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Biomedical subjects

P C Warnke

Publications and source records attributed to P C Warnke.

At least 19 recordsLinked to original sources
PubMed2001

Immediate and long term outcome after infrathalamic and thalamic lesioning for intractable Tourette's syndrome.

OBJECTIVE: The surgical treatment of intractable Tourette's syndrome is controversial. Experience with 17 consecutive patients treated between 1970 and 1998 is reviewed and the efficacy and safety of surgical treatment is assessed. METHODS: These patients were retrospectively reclassified into subtypes according to the protocol of the Tourette's Syndrome Study Group. One patient was excluded from the study. Ventriculography based stereotactic zona incerta (ZI) and ventrolateral/ lamella medialis thalamotomy (VL/LM) were performed on all patients. The preoperative, postoperative, and late tic severities were assessed by the tic severity rating scale. The median follow up of 11 patients (65%) was 7 years (range 3.5-17 years) and six patients were lost to long term follow up. RESULTS: Median age was 23 years (range 11-40) at the time of surgery. Median duration of illness was 14 years (range 3-33). The mean preoperative motor and vocal tic severities were estimated to be 4.44 (SD 0.63) and 3.81 (SD 0.66), respectively. Unilateral ZI lesioning and VL/LM lesioning selected by asymmetry of symptoms provide an effective control of tic severity (p motor and vocal<0.001). In attenuation of contralateral symptoms, a second surgical intervention in the relevant side could reduce tic severity sufficiently (p motor<0.01; p vocal<0.005). Transient complications occurred in 68% of patients. Only one permanent complication was registered in six patients followed up after unilateral surgery. Two out of five patients followed up after bilateral surgery had disabling side effects of surgery. CONCLUSIONS: ZI and VL/LM lesioning provide a significant long term reduction of tic severity in intractable Tourette's syndrome. Adequate selection of the side of first intervention might prevent the patient from increased risk of bilateral surgery.

Adolescent↗
PubMed2001

The effects of continuous and single-dose radiation on choline uptake in organotypic tissue slice cultures of rabbit hippocampus.

The objective of the present study was to determine the time-dependent course of choline uptake in mature organotypic slice cultures of rabbit hippocampal formation and to assess the effects of continuous and single high-dose irradiation on choline uptake in cultivated slices in vitro. Transverse slices of hippocampus were dynamically incubated in a cerebrospinal fluid-like culture medium for 72 h. To study the changes in choline uptake longitudinally, the slice cultures were processed with 0.1 microM [3H]-choline, and tritium accumulation was counted. Two different gamma irradiation sources (125I seeds and a clinical 60Co source) were used as representative models of interstitial radiosurgery and other radiosurgical techniques. A total dose of approximately 6000 cGy was delivered to the brain slices in one session or in a continuous, relatively low-dose rate fashion, and their effects on high-affinity choline uptake were examined. In another set of experiments with 125I, 5 microM hemicholinium-3 was used in choline uptake procedures as a competitive high-affinity choline uptake inhibitor. The results can be summarized as follows: (1) in the control group of the hippocampal tissue culture, there was a significant increase in tritium accumulation values from 0 to 48 h and a decrease thereafter; (2) continuous 125I irradiation caused a highly significant depression of the accumulation of tritium compared to that observed in the control group throughout its application for 72 h; (3) there was no significant change in the accumulation of tritium in the slices after single high-dose rate irradiation with a 60Co source; and (4) 5 microM hemicholinium significantly depressed the accumulation of tritium in both the control and the 125I-irradiated groups, and there was no longer a difference between 125I-irradiated and control groups when both groups were treated with hemicholinium. These results demonstrate that the delivery of continuous but relatively low-dose rate gamma irradiation is more efficacious than single high-dose external irradiation on high-affinity choline uptake in hippocampal nervous tissue. The results also indicate that continuous irradiation specifically affected the high-affinity energy-dependent choline uptake mechanism, whereas nonspecific choline uptake did not seem to be disturbed.

Acetylcholine↗
PubMed2000

Early effects of PRS-irradiation for 9L gliosarcoma: characterization of interphase cell death.

