Biomedical subjects

B Volk

Publications and source records attributed to B Volk.

At least 37 records · Page 2Linked to original sources

PubMed1999

The role of tumor resection in the treatment of glioblastoma multiforme in adults.

BACKGROUND: The therapeutic impact of tumor resection is poorly defined. Therefore the current study was conducted. METHODS: A retrospective, 2-institutional study was conducted (1991-1994) to compare the treatment results of stereotactic biopsy plus radiation therapy (99 patients; tumor dose: 60 gray [Gy]) with those of surgical resection plus radiation therapy (126 patients; tumor dose: 60 Gy). Only adult patients with supratentorial, lobar located, de novo glioblastoma were included. Survival time was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from the multivariate Cox proportional hazards model. RESULTS: Patients were categorized in the Radiation Therapy Oncology Group (RTOG) Classes IV (46 patients), V (157 patients), and VI (22 patients). The resection group and the biopsy group did not differ in terms of age, pretreatment Karnofsky performance status KPS), gender, duration of symptoms, presenting symptoms, tumor location, tumor size, and the frequency of midline shift. Patients in the biopsy group more often were found to have left-sided tumors (P < 0.001). Transient perioperative morbidity and mortality rates were 1% and 1%, respectively, in the biopsy group and 5% and 1.6%, respectively, in the resection group (P > 0.05). The median survival time was 37 weeks for the resection group and 33 weeks for the biopsy group. The difference was not statistically significant (P = 0.09). The most favorable pretreatment prognostic factor was patient age < 60 years (P < 0.01). Tumor resection was highly effective in patients with midline shift (P < 0.01). In patients without midline shift radiation therapy alone was found to be as effective as tumor resection plus radiation therapy (P = 0.5). Patients with midline shift were more likely to have a worse KPS during the course of primary radiation therapy (P < 0.05). CONCLUSIONS: For RTOG Classes IV-VI patients with moderate mass effect of the tumor, radiation therapy alone is a rational treatment strategy. Tumor resection should be performed in patients with pretreatment midline shift whenever possible.

Adult↗

PubMed1999

Inhibition of NF-kappaB potentiates amyloid beta-mediated neuronal apoptosis.

One mechanism leading to neurodegeneration during Alzheimer's disease (AD) is amyloid beta peptide (Abeta) neurotoxicity. Abeta elicits in cultured central nervous system neurons a biphasic response: a low-dose neurotrophic response and a high-dose neurotoxic response. Previously we reported that NF-kappaB is activated by low doses of Abeta only. Here we show that NF-kappaB activation leads to neuroprotection. In primary neurons we found that a pretreatment with 0.1 microM Abeta-(1-40) protects against neuronal death induced with 10 microM Abeta-(1-40). As a known neuroprotective agent we next analyzed the effect of tumor necrosis factor alpha (TNF-alpha). Maximal activation of NF-kappaB was found with 2 ng/ml TNF-alpha. Pretreatment with TNF-alpha protected cerebellar granule cells from cell death induced by 10 microM Abeta-(1-40). This protection is described by an inverted U-shaped dose response and is maximal with a NF-kappaB-activating dose. The molecular specificity of this protective effect was analyzed by specific blockade of NF-kappaB activation. Overexpression of a transdominant negative IkappaB-alpha blocks NF-kappaB activation and potentiates Abeta-mediated neuronal apoptosis. Our findings show that activation of NF-kappaB is the underlying mechanism of the neuroprotective effect of low-dose Abeta and TNF-alpha. In accordance with these in vitro data we find that nuclear NF-kappaB immunoreactivity around various plaque stages of AD patients is reduced in comparison to age-matched controls. Taken together these data suggest that pharmacological NF-kappaB activation may be a useful approach in the treatment of AD and related neurodegenerative disorders.

Amyloid beta-Peptides↗

PubMed1999

Sites of simian foamy virus persistence in naturally infected African green monkeys: latent provirus is ubiquitous, whereas viral replication is restricted to the oral mucosa.

