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Biomedical subjects

R I Ernestus

Publications and source records attributed to R I Ernestus.

At least 19 recordsLinked to original sources
PubMed2005

Variability in infectivity of primary cell cultures of human brain tumors with HSV-1 amplicon vectors.

We investigated the variability in infectivity of cells in primary brain tumor samples from different patients using an HSV-1 amplicon vector. We studied the infectivity of HSV-1 amplicon vectors in tumor samples derived from neurosurgical resections of 20 patients. Cells were infected with a definite amount of HSV-1 amplicon vector HSV-GFP. Transduction efficiency in primary tumor cell cultures was compared to an established human glioma line. Moreover, duration of transgene expression was monitored in different tumor cell types. All primary cell cultures were infectable with HSV-GFP with variable transduction efficiencies ranging between 3.0 and 42.4% from reference human Gli36 Delta EGFR glioma cells. Transduction efficiency was significantly greater in anaplastic gliomas and meningiomas (26.7+/-17.4%) compared to more malignant tumor types (glioblastomas, metastases; 11.2+/-8.5%; P=0.05). To further investigate the possible underlying mechanism of this variability, nectin-1/HevC expression was analyzed and was found to contribute, at least in part, to this variability in infectability. The tumor cells expressed the exogenous gene for 7 to 61 days with significant shorter expression in glioblastomas (18+/-13 d) compared to anaplastic gliomas (42+/-24 d; P<0.05). Interindividual variability of infectivity by HSV-1 virions might explain, at least in part, why some patients enrolled in gene therapy for glioblastoma in the past exhibited a sustained response to HSV-1-based gene- and virus therapy. Infectivity of primary tumor samples from respective patients should be tested to enable the development of efficient and safe herpes vector-based gene and virus therapy for clinical application.

Brain Neoplasms↗
PubMed2002

Early rehabilitative concepts in therapy of the comatose brain injured patients.

OBJECTIVES: To evaluate the changes of vegetative parameters and behavioural assessment in comatose patients after severe brain injury during the Multimodal-Early-Onset-Stimulation (MEOS) in early rehabilitation. MATERIAL AND METHODS: We studied 16 predominantly male (3:1) patients, age mean 43.6 (16-77) years. Mean coma duration was 22.2 (8-41) days, therapy duration (MEOS) 9.8 (1-30) days. The initial GCS was 6.6 (3-9), KRS 5.3 (0-15). Including criteria for therapy: Severe head trauma, coma for at least 48 hours (GCS < 8), vegetative stability, normal intracranial pressure, abandon of mechanical ventilation, sedation and severe infections. MEOS was finished in achieving GCS > 9, follow-up investigations were made after 2 years. RESULTS: We identified significant changes in two vegetative parameters (heart/respiratory frequencies), even in deep coma (GCS 3-4). Most significant changes were caused by tactile and acoustic stimulation. Standardized behavioural assessment turned out to be particularly advisable in cases of medium coma (GCS 5-7). Stimulation of tactile and acoustic senses resulted mainly in mimical, head and eye movements. Follow-up was possible in 14 patients: One remained in a vegetative state (GOS 2), two exhibited severe neurologic/neuropsychologic deficits, depending on care (GOS 3), six substained major functional deficits (GOS 4), at though they were able to perform the tasks of daily life on their own, three patients reached GOS 5. Two returned to their former jobs. DISCUSSION AND CONCLUSION: The present results indicate that stimulation therapy should be based on a close observation of patterns of behaviour, and, at least in deep coma stages, involve the registration of vegetative parameters. It may be sensitive to identify parameters predicting a favourable or unfavourable outcome. Preliminary data seem to support the hypothesis that the absence of any response to external stimuli is indicative of an unfavourable outcome.

Acoustic Stimulation↗
PubMed2001

1H- and (31)P-MR spectroscopy of primary and recurrent human brain tumors in vitro: malignancy-characteristic profiles of water soluble and lipophilic spectral components.

