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H Maximilian Mehdorn

Publications and source records attributed to H Maximilian Mehdorn.

At least 19 recordsLinked to original sources
PubMed2006

Overexpression of midkine contributes to anti-apoptotic effects in human meningiomas.

Meningiomas are the second most common intracranial tumours. Most meningiomas grow slowly; however, atypical and anaplastic meningiomas show an aggressive biological behaviour. Overexpression of growth factors is considered to be a cause of carcinogenesis. Midkine and pleiotrophin are heparin-binding growth factors that promote growth, survival, migration and differentiation of various target cells. Both molecules are highly expressed during human embryogenesis but are rarely seen in the adult. We show that in relation to normal dura and arachnoid tissues, midkine was overexpressed in meningiomas on the mRNA and protein level, whereas pleiotrophin was not. Thereby, not only the intact but also the truncated form of midkine could be observed. The expression of midkine receptors was variable in different samples. Midkine stimulation of cultured meningioma cells induced phosphorylation of Akt, whereas no increase in phosphorylation of p42/44 MAPK or p38 MAPK could be detected. Midkine did not influence the proliferation of meningioma cells in vitro, but it did protect meningioma cells from camptothecin-mediated apoptotic cell death through reduction in the amounts of active caspase-3. These findings provide evidence for the overexpression of midkine in meningiomas which contributes to protection from cell death in these second most common intracranial tumours.

Aged↗
PubMed2006

Glioblastoma--the consequences of advanced patient age on treatment and survival.

Glioblastoma is the most common primary brain tumor. Recent evidence suggests that aggressive treatment is also effective in elderly patients. However, large patient series are missing. The aim of this retrospective study was to determine prognostic factors in a large series (n=345) of elderly patients surgically treated for newly diagnosed glioblastoma (WHO grade IV) at a single institution between 1991 and 2002. U-tests (Mann Whitney), chi-square tests, log-rank tests/Kaplan-Meier plots and Cox regression models were used for statistical analysis. Based on the maximum difference in median survival, a threshold of 60 years was used to separate younger from older patients. In total, 185 patients (53.6%) were over 60 years old. In these individuals, total tumor resection, radiotherapy and reoperation for tumor recurrence were identified as independent prognostic factors. When total surgical resection was combined with radiotherapy and reoperation, Kaplan-Meier analysis revealed a median survival of up to 64 weeks in elderly patients. Our data indicate that total tumor resection, radiotherapy and reoperation should also be considered in selected elderly patients. Age alone should not generally exclude elderly individuals from aggressive treatment.

Adult↗
PubMed2006

A randomized trial of deep-brain stimulation for Parkinson's disease.

BACKGROUND: Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management. METHODS: In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III). RESULTS: Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08). CONCLUSIONS: In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].).

Activities of Daily Living↗
PubMed2006

Differential expression of matrix metalloproteinases in brain- and bone-seeking clones of metastatic MDA-MB-231 breast cancer cells.

Matrix Metalloproteinases (MMPs) play a crucial role in breast cancer metastasis. We examined the mRNA and protein expression of several MMPs in brain- and bone-seeking clones of MDA-MB-231 breast cancer cells, their transcriptional regulation and their functional role in the metastatic process. MMP mRNA expression was examined using real-time reverse transcription polymerase chain reaction. Protein expression was examined using enzyme linked immunosorbent essay (ELISA). The inducibility of mRNA and protein expression was tested with TPA (phorbol 12-myristate 13-acetate; 50 microM); epidermal growth factor and transforming growth factor beta (20 ng/ml both). Migration and invasion assays were performed with the QCM 96-Well Migration/Invasion Assay (8 microm; Chemicon) over 24 h with or without specific MMPs inhibitors (MMP Inhibitor I Mix (5 microM); MMP-2/MMP-9 Inhibitor III (50 microM); EMD Biosciences). We found significantly higher mRNA expression of MMP-1 and -9 in brain-seeking 231-clones in comparison to -bone and -parental cells. In contrast, the mRNA expression of MMP-3 and -14 was comparable in all cells lines examined and MMP-13 expression was lower in both selective metastatic lines. MMP-2 and -8 were not expressed. ELISA revealed a higher amount of total as well as active MMP-1 and -9 in brain-seeking cells. TPA stimulation showed that MMP-1 and -9 transcription was inducible on the mRNA and protein level in 231-parental but not in 231-brain or -bone. 231-brain showed the highest migration and invasive capacity which could be decreased by the application of MMP-1 and/or MMP-9 inhibitor. Our results indicate functional importance of MMP-1 and -9 overexpression in brain metastasis in an in vitro model.

