a realistic boundary element method (BEM) head model) was used to localize and to study the propagation of interictal epileptiform EEG activity in 13 pre-surgical patients with TLE. RESULTS: In all but one patient with mesial temporal lesions, an initial activation maximum corresponding to the ascending part of averaged sharp waves was found in the ipsilateral anterior basolateral temporal lobe, mostly extending up to the affected mesial structures whose resection rendered the patients seizure-free. In all 3 patients with lateral temporal lesions, the activation was initially confined to temporal neocortex immediately adjacent to the epileptogenic lesion. Towards the peak of sharp waves, two patients showed a propagation of interictal activity to anterior and posterior and partly contralateral temporal regions. A conventional EEG analysis based on amplitude maxima or phase reversal would have missed the initial onset zone. CONCLUSIONS: The findings demonstrate that CCD reconstruction can be a valuable additional non-invasive component in the multimodal pre-surgical evaluation of epilepsy patients.

Adolescent↗
PubMed2001

Reconsideration of biallelic inactivation of the VHL tumour suppressor gene in hemangioblastomas of the central nervous system.

OBJECTIVES: Cerebellar haemangioblastoma occurs sporadically or as a component tumour of autosomal dominant von Hippel-Lindau disease. Biallelic inactivation of the VHL tumour suppressor gene, which is located on chromosome 3p, has been shown to be involved in the pathogenesis of both tumour entities. Mechanisms of VHL inactivation are intragenic mutations, mitotic recombination events, and hypermethylation of the promoter region. The systematic and complete examination of these genetic and epigenetic phenomena in large series of von Hippel-Lindau disease related and sporadic hemangioblastomas has, thus far, not been performed. METHODS: In the largest series to date, 29 von Hippel-Lindau disease associated and 13 sporadic haemangioblastomas were investigated for all suggested inactivating mechanisms of the VHL gene using single strand conformational polymorphism (SSCP), loss of heterozygosity (LOH), and methylation analyses. Additionally, corresponding blood samples of all patients were screened for VHL germline mutations by SSCP and Southern blotting. RESULTS: Germline mutations were identified in 94% of patients with von Hippel-Lindau disease and their tumours and 62% of these hemangioblastomas showed LOH of chromosome 3p. Of the 13 sporadic tumours, 23% showed a single somatic mutation of the VHL gene that was not present in the germline. 3p LOH was identified in 50% of informative sporadic tumours. No von Hippel-Lindau disease related or sporadic tumour demonstrated VHL promoter hypermethylation. CONCLUSIONS: For most von Hippel-Lindau disease related haemangioblastomas, the inactivation or loss of both alleles of the VHL gene, as predicted by the Knudson two hit theory, is required. However, in a subset of tumours including most sporadic haemangioblastomas, the genetic pathways involved in tumorigenesis have yet to be defined and may represent alterations of a different pathway or pathways.

Adolescent↗
PubMed2000

Cortical reorganization following multiple subpial transection in human brain - a study with positron emission tomography.

We investigated the cortical activation pattern in a 30-year-old woman 4 years after multiple subpial transection (MST) of the right fronto-parietal cortex and six healthy controls using positron emission tomography. Sequential finger-to-thumb opposition at the frequency of 1.5 Hertz contralateral to the operated hemisphere was used as the activation paradigm. We found preserved cortical activation in the transected fronto-parietal cortex and additional activation of the prefrontal cortex bilaterally and the inferior parietal cortex contralaterally when compared with the control group. This activation pattern indicates that MST induces a rather selective lesion leaving the cortical structures functionally intact. However, it necessitates the recruitment of additional motor areas.

Adult↗
PubMed2000

Clinical relevance of quantified intracranial interictal spike activity in presurgical evaluation of epilepsy.

PURPOSE: Electrocorticograms of 32 patients with medically intractable seizures, recorded through intracranial electrodes, were retrospectively analyzed. The objective was to assess whether quantitative analysis of interictal spikes may be used for delineation of the epileptogenic zone. METHODS: We used a newly developed computer program for automatic detection of interictal spikes and averaging procedures. This allowed determination of the earliest spike of each spike cluster, the maximal averaged spike amplitude, the highest spike frequency, and the shortest averaged spike duration at each recording site. RESULTS: The following results were obtained: (a) Within a zone </=2 cm from the site of seizure origin, we localized the averaged earliest spike of a spike cluster in 27 (84%) of 32 patients, the highest averaged spike amplitude in 24 (75%) of 32, the shortest averaged spike duration in 22 (69%) of 32, and the maximal spike frequency in 17 (53%) of 32; (b) No correlation was found between spike occurrence and histopathology; (c) No evidence was found for decreased postoperative seizure control in patients with several multilobar or bihemispheric occurrence of spike clusters. CONCLUSIONS: The zones of the earliest spike and seizure origin demonstrate a high correlation that favors a common epileptic generator. Removal of all brain areas demonstrating spike clusters is unnecessary to achieve seizure control. Quantification of interictal spike activity is a valuable tool for localization of the seizure generator.

Adolescent↗
PubMed1999

Safety of single and repetitive focal transcranial magnetic stimuli as assessed by intracranial EEG recordings in patients with partial epilepsy.

