Search PubMed⌕ Search

Biomedical subjects

O Gratzl

Publications and source records attributed to O Gratzl.

At least 37 records · Page 2Linked to original sources
PubMed1999

Acute effects of an aminosteroid on microdialytically measured parameters after experimental middle cerebral artery occlusion in the rat.

The effects of the neuroprotective aminosteroid U74389G were monitored microdialytically in rat cortex during 4 h after permanent middle cerebral artery occlusion. Either U74389G or vehicle only was administered one hour before and 2 h after operation. The dialysate was analysed for on-line pH, ascorbic acid, uric acid, glucose and lactate. In aminosteroid treated animals the levels of ascorbic and uric acids were lower in dialysates after occlusion, total release of lactate was significantly reduced and on-line pH was significantly higher than in control animals. Lesion volume at 4 h, which was significantly reduced in treated animals, correlated positively with ascorbic acid release and on-line pH. Results suggest that neuroprotective effects of aminosteroids might be explained by: (a) preservation of intracellular levels of the radical scavenger ascorbic acid with possible concomitant reduction of glutamate release; and (b) reduced lactate release and increased pH which might influence oedema positively. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗
PubMed1999

Predictive value of cerebrospinal fluid (CSF) lactate level versus CSF/blood glucose ratio for the diagnosis of bacterial meningitis following neurosurgery.

The value of cerebrospinal fluid (CSF) lactate level and CSF/blood glucose ratio for the identification of bacterial meningitis following neurosurgery was assessed in a retrospective study. During a 3-year period, 73 patients fulfilled the inclusion criteria and could be grouped by preset criteria in one of three categories: proven bacterial meningitis (n = 12), presumed bacterial meningitis (n = 14), and nonbacterial meningeal syndrome (n = 47). Of 73 patients analyzed, 45% were treated with antibiotics and 33% with steroids at the time of first lumbar puncture. CSF lactate values (cutoff, 4 mmol/L), in comparison with CSF/blood glucose ratios (cutoff, 0.4), were associated with higher sensitivity (0.88 vs. 0.77), specificity (0.98 vs. 0.87), and positive (0.96 vs. 0.77) and negative (0.94 vs. 0.87) predictive values. In conclusion, determination of the CSF lactate value is a quick, sensitive, and specific test to identify patients with bacterial meningitis after neurosurgery.

Adult↗
PubMed1999

Operated low grade astrocytomas: a long term PET study on the effect of radiotherapy.

The role of postoperative radiotherapy in patients with low grade gliomas is not established yet. PET with 11C methionine (MET) and 18F fluorodeoxyglucose (FDG) was used to perform cross sectional comparisons as well as within patient follow up studies in 30 operated patients with fibrillary astrocytoma WHO II. Uptake of tracer by tumour was quantified by radioactivity concentration ratios in tumour over contralateral brain (T/C). Comparing patients who did (n=13) or did not (n=17) receive external radiotherapy subsequent to first tumour resection, no differences in MET and FDG T/C between both groups were found during a postoperative period of 94 months (when recurrence and malignant progression of low grade astrocytomas are expected). Malignant progression occurred at a similar rate in both patient groups at a mean (SD) postoperative interval of 46 (26) months. Irrespective of whether radiotherapy was applied or not, malignant tumour recurrences showed higher T/C values (MET: 1.70 (0.64), FDG: 0.98 (0.23)) than recurrences without signs of malignancy (MET: 1.21 (0.21), FDG: 0.82 (0.08)) (Mann-Whitney: MET p=0.086, FDG p=0.035). The data show a relative lack of radiotherapy administered immediately after first tumour resection. In the course of disease, patients with tumours undergoing malignant progression may be identified with PET tracer methods.

Adult↗
PubMed1999

Effect of radiotherapy on brain glucose metabolism in patients operated on for low grade astrocytoma.

