Search PubMed⌕ Search

Biomedical subjects

V Sturm

Publications and source records attributed to V Sturm.

At least 37 records · Page 2Linked to original sources
PubMed2000

N-type calcium channel blockers - tools for modulation of cerebral functional units?

According to in vitro and in vivo studies, the direct application of N-type calcium channel blockers as for instance omega-conotoxin GVIA (omega-ctx) potently inhibits the release of neurotransmitters like dopamine. To find out whether this effect could be used for modulation of neurological functions, omega-ctx was used for continuous infusion into the functionally well characterized rat striatum. Over the 2-week time course of intrastriatal application, rats developed a decrease in spontaneous motor activity, spontaneous rotational asymmetry towards the side of application, and behavioral supersensitivity to apomorphine. After the end of infusion period, all functional deficits showed reversibility. The pattern of spontaneous neurological deficits - in particular supersensitivity to apomorphine - points to a substantial unilateral alteration of dopaminergic transmission due to omega-ctx, which is suggested also by an increase in dopamine receptor protein expression within the ipsilateral striatum. Time course and reversibility of neurological deficits caused by omega-ctx, as well as a lack of dopamine depletion contrast findings after selective destruction of dopaminergic neurons and support a functional modulation of dopaminergic transmission. The present study suggests that omega-ctx is an effective potent tool for the unilateral and reversible intracerebral modulation of neuronal circuits. Intracerebral application of omega-ctx could possibly open the way to therapeutic interventions.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Computer simulation of cytotoxic and vascular effects of radiosurgery in solid and necrotic brain metastases.

PURPOSE: Solid and necrotic brain tumors respond to radiosurgery, although necrotic lesions often contain a significant proportion of hypoxic cells which cannot become reoxygenated during the short overall treatment time of single dose application. In addition to the direct cytotoxic action, delayed vascular occlusion followed by ischemic tumor cell death could contribute to the effect of radiosurgery. MATERIALS AND METHODS: In order to determine the impact of the two possible effects on tumor response, a 3-dimensional computer simulation was developed and fitted to response data obtained from 90 patients who were treated by LINAC radiosurgery for 1-3 brain metastases with median marginal doses of 20 Gy. Complete response rates were as follows: small, solid lesions (diameter 0.4-1 cm), 52% (12/23); large solid lesions (1.1-5.2 cm), 28% (17/60); large necrotic lesions, 12% (6/50). The 3-dimensional computer model simulated the growth of small solid and large, solid or necrotic tumors situated in a vascularized stroma. Oxygen supply, tumor cell division (cell cycle time 5 days), neovascularization, tumor cell kill by single dose irradiation (linear-quadratic model, alpha/beta=10 Gy, oxygen enhancement ratio 3.0) and time-dependent vascular occlusion (alpha/beta=3 Gy) were modeled by Monte-Carlo simulation techniques. RESULTS: In the presence of neovascularization, solid tumors with a hypoxic fraction of 1-2% developed. Without neoangiogenesis, central necrosis occurred, and tumors had a hypoxic fraction of 20-25%. Assuming a pure cytotoxic effect of radiosurgery, neither the dose-response relationship for the solid lesions of different size nor that for the large lesions with solid or necrotic appearance could be reproduced for any given level of radiosensitivity. This was only possible by introducing a vascular effect that led to the occlusion of >/=99% of the vessels at the border of the target volume within 1 year after irradiation. In the presence of the vascular effect, the apparent radiosensitivity of the tumor cells was increased by 50-100%. Calculations of the dose-equivalent for the vascular effect show that it contributes 19-33% of the overall effect of single dose radiosurgery. CONCLUSION: This simulation study suggests that the therapeutic effect of single radiosurgery in malignant brain tumors cannot be understood without the consideration of vascular effects. The computer model might serve as a basis for exploring new treatment modalities that modify both cytotoxic and vascular effects of radiosurgery.

Blood Vessels↗
PubMed2000

On isocentre adjustment and quality control in linear accelerator based radiosurgery with circular collimators and room lasers.

