Biomedical subjects

Josef Zentner

Publications and source records attributed to Josef Zentner.

29 records · Page 2Linked to original sources

PubMed2003

Implications of vascular endothelial growth factor, sFlt-1, and sTie-2 in plasma, serum and cerebrospinal fluid during cerebral ischemia in man.

The relation between cerebral ischemia and local release of angiogenic factors was investigated after subarachnoid hemorrhage (SAH) in humans. Time-dependent concentration-changes of vascular endothelial growth factor (VEGF), sFlt-1 and sTie-2 extracted from plasma, serum, and cerebrospinal fluid (ventricular, cisternal, and lumbar) were analyzed in 15 patients surgically treated for ruptured aneurysms of the anterior circulation (Hunt and Hess grades I-V). Data were related to brain Po2 (Pbro2) and cerebral energy metabolites (extracellular lactate, pyruvate, glutamate, and glycerin concentrations) as well as clinical and radiologic reference data. Delayed impairment of cerebral perfusion secondary to progressive microcirculatory alterations was associated with reduced local Pbro2 and energy metabolism (increased lactate-pyruvate ratio, glutamate and glycerine levels). Elevated serum/plasma and CSF concentrations of VEGF, sFlt-1, and sTie-2 matched the scale of ischemic tissue hypoxia. Excessive VEGF/sFlt-1 and sTie-2 levels were related to Pbro2 values consistently less than 5 mm Hg, glutamate concentrations greater than 300 micromol/L, lactate-pyruvate ratio greater than 300, cerebral infarction, and reduced outcome (P < 0.01). Delayed microcirculatory impairment was mirrored by distinct elevation of cisternal and arterial VEGF and sFlt-1 concentrations, suggesting local induction of angiogenesis. Arterial levels of VEGF, sFlt-1, and sTie-2 reflect both extent and time course of compensatory, yet clinically inefficient, angiogenesis in the absence of general hypoxia.

Adult↗

PubMed2003

Fungal granuloma of the sphenoid sinus and clivus in a patient presenting with cranial nerve III paresis: case report rand review of the literature.

OBJECTIVE AND IMPORTANCE: Isolated fungal granulomas originating within the sphenoid sinus are extremely rare in immunocompetent patients. In their symptoms and morphological appearance, these lesions may be mistaken for pituitary tumors. We report such a case and review the literature. CLINICAL PRESENTATION: A 74-year-old man presented with a 3-week history of Cranial Nerve III paresis. The patient had a long-term history of snuff abuse. Computed tomography demonstrated a space-occupying lesion of the sellar and sphenoid sinus region with displacement of the cavernous sinus. INTERVENTION: The lesion was operated on via a transnasal-transsphenoidal approach. After the sphenoid sinus was opened, mucus extruded spontaneously, and a brownish, crumbly mass was found and removed. The lesion had completely eroded the sella and clivus. Histological analysis revealed numerous Aspergillus hyphae. Postoperatively, the IIIrd cranial nerve paresis resolved completely within a few days. No systemic fungal infection was found in extensive serological studies. There was no evidence of immunosuppression. CONCLUSION: Fungal granuloma must be included in the differential diagnosis of lesions in the sellar region, even in nonimmunosuppressed patients. Early diagnosis and transsphenoidal extirpation is crucial with this potentially life-threatening disease.

Aged↗

PubMed2002

Anterograde tracing of human hippocampus in vitro-a neuroanatomical tract tracing technique for the analysis of local fiber tracts in human brain.

Hippocampal slices were obtained from hippocampi of patients with temporal lobe epilepsy or from patients with mass lesions located in the temporal lobe. Hippocampal slices were kept alive in a slice chamber and the anterograde tracer neurobiotin was iontophoretically injected into the granule cell layer of the dentate gyrus. Single injections resulted in the labeling of small groups of granule cells. The axonal arbor of these cells could be partially reconstructed and single mossy fibers could be followed from the soma to the inner molecular layer of the sclerotic dentate gyrus. Electron microscopy revealed asymmetric mossy fiber synapses on spiny neurons in the inner molecular layer, presumably granule cells. These data demonstrate that in vitro anterograde tracing can be employed to study the local connectivity of the human brain at the light and electron microscopic level.