Foamy viruses (FV), retroviruses of the genus Spumavirus, are able to infect a wide variety of animal species and replicate in nearly all types of cultured cells. To identify the cells targeted by FV in the natural host and define the sites of viral replication, multiple organs of four African green monkeys naturally infected with simian FV type 3 were investigated for the presence of FV proviral DNA and viral transcripts. All organs contained significant amounts of FV proviral DNA. In addition to proviruses containing the complete transactivator gene taf, proviral genomes carrying a specific 295-bp deletion in the taf gene were detected in all monkeys. As in the case of human foamy virus the deletion leads to the formation of the bet gene that is regarded to be instrumental in the regulation of viral persistence. FV RNA was detected by RT-PCR and in situ hybridization only in the oral mucosa of one monkey. No other samples contained detectable levels of viral transcripts. Histopathological changes were not observed in any of the tissue samples analyzed. Our results show that the natural history of FV is characterized by latent infection in all organs of the host and by minimal levels of harmless viral replication in the oral mucosa. The broad host cell range in vivo further encourages the development of FV-derived vectors for therapeutic gene delivery.

Animals↗

PubMed1999

Mapping of cytoskeletal components in the hippocampal formation of the tree shrew (Tupaia belangeri).

The distribution of the major cytoskeletal components in frontal cryosections of the hippocampal formation of adult male tree shrews (Tupaia belangeri) was immunohistochemically investigated by using commercially available antibodies. Actin-immunolabeling was evident in all layers of the dentate gyrus as well as in the regio superior (CA1) and the regio inferior (CA3). Neurofilament 160 was detected only in the molecular layer of the dentate gyrus and in the axons of the granule cells (mossy fibers). For beta-tubulin, the microtubule associated proteins (MAPs) MAP2AB, MAP2ABC and Tau, immunoreactivity was evident within the granule cells and within the somatodendritic compartment of pyramidal neurons. Granule cells and the somata of the pyramidal neurons were intensely labeled for kinesin. Our findings show the elaborate expression of cytoskeletal proteins in the hippocampal formation of the tree shrew, relatively similar to what is seen in other species but with also some important differences, such as the immunonegativity of the axonal compartment for Tau in the tree shrew, which is contrary to what we see in the mouse (unpublished data). These findings provide useful insights regarding the organization of the hippocampal formation of the tree shrew and are fundamental for further research in this field.

Actins↗

PubMed1999

Testosterone metabolism in rat brain is differentially enhanced by phenytoin-inducible cytochrome P450 isoforms.

Many cytochrome P450 (P450) isoforms are selectively inducible by xenobiotics, e.g. pharmaceuticals like the anti-epileptic drug phenytoin. Some of these P450 enzymes are involved in the metabolism of gonadal hormones and are of great importance, especially in early brain development. In this study, the hydroxylation of testosterone by rat brain microsomes from control and phenytoin-induced animals was examined by use of high performance liquid chromatography (HPLC) provided with a photodiode array detector (PDA). In control rats, testosterone is converted by cytochrome(s) P450 to 6alpha-hydroxytestosterone (OHT) as the main metabolite and 6beta-OHT as well as androstenedione as minor metabolites. After phenytoin treatment, brain microsomes showed a strong increase of testosterone metabolism to 2alpha-, 6beta-, 16alpha-, 16beta-OHT and androstenedione, whereby 16alpha-OHT was the main degradation product. These metabolites indicated the action of isoforms of the P450 subfamilies CYP2B, CYP2C and CYP3A. Inhibition experiments with antibodies against CYP2B1/2 and with the CYP2B specific inhibitor orphenadrine indicated the occurrence of members of this subfamily which are known to catalyse the oxidation of testosterone to 16alpha-OHT, 16beta-OHT and androstenedione. Western blots revealed the phenytoin-inducible expression of CYP2B1 and the constitutive expression of CYP3A. The latter is involved in the 6beta-hydroxylation of testosterone which was found correspondingly in control microsomes. Distinct CYP2C isoforms involved in the hydroxylation of testosterone in phenytoin-induced microsomes are not yet identified. The highly increased testosterone metabolism by phenytoin-dependent induction of specific cytochrome P450 isoforms in adult rat brain illustrates the potential influence of exogenous substances on internal regulative and metabolic pathways in the brain.

Androstenedione↗

PubMed1999

Molecular genetic analysis as a tool for evaluating stereotactic biopsies of glioma specimens.