We have developed a densitometric method for measuring the isocentric accuracy and the accuracy of marking the isocentre position for linear accelerator based radiosurgery with circular collimators and room lasers. Isocentric shots are used to determine the accuracy of marking the isocentre position with room lasers and star shots are used to determine the wobble of the gantry and table rotation movement, the effect of gantry sag, the stereotactic collimator alignment, and the minimal distance between gantry and table rotation axes. Since the method is based on densitometric measurements, beam spot stability is implicitly tested. The method developed is also suitable for quality assurance and has proved to be useful in optimizing isocentric accuracy. The method is simple to perform and only requires a film box and film scanner for instrumentation. Thus, the method has the potential to become widely available and may therefore be useful in standardizing the description of linear accelerator based radiosurgical systems.

Algorithms↗
PubMed2000

Differentiation of green fluorescent protein-labeled embryonic stem cell-derived neural precursor cells into Thy-1-positive neurons and glia after transplantation into adult rat striatum.

OBJECT: The aim of this investigation was to assess new information concerning the capacity of transplanted embryonic stem cell (ESC)-derived neuronal cells to migrate into host brain and to evaluate these cells as a possible source for cell replacement therapy in neurodegenerative disorders such as Parkinson's disease (PD). METHODS: The authors investigated the ability of ESC-derived neural precursor cells to migrate and differentiate in a host striatum by using a D3-derived ESC clone that was transfected stably with a chicken beta-actin cytomegalovirus enhancer-driven green fluorescent protein (GFP)-labeled construct. This procedure allowed easy monitoring of all transplanted cells because of the green fluorescent labeling of donor cells. This approach also afforded easy estimation of cell integration and simultaneous observation of the entire transplanted cell population in relation to immunocytochemically identified neuronal and glial differentiation. After selection of nestin-positive neural precursor cells in a synthetic medium, they were implanted into the striatum of male adult Wistar rats. Their integration was analyzed on morphological studies performed 3 days to 4 weeks posttransplantation. CONCLUSIONS: The investigators found that after transplantation, a subpopulation of GFP-labeled cells differentiated into various neural morphological types that were positive for the mouse-specific Thy-1 antigen, which is known be expressed on neurons, as well as being positive for the astroglial marker glial fibrillary acidic protein. Moreover, GFP-expressing cells that were negative for either of these markers remained close to the injection site, presumably representing other derivatives of the neural lineage. Together, these findings contribute to basic research regarding future transplantation strategies in neurodegenerative diseases such as PD.

Animals↗
PubMed2000

Enhanced accuracy in differential diagnosis of radiation necrosis by positron emission tomography-magnetic resonance imaging coregistration: technical case report.

OBJECTIVE AND IMPORTANCE: To demonstrate the usefulness of positron emission tomography-magnetic resonance imaging (MRI) coregistration for differentiation of radiation necrosis and recurrent tumor in stereotactic planning. CLINICAL PRESENTATION: T1-weighted MRI scans of a 43-year-old woman revealed a contrast-enhancing lesion 4 years after open removal of a recurrent, right parieto-occipital Grade II oligodendroglioma and subsequent external radiation therapy. The suspected contrast-enhancing lesion revealed only moderate tracer uptake (1.3 times the uptake in the contralateral normal cortex) in a coregistered [11C]methionine positron emission tomographic scan. Approximately 15 mm posterior and mesial to the center of the contrast-enhancing lesion, however, an area of higher tracer uptake was found (1.8 times that of the contralateral normal cortex), which exhibited only very minor contrast enhancement on MRI. TECHNIQUE: The coregistered images were used for planning stereotactic serial biopsies, from the contrast-enhancing lesion as well as from the area with higher methionine uptake. Histological examination demonstrated that the contrast-enhancing lesion with low methionine uptake was necrotic tissue, and the nonenhancing area with high methionine uptake was recurrent tumor. CONCLUSION: High-resolution positron emission tomography and modern coregistration techniques allow differentiation of contrast enhancement and methionine uptake in irradiated brain tissue within small areas. High methionine uptake is typical for recurrent tumor tissue and can be differentiated from minor tracer accumulation resulting from disruption of the blood-brain barrier or macrophage activity within the necrotic area.