Biotin↗

PubMed2002

Role for reelin in the development of granule cell dispersion in temporal lobe epilepsy.

The reelin signaling pathway plays a crucial role during the development of laminated structures in the mammalian brain. Reelin, which is synthesized and secreted by Cajal-Retzius cells in the marginal zone of the neocortex and hippocampus, is proposed to act as a stop signal for migrating neurons. Here we show that a decreased expression of reelin mRNA by hippocampal Cajal-Retzius cells correlates with the extent of migration defects in the dentate gyrus of patients with temporal lobe epilepsy. These results suggest that reelin is required for normal neuronal lamination in humans, and that deficient reelin expression may be involved in migration defects associated with temporal lobe epilepsy.

Adaptor Proteins, Signal Transducing↗

PubMed2002

DNA topoisomerase IIalpha predicts progression-free and overall survival in pediatric malignant non-brainstem gliomas.

Malignant non-brainstem glioma (MNBG) is a rare pediatric brain tumor. The prognosis for children harboring this lesion remains largely unpredictable. Assessment of histologic features alone only provides a marginal insight into the biologic behavior of these lesions. Hence, the identification of novel molecular markers capable of characterizing these lesions more accurately with respect to their biologic aggressiveness is definitely needed. Our current study examined the expression of nuclear DNA topoisomerase IIalpha (TIIalpha), a novel marker of cell cycle turnover and a determinant of tumor cell resistance to chemotherapy, in a series of 17 archival pediatric MNBGs. TIIalpha expression was found to extend over a wide range in the study cohort (3.9-69.1%). A cutoff labeling index of 12% was found to define 2 prognostic subgroups (TIIalpha <12 vs. >or=12) with profoundly different 5-year progression-free survival (60% vs. 8%; p = 0.0108, log-rank test) and overall survival (100% vs. 8%; p = 0.0038) rates. TIIalpha expression was significantly linked to MIB-1 antibody labeling of the Ki-67 nuclear antigen (R = 0.919, p < 0.001). A high TIIalpha labeling index remained associated with short progression-free survival (p = 0.022) and overall survival (p = 0.022) in multivariate analysis (Cox regression). In conclusion, considering that TIIalpha expression was not related to histopathologic grade, biological characteristics as assessed by TIIalpha labeling may complement the information obtained by tumor morphology as a means of improving the accuracy of patient prognosis prediction.

Adolescent↗

PubMed2002

Brain-tumour drug resistance: the bare essentials.

Chemotherapy lacks efficacy in most histological types of primary human brain tumours and has, for most types, failed to improve outcome for patients. The unsatisfactory results with chemotherapeutic intervention in these cancers have been chiefly attributed to tumour-cell resistance. This review summarises some of the major molecular markers that, although neither exclusive for nor specific to brain tumours, have been associated with the formation of a chemoresistant phenotype. Elucidation of the cellular mechanisms involved in resistance regulation is needed for future progress in efficient approaches to selective modulation of drug resistance in these lesions.

Animals↗

PubMed2002

Comparison of the ORL1 receptor-mediated inhibition of noradrenaline release in human and rat neocortical slices.

The effects of nociceptin/orphanin (N/OFQ) and the selective ORL1 antagonist J-113397 (1-[(3R,4R)-1-cyclo-octylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one) were studied on electrically-evoked release of [(3)H]-noradrenaline ([(3)H]-NA) from human and rat neocortical slices. Specimens of human tissue were obtained during neurosurgery. Slices were preincubated with 0.1 microM [(3)H]-NA, superfused in the presence of desipramine, idazoxan, and naloxone (1 microM each), and stimulated electrically up to three times under conditions (4 pulses, 100 Hz, 2 ms, 60 mA) that prevent inhibition of evoked [(3)H]-NA release by endogenous modulators accumulating during ongoing stimulation. N/OFQ decreased electrically-evoked [(3)H]-NA release in both human and rat neocortical slices in a concentration-dependent manner. The respective pEC(50) values were 7.74 [CI(95): 7.47, 8.04] and 7.64 [CI(95): 7.48, 7.77], and the maximal inhibitions were 36.9% [CI(95): 32.4%, 41.8%] and 66.4% [CI(95): 61.7%, 72.7%]. N/OFQ (1 microM) inhibited K(+) (15 mM)-evoked [(3)H]-NA release from neocortical slices of both species by a similar magnitude, either in the presence or absence of tetrodotoxin. The nonpeptide ORL1 antagonist J-113397 competitively attenuated, with similar potency, the inhibition of electrically-evoked [(3)H]-NA release by N/OFQ in both species (pA(2) values: human, 8.16 [CI(95): 7.64, 8.64]; rat, 8.47 [CI(95): 8.27, 8.67]). J-113397 (0.1 microM) by itself did not alter either the evoked or spontaneous [(3)H]-NA release, suggesting that presynaptic ORL1 receptors are not activated by endogenous N/OFQ under the stimulation conditions employed. This study provides the first evidence that N/OFQ modulates [(3)H]-NA release in human neocortex via specific ORL1 receptors most likely located on noradrenergic axon terminals.