Over the last years, distinct genetic lesions have been associated with individual tumor entities. Stereotactic biopsy has become an essential diagnostic tool in surgical neuro-oncology. In order to evaluate the potential of molecular analyses in stereotactic biopsies, we examined a series of 156 human brain tumors from patients undergoing stereotactic biopsy for molecular alterations typically seen in astrocytic gliomas and compared those results with a control group of 268 astrocytic tumors obtained at open surgery. Stereotactic biopsies of astrocytomas with borderline histopathological features between the WHO grades II and III showed a higher rate of allelic losses on chromosome 10 than those of the WHO grade II from open surgery (p = 0.011). Stereotactic biopsies of astrocytomas with borderline histopathological features between the WHO grades III and IV showed a higher rate of allelic losses on chromosome 10 than those of the WHO grade III from open surgery (p = 0.013). This indicates that stereotactic biopsies with features intermediate between grades are likely to correspond to the higher malignancy grade. Our data demonstrate that molecular genetic approaches can be successfully applied to stereotactic glioma biopsies. The difference in the distribution of malignancy associated genetic alterations between a stereotactic and openly resected group of gliomas indicates that histopathology may underestimate the malignant potential in some stereotactic specimens. We propose to further evaluate the molecular analysis of stereotactic glioma biopsies as a useful adjunct to standard histopathological procedures.

Biopsy↗

PubMed1998

Effect of phenytoin on cytochrome P450 2B mRNA expression in primary rat astrocyte cultures.

Studies on cytochrome P450 2B (CYP2B) in the brain have essentially been focused on protein characterization and regional distribution. Due to the high sequence homology between the closely related CYP2B1 and 2B2 isoforms and the low amounts of the corresponding mRNAs few efforts have been made to analyze the expression, regulation, and inducibility of these P450 genes in a specific cell type. In the present study, we investigated CYP2B mRNA expression in primary rat astrocyte cultures under the influence of the anti-epileptic drug phenytoin, which is known to be a CYP2B inducing agent in liver. In situ hybridization with a digoxigenin (DIG)-labeled cRNA probe demonstrated that 30-40% of the astrocytes strongly expressed a CYP2B mRNA-specific signal within the first week of cultivation. With increasing age (> 14 days) a greater percentage of cells (>90%) expressed mRNA for P450 2B. However, the level of transcriptional activity was substantially lower than in younger cultures. To discriminate between the 2B1 and 2B2 isoforms the reverse transcription/polymerase chain reaction (RT/PCR) procedures were proved for rat hepatic mRNA as a control assay. Subsequently, the application of this method on cultured astrocytes confirmed that these brain cells may express CYP2B1 mRNA. CYP2B2 mRNA could not be detected in astrocyte cultures at any age examined. Phenytoin led to the down regulation of CYP2B1 mRNA, which contrasts with the drug inducing effect on hepatic CYP2B1 and 2B2 levels. After 4 hr of exposure of phenytoin to the astrocytes no amplification product could be detected at all. Phenytoin did not induce either CYP2B1 or 2B2 expression.

Alternative Splicing↗

PubMed1998

Diagnosis of idiopathic myositis: value of 99mtechnetium pyrophosphate muscle scintigraphy and magnetic resonance imaging in targeted muscle biopsy.

Our objective was to study the value of 99mtechnetium-pyrophosphate (99mTc-PYP) muscle scintigraphy and magnetic resonance imaging (MRI) in detecting areas of likely muscle inflammation and in increasing the rate of positive muscle biopsies in patients with suspected myositis. The results showed that in 13 out of 13 patients with clinical and/or signs of inflammatory muscle disease, increased 99mTc-PYP uptake was demonstrated at different muscle sites 3 h after isotope injection. Subsequent MRI of symmetric muscle areas with enhanced 99mTc-PYP uptake revealed signal patterns suggesting inflammation in all cases. Biopsy of these targeted muscles demonstrated characteristic histopathologic signs of muscle inflammation in 9 out of 13 patients. Four of these 9 patients had clinically atypical disease or did not show elevated creatine phosphokinase levels. Seven of these 9 patients had not been pretreated with corticosteroids. In 4 patients only muscle fiber atrophy and/or necrosis without cellular infiltrations was seen. These 4 patients had received either high doses of corticosteroids or low doses over longer periods of time before muscle biopsy. In conclusion, the combination of 99mTc-PYP muscle scintigraphy and MRI demonstrated muscle areas with maximum inflammatory signal patterns. Targeting of muscles by MRI only will probably yield reliable results of muscle biopsy in cases of clinically and serologically characteristic myositis. 99mTc-PYP muscle scintigraphy may provide useful initial information about localization of inflamed muscle tissue, especially in atypical disease. Treatment with corticosteroids prior to histologic diagnosis may abolish inflammatory infiltrations in affected muscle tissue.

Adolescent↗

PubMed1998

Myositis of small foot muscles.