In vitro NMR spectroscopy was performed on specimen of human brain tumors. From all patients, tissue samples of primary tumors and their first recurrences were examined. (31)P- and (1)H-spectra were recorded from samples of meningioma, astrocytoma and glioblastoma. A double extraction procedure of the tissue samples permitted acquisition of information from the membrane fraction and from the cytosolic fraction. (31)P-spectra were used to analyze the lipophilic fraction (phospholipids of the membrane) of the tissue extracts, while the (1)H-spectra reflected information on the metabolic alterations of the hydrophilic, cytosolic fraction of the tissue. The tumor types showed distinctive spectral patterns in both the (31)P- and the (1)H-spectra. Based on the total detectable (31)P signal, the level of phosphatidylcholine was about 34% lower in primary astrocytomas than in primary glioblastomas (p = 0.0003), whereas the level of sphingomyelin was about 45% lower in primary glioblastomas than in primary astrocytomas (p = 0.0061). A similar tendency of these phospholipids was observed when comparing primary and recurrent astrocytoma samples from the same individuals [+15% (p = 0.0103) and -23% (p = 0.0314) change, respectively]. (1)H-spectra of gliomas were characterized by an increase of the ratios of alanine, glycine and choline over creatine as a function of the degree of malignancy. In agreement with findings in the (31)P-spectra, the (1)H-spectra of recurrent astrocytomas showed metabolic profiles of increased malignancy in comparison to their primary occurrence. Since gliomas tend to increase in malignancy upon recurrence, this may reflect evolving tumor metabolism. (1)H-spectra of meningiomas showed the highest ratio of alanine over creatine accompanied by a near absence of myo-inositol. Phospholipid profiles of meningiomas showed higher fractional contents of phosphatidylcholine along with lower phosphatidylserine compared to astrocytomas, while higher phosphatidylethanolamine and sphingomyelin fractional contents distinguished meningiomas from glioblastomas. The extraction method being used in this study combined with high-resolution (1)H- and (31)P-MRS provides a wide range of biochemical information, which enables differentiation not only between tumor types but also between primary and recurrent gliomas, reflecting an evolving tumor metabolism.

Analysis of Variance↗
PubMed2001

Regional distribution of ornithine decarboxylase activity and polyamine levels in experimental cat brain tumors.

Biosynthesis of the polyamines putrescine, spermidine, and spermine, and activation of the first key enzyme ornithine decarboxylase (ODC) are closely associated with cellular proliferation. In the present study, the distribution of ODC activity and polyamine levels was investigated for the first time regionally in experimental brain tumors of the cat. Brain tumors were produced by stereotactic xenotransplantation of rat glioma cells. Twenty days after implantation, the brains were frozen in situ, cut into slices, and cryostat sections and tissue samples were taken to determine ODC activity and polyamine levels biochemically. The quantified data were color-coded to present the regional distribution of ODC activity and polyamine levels in the respective section. ODC activity significantly increased in some areas within the tumor, whereas peritumoral tissue showed no difference to the non-tumoral, contralateral hemisphere. This increase turned out in parallel to a high number of mitoses in the same tumor parts (r=0.861). Putrescine levels increased both, in the whole tumor and in the peritumoral edema. Regional differences in putrescine content did not correlate with solid and proliferative parts of the tumor. Spermidine and spermine levels were only slightly increased in some parts of the tumor. Thus, these experiments show the close correlation of a high mitotic rate and activation of ODC within experimental gliomas and underline the relevance of ODC as a biochemical marker of proliferation in brain tumors.

Animals↗
PubMed2001

ODC mRNA as a prognostic factor for predicting recurrence in meningiomas.

In proliferating neoplastic cells, activity of the enzyme ornithine decarboxylase (ODC) increases. Among other brain tumors, ODC activation could also be observed in meningiomas. In the present study, we have investigated ODC gene expression in primary and recurrent meningiomas at the transcriptional level. ODC mRNA (messenger ribonucleic acid), ODC activity, number of mitoses, and Ki-67 index as a marker for nuclear proliferation were quantified in three different groups of meningiomas: tumors without recurrence in a 8.4 years median follow-up period, tumors with recurrence within a median follow-up of 3.0 years, and their corresponding recurrent tumors. ODC mRNA level was significantly higher in meningiomas with later recurrence as compared to meningiomas without recurrence (p < or = 0.01), whereas it declined in the recurrences of the second group (p < or = 0.001). In contrast, ODC activity showed no difference between the two groups of primary tumors, but a significant increase of enzyme activity could be observed in the recurrences as compared to the correponding primary tumors (p < or = 0.001). Likewise, an increase of the Ki-67 index could be detected in the recurrent group (p < or = 0.001). These results suggest that ODC mRNA may represent a prognostic factor for predicting recurrence in meningiomas.

Adult↗
PubMed2001

The fronto-orbital osteotomy as plastic-reconstructive approach to the anterior and middle skull base.