Bone Neoplasms↗
PubMed2006

Matrix-degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas.

Brain tumors, in particular glioblastomas, have a high morbidity and mortality, mainly due to their invasive nature. A prerequisite for this invasiveness is cell migration based on increased expression of proteases digesting the extracellular matrix. Brevican, an important extracellular proteoglycan that is upregulated in glioblastomas, can be degraded by certain proteases. We demonstrate that in human glioblastomas secretory proteases like ADAMTS4 and ADAMTS5 (aggrecanases 1 and 2; ADAMTS = a disintegrin and metalloproteinase with thrombospondin motifs) are expressed on the mRNA and protein levels in considerable amounts. Real-time RT-PCR shows a higher levels of ADAMTS4 and 5 expressions in glioblastomas in situ, compared to cultured human glioblastoma cells. The upregulation of these proteases in vivo by cytokines may explain this difference. In vitro, transforming growth factor-beta induces ADAMTS4, but less ADAMTS5, and interleukin-1beta ADAMTS5, but not ADAMTS4. As demonstrated by immunohistochemistry and confocal microscopy in situ, ADAMTS5 expression is confined to proliferating glioblastoma cells of surgical tumor sections and with lower intensity to astroglial cells in normal brain sections, as opposed to brevican. In vitro, glioblastoma-derived ADAMTS5 degrades recombinant human brevican to several smaller fragments. Our results show that ADAMTS4 and 5 are upregulated on proliferating glioblastoma cells and these proteases may contribute to their invasive potential.

ADAM Proteins↗
PubMed2006

Cannabinoid receptors in human astroglial tumors.

In animal models, cannabinoids are reported to inhibit the growth of tumors, including gliomas. These effects have been claimed to be mediated via cannabinoid receptors 1 and 2 (CB1, CB2). To elucidate a possible relevance for treatment of human gliomas, we investigated receptor subtype expression in surgical material of solid human astrocytomas, gliomas and cultivated glioma cells by quantitative reverse transcriptase polymerase chain reaction, western blot and immunohistochemistry and assayed their functionality. In normal brain, cultivated glioma cells and solid tumors, CB1 mRNA was expressed to a much greater extent than CB2, which in some samples was even undetectable. Expression of both receptor subtypes was unrelated to malignancy, varied between patients, and was not significantly increased in relation to normal brain tissues. In normal brain, CB1 protein was localized on astroglial and other cell types; in gliomas, it was found on astroglial/glioma cells. CB2 protein was detected on microglial cells/macrophages but rarely on astroglial cells. Functionally, CB1 receptor agonists reduced elevated cyclic AMP levels and slightly reduced proliferation of glioma cells in vitro, but did not induce apoptosis. We conclude that cannabinoid therapy of human gliomas targets not only receptors on tumor, but also on other cell types. Therefore, complex and potential side-effects should be considered carefully.

Apoptosis↗
PubMed2006

Chronic recurrent subarachnoid hemorrhage from a trigeminal nerve malignant peripheral nerve sheath tumor: case report.

OBJECTIVE: Clinically significant intratumoral or peritumoral bleeding from trigeminal nerve tumors is very rare. CLINICAL PRESENTATION: We report the case of a 59-year-old man who presented with recurrent subarachnoid hemorrhage from a left trigeminal nerve malignant peripheral nerve sheath tumor. He presented with decreased consciousness, left facial hypesthesia, and left facial weakness. Trigeminal neuralgia was present for 18 months. Cranial computed tomographic and magnetic resonance imaging scans revealed a left parapontine mass with cystic changes and intratumoral bleeding. Furthermore, signs of hemosiderosis of the subarachnoid space were noted. Lumbar puncture revealed fresh bleeding. Angiography detected no aneurysm or other causes of bleeding. The patient became fully alert within hours, the facial weakness improved within a few days. There was no evidence of vasospasm or persisting hydrocephalus. He underwent left-sided suboccipital craniotomy for macroscopically total tumor removal. INTERVENTION: The patient underwent total tumor removal via a left suboccipital approach. Intraoperatively, evidence of recurrent intratumoral bleeding was noted. Histological examination revealed a malignant peripheral nerve sheath tumor (World Health Organization Grade III). Postoperatively, the hypesthesia improved significantly. The patient was transferred to radiotherapy for external beam radiation. CONCLUSIONS: This is the first report regarding a malignant peripheral nerve sheath tumor of the trigeminal nerve that caused clinically significant subarachnoid hemorrhage caused by intratumoral bleeding.