Adult↗
PubMed1999

Interstitial irradiation with stereotactically implanted I-125 seeds for the treatment of cerebral glioma.

Owing to its low rate of side effects and its high efficacy, interstitial irradiation with low-activity seeds should be the first therapeutic step in small (maximal diameter 40 mm), well-circumscribed, low-grade gliomas affecting the brain stem, other midline structures, or eloquent cerebral areas. In anaplastic gliomas, a therapeutic schedule using low-activity seeds and combining interstitial irradiation with radiotherapy (reduced boost dose of 15-30 Gy) seems to be more effective than interstitial irradiation alone. Compared with interstitial irradiation with high-activity seeds, this combined irradiation schedule caused no space-occupying radiation necrosis. Thus, it can be recommended as up-front treatment in patients with small (maximal diameter <40 mm) inoperable anaplastic gliomas. The use of high-activity I-125 seeds and interstitial irradiation at comparably high dose rates, integrating a small penumbra of normal brain tissue into the treatment volume, improved survival significantly in patients with primary highly malignant gliomas. In patients with recurrent tumors, the same treatment schedule did not substantially prolong survival compared with results obtained after resection plus radiotherapy. Owing to the high frequency of space-occupying radiation necrosis (40-60%), this schedule is only applicable in surgically accessible tumors. The application of low-activity I-125 seeds (in primary glioblastomas in combination with radiotherapy, in recurrent tumors without radiotherapy) yielded a median survival comparable with conventionally treated patients. There was no need for reoperation because of radiation necrosis. Thus, this treatment schedule is useful in both operable and surgically inaccessible glioblastomas.

Journal Article↗
PubMed1999

Computer-guided laser probe for ablation of brain tumours with ultrashort laser pulses.

A computer-guided laser probe has been developed for the application of ultrashort-pulsed lasers in neurosurgery. It is part of a novel operation concept for the treatment of deep-seated brain tumours. The system combines the positioning accuracy of stereotactic or neuronavigated instruments with the precise and therefore gentle characteristics of surgical lasers. The probe has an outer diameter of 5.5 mm and is directly inserted into the target volume. By a synchronized movement of three coaxial tubes, which guide the embedded optics, the laser radiation is focused at any time onto the current tissue surface. Since every single laser pulse has only a small effective volume of about 8 x 10(5) microm3, the application of a large number of succeeding pulses can be adapted to required geometries. Tissue fragments are removed from the growing operation cavity by continuous irrigation and suction through the laser probe. Blood vessels are detected by a confocal laser-scanning microscope, which is integrated into the probe, and can be closed by an additional coagulating laser. In this paper, the design and technical properties of the laser probe as well as its use in ablation and coagulation experiments are presented. A description of the overall operation system is given.

Animals↗
PubMed1999

The role of ventral medial wall motor areas in bimanual co-ordination. A combined lesion and activation study.

Two patients with midline tumours and disturbances of bimanual co-ordination as the presenting symptoms were examined. Both reported difficulties whenever the two hands had to act together simultaneously, whereas they had no problems with unimanual dexterity or the use of both hands sequentially. In the first patient the lesion was confined to the cingulate gyrus; in the second it also invaded the corpus callosum and the supplementary motor area. Kinematic analysis of bimanual in-phase and anti-phase movements revealed an impairment of both the temporal adjustment between the hands and the independence of movements between the two hands. A functional imaging study in six volunteers, who performed the same bimanual in-phase and anti-phase tasks, showed strong activations of midline areas including the cingulate and ventral supplementary motor area. The prominent activation of the ventral medial wall motor areas in the volunteers in conjunction with the bimanual co-ordination disorder in the two patients with lesions compromising their function is evidence for their pivotal role in bimanual co-ordination.