Introduction: A combined extra-intracranial access for the operative exploration of tumours of the anterior and middle skull base is indicated when the tumour extends intracranially and simultaneously into the nasal cavity, the paranasal sinuses or the orbit. Methods: Two standardized modifications of the fronto-orbital osteotomy, the fronto-orbito-nasal and the fronto-orbito-zygomatic osteotomy, allow safe removal of skull base tumours in these locations. In extensive skull base tumours, a modified bilateral fronto-orbital-zygomatic osteotomy can be used. Results: Between February 1993 and July 2000 skull base tumours in 111 patients were resected using the presented methods. The most frequent tumour type was meningioma in 29 cases. Complications were encountered in 13 cases (11.7%). Conclusion: The advantages over other approaches are good extra- and intracranial overview and minimal cerebral trauma. Additional transfacial incisions are not usually necessary. Exact repositioning of the fronto-orbital segments leads to optimal aesthetic results. Copyright 2001 European Association for Cranio-Maxillofacial Surgery.

Journal Article↗
PubMed2001

[MRI with cerebrospinal fluid measurement before and after endoscopic ventriculostomy and aqueductal stenosis].

PURPOSE: Evaluation of MR imaging and CSF flow measurement for planning and follow-up of neuroendoscopic third ventriculostomy in occlusive triventricular hydrocephalus. METHOD: 17 patients with occlusive hydrocephalus due to idiopathic or neoplastic aqueductal stenosis were examined before and after surgery with cardiac-gated T2-weighted and cardiac-gated phase contrast cine sequences. The visibility of anatomic structures and the patency of the ventriculostomy were evaluated. RESULTS: In all 17 patients, the relevant anatomic structures were visible. The cine sequence demonstrated occlusion of the aqueduct and patency of the ventriculostomy in all cases, even in patients with doubtful clinical patterns. CONCLUSIONS: MR imaging with additional cardiac-gated cine sequences allows exact preoperative diagnosis of occlusive hydrocephalus as well as patient selection and planning for endoscopic third ventriculostomy. Non-invasive follow-up, especially in patients with a doubtful clinical pattern, is possible.

Adolescent↗
PubMed2001

Polyamine metabolism in brain tumours: diagnostic relevance of quantitative biochemistry.

OBJECTIVE: Activation of polyamine metabolism is closely associated with cellular proliferation. The purpose was to investigate whether the content of the polyamines putrescine, spermidine, and spermine, and the activity of the first metabolic key enzyme of polyamine metabolism, ornithine decarboxylase (ODC), represent biochemical markers of malignancy in brain tumours. METHODS: The concentration of putrescine, spermidine, and spermine, and the activity of ODC were biochemically quantified in tissue samples obtained during open microsurgery of 670 patients with brain tumours. Biochemical analysis and histopathological classification were carried out in serial tumour samples. RESULTS: The activity of ODC was very low in peritumoral non-neoplastic brain tissue (0.9 (SD 0.6) nmol/g/h). It was significantly higher in gliomas and it significantly increased with a higher grade of malignancy (grade I 2.7 (2.8) nmol/g/h, grade II 3.1 (4.0) nmol/g/h, grade III 5.7 (5.6) nmol/g/h, grade IV 10.6 (11.7) nmol/g/h). High enzyme activity was also found in medulloblastomas (25.5 (15.1) nmol/g/h), malignant lymphomas (52.1 (42.1) nmol/g/h), and metastases from carcinoma (14.9 (22.1) nmol/g/h). Lowest values were measured in epidermoid cysts (0.5 (0.2) nmol/g/h), craniopharyngiomas (1.2 (0.9) nmol/g/h), angioblastomas (1.6 (1.7) nmol/g/h), and neurinomas (2.0 (1.8) nmol/g/h). By contrast with ODC activity, polyamine concentrations did not correlate with the grade of malignancy. Correlation of regional biochemical and histomorphological data in rapidly growing neoplasms showed high enzyme activity in solid tumour parts and low activity in necrotic areas. CONCLUSIONS: Novel data relating ODC activation and polyamine concentrations to neuropathology is presented indicating that high ODC activity represents a biochemical marker of malignancy in brain tumours. This information is important for clinical and therapeutic investigations.

Brain Neoplasms↗
PubMed2001

Spermidine: A predictor for neurological outcome and infarct size in focal cerebral ischemia?