We characterized the interphase cell death of 9L gliosarcoma after high-dose-rate, low-energy photon irradiation using the Photon Radiosurgery System (PRS), a novel device for interstitial radiotherapy. Within 24 hours after irradiation with a dose of 18 Gray, 22.0% of cells underwent metabolic cell death, whereas dead cells in controls stayed less than 5.0% (p<0.005). In the majority of sensitive cells, loss of membrane integrity preceded the lethal morphological changes. The response was dose-dependent over the range of 9-18 Gray, but saturation was obtained over 18 Gray. On the other hand, a significant (p < 0.01) increase in the number of TUNEL-positive cells with apoptotic morphology was detected 6-24 hours after irradiation, but the fraction remained 1.9-2.1% of the population and was independent of the doses between 9 and 25 Gray. Apoptotic cells were rarely observed in the control cells (0.3-0.6%). Our data indicate that single high-dose irradiation induces both necrotic and apoptotic interphase cell death in 9L gliosarcoma, but rapid cell death mostly occurs through the non-apoptotic pathway.

Apoptosis↗
PubMed1999

[Neuronavigation. Computer-assisted neurosurgery].

The use of stereotactic methods for the resection of subcortical lesions is heavily advocated in clinical neurosurgery introducing the term "neuronavigation". Though being an unequivocally elegant technique for the localisation and delineation of pathological lesions in the central nervous system neuronavigation has not been validated by any prospective randomized controlled trial. The method is prone to significant errors as to the intraoperative localisation based upon preoperative three-dimensional images. The maximum error can be up to 2.6 cm depending on the extent of the so-called brain shift. In comparison classical frame based stereotaxy has a mean error of +/- 1 mm and remains the gold standard for the exact three-dimensional localisation of a given lesion. The value of neuronavigation is evident for small deep seated vascular lesions. For metastatic tumors or skull base tumors the usefulness is rather marginal because alternative therapies are available with proven and equivalent efficacy and reduced morbidity on one hand, and because of the anatomy of the tumor which makes neuronavigation unnecessary. For the currently most common application of neuronavigation, i.e. surgery of gliomas, no significant improvements of therapeutic results can be expected from neuronavigation. The biology of gliomas limits any mechanical approaches.

Brain Neoplasms↗
PubMed1999

Vascular endothelial growth factor expression, vascular volume, and, capillary permeability in human brain tumors.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and a potent inducer of vascular permeability. In this study, we determined whether expression of VEGF is correlated with in vivo measurements of the capillary permeability and vascular volume of primary human brain tumors. METHODS: Tumor samples (seven glioblastomas, one anaplastic astrocytoma, two low-grade astrocytomas, one pilocytic astrocytoma, and three primary cerebral lymphomas) were stereotactically obtained from 14 patients. A semiquantitative polymerase chain reaction was used to quantify the relative expression of VEGF messenger ribonucleic acid in the tumors. VEGF protein was demonstrated in tissue sections by immunohistochemical techniques. A two-compartment dynamic computed tomographic method was used to quantitatively measure the aforementioned parameters in the regions from which the biopsies were obtained. RESULTS: In glial tumors, there was significant correlation of VEGF messenger ribonucleic acid levels with capillary permeability (P < 0.05) and vascular volume (P < 0.01). Although all primary cerebral lymphomas showed considerable increases in capillary permeability and vascular volume, VEGF expression was only slightly upregulated in these tumors. CONCLUSION: Our findings are consistent with the hypothesis that VEGF may be responsible for endothelial cell proliferation and vascular permeability in glial tumors. This relationship has implications for clinical applications, i.e., assessment of delivery of water-soluble drugs, treatment of edema, and antiangiogenesis therapy based on inhibition of VEGF function.

Adult↗
PubMed1998

Regional cerebral blood flow in peritumoral brain edema during dexamethasone treatment: a xenon-enhanced computed tomographic study.