Adult↗
PubMed1998

Indication and results of stereotactic surgery for advanced Parkinson's disease

In the past decade there has been a resurgence of interest in neurosurgical interventions for the treatment of medically intractable Parkinson's disease. The reasons for this development include improved surgical techniques, a better understanding of the pathophysiology of Parkinson's disease providing the scientific rationale for such interventions, and the clinical problems of long-term levodopa treatment. Among the modern stereotactic procedures that are now available for the treatment of patients with advanced Parkinson's disease and levodopa-induced side effects, the effects of pallidotomy are best studied. More recently, chronic high-frequency stimulation of the internal pallidum and subthalamic nucleus have been proposed as surgical alternatives. This article reviews the most recent reports concerning the indication and results of stereotactic surgery for the treatment of advanced Parkinson's disease.

Journal Article↗
PubMed1998

Bilateral high-frequency stimulation of the internal globus pallidus in advanced Parkinson's disease.

We report here the results of an open prospective study in 9 patients suffering from severe Parkinson's disease with on/off fluctuations and restricted off-period mobility, who underwent bilateral implantation of stimulating electrodes in the internal pallidum. At 3-month follow-up, the total Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the medication-off state was reduced from 54.1+/-14.8 to 23.9+/-11.7 (44.2%) when stimulation was turned on. Comparison of UPDRS subscores revealed significant improvements for tremor, rigidity, bradykinesia, gait and posture, and dyskinesias. The results of the clinical scoring could be confirmed by significant changes in the quantitative assessment of hand function and walking. Bilateral pallidal stimulation reduced the amount and severity of on/off fluctuations. Additional follow-up at 6 months (n=6), 9 months (n=6), and 12 months (n=4) did not show a decline in effectiveness of stimulation. There was no permanent morbidity associated with the procedure. A subtle reduction of verbal fluency, which was not evident to the patients, was the only cognitive side effect of the procedure in neuropsychological testing. Chronic bilateral high-frequency stimulation of the internal pallidum seems to be a neurologically safe and highly effective treatment for "off" symptoms, dyskinesias, and motor fluctuations in advanced stages of Parkinson's disease.

Adult↗
PubMed1998

Computerized optimization of multiple isocentres in stereotactic convergent beam irradiation.

A method for the fully computerized determination and optimization of positions of target points and collimator sizes in convergent beam irradiation is presented. In conventional interactive trial and error methods, which are very time consuming, the treatment parameters are chosen according to the operator's experience and improved successively. This time is reduced significantly by the use of a computerized procedure. After the definition of target volume and organs at risk in the CT or MR scans, an initial configuration is created automatically. In the next step the target point positions and collimator diameters are optimized by the program. The aim of the optimization is to find a configuration for which a prescribed dose at the target surface is approximated as close as possible. At the same time dose peaks inside the target volume are minimized and organs at risk and tissue surrounding the target are spared. To enhance the speed of the optimization a fast method for approximate dose calculation in convergent beam irradiation is used. A possible application of the method for calculating the leaf positions when irradiating with a micromultileaf collimator is briefly discussed. The success of the procedure has been demonstrated for several clinical cases with up to six target points.

Arteriovenous Malformations↗
PubMed1998

Linear accelerator radiosurgery for recurrent malignant tumors of the skull base.