Adolescent↗

PubMed2002

Motor-evoked potential facilitation during progressive cortical suppression by propofol.

UNLABELLED: We characterized the effects of various stimulation patterns on motor-evoked potentials (MEPs) elicited by repetitive transcranial magnetoelectric stimulation at different levels of cortical suppression by propofol. In 20 patients undergoing lumbar disk surgery, propofol target plasma concentrations (PTPCs) were increased incrementally by target plasma-level controlled infusion during the induction of anesthesia. MEPs were recorded from the muscles of the upper extremities after single, double, and quadruple magnetoelectric stimulation at 500, 200, and 100 Hz. The mean PTPC during loss of responsiveness to verbal instructions (CP50) was 3 microg/mL (CP(95), 5 microg/mL). At PTPCs <3 microg/mL, maximal MEP amplitudes were elicited by quadruple stimulation at 100 Hz. At PTPCs > or =3 microg/mL, four pulses at 200 Hz yielded peak MEP amplitudes. Therefore, quadruple magnetoelectric stimulation at 100 Hz yields peak myogenic responses in awake patients. With progressive cortical suppression resulting from PTPCs beyond 3 microg/mL, the most effective stimulation frequency shifts to 200 Hz. This may be explained by a differential dose-dependent action of propofol on GABAergic cortical interneurons, corresponding to the clinically observed state of vigilance. Recording of spinal cord evoked potentials will aid in further elucidation of the modulatory effects of general anesthesia on intracortical facilitation. IMPLICATIONS: We investigated the effect of different transcranial magnetoelectric stimulation paradigms on motor-evoked potentials during different levels of cortical suppression by propofol. The most effective stimulation frequency seems to change from 100 to 200 Hz during progressive propofol dose escalation, possibly because of specific interaction with cortical interneurons.

Adult↗

PubMed2002

Does tissue oxygen-tension reliably reflect cerebral oxygen delivery and consumption?

We investigated the value of brain oxygen partial pressure (P(br)O(2)) with respect to predicting cerebral energetic failure in a rabbit model of global cerebral ischemia and hypoxia. Local cortical blood flow (l(co)CBF), P(br)O(2), extracellular lactate, pyruvate, and glutamate concentrations, as well as microvascular hemoglobin saturation (S(mv)O(2)), cytochrome oxidase redox level (Cyt a+a(3) oxidation), and brain electrical activity, were assessed during variable degrees of cerebral ischemia and hypoxia, induced by cisternal infusion of artificial cerebrospinal fluid or an admixture of nitrous oxide to inspiratory gas in 10 animals each. Arteriovenous difference in oxygen content, cerebral metabolic rate for oxygen, and oxygen extraction were derived from multimodal data. P(br)O(2), S(mv)O(2), and Cyt a+a(3) oxidation were closely related to cerebral blood flow and indices of oxidative metabolism. P(br)O(2) </=8 mm Hg corresponded to l(co)CBF </=15 mL. 100 g(-1). min(-1), S(mv)O(2) </=9%, Cyt a+a(3) oxidation </=20%, and progressive loss of brain electrical activity. Adequate tissue oxygenation was reflected by cerebral metabolic rate for oxygen >/=2.8 mL. 100 g(-1). min(-1), arteriovenous difference in oxygen content </=12.5 mL O(2). 100 mL(-1), and oxygen extraction </=60%. Meaningful interpretation of low P(br)O(2), especially with respect to definition of energetic thresholds, requires complementary information from simultaneous assessment of l(co)CBF and tissue oxygen extraction. IMPLICATIONS. The relationship between brain oxygen partial pressure and several variables of energy metabolism was investigated during variable degrees of cerebral ischemia and hypoxia in a rabbit model. Correct interpretation of individual brain oxygen partial pressure values, especially with respect to definition of energetic thresholds, requires complementary information from assessment of cerebral blood flow and tissue oxygen extraction.