BACKGROUND AND PURPOSE: Polyamines are mainly restricted to the intracellular space. During focal cerebral ischemia, polyamines are released from the intracellular compartment. Experimental studies have implicated a marked elevation in brain tissue and blood. The aim of our study was to investigate whether the elevation of polyamines in the blood of patients with focal cerebral ischemia correlates with the clinical outcome and the infarct volume. METHODS: Polyamines were measured in 16 patients with focal cerebral ischemia and in 8 healthy control subjects. Blood samples for polyamine measurement were taken at admission and at fixed time points for the next 28 days. Polyamines were analyzed in red blood cells by a high-pressure liquid chromatography system. Clinical findings were recorded with the NIH Stroke Scale score. Volume of infarction was analyzed from cranial CT at admission and on days 4 to 6 after ischemia. RESULTS: A significant increase of the spermidine level in the peripheral blood could be observed in all patients with focal cerebral ischemia as compared with control subjects (P:<0.01), starting with the admission. Spermidine values correlated positively with the clinical outcome at several time points in the first 48 hours (r=0.90 to 0.40; P:<0.01) and with the infarct volume in cranial CT on days 4 to 6 (r=0.91; P:<0.01). CONCLUSIONS: As hypothesized from experimental data, polyamine levels in blood increase in patients after focal cerebral ischemia. The results indicate that the peripheral spermidine level is closely associated with the clinical outcome as well as with the infarction volume. Therefore, polyamines may be used as a novel predictor for the prognosis of patients with focal cerebral ischemia.

Aged↗
PubMed2000

Prognostic significance of preoperative electrophysiologic investigation for facial nerve outcome in acoustic neuroma surgery.

The prognostic significance of transcranial magnetic stimulation and nasal muscle F-wave recording to predict postoperative facial nerve function was assessed in 24 patients with unilateral acoustic neuromas (mean diameter, 31 mm) and clinically intact facial nerve function. Latency of F waves and response to cortical magnetic stimulation, as well as F ratios, central motor conduction time, and the ratio of response latency to cortical and cisternal magnetic stimulation were significantly increased. Outcome analysis revealed no significant correlation between preoperative electrophysiologic changes and postoperative facial nerve function. However, a significant correlation with tumor diameter was detected. Thus, acoustic neuroma size seems to be the best predictor of facial nerve function after surgery.

Adult↗
PubMed2000

Lymphocytic adenohypophysitis mimicking a pituitary macroadenoma.

A 24-year-old woman developed headache and rapidly progressive visual disturbances during the last trimester of her first pregnancy. Magnetic resonance tomography (MRI) of the brain documented an intra- and suprasellar mass lesion. For preservation of vision, transsphenoidal microsurgical decompression was performed. Immediately postoperatively, visual acuity improved and hemianopia resolved. Histological examination yielded the diagnosis of primary lymphocytic adenohypophysitis. This is a rare inflammatory pituitary disease. There are no typical clinical, laboratory, or radiological findings that allow precise preoperative diagnosis. Even though this autoimmune disorder is principally steroid-responsive, an improvement of visual disturbances under steroid therapy cannot be predicted. Therefore, surgery is justified not only to establish the diagnosis, but also to restore vision by decompression of the optic nerves and the chiasm.

Adenoma↗
PubMed2000

Histological study of lumbar intervertebral disc herniation in adolescents.

Herniated intervertebral discs are rare in children and adolescents constituting approximately 1-5% of all patients undergoing surgery for lumbar and lumbosacral intervertebral disc herniation. Preceding traumata and congenital anomalities have been reported as important factors for the pathogenesis of intervertebral disc prolapses in young patients. The present histological study is based upon 15 patients with lumbar disc herniation within an age range from 14 to 19 years. Only in one case, was adequate trauma reported. All patients exhibited degenerative changes of the disc, similiar to those observed in adults. These changes were marked in 11 patients (73%). Thus, as known from adults, also in isolated traumatic disc herniation of adolescence, pre-existing degeneration of the disc has to be considered. If such changes are present, trauma has the significance of only transitory deterioration of the previous disc degeneration.

Adolescent↗
PubMed1999

Ganglioside profiles in human gliomas: quantification by microbore high performance liquid chromatography and correlation to histomorphology and grading.