Idiopathic focal myositis is a rare clinical entity and is mostly localized in the neck and thigh muscles presenting as a pseudotumor. We describe a 49-year-old patient with inflammation restricted to the small muscles of one forefoot. Systemic disease was not present and progression to polymyositis did not occur within 2 years of follow-up. The myositis improved promptly after initiation of immunosuppressive therapy with corticosteroids and azathioprine. This unusual location of focal myositis has not been previously reported.

Adrenal Cortex Hormones↗

PubMed1998

Phenytoin alters Purkinje cell axon morphology and targeting in vitro.

In adult mice, administration of the anticonvulsive drug phenytoin caused focal swellings along the Purkinje cell axon correlated with ataxia and incoordination of movements. In our model, we used murine cerebellar slice cultures to study the influence of phenytoin on postnatal Purkinje cell axon differentiation. Almost all of our untreated cultures developed to mature-like cerebellar tissue. Immunohistochemistry with anti-calbindin-D28k or UCHTI (anti-CD3) antibodies revealed numerous Purkinje cell axons in the white matter. In the area of the deep cerebellar nuclei, immunolabelled axons formed a large axonal plexus. The few neurofilament-positive neurons in this area were densely covered with Purkinje cell axon terminals. The synaptophysin immunoreactivity revealed connections between the terminals and the neurons of the deep cerebellar nuclei. Treatment of cerebellar slice cultures with phenytoin (10-80 microM) for 10-16 days resulted in focal swellings of different size along the axon. The number of swellings increased with an increasing dosage. At concentrations of 40 microM phenytoin, Purkinje cell axons seemed to be unable to invade the deep cerebellar nuclei, but numerous aberrant, recurrent collaterals could be detected immunohistochemically with the two specific Purkinje cell antibodies. Possible cytotoxic effects after treatment, such as dendritic degeneration and a decrease in the number of immunolabelled Purkinje cells, were observed above 40 microM phenytoin. These data suggest that the response of juvenile Purkinje cells is dependent upon the dosage of the antiepileptic drug because of morphological alterations as well as a misrouting of previously established connections.

Adult↗

PubMed1998

Expression of matrix metalloproteinases and their tissue inhibitors in human brain tumors.

In this study, we investigated the expression patterns of 15 matrix metalloproteinases (MMPs) and three tissue inhibitors of metalloproteinase in gliomas, medulloblastomas, and normal brain tissue. By Northern blot analysis we found increased levels of mRNAs encoding for gelatinase A, gelatinase B, two membrane-type MMPs (mt1- and mt2-MMP), and tissue inhibitors of metalloproteinase-1 in glioblastomas and medulloblastomas. We observed a significant increase of mt1-MMP, gelatinase A, gelatinase B, and tissue inhibitors of metalloproteinase-1 in glioblastomas as compared with low-grade astrocytomas, anaplastic astrocytomas, and normal brain. In medulloblastomas, the expression of mt1-MMP, mt2-MMP, and gelatinase A were also increased, but to a lesser extent than that observed in glioblastomas. These data were confirmed at the protein level by immunostaining analysis. Moreover, substrate gel electrophoresis showed that the activated forms of gelatinases A and B were present in glioblastomas and medulloblastomas. These results suggest that increased expression of mt1-MMP/gelatinase A is closely related to the malignant progression observed in gliomas. Furthermore, the present study demonstrates, to our knowledge for the first time, that medulloblastomas express high levels of MMP.

Adult↗

PubMed1998

Endolymphatic sac tumours.

This review article surveys clinical and pathological literature on endolymphatic sac tumours (ELST) and summarizes characteristics that describe the entity. ELST are rare neuroectodermal neoplasms in the petrous bone, originating from inner ear structures. They can be encountered sporadically or in von Hippel-Lindau disease. The most prominent symptom is sensorineural deafness. Historically, nomenclature of invasive adenoid tumours in the petrous bone has been divergent, the term papillary adenocarcinoma used most frequently. Histologically, they have a follicular or papillary and adenoid pattern that can be easily confused with various other neoplastic conditions including metastatic carcinoma. It remains to be verified whether similar tumours (papillary adenocarcinomas) can originate from the middle ear. Middle ear adenomas have a similar appearance but probably originate from neural crest cells in the middle ear. ELST can express a variety of epitopes (including cytokeratin and neuroectodermal markers) which can be detected immunohistochemically. In cases in von Hippel-Lindau disease the cerebello-pontine angle should be included in routine radiological examinations to detect ELST before the tumours lead to deafness. In apparently sporadic cases of ELST, genetic testing for von Hippel-Lindau disease should be considered. Correct distinction of ELST from metastatic carcinoma prevents futile searches for unknown primary tumours.