Chronic Disease↗
PubMed2005

Improving the amplitude-modulated control experiment for multislice continuous arterial spin labeling.

The use of an amplitude-modulated radiofrequency (RF) pulse for a control experiment is a proven method to control for off-resonance effects in multislice continuous arterial spin labeling (CASL) experiments. This method is also known as double adiabatic inversion. The adiabaticity factor of a single half-pulse, beta(1/2), and a new dimensionless parameter alpha, which is obtained from the labeling parameters and the flow velocity, are introduced. This makes it possible to distinguish three distinct cases: 1) With low alpha, a double inversion occurs. 2) With alpha > or = approximately 4, the efficiency with which the longitudinal magnetization is returned to the z-axis depends on the phase of the amplitude modulation at the time the spins cross the center of the labeling plane. 3) In the intermediate region, the efficiency shows undesirable fluctuations. In a Bloch equation simulation, three optimized parameter sets are determined. Near ideal performance should always be achieved by combinations of parameters for which beta(1/2) > or = approximately 2 and alpha approximately pi/beta(1/2). The efficiency increases were realized in a volunteer study, showing the practical application of the suggested optimization.

Adult↗
PubMed2005

Continuous artery-selective spin labeling (CASSL).

A new technique for selective spin labeling of individual arteries is presented. It is based on continuous arterial spin labeling (CASL) with an amplitude-modulated control experiment. Precessionary motion of the labeling gradient about the axis of the artery, combined with an appropriate frequency modulation of the labeling RF pulse, restricts the adiabatic inversion to the desired artery. In phantom studies, it was found that the level of selectivity could be controlled by the sequence parameters, and that the achievable labeling efficiency was at a level of approximately 80% compared to a regular, nonselective CASL experiment. In a volunteer study we acquired high-quality images of the perfusion territories of the internal carotid artery (ICA), the basilar artery (BA), the middle cerebral artery (MCA), and both anterior cerebral arteries (ACAs). The results show the method's flexibility for different geometries and flow velocities. Potential applications include perfusion territory imaging of smaller cerebral arteries, and selective angiography techniques.

Adult↗
PubMed2005

Feasibility of combined operation and perioperative intensity-modulated brachytherapy of advanced/recurrent malignancies involving the skull base.

PURPOSE: To assess the technical feasibility and toxicity of combined operation and perioperative intensity-modulated fractionated interstitial brachytherapy (IMBT) in advanced-stage malignancies involving the skull base with the goal of preserving the patients' senses of sight. PATIENTS AND METHODS: This series consisted of 18 consecutive cases: ten patients with paranasal sinus carcinomas, five with sarcomas, two with primitive neuroectodermal tumors (PNETs), and one with parotid gland carcinoma. After, in most cases, subtotal surgical resection (R1-R2: carried out so that the patients' senses of sight were preserved), two to twelve (mean five) afterloading plastic tubes were placed into the tumor bed. IMBT was performed with an iridium-192 stepping source in pulsed-dose-rate/high-dose-rate (PDR/HDR) afterloading technique. The total IMBT dose, ranging from 10 to 30 Gy, was administered in a fractionated manner (3-5 Gy/day, 5 days/week). RESULTS: Perioperative fractionated IMBT was performed in 15 out of 18 patients and was well tolerated. Complications that partially prevented or delayed IMBT in some cases included cerebrospinal fluid leakage (twice), meningitis (twice), frontal brain syndrome (twice), afterloading tube displacement (twice), seizure (once), and general morbidity (once). No surgery- or radiation-induced injuries to the cranial nerves or eyes occurred. Median survival times were 33 months after diagnosis and 16 months after combined operation and IMBT. CONCLUSION: Perioperative fractionated IMBT after extensive but vision-preserving tumor resection seems to be a safe and well-tolerated treatment of advanced/recurrent malignancies involving the skull base. These preliminary data suggest that combined operation and perioperative fractionated IMBT is a palliative therapeutic option in the management of fatal malignancies involving the base of the skull, a strategy which leaves the patients' visual acuity intact.