OBJECTIVE: To assess the effect of postoperative radiotherapy on brain glucose metabolism (CMRGlu) of operated patients with low grade astrocytomas. METHODS: PET and 18F-fluorodeoxyglucose was used to measure absolute CMRGlu in patients with fibrillary astrocytoma (WHO II) of the frontal lobe, who did (n=7) or did not (n=12) receive radiotherapy subsequent to first debulking tumour resection. In addition, statistical parametric mapping (SPM95) was applied to assess the pattern of relative CMRGlu associated with the frontal tumour. Data were compared with 12 healthy controls. RESULTS: A global reduction of absolute CMRGlu was found when either patients with or without radiotherapy were compared with controls (ROI analysis). Brain areas of relative CMRGlu reduction were found in the brain ipsilateral and contralateral to the tumour, comparing both patient groups with controls by SPM ("tumour diaschisis effect"). Superimposed, absolute CMRGlu in the contralateral frontal, parietal, occipital cortex as well as in the white matter was on average 17% lower in patients receiving radiotherapy than in patients who did not. CONCLUSIONS: The data discriminate a tumour effect from a radiotherapy effect, and support the view of adverse effects of radiotherapy on brain not directly involved by tumour.

Adult↗
PubMed1999

Trigeminocardiac reflex during surgery in the cerebellopontine angle.

OBJECT: In different experimental studies authors have analyzed the autonomic responses elicited by the electrical, mechanical, or chemical stimulation of the trigeminal nerve system. The trigeminocardiac reflex (TCR) is a well-recognized phenomenon that consists of bradycardia, arterial hypotension, apnea, and gastric hypermotility. It occurs during ocular surgery and during other manipulations in and around the orbit. Thus far, it has not been shown that central stimulation of the trigeminal nerve can also cause this reflex. METHODS: The TCR was defined as clinical hypotension with a drop in mean arterial blood pressure (MABP) of more than 20% and bradycardia lower than 60 beats/minute. Pre-, intra-, and postoperative heart rate (HR) and MABP were reviewed retrospectively in 125 patients who underwent surgery for tumors of the cerebellopontine angle (CPA), and they were divided into two groups on the basis of the occurrence of the TCR during surgery. Of the 125 patients, 14 (11%) showed evidence of the TCR during dissection of the tumor near the trigeminal nerve at the brainstem. Their HRs fell 38% and their MABPs fell 48% during operative procedures as compared with preoperative levels. After cessation of manipulation, the HRs and the MABPs returned to preoperative levels. Risk factors for the occurrence of the TCR were compared with results from the literature. CONCLUSIONS: The authors' results show the possibility of occurrence of a TCR during manipulation of the central part of the trigeminal nerve when performing surgery in the CPA.

Adolescent↗
PubMed1999

Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas.

Human gliomas, especially of low-grade type, have been shown to express high-affinity somatostatin receptor type 2 (J-C. Reubi et al., Am. J. Pathol, 134: 337-344, 1989). We enrolled seven low-grade and four anaplastic glioma patients in a pilot study using the diffusible peptidic vector 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) for receptor targeting. The radiopharmakon was locoregionally injected into a stereotactically inserted Port-a-cath. DOTATOC competes specifically with somatostatin binding to somatostatin receptor type 2 in the low nanomolar range as shown by a displacement curve of 125I-[Tyr3]-octreotide in tumor tissue sections. Diagnostic (111)In-labeled DOTATOC-scintigraphy following local injection displayed homogeneous to nodular intratumoral vector distribution. The cumulative activity of regionally injected peptide-bound 90Y amounted to 370-3300 MBq, which is equivalent to an effective dose range between 60 +/- 15 and 550 +/- 110 Gy. Activity was injected in one to four fractions according to tumor volumes; 1110 MBq of 90Y-labeled DOTATOC was the maximum activity per single injection. We obtained six disease stabilizations and shrinking of a cystic low-grade astrocytoma component. The only toxicity observed was secondary perifocal edema. The activity:dose ratio (MBq:Gy) represents a measure for the stability of peptide retention in receptor-positive tissue and might predict the clinical course. We conclude that SR-positive human gliomas, especially of low-grade type, can be successfully targeted by intratumoral injection of the metabolically stable small regulatory peptide DOTATOC.

Adult↗
PubMed1999

Treatment of syringomyelia after posttraumatic paraparesis or tetraparesis.