Diagnosis, Differential↗

PubMed1998

Borna disease virus-induced neurological disorder in mice: infection of neonates results in immunopathology.

Borna disease virus (BDV) is a neurotropic nonsegmented negative-stranded RNA virus that persistently infects warm-blooded animals. In horses and other natural animal hosts, infections with BDV cause meningoencephalitis and behavioral disturbances. Experimental infection of adult mice takes a nonsymptomatic course, an observation previously believed to indicate that this animal species is not suitable for pathogenesis studies. We now demonstrate that BDV frequently induces severe neurological disease in infected newborn mice. Signs of neurological disease were first observed 4 to 6 weeks after intracerebral infection. They included a characteristic nonphysiological position of the hind limbs at an early stage of the disease and paraparesis at a later stage. Histological examination revealed large numbers of perivascular and meningeal inflammatory cells in brains of diseased mice and, unexpectedly, no increase in immunoreactivity to glial fibrillar acidic protein. The incidence and severity of BDV-induced disease varied dramatically among mouse strains. While only 13% of the infected C57BL/6 mice showed disease symptoms, which were mostly transient, more than 80% of the infected MRL mice developed severe neurological disorder. In spite of these differences in susceptibility to disease, BDV replicated to comparable levels in the brains of mice of the various strains used. Intracerebral infections of newborn beta2-microglobulin-deficient C57BL/6 and MRL mice, which both lack CD8+ T cells, did not result in meningoencephalitis or neurological disease, indicating that the BDV-induced neurological disorder in mice is a cytotoxic T-cell-mediated immunopathological process. With this new animal model it should now be possible to characterize the disease-inducing immune response to BDV in more detail.

Animals↗

PubMed1997

Possible role of cytochrome P450 in inactivation of testosterone in immortalized hippocampal neurons.

The hippocampus as part of the limbic system is sensitive to gonadal hormones. The time-dependent expression of steroid receptors and the testosterone converting enzyme aromatase (CYP19) is well studied. In contrast, little is known about other cytochrome P450 enzymes in hippocampus which inactivate the gonadal hormones. For investigation of the total cytochrome P450 content and the expression of testosterone degrading CYP2B10 we used embryonic (E18) in comparison to postnatal (P21) immortalized hippocampal neurons. These embryonic neurons were demonstrated to react to hormones according a 'critical period' of sexual differentiation: testosterone treatment (1 microM to 5 microM in the culture medium) resulted in a decrease of beta-tubulin, as showed by immunocytochemistry and Western blotting. Measurements with reduced CO-difference spectrum elucidated that the P450 concentration in the embryonic neurons (10.2 pmol/mg protein; S.D. +/- 1.9) was twice as high as in the postnatal ones (5.2 pmol/mg protein; S.D. +/- 1.0). Correspondingly, a high value of the mitochondrial subfraction of approx. 141 pmol P450/mg protein was found in the embryonic neurons relative to the mitochondrial value of 37.7 pmol P450/mg protein in the postnatal neurons. Our results suggest a differential expression of cytochrome P450 during development. CYP2B10 was proved by electron microscopy and hormone degrading activity.

Age Factors↗

PubMed1997

Transcription factor NF-kappaB is activated in primary neurons by amyloid beta peptides and in neurons surrounding early plaques from patients with Alzheimer disease.

Amyloid beta peptide (A beta)-containing plaques are a hallmark of Alzheimer disease. Here, we show that the neurotoxic A beta, a major plaque component, is a potent activator of the transcription factor NF-kappaB in primary neurons. This activation required reactive oxygen intermediates as messengers because an antioxidant prevented A beta-induced NF-kappaB activation. Maximal activation of NF-kappaB was found with 0.1 microM A beta-(1-40) and 0.1 microM A beta-(25-35) fragments, making a role for NF-kappaB in neuroprotection feasible. Using an activity-specific mAb for the p65 NF-kappaB subunit, activation of NF-kappaB also was observed in neurons and astroglia of brain sections from Alzheimer disease patients. Activated NF-kappaB was restricted to cells in the close vicinity of early plaques. Our data suggest that the aberrant gene expression in diseased nervous tissue is at least in part due to A beta-induced activation of NF-kappaB, a potent immediate-early transcriptional regulator of numerous proinflammatory genes.