The efficacy of linear accelerator-based radiosurgery for patients who have preirradiated recurrent nasopharyngeal carcinomas and unresectable recurrent sarcomas invading the base of skull was assessed. Thirteen patients were treated: 8 patients had carcinomas arising from the nasopharynx (lymphoepithelioma, 4; squamous cell carcinoma, 2; adenoid-cystic, 2); 5 patients had sarcomas (rhabdomyosarcoma, 1; chordoma, 1; chondrosarcoma, 1; hemangiopericytoma, 2). All patients had had repeated tumor resections or irradiation, hindering any further conventional fractionated radiotherapy or surgery. Convergent-beam irradiation was performed with a modified linear accelerator (8-MeV photons). Because of irregular tumor configuration, multiple (up to seven) isocenters had to be used in 10 of 13 patients to match the target volume with the reference isodose (60%-80%). Each isocenter was irradiated with 6 to 10 arcs. The median planning target volume was 33 mL (4-128 mL) and the median dose was 15 Gy (9-24 Gy). Median survival time was 9 months in 8 patients who had recurrent nasopharyngeal carcinomas. Three patients who had complete or partial tumor remission survived 1.5 to 3.5 years. All of the sarcoma patients responded to radiosurgery. After a follow-up of 28 to 67 months, 4 of 5 patients are alive. This investigation demonstrates that radiosurgery is an effective tool in palliative treatment for patients who have recurrent, extensively pretreated nasopharyngeal cancer. Patients who have recurrent sarcomas of the base of skull may be treated for long-term palliation or even for cure.

Adult↗
PubMed1997

Risk analysis of LINAC radiosurgery in patients with arteriovenous malformation (AVM).

The purposes of this analysis were the evaluation of the toxicity of stereotactic single dose irradiation in patients with an arteriovenous malformation (AVM) and the comparison of the authors' own results with already existing risk prediction models. Computed-tomography (CT) or magnetic-resonance (MR) images, and clinical data of patients treated with linear accelerator radiosurgery for an AVM were analysed retrospectively. Using the Cox proportional hazards model (1), the relevance of treatment parameters and dose-volume relationships to the occurrence of radiation-induced tissue changes (oedema and localised blood-brain-barrier breakdown) were assessed. The 81 patients selected for analysis had a mean follow-up of 28.9 months (range: 9.0-65.7 months). Radiation-induced tissue changes (22 out of 81 i.e. 27.2%) were documented on CT or MR images 6.3-33.8 months after radiosurgery (median time: 12.8 months). The actuarial risk at 2 years was 32.1% for the development of neuroradiological changes and 20.1% for the development of symptomatic tissue alteration. The coefficient of total volume receiving a minimum dose of 10 Gy (VTREAT10) reached statistical significance in a Cox proportional hazards model. These results demonstrate the particular vulnerability of normal brain tissue to single dose irradiation. Optimal conformation of the therapeutic isodose line to the 3D configuration of the target volume may help to reduce side effects.

Actuarial Analysis↗
PubMed1997

Cystic craniopharyngioma: long-term results after intracavitary irradiation with stereotactically applied colloidal beta-emitting radioactive sources.

OBJECTIVE: Long-term follow-up data were analyzed to assess the value of intracavitary irradiation with stereotactically applied beta-emitting radioisotopes for the treatment of craniopharyngioma cysts. METHODS: Sixty-two of 70 consecutive patients with predominantly cystic craniopharyngiomas were selected for retrospective analysis. Beta-Emitting isotopes were injected intracystically using a computed tomography-guided and computer-assisted three-dimensional stereotactic treatment planning and application system (cumulative dose to the inner surface of the cyst wall, 200 Gy). RESULTS: The tumor response rate gained with yttrium-90-labeled silicate (66 of 78 cysts) or phosphorous-32-labeled chromic phosphate (8 of 78 cysts) was 79.5%. Four cysts treated with rhenium-186-labeled sulfate did not respond. Mean survival after intracavitary irradiation was 9.0 +/- 0.9 years (median follow-up, 11.9 yr). In patients with solitary cysts, the mean survival was 12.5 +/- 1.4 years (actuarial 5- and 10-yr survival rates, 80 and 64%, respectively). Six months postoperatively, visual deficits (38 of 62 patients) had improved in 23 patients and were stable in 15 patients. The side effects that occurred 6 to 12 months after treatment with yttrium-90 were complete blindness (three patients), worsening of visual field cuts (one patient), third nerve palsy (one patient), and diabetes insipidus and/or panhypopituitarism (three patients). CONCLUSIONS: Intracavitary irradiation using yttrium-90 or phosphorous-32 is highly effective in the treatment of cystic craniopharyngiomas. If applied as initial treatment in patients with solitary cysts, it is the only required therapy over a long period.