OBJECTIVE: Regional cerebral flood flow (rCBF) in peritumoral brain edema is assumed to be decreased because of increased interstitial pressure. Impaired blood flow might lead to local hypoxia, altered metabolism, and disturbed ion homeostasis, thus causing neurological sequelae. Steroid treatment is thought to positively influence the sequelae of brain edema. We aimed to determine the rCBF in peritumoral edema in humans receiving dexamethasone treatment and the relationship of rCBF to global CBF. METHODS: We measured rCBF in 11 patients with untreated anaplastic gliomas or glioblastomas that were World Health Organization Grade III or IV restricted to one hemisphere with significant peritumoral edema who were receiving a standard dose of dexamethasone. rCBF was determined using stable xenon-enhanced computed tomography in a stereotactic frame. Edema was defined both by means of actual histology (stereotactic biopsies) and by imaging criteria. RESULTS: rCBF in peritumoral edema was decreased by 32% as compared with contralateral normal white matter. In each patient, this reduction was linearly related to blood flow in nonaffected white matter and cortex. The flow ratio in the different compartments was 1 (edema):1.5 (contralateral white matter):2.7 (contralateral cortex). Absolute perfusion values in contralateral cortex (means +/- standard deviations) (29.9+/-7.1 ml/100 g/min) and contralateral white matter (16.1+/-3.7 ml/100 g/min) were significantly decreased as well. CONCLUSION: Our study demonstrated that rCBF in peritumoral brain edema during steroid treatment is still decreased and is in a range in which it may cause neurological sequelae. Also, global CBF was decreased in all patients.

Adult↗
PubMed1997

Significant reduction of seizure incidence and increase of benzodiazepine receptor density after interstitial radiosurgery in low-grade gliomas.

Epilepsy is the leading symptom in low grade gliomas. In order to evaluate the effect of interstitial radiosurgery on seizure incidence the authors retrospectively analysed the outcome of 80 patients with temporal grade-II astrocytomas and a history of epilepsy. Patients were treated by 125-iodine temporary implants using 60 Gy as reference dose. The dose rate was 9.6 +/- 1.6 cGy/h. Median follow-up was 4.1 years. In 20 patients benzodiazepine receptor imaging was performed using single photon emission computed tomography and iomazenil. Treatment with carbamazepine alone led to a significant reduction in seizure incidence with 28% of patients being seizure-free (p < 0.05). Interstitial radiosurgery led to a further reduction of seizures rendering 40% of patients seizure-free after 3 months. After 6 months only 21% of patients still had seizures that were refractory to medical treatment (p < 0.01). SPECT imaging revealed that all tumours had a significant reduction of benzodiazepine receptors which also applied to the surrounding brain. After interstitial radiosurgery of tumours, receptor density increased in brain adjacent to the tumour (0.68 to 0.94 ratio ipsi to contralateral brain, p < 0.01) coincident with significant tumour shrinkage. Thus, in epileptogenic temporal low grade gliomas, interstitial radiosurgery not only reduced the tumour burden but also effectively treated the concomitant epilepsy, resulting in 79% of patients being seizure-free after combined treatment by radiosurgery and anticonvulsive medication. These results compare favourably to the outcome after resection in lesional epilepsy raising the issue of radiosurgery as a less invasive alternative to open epilepsy surgery.

Adult↗
PubMed1997

Effect of LINAC radiosurgery on regional cerebral blood flow, glucose metabolism and sodium-potassium AtPase in skull base meningiomas and metastasis.

Stereotactic radiosurgery is an elegant alternative to microsurgery in both skull base meningiomas and solitary brain metastasis. Though efficacy for both entities has been established prognostic variables pertaining to individual tumour biology have not yet been identified. Therefore the authors measured regional glucose utilisation, thallium-uptake and blood flow in 20 patients (10 meningiomas, 10 metastasis) before and after LINAC radiosurgery. Measurements were performed using SPECT and stable xenon-CT. The mean tumour dose given was 16.3 and 19.5 Gy in meningiomas and metastasis respectively. Metastatic tumours were hypermetabolic in comparison to contralateral normal brain and responders to radiosurgery showed a lower tumour/brain ratio than non-responders (1.43 vs 0.91 respectively, p < 0.01). Meningiomas did not exhibit hypermetabolism and therapeutic outcome was not related to glucose utilisation. Thallium-uptake, however, was closely related to therapeutic response in meningiomas (1.37 vs 2.2 in responders vs non-responders, p < 0.01). This relationship could not be established in metastatic lesions. Blood flow was widely distributed in both meningiomas and metastasis (26-72.8 and 30.2-70.8 ml/100 g/min). rCBF did not correlate with therapeutic outcome. Using FDG-SPECT and thallium-201-SPECT the authors were able to distinguish between tumours likely to respond to stereotactic radiosurgery and those not prone to respond. Furthermore the methodology can be used to monitor therapeutic response in treated tumours before morphologic changes occur.