This retrospective study of 12 patients with syringomyelia related to spinal cord trauma with paraplegia or tetraplegia and secondary progressive neurologic deficits was conducted to evaluate various surgical treatments. Judging by the results of postoperative neuroradiologic examinations, 75% had incomplete reduction of the spinal fracture at the time of initial surgery. The secondary neurologic deterioration occurred within a delay of 146 +/- 16 months and included ascending sensory deficits in 92%, deafferentation pain in 83%, and increased motor weakness in 33%. There was a positive correlation between the severity of symptoms, incomplete reduction of spinal fracture, and the degree of arachnoid scarring in preoperative neuroradiologic examinations. Syringoperitoneal shunting was performed in 83% of patients, and laminectomy with arachnoid lysis and dural grafting were performed in 17%. Pain was improved in 75%, sensory deficits in 25%, and motor weakness in 8%. During the follow-up period of 44 +/- 25 months, 30% of patients with syringoperitoneal shunting required repeated operation for obstruction or infection, whereas the syringomyelia remained collapsed in the two patients with laminectomy with arachnoid lysis and dural grafting, but this did not require additional surgery. In conclusion, laminectomy with arachnoid lysis and dural grafting seems to be a promising alternative treatment for patients with secondary neurologic deterioration after traumatic paraplegia or tetraplegia. Syringoperitoneal shunting may be reserved for patients without severe arachnoid scarring.

Adult↗
PubMed1998

Somatic deletion mapping on chromosome 10 and sequence analysis of PTEN/MMAC1 point to the 10q25-26 region as the primary target in low-grade and high-grade gliomas.

The 10q25-26 region between the dinucleotide markers D10S587 and D10S216 is deleted in glioblastomas and, as we have recently shown, in low-grade oligodendrogliomas. We further refined somatic mapping on 10q23-tel and simultaneously assessed the role of the candidate tumor suppressor gene PTEN/MMAC1 in glial neoplasms by sequence analysis of eight low-grade and 24 high-grade gliomas. These tumors were selected for partial or complete loss of chromosome 10 based on deletion mapping with increased microsatellite marker density at 10q23-tel. Three out of eight (38%) low-grade and 3/24 (13%) high-grade gliomas exclusively target 10q25-26. We did not find a tumor only targeting 10q23.3, and most tumors (23/32, 72%) showed large deletions on 10q including both regions. The sequence analysis of PTEN/MMAC1 revealed nucleotide alterations in 1/8 (12.5%) low-grade gliomas in a tumor with LOH at l0q21-qtel and in 5/21 (24%) high-grade gliomas displaying LOH that always included 10q23-26. Our refined mapping data point to the 10q25-26 region as the primary target on 10q, an area that also harbors the DMBT1 candidate tumor suppressor gene. The fact that we find hemizygous deletions at 10q25-qtel in low-grade astrocytomas and oligodendrogliomas - two histologically distinct entities of gliomas - suggests the existence of a putative suppressor gene involved early in glial tumorigenesis.

Amino Acid Substitution↗
PubMed1998

Interhemispheric pressure gradients in severe head trauma in humans.

Interhemispheric pressure gradients may occur following severe head trauma in patients even in the absence of intracranial space occupying lesions. A higher ICP of the contralateral hemisphere may escape routine unilateral ICP monitoring. Clinical signs and CT scans do not seem to predict reliably a lateralized ICP. According to our data with a limited number of patients, interhemispheric pressure gradients seem to occur in the initial posttraumatic phase in some patients, and they seem to resolve following adequate ICP treatment after several hours. Therefore, simultaneous bilateral ICP measurement may be warranted in the initial posttraumatic phase.

Adolescent↗
PubMed1998

Prostate-specific antigen in the cerebrospinal fluid leads to diagnosis of solitary cauda equina metastasis: a unique case report and review of the literature.