The composition and the content of gangliosides changes during physiological growth and differentiation as well as in neoplastic cell transformation. In order to determine if ganglioside profiles correlate with brain tumour malignancy, the ganglioside distribution was determined in 31 gliomas of astrocytic origin and in non-tumour tissue by a recently developed microbore high performance liquid chromatography (HPLC) method. Glioma malignancy was graded according to the grading system proposed by the World Health Organization (WHO) in 1993. In general, an increase of GD3 and a decrease of normal brain gangliosides correlated with a higher grade of malignancy. Pilocytic astrocytomas Grade I had a distinctive ganglioside profile, histologically as well as biochemically. Although they are low-grade gliomas, the pilocytic astrocytomas exhibited a GD3 content comparable to anaplastic gliomas and could only be biochemically distinguished from other tumour grades by relatively high type "b" ganglioside levels. Thus, ganglioside composition not only reflects anaplasia but can also be used to indicate biological characteristics of tumours of different histogenetic origin.

Astrocytoma↗
PubMed1998

Acute nontraumatic spinal epidural hematomas. An important differential diagnosis in spinal emergencies.

STUDY DESIGN: The clinical data of five patients with spontaneous spinal epidural hematoma (SSEH) were reviewed. OBJECTIVES: To assess the clinical outcome of patients with SSEH after surgical decompression. SUMMARY OF BACKGROUND DATA: The outcome in SSEH is essentially determined by the timing of the operation. Therefore, early and precise diagnosis is necessary. METHODS: A retrospective analysis of five patients with SSEH was performed. The clinical data were stratified according to the Frankel Score. Special interest was given to the relevance of rapid and exact diagnosis and immediate therapeutic intervention. RESULTS: Diagnosis of SSEH was established preoperatively by means of computed tomography (one case) or magnetic resonance imaging (three patients) and intraoperatively in one case. Lumbar myelography had been false negative in one patient, computed tomography false-negative in two patients. Surgical decompression was performed in four patients within 24 hours after the onset of symptoms. Favorable postoperative functional results were found only in one patient whose symptoms had been present for less than 12 hours and in the case of an incomplete cauda equina syndrome. CONCLUSIONS: The results of the current series demonstrate both the superiority of magnetic resonance imaging for diagnosis of SSEH as well as the necessity of early decompressive surgery in cases of sensorimotor paralysis after SSEH.

Acute Disease↗
PubMed1998

11C-methionine PET for differential diagnosis of low-grade gliomas.

Management of low-grade gliomas continues to be a challenging task, because CT and MRI do not always differentiate from nontumoral lesions. Furthermore, tumor extent and aggressiveness often remain unclear because of a lack of contrast enhancement. Previous studies indicated that large neutral amino acid tracers accumulate in most brain tumors, including low-grade gliomas, probably because of changes of endothelial and blood-brain barrier function. We describe 11C-methionine uptake measured with PET in a series of 196 consecutive patients, most of whom were studied because of suspected low-grade gliomas. Uptake in the most active lesion area, relative to contralateral side, was significantly different among high-grade gliomas, low-grade gliomas, and chronic or subacute nontumoral lesions, and this difference was independent from contrast enhancement in CT or MRI. Corticosteroids had no significant effect on methionine uptake in low-grade gliomas but reduced uptake moderately in high-grade gliomas. Differentiation between gliomas and nontumoral lesions by a simple threshold was correct in 79%. Recurrent or residual tumors had a higher uptake than primary gliomas. In conclusion, the high sensitivity of 11C-methionine uptake for functional endothelial or blood-brain barrier changes suggests that this tracer is particularly useful for evaluation and follow-up of low-grade gliomas.

Adult↗
PubMed1997

Connective tissue reactions in subdural haematomas: imaging with contrast-enhancement MRI.

The sensitivity of contrast enhanced magnetic resonance imaging (MRI) in the detection of connective tissue reactions accompanying the maturation of subdural haematomas (SDH) was studied. An outer enhancing layer between the SDH and the tabula interna of the vault was shown in 16 out of 17 cases. In early SDH this outer enhancing layer presumably is due to vascular congestion and/or increased vascular permeability. A thickening of the outer enhancing layer and/or an inner enhancing layer between the haematoma and the subarachnoid space was visible in 9 patients and represented a haematoma capsule formed by proliferating granulation tissue. In 5 SDH septations were found, 3 SDH consisted almost completely of enhancing granulation tissue. Thus, contrast enhanced MRI delivers additional information about the structure of SDH, which are useful for determining the extent of surgical treatment especially in chronic SDH.

Adolescent↗