Animals↗

PubMed2002

Cerebellar hemorrhage arising postoperatively as a complication of supratentorial surgery: a retrospective study.

OBJECT: Postoperative cerebellar hemorrhage as a complication of supratentorial surgery is an increasingly recognized clinical entity. So far, it has remained unclear whether this complication constitutes an intraoperative or postoperative event. The observation of such cases prompted the authors to analyze retrospectively their series of supratentorial craniotomies. The aim of this study was to determine the incidence of cerebellar hemorrhage and its temporal relationship to supratentorial surgery. METHODS: The authors reviewed discharge notes and reports on postoperative computerized tomography (CT) scans for 1650 patients who had undergone supratentorial craniotomy between January 1998 and February 2001. The retrospective study led to the identification of 10 patients who had sustained cerebellar hemorrhage as a complication of supratentorial surgery. Because it was routine to perform CT scanning following craniotomy, an early CT scan obtained within the 1st postoperative hour (mean 24 minutes after wound closure) was available in eight of the 10 patients. In seven of these patients no hemorrhage was found immediately after surgery, and in only one patient was there the suspicion of cerebellar hemorrhage. In the whole series of 10 patients, cerebellar hemorrhage was detected during the later postoperative course, after a mean interval of 7 hours and 35 minutes (range 1 hour and 49 minutes-144 hours) following surgery. The incidence of cerebellar hemorrhage was 0.6% of all patients who underwent supratentorial surgery. Among patients suffering from epilepsy the incidence was 4.6%, and in those patients who underwent temporal lobe resection it was 12.9%. CONCLUSIONS: The authors have demonstrated that cerebellar hemorrhage as a complication of supratentorial surgery arises not as an intraoperative event, but as a postoperative event. Resective nontumorous temporal lobe procedures place patients at particular risk for this complication. Evidence suggests that the complication might be precipitated by postoperative suction drainage.

Adult↗

PubMed2002

Total intravenous anesthesia for intraoperative monitoring of the motor pathways: an integral view combining clinical and experimental data.

OBJECT: Monitoring of descending corticospinal pathways by using motor evoked potentials (MEPs) has proven to be useful in preventing permanent neurological deficits during cranial and spinal procedures. Difficulties in interpretation of intraoperative changes in potentials may largely be attributed to the effects of anesthesia. Development of suitable intravenous anesthesia protocols specifically tailored for MEP monitoring, including plasma level target-controlled infusion (TCI), requires precise knowledge of the specific neurophysiological properties of the various agents. METHODS: The effects of alfentanil, sufentanil, fentanyl, remifentanil, thiopental, midazolam, etomidate, ketamine, and propofol on neurogenic and myogenic MEPs were evaluated in an integral study combining clinical data obtained in 40 patients and experimental investigations conducted in 140 animals. The dose-dependent modulation of MEPs after electrical and magnetoelectrical stimulation of the motor cortex was recorded from peripheral muscles and the spinal cord. The results were as follows: opioids, propofol, and thiopental suppressed myogenic, but not neurogenic MEPs in a dose-dependent fashion; remifentanil exerted the least suppressive effects. Etomidate and midazolam did not suppress myogenic MEP, even at plasma concentrations sufficient for anesthesia. Ketamine induced moderate reduction of compound muscle action potential amplitudes only at high doses. Remifentanil and propofol administered via TCI systems allowed recording of myogenic potentials within a defined target plasma concentration range. CONCLUSIONS: Development of standardized total intravenous anesthesia/TCI protocols by using anesthetic agents such as propofol, remifentanil, ketamine, and midazolam, which have favorable pharmacokinetic and neurophysiological properties, will enhance the quality of intraoperative MEPs and promote the use of MEP monitoring as a useful tool to reduce surgery-related morbidity.

Adult↗