Adolescent↗
PubMed1997

11C-methionine and 18F-2-fluorodeoxyglucose positron emission tomography: a tool for diagnosis of cerebral glioma and monitoring after brachytherapy with 125I seeds.

Forty-six patients with suspected brain tumors were investigated by positron emission tomography (PET). Using 11C-methionine PET, the spatial extent of increased uptake in gliomas was larger than that of contrast enhancement on CT/MR images in 67% or the same in 33%. Ten of 46 patients treated with brachytherapy for low-grade gliomas were also investigated with 18F-2-fluorodeoxyglucose (FDG)-PET. One year after seed implantation, the glucose metabolism had not changed, but the decline of methionine uptake was significant. In conclusion, 11C-methionine PET may improve tumor delineation and, following brachytherapy, provides more information on the therapeutic effects than FDG.

Adult↗
PubMed1996

Risk analysis of linear accelerator radiosurgery.

PURPOSE: To evaluate the toxicity of stereotactic single-dose irradiation and to compare the own results with already existing risk prediction models. METHODS AND MATERIALS: Computed tomography (CT) or magnetic-resonance (MR) images, and clinical data of 133 consecutive patients treated with linear accelerator radiosurgery were analyzed retrospectively. Using the Cox proportional hazards model the relevance of treatment parameters and dose-volume relationships on the occurrence of radiation-induced tissue changes (edema, localized blood-brain barrier breakdown) were assessed. RESULTS: Sixty-two intraparenchymal lesions (arteriovenous malformation (AVM): 56 patients, meningioma: 6 patients) and 73 skull base tumors were selected for analysis. The median follow-up was 28.1 months (range: 9.0-58.9 months). Radiation-induced tissue changes (32 out of 135, 23.7%) were documented on CT or MR images 3.6-58.7 months after radiosurgery (median time: 17.8 months). The actuarial risk at 2 years for the development of neuroradiological changes was 25.8% for all evaluated patients, 38.4% for intraparenchymal lesions, and 14.6% for skull base tumors. The coefficient: total volume recieving a minimum dose of 10 Gy (VTREAT10) reached statistical significance in a Cox proportional hazards model calculated for all patients, intraparenchymal lesions, and AVMs. In skull base tumors, the volume of normal brain tissue covered by the 10 Gy isodose line (VBRAIN10) was the only significant variable. CONCLUSIONS: These results demonstrate the particular vulnerability of normal brain tissue to single dose irradiation. Optimal conformation of the therapeutic isodose line to the 3D configuration of the target volume may help to reduce side effects.

Adolescent↗
PubMed1996

LINAC-radiosurgery (LINAC-RS) in pituitary adenomas: preliminary results.

From 8/90 through 4/94, 32 consecutive patients with recurrent pituitary macroadenoma (PA) were treated with LINAC-RS after tumour resection and/or radiotherapy. Single doses ranging from 8-20 Gy (median: 14.5 Gy) were applied in 14 patients with acromegaly, 5 with Cushing's disease, 4 with Nelson tumours, 5 with prolactinomas and in 4 with nonfunctioning PA's. Retrospective analysis of 26 patients with a follow-up of > or = 6 months revealed no significant endocrinologic response in patients with Cushing's disease, Nelson tumour or prolactinoma. In contrast in 12 evaluated patients with acromegaly within 6-36 months after LINAC-RS the median GH-value decreased significantly. In 3 nonfunctioning PA's a tumour volume reduction has been observed. We conclude, that LINAC-RS with moderate single doses might be a safe and beneficial treatment in patients with acromegaly or nonfunctioning PA's resistant to conventional therapy. In Cushing's disease, Nelson tumours or prolactinomas higher doses seem to be required.

Adenoma↗