Adolescent↗
PubMed2005

Management of tectal glioma in childhood.

Tectal glioma is a topographical diagnosis including tumors of different histology, mainly low-grade astrocytomas. Clinical symptoms are usually associated with increased intracranial pressure. This report discusses the management of this rare tumor in children. Clinical charts of 12 children with tectal glioma treated in our department between 1976 and 2001 were retrospectively reviewed. The mean age at the time of diagnosis was 6.75 years (range, 4 weeks to 16 years). The duration between first symptoms and the diagnosis of tectal glioma was in the range of 2 days to 9 years. Ten patients presented with symptoms associated with increased intracranial pressure, one patient presented with ataxia, and in one case tectal glioma was an incidental finding. First-line therapy was endoscopic third ventriculostomy in 5 cases (42%), ventriculoperitoneal shunting in 6 cases (50%), and combined partial tumor resection and shunting in one case. Histology was obtained in 5 cases (low-grade astrocytoma, n = 4; ependymoma, n = 1). All patients had good neurologic function at the end of follow-up. Tectal glioma represents a distinct subgroup of brainstem tumors associated with a good (or favorable) prognosis. Effective treatment for hydrocephalus is essential; the tumor should be monitored by regular clinical examination and magnetic resonance imaging. Biopsy is warranted in cases with tumor progression.

Adolescent↗
PubMed2005

Neuropsychological findings in patients with intraventricular tumors.

BACKGROUND: Intraventricular tumors are quite rare and become symptomatic with hydrocephalus-related signs such as headache, double vision, and seizures. Also, most of the patients show neuropsychological deficits, especially memory problems and lack of attention. METHODS: We reviewed the charts and computed tomographic/magnetic resonance images of 15 patients with tumors of the lateral and third ventricle, who were also examined by a neuropsychologist pre- and postoperatively. Neuropsychological testing included tests of attention, memory, executive functions, and concentration. RESULTS: Between 1995 and 2003, 7 patients with colloid cysts of the third ventricle (3 men, 4 women; mean age, 38 years), 5 patients with meningiomas of the lateral ventricle (2 men, 3 women; mean age, 51 years), and 3 patients with astrocytomas and ependymoma (2 men, 1 woman; mean age, 38 years) were treated. All patients with colloid cysts and meningiomas showed mental changes, especially attention and memory deficits. Symptoms improved markedly after surgical intervention. The 3 patients with astrocytoma and ependymoma showed normal results pre- and postoperatively. CONCLUSION: Neuropsychological testing is very useful in patients with intraventricular lesions and important for follow-up examinations. It should be included in every workup examination in this small patient group.

Adult↗
PubMed2005

Clinical and histological features of multiple meningiomas compared with solitary meningiomas.

Between 1991 and 2002, 456 patients with an intracranial meningioma were treated. Thirty-nine of these had more than one meningioma (8.6%). The mean age was 58 years (27-85 years). Sex distribution was 8.8:1 (35 female, four male). There was no associated spinal meningioma. No patient had neurofibromatosis. In 19 patients all meningiomas were removed. Twelve showed the same histology, seven had different histological features. In the remaining 20 patients only the symptomatic meningioma was removed. Recurrences occurred in 11 patients (28.2%). Six patients died during follow-up. Multiple meningiomas have their own clinical features. Besides a high female preponderance, PR expression was stronger in multiple meningiomas than in solitary meningiomas while p53 status and MIB-1 LI were similar between the two groups. Progesterone receptor, p53 status and MIB-1 LI were valuable markers for predicting a patient's outcome in multiple meningiomas. The number of meningiomas is growing in patients with recurrent meningiomas.