Alzheimer Disease↗

PubMed1997

Supratentorial World Health Organization Grade 2 astrocytomas and oligoastrocytomas. A new pattern of prognostic factors.

BACKGROUND: Prognostic factors for adult patients with supratentorial World Health Organization (WHO) Grade 2 astrocytomas and poorly defined. METHODS: The prognostic importance of pretreatment patient- and tumor-related factors was analyzed retrospectively in 197 adult patients with supratentorial astrocytomas (n = 153) or oligoastrocytomas (n = 44) using the multivariate Cox proportional hazards model. Endpoints were death and date of malignant transformation. All patients were treated similarly between 1979 and 1992 with iodine-125 implants as the primary treatment. RESULTS: A new prognostic pattern was detected. Unfavorable prognostic factors with regard to survival were 1) a tumor volume > or = 20 mL; 2) a performance status < or = 80; and 3) age > or = 40 years for the female subpopulation. Midline shift (another important tumor-related factor after univariate analysis) was highly correlated with tumor volume and therefore not included in the multivariate model. Risk factors of malignant transformation were 1) a tumor volume > or = 20 mL; 2) an enhancement in the computed tomography scan; and 3) age > or = 40 years for the female subpopulation. Prognostic factors created subsets of patients with 5-year survival rates ranging from as low as 5% to as high as 79%. CONCLUSIONS: Any treatment decision or evaluation of treatment efficacy should take into account the strong influence of both patient- and tumor-related factors. Any further study design should consider the detected interaction between gender and age and the importance of tumor volume.

Adult↗

PubMed1997

Congenital axonal neuropathy caused by deletions in the spinal muscular atrophy region.

Three newborn siblings presented with generalized weakness, asphyxia, facial diplegia, and external ophthalmoplegia. Electrophysiological testing showed inexcitability of motor and sensory nerves and myographic signs of denervation. Nerve biopsies and postmortem examination showed loss of myelinated fibers and axonal damage in sensory and mixed nerves. Many spinal motor neurons were chromatolytic although their number was normal. Molecular genetic investigations revealed a homozygous deletion of the survival motor neuron (SMN) gene and a loss of markers Ag1-CA and C212 in the paternal haplotype. These findings are consistent with the diagnosis of an unusually severe type of spinal muscular atrophy. Given the large extent of the deletion, it must be considered that the unusual severe phenotype with involvement of brainstem nuclei and afferent nerves might also be due to changes of yet unknown genes neighboring the SMN gene.

Axons↗

PubMed1997

The risk of interstitial radiotherapy of low-grade gliomas.

BACKGROUND AND PURPOSE: The risk of side effects of low activity (i.e. <20 mCi) Iodine-125I (125I) interstitial radiotherapy was analyzed in patients with low-grade gliomas. MATERIALS AND METHODS: Permanent (247 patients) or temporary 125I-implants (268 patients) were used with a median reference dose of 60 Gy and 100 Gy, respectively, which was calculated to the outer rim of the tumour. The mean dose rate for temporary implants was low (median, 10 cGy/h). Risk factors were obtained from the multivariate proportional-hazards model. RESULTS: Radiogenic complications occurred in 39/515 patients (28 patients with transient symptoms and 11 patients with progressive symptoms). The most important risk factor was the volume of the intratumoural 200 Gy isodose. Available experimental data have associated a high dose zone in this range with the size of the treatment induced radionecrosis. Rapid tumour shrinkage (decrease of the tumour volume > or =50%) within the first 6 months with subsequent centripetal movement of non-pathologic tissue into the high dose zone and a reimplantation were additional risk factors. Radiation injury after rapid tumour shrinkage could be better avoided with temporary implants. A 200 Gy isodose volume <4.5 ml corresponded to an estimated risk of radiogenic complications <3%. There was a steep increase of the risk beyond this limit. Translation of the 200 Gy isodose volume in terms of the treatment volume and the reference dose allows rational treatment planning. The estimated risk of a temporary implant with an applied reference dose of 60 Gy and a treatment volume <23 ml was <3%. CONCLUSIONS: The intratumoural necrotizing effect of a low activity 125I implant limits its application to small treatment volumes. Radiation injury outside the treatment volume can be better avoided with temporary implants in the case of rapid tumour shrinkage.

Adolescent↗