The safety of single and repetitive (paired and quadruple) focal transcranial magnetic stimuli as possible inducers of epileptic discharges or clinically manifest seizures was investigated in 21 patients with intractable epilepsy during invasive presurgical monitoring. Subdural and/or intracerebral depth electrodes had been implanted in close proximity to the suspected epileptogenic zone, and the anticonvulsant medication had been reduced. Focal transcranial magnetic stimuli were applied by a Magstim QuadroPulse magnetic stimulator over the hand area of the motor cortex ipsilateral to the epileptogenic focus at intensities of 120% and 150% of motor threshold and additionally as close as possible to the suspected epileptogenic zone at 40-100% of maximal stimulator output. Stimulation did not induce any complex partial or secondary generalized tonic-clonic seizures. One patient with hippocampal sclerosis experienced an aura associated with rhythmic electroencephalographic discharges restricted to the ipsilateral intrahippocampal depth electrode after stimulation over his left temporal lobe. This patient, however, also had frequent spontaneously occurring auras with focal ictal discharges originating from this hippocampus. Interictal discharges were not influenced significantly by single or repetitive magnetic stimuli. In conclusion, from this study there is no evidence that single or serial focal transcranial magnetic stimuli activate epileptogenic foci. At least four high-frequency repetitive stimuli of high intensity may thus be applied with a low risk of seizure induction even in patients with low seizure threshold.

Adolescent↗
PubMed1999

Nosocomial infections in a neurosurgery intensive care unit.

In order to identify overall and site-specific nosocomial infection (NI) rates in patients receiving neurosurgical intensive care therapy, a prospective study was started in February 1997 in the eight-bed neurosurgical ICU of the University Hospital of Freiburg, Germany. Case records were reviewed twice a week, all microbiology reports were reviewed and ward staff was consulted. NI were defined according to the CDC-criteria and were categorised into specific infection sites. Within 20 months, 545 patients with a total of 5,117 patient days were investigated (mean length of stay: 9.4 days). 113 NI were identified in 90 patients (72 pts. with one, 13 with two and 5 with three infections, respectively). A moderate to high overall incidence (20.7/100 pts.) and a moderate incidence density (22.1/1,000 patient days) of NI in the neurosurgical ICU could be documented; these figures are well within the range of published data. Site specific incidence rates and incidence densities were: 1 bloodstream infection per 100 patients (0.9 central line-associated BSIs per 1,000 central line-days), 9 pneumonias per 100 patients (15.1 ventilator-associated pneumonias per 1,000 ventilator-days), 7.3 urinary tract infections per 100 patients (8.5 urinary catheter-associated UTIs per 1,000 urinary catheter-days). Additionally, 1.1 cases of meningitis, 0.7 brain abscesses/ventriculitis, and 1.7 other infections (surgical site infection, bronchitis, catheter related local infection, diarrhoea) were documented per 100 patients, respectively. 14.6% of isolated pathogens were E. coli, 10.2% enterococci, 9.6% S. aureus, 6.4% CNS, 6.4% Klebsiella spp., 5% Enterobacter spp. and 5% Pseudomonas spp. In 11 cases of NI no pathogen could be isolated.

Adolescent↗
PubMed1999

Minimally invasive stereotactically-guided extirpation of brain stem cavernoma with the aid of electrophysiological methods.

The surgical extirpation of brain stem cavernomas always includes a risk of neurological deficits. To minimize the risk of deficits and control the motor and sensory function intraoperative monitoring of SEP and MEP seems to be helpful. The high density of motor and sensory fibers within the brain stem makes bilateral intraoperative monitoring necessary. The following case demonstrates a stereotactically-guided supratentorial, transventricular approach for extirpation of a brain stem cavernoma. Sensory and motoric functions were observed by transcranial recording of SEP's and by transcranial stimulation of motor cortex.

Adult↗
PubMed1999

Influence of fentanyl, alfentanil, and sufentanil on motor evoked potentials.

The effects of the opioids fentanyl, alfentanil, and sufentanil on motor pathways were studied in a total of 30 rabbits. Compound muscle action potentials (CMAP) were recorded from the extensor muscles of the upper extremity as well as evoked spinal cord potentials (ESCP) from the thoracic epidural space in response to electrical stimulation of the motor cortex. After establishing stable baseline values, an equipotent intravenous bolus of one of the three opioids was applied that abolished reflex motor response to noxious stimulation. Motor evoked potentials (MEP) were recorded from the time of bolus administration until recovery of MEP amplitudes and latencies. Afterwards, the opioids were administered continuously with cumulative dosage up to total absence of motor evoked response. Our results show a dose-dependent suppression of the CMAP: When reflex movement to noxious stimulation was extinguished, we found a significant (P < .001) reduction of the amplitudes to 34+/-18% (mean +/- SD) in the fentanyl group, to 43+/-24% in the alfentanil group, and to 53+/-20% of baseline values in the sufentanil group. Increasing opioid plasma levels were associated with complete extinction of the CMAP. We hypothesize that the descending volleys within motor pathways are mainly inhibited at a spinal level, because ESCP, particularly the number of spinal I-waves, are not severely affected even when CMAP are completely suppressed. In conclusion, intraoperative monitoring of descending pathways by means of MEP during anesthesia with opioids is feasible at anesthetic plasma concentrations maintaining a surgical level of analgesia. Even with high opioid plasma levels, a valid MEP monitoring could be performed evaluating neural activity of spinal MEP.

Action Potentials↗