A 79-year-old male patient presented with a subacute cauda syndrome caused by an intradural metastasis of the lumbosacral caudate fibres from an adenocarcinoma of the prostate, which had been treated 5 years earlier with external beam radiation therapy. Diagnosis could not be established by repeated magnetic resonance images (MRIs) during a 2-year period of increasingly severe radicular pain. Eventually, a small tumour mass could be visualized on the fourth MRI. Repeated normal serum prostate-specific antigen (PSA) did not hint at a prostate cancer metastasis (range 2.4-5.1 ng ml(-1)); however, PSA in the cerebrospinal fluid was found to be elevated (29.1 ng ml(-1)). Empirical radiation therapy of the caudate region did not improve radicular pain. Therefore, an exploratory surgical procedure was conducted, which confirmed the suspicion of an intradural prostate cancer metastasis. In conclusion, PSA in the cerebrospinal fluid provides a useful diagnostic tool for detecting intradural prostate cancer metastasis.

Adenocarcinoma↗
PubMed1998

Rifampin concentrations in various compartments of the human brain: a novel method for determining drug levels in the cerebral extracellular space.

Antimicrobial therapy for brain infections is notoriously difficult because of the limited extent of knowledge about drug penetration into the brain. Therefore, we determined the penetration of rifampin into various compartments of the human brain, including the cerebral extracellular space (CES). Patients undergoing craniotomy for resection of primary brain tumors were given a standard dose of 600 mg of rifampin intravenously before the operation. A microdialysis probe (10 by 0.5 mm) was inserted into the cortex distantly from the resection and was perfused with two different rifampin solutions. Rifampin concentrations in the CES were calculated by the no-net-flux method. Intraoperatively, samples were taken from brain tumor tissue, perifocal tissue, and normal brain tissue in the case of pole resections. Rifampin concentrations in the various samples were determined by using a bioassay with Sarcinea lutea. In the various compartments, rifampin concentrations were highest within tumors (1.37 +/- 1.34 microg/ml; n = 8), followed by the perifocal region (0.62 +/- 0.67 microg/ml; n = 8), the CES (0.32 +/- 0.11 microg/ml; n = 6), and normal brain tissue (0.29 +/- 0.15 microg/ml; n = 7). Rifampin concentrations in brain tumors do not adequately reflect concentrations in normal brain tissue or in the CES. Rifampin concentrations in the CES, as determined by microdialysis, are the most reproducible, and the least scattered, of the values for all compartments evaluated. Rifampin concentrations in all compartments exceed the MIC for staphylococci and streptococci. However, CES concentrations may be below the MICs for some mycobacterial strains.

Adult↗
PubMed1998

Clinical assessment of a novel antiadhesion barrier gel: prospective, randomized, multicenter, clinical trial of ADCON-L to inhibit postoperative peridural fibrosis and related symptoms after lumbar discectomy.

A prospective, multicenter, randomized, double-blind, controlled study of ADCON-L Anti-Adhesion Barrier Gel (a medical device by Gliatech Inc, Cleveland, OH) was conducted in 298 patients undergoing first-time lumbar discectomy to evaluate the safety and effectiveness of ADCON-L in preventing postoperative peridural fibrosis and in improving patient clinical outcome. After lumbar discectomy, patients were randomized to receive either ADCON-L gel or nothing (control group) at the conclusion of the surgical procedure. Six months after surgery, peridural scar was evaluated by magnetic resonance imaging, and postoperative pain and straight-leg-raise angle were assessed. No statistically significant differences between the ADCON-L and control groups were observed in terms of adverse events or wound healing characteristics. ADCON-L gel was shown to be safe and to significantly inhibit peridural scar compared with the control group (P = 0.002). That peridural scarring was reduced with ADCON-L gel was further supported by direct visualization of scar tissue at reoperation in both groups. ADCON-L-treated patients had better clinical outcomes than did control patients. The incidence of activity-related pain was significantly reduced (P = 0.013), straight-leg-raise examination scores were significantly improved (P = 0.024 on the operative side and P = 0.015 on the nonoperative side), and ADCON-L reduced low back pain when it was most severe (P = 0.047) and at the end of the day (P = 0.044).

Adult↗
PubMed1997

New deletion in low-grade oligodendroglioma at the glioblastoma suppressor locus on chromosome 10q25-26.