Adult↗
PubMed2005

Hydrocephalus in children with posterior fossa tumors: role of endoscopic third ventriculostomy.

OBJECT: Controversy exists regarding the indication for endoscopic third ventriculostomy (ETV) in children with hydrocephalus caused by posterior fossa tumors. The authors present their treatment modalities and discuss the role of ETV in the management of hydrocephalus. METHODS: The authors retrospectively reviewed the cases of 58 children who were admitted to their clinic consecutively with posterior fossa tumors between January 1999 and December 2003. Fifty-two patients presented with hydrocephalus. The mean age at the time of admission was 6 years and 3 months. The mean follow-up period was 25 months. The authors evaluated how many children required a cerebrospinal fluid (CSF) draining procedure (external ventricular drain [EVD], ventriculoperitoneal [VP] shunt, or ETV) prior to or following tumor removal. Only six patients (11.5%) required permanent treatment for hydrocephalus. Four patients received a VP shunt and two patients underwent ETV. A temporary EVD was placed in five patients (two required a shunt). Forty-six patients (88.5%) did not require a permanent CSF draining procedure. CONCLUSIONS: For children with posterior fossa tumors, ETV is not indicated as a standard operation either prior to or following tumor removal. Only six of 52 children presenting with hydrocephalus required a permanent CSF draining procedure. Endoscopic third ventriculostomy may be suitable for patients with fourth ventricle outflow obstruction and persisting or progressive hydrocephalus following tumor removal.

Adolescent↗
PubMed2005

Endoscopic third ventriculostomy in infants.

OBJECT: The failure rate following endoscopic third ventriculostomy (ETV) in infants younger than 1 year of age has been reported to be higher compared with that of older children. The authors present results of ETVs in such infants and advocate that success or failure of the procedure depends not on the age of the patient but on the cause of the hydrocephalus. METHODS: The authors retrospectively reviewed the management and outcome of 18 ETVs in infants for the treatment of hydrocephalus. The surgeries were performed between November 1996 and October 2002. The mean age at the time of surgery was 150 days (range 9-354 days). The minimal follow-up period was 18 months and the mean was 50 months. The authors divided the patients into the following three groups: obstructive hydrocephalus (four infants), communicating hydrocephalus (10 infants), and hydrocephalus associated with myelomeningocele (four infants). No perioperative death occurred, and perioperative transient morbidity related to ETV was low. The success of the procedure was determined by the cause of the hydrocephalus. Infants with obstructive hydrocephalus had a 100% success rate (four of four), and infants with communicating hydrocephalus had a 10% success rate (one of 10). In infants with hydrocephalus related to myelomeningocele, the success rate was 50% (two of four). CONCLUSIONS: The authors conclude that ETV presents an effective alternative for the treatment of obstructive hydrocephalus in infants younger than 1 year of age. Age does not present a contraindication for ETV, nor does it increase the perioperative risk. The success of ETV is determined by the cause of the hydrocephalus.

Age Factors↗
PubMed2004

Surgical treatment for brain metastases: prognostic factors and survival in 177 patients.

Brain metastases are an increasingly frequent complication of cancer. Advances in diagnosis and treatment have led to wider indications for surgery. We present a single-institution series of 177 patients and discuss our results with regard to the literature. Special focus is on patients with advanced age, multiple brain metastases, extracranial metastases, and brain metastasis recurrence. All patients underwent craniotomy for the resection of solid tumor brain metastases between 1994 and 2001 in our department. Perioperative morbidity and mortality as well as survival were evaluated. The median patient age was 59 years (range 32-86 years). In 177 patients, 348 brain metastases were detected, of which 68.0% were supratentorial and 32.0% were infratentorial. According to univariate analysis, the following parameters were significantly associated with prolonged patient survival: (1) age <70 years, (2) one to three intracranial metastases, (3) favorable postoperative performance, (4) resection of all intracranial lesions, and (5) recraniotomy for brain metastasis recurrence. In contrast, the presence of extracranial metastases, metachronous diagnosis, and solitary brain metastases had no influence on survival. As expected, younger age and limited number of brain metastases (up to three) are favorable prognostic factors. Remarkably, the presence of extracranial metastases had no influence on patient survival.

Adult↗