Adult↗
PubMed1997

Vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenesis and vascular permeability factor which is expressed in high amounts in perinecrotic palisading cells in human glioblastomas. In vitro VEGF gene expression is enhanced approximately ten times by hypoxia. Current evidence suggests, that hypoxia is also the driving force for VEGF gene expression in glioblastoma cells in vivo and represents the most important trigger for tumor angiogenesis and edema. Our approaches to inhibit tumor angiogenesis and edema formation in glioblastoma patients will concentrate on the disruption of VEGF/VEGF receptor signal transduction pathway in vivo.

Animals↗
PubMed1995

The effects of dexamethasone on transcapillary transport in experimental brain tumors: II. Canine brain tumors.

We studied the effect of dexamethasone on transcapillary transport in ten Avian Sarcoma Virus (ASV)-induced canine brain tumors, before and one week after administration of dexamethasone, 2.5 mg/kg/day. A computed tomographic (CT) method was used to measure regional values of K1 (blood-to-tissue transfer constant), k2 (tissue-to-blood efflux constant), and Vp (tissue plasma vascular space) of meglumine iothalamate (Conray-60); the values were reconstructed for each 0.8 x 0.8 x 5 mm volume element of the CT data. For all tumors considered together, there was a decrease in the whole tumor K1 value of meglumine iothalamate from 26 +/- 2.2 (SE) before dexamethasone to 24 +/- 2.9 microliters/g/min after dexamethasone. Vp decreased from 7.2 +/- 0.7 to 6.7 +/- 0.9 ml/100 g, and the size of the tumor extracellular space (Ve) decreased from 0.30 to 0.26 ml/g. These changes were not statistically significant. However, when each tumor was used as its own control, K1 significantly decreased after dexamethasone in four tumors, significantly increased in two and was unchanged in four. These results suggest that decreased blood-to-tissue transport may be one mechanism underlying resolution of tumor associated cerebral edema in some brain tumors and that the effects of dexamethasone on blood-to-tissue transport in brain tumors are variable from one tumor to the next. Decreased 'permeability' may not be the sole mechanism by which dexamethasone reduces tumor-associated cerebral edema.

Animals↗
PubMed1995

Interstitial radiosurgery of low-grade gliomas.

The treatment of patients with low-grade gliomas remains a subject of controversy, especially with respect to new treatment modalities such as interstitial radiosurgery (brachytherapy), radiosurgery, and stereotactic radiotherapy. In a retrospective analysis conducted between 1979 and 1991, the authors studied the results of interstitial radiosurgery in 455 patients with low-grade gliomas (World Health Organization (WHO) Grade I+WHO Grade II) with regard to survival time, quality of life, the risk of malignant transformation, and the risk profile of the treatment concept. Interstitial radiosurgery with iodine-125 was performed using permanent (1979-1985) or temporary implants (after 1985) with low-dose rates (< or = 10 cGy/hr) and a reference dose of 60 to 100 Gy calculated to the outer rim of the tumor. The 5- and 10-year survival rates in patients with pilocytic astrocytomas (97 patients) were 84.9% and 83%, and in patients with WHO Grade II astrocytomas (250 patients) 61% and 51%, respectively. Five-year survival rates for patients with oligoastrocytomas (60 patients), oligodendrogliomas (27 patients), and gemistocytic astrocytomas (21 patients) were 49%, 50%, and 32%, respectively. In the group with WHO Grade II gliomas, young age and a good performance status were associated with a better prognosis. Unfavorable factors were midline shift, enhancement on computerized tomography (CT) scan, and tumor recurrence after previous radiotherapy or surgery. Tumor location had no influence on the prognosis (247 patients in this series had deep-seated tumors). Malignant transformation was the major cause of death. Important risk factors for malignancy were the patient's age, tumor enhancement in CT scan, and tumor recurrence after previous surgery or radiotherapy. Perioperative mortality was 0.9% and perioperative morbidity was 1.7%. Radiogenic complications were observed in 2.7% of all patients, most often in larger tumors and after using permanent implants. The authors conclude that interstitial radiosurgery represents a specific treatment modality for selected patients with unifocal circumscribed low-grade gliomas with a diameter of less than 4 cm in any location. The efficacy of this treatment lies in the same range as the best results after surgery and radiotherapy.

Adolescent↗