Loss of heterozygosity on chromosome 10 is considered to be associated with the progression of glioblastomas. Two closely related regions have recently been proposed to contain the glioblastoma suppressor locus on chromosome 10q25-26; a 1 cM region between the polymorphic (CA)n-repeat markers D10S587 and D10S216, and an area of 5 cM between the markers D10S221 and D10S209. To confirm and further delineate this region, we analyzed 51 glioblastomas and 11 intermediate and low-grade gliomas for loss of heterozygosity on chromosome 10. 47/62 mostly malignant gliomas displayed complete loss of chromosome 10 and nine tumors were unaltered, whereas four glioblastomas and two low-grade oligodendrogliomas had partial loss on distal 10q. With these six tumors, we constructed a deletion map with increased marker density at 10q25-26 which shows two centromeric breakpoints at the markers D10S587 and D10S216, thus only confirming the distal, but not the proximal candidate glioblastoma suppressor locus. Two out of four low-grade oligodendrogliomas displayed partial deletions on 10q25-26. This suggests that deletion on chromosome 10 is not merely a late event in the progression of glioblastomas, but could play a role earlier in the development of gliomas.

Brain Neoplasms↗
PubMed1997

Biodistribution of 111In-labelled SCN-bz-DTPA-BC-2 MAb following loco-regional injection into glioblastomas.

We analyzed the biodistribution of the 111In-labelled murine anti-tenascin-C MAb BC-2 after intralesional injection in 15 glioblastoma patients. The activated ligand DTPA was conjugated via the isothiocyanato-benzyl group onto BC-2. Conjugates were labelled with 111In, displaying immunoreactivity greater than 90% and labelling efficiency of 99 +/- 1%. In contrast to i.v. injections, excellent tumor uptake was obtained by direct intralesional injection of conjugates that showed only slow systemic release. In serum, conjugates were found to be intact; in urine, only low-molecular-weight decay products were detected. In 8 patients, outflow from the site of injection into systemic circulation was low; daily activity in the serum and urine was found to be below 2% of the total injected radioactivity; most of the injected activity was retained within the tumor, resulting in effective half-lives of 58 +/- 5 hr. In contrast, higher outflow up to 10% of regionally injected 111In-DTPA-BC-2 MAb into systemic circulation resulted in considerable shortening of the effective half-lives to 20 to 40 hr in 7 patients. This outflow was found to correlate with tumor size and blood/brain barrier disruption. In one patient, HPLC analysis of tumor cyst fluid 3 and 6 days after intralesional injection revealed conjugates to be intact and allowed the estimate of about 70% of the total injected 111In-DTPA-BC-2 to be confined to tumor tissue. We conclude that different outflow patterns can be observed following locoregional injection of 111In-DTPA-BC-2, leading to considerable variations in the effective half-lives of isotopes within the tumor, requiring adjustment of the radiation dose in therapeutic trials.

Aged↗
PubMed1996

Microdialytic monitoring of the cortex during neurovascular surgery.

Using microdialysis combined with suitable analytical methods, levels of metabolites in the extracellular fluid of the cerebral cortex were monitored during neurovascular surgery (9 aneurysm and 5 bypass operations). Our aim was to use microdialysis to detect any local ischaemia which could be caused by brain retraction, temporary clipping and dissecting manoevres. For this purpose, parameters were quantified whose levels in the dialysate are known to be influenced by ischaemia (on-line pH, ascorbic acid, uric acid, glutathione, cysteine, glucose, lactate). In the aneurysm series, the on-line pH fell after introduction of the retractor, and rose after removal: also, in many cases, levels of ascorbic acid, glutathione and lactate increased and glucose decreased. These changes are all in accordance with ischaemic conditions in the region of the probe; they disappeared at the end of retraction, or sometimes even before. During the bypass operations, there were no marked changes in on-line pH or in any of the measured parameters. However, in 2 of these patients ascorbic acid, uric acid and glucose levels were very high during the whole measurement, indicating possible changes in metabolism caused by inadequate perfusion (carotid artery stenosis). We conclude that microdialysis is a sensitive method of detecting intraoperative changes in cerebral metabolism.

Carotid Artery Diseases↗