Clinical presentation of young people (10–24 years old) with brain tumors: results from the international MOBI-Kids study

Journal of Neuro-Oncology - We used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in...     

Producing parallel x rays with a bent-crystal monochromator and an x-ray tube

A bent Laue monochromator and a conventional x-ray tube were used to produce a fan beam that was parallel in the plane perpendicular to the plane of the fan. The x-ray fan beam was tunable in energy and had about 12% energy bandwidth at a slice height of 5 mm when tuned to 50 keV. The beam's energy was slightly coupled to the vertical position on the beam's height. The slice height could be varied from 1 to 10 mm. The flux at 50 keV was approximately 2x10(6) photons/mm2/s with a rotating anode tungsten x-ray tube operating at 120 kVp and 100 mA. The narrow energy bandwidth of the beam produced is advantageous over a conventional divergent polychromatic beam for all radiography applications, while the parallelism of the beam enhances its intensity by about threefold and offers some advantages for computed tomography.     

LC-MS-MS analysis of the neuroleptics clozapine,flupentixol, haloperidol,penfluridol, thioridazine,and zuclopenthixol in hair obtained from psychiatric patients

Hair samples of psychiatric patients were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS-MS) for the neuroleptics clozapine, flupentixol, haloperidol, penfluridol, thioridazine, and zuclopenthixol. In the study, these neuroleptics were administered to the patients regularly for a minimum of six months. Sample preparation was performed by washing, powdering with a ball mill, extraction of drugs from hair by ultrasonication with methanol, cleanup by solid-phase extraction and subsequent LC-MS-MS analysis using multiple reaction monitoring (MRM). Calibration was performed for all drugs in the range of 0.05 to 10 ng/mg using spiked hair powder and doxepin-d3 as internal standard. Twenty to 50 mg of hair powder was used and the detection limits of LC-MS-MS were below 0.05 ng/mg for all drugs tested. Therapeutic dosage, number of subjects, hair color, and detected amounts of drugs were as follows: clozapine (150400 mg/day; n = 3, light brown, medium brown, black; 0.47-0.92 ng/mg), haloperidol (150 mg/3 weeks; n = 1, black/gray; 12.2 ng/mg), penfluridol (20-30 mg/week; n = 2, medium brown, black; 0.08 ng/mg; not detected in one case), thioridazine (100-400 mg/day; n = 4, light brown, medium brown, black; 0.33-9.91 ng/mg, not detected in one case). Besides the active drugs also the desmethyl-metabolites of clozapine and thioridazine were detected by LC-MS-MS. However, flupentixol (5 mg/day; light brown hair) and zuclopenthixol (350 mg/3 weeks; light brown hair) were not detected by these methods in one case each, although the drugs were administered regularly to these patients. The comparison of dosage and hair color in two cases with thioridazine and penfluridol suggests that other interindividual factors may have an influence on drug concentration in hair.     

Expression pattern of the urokinase-plasminogen activator system in rat DS-sarcoma: role of oxygenation status and tumour size

The urokinase plasminogen activator system plays a central role in malignant tumour progression. Both tumour hypoxia and enhancement of urokinase plasminogen activator, urokinase plasminogen activator-receptor and plasminogen activator inhibitor type 1 have been identified as adverse prognostic factors. Upregulation of urokinase plasminogen activator or plasminogen activator inhibitor type 1 could present means by which hypoxia influences malignant progression. Therefore, the impact of hypoxia on the expression pattern of the urokinase plasminogen activator system in rat DS-sarcoma in vivo and in vitro was examined. In the in vivo setting, tumour cells were implanted subcutaneously into rats, which were housed under either hypoxia, atmospheric air or hyperoxia. For in vitro studies, DS-sarcoma cells were incubated for 24 h under hypoxia. Urokinase plasminogen activator and urokinase plasminogen activator-receptor expression were analysed by flow cytometry. Urokinase plasminogen activator activity was measured using zymography. Plasminogen activator inhibitor type 1 protein levels in vitro and in vivo were examined with ELISA. PAI-1 mRNA levels were determined by RT-PCR. DS-sarcoma cells express urokinase plasminogen activator, urokinase plasminogen activator-receptor, and plasminogen activator inhibitor type 1 in vitro and in vivo. The urokinase plasminogen activator activity is enhanced in DS-sarcomas compared to normal tissues and rises with increasing tumour volume. The oxygenation level has no impact on the urokinase plasminogen activator activity in cultured DS-sarcoma cells or in solid tumours, although in vitro an increase in plasminogen activator inhibitor type 1 protein and mRNA expression after hypoxic challenge is detectable. The latter plasminogen activator inhibitor type 1 changes were not detectable in vivo. Hypoxia has been demonstrated to contribute to the upregulation of some components of the system in vitro, although this effect was not reproducible in vivo. This may indicate that the serum level of plasminogen activator inhibitor type 1 is not a reliable surrogate marker of tumour hypoxia.     

Postmastectomy Electron-Beam-Rotation Irradiation in Locally Advanced Breast Cancer

BACKGROUND: Different radiotherapy techniques are used for postmastectomy irradiation. We review the results with the electron-beam-rotation technique in advanced breast cancer patients. Main endpoint was local tumor control. PATIENTS AND METHODS: From 1990 to 1998 119 patients with adverse pathology features (pT3 17% of patients, pT4 42%, multicentricity 36%, pN >/= 3 positive nodes and/or pN1biii 81%, close margins 30%) underwent electron-beam-rotation irradiation of the chest wall with daily fractions of 2.0-2.5 Gy per day to 50 Gy total dose after modified radical mastectomy and axillary lymph node dissection. A local boost of 10 Gy and/or irradiation of locoregional lymph nodes were applied depending on the completeness of resection and lymph node involvement. RESULTS: After a median follow-up of 73 months for patients at risk the 5-year local tumor control, local tumor control first event, disease-free, and overall survival were 82%, 92%, 57%, and 63% (Kaplen Meier analysis), respectively. Significant predictors of poor local tumor control were maximal tumor diameter >/= 5 cm (p = 0.01), "close margins" or residual tumor (p < 0.01), four or more involved axillary lymph nodes (p = 0.02), two or more involved lymph node levels (p = 0.04), negative estrogen receptor status (p = 0.03), and high-grade histopathology (GIIb-III, p < 0.01). The subgroup analysis showed a high local failure rate of 37% for high-grade (GIIb-III) and estrogen receptor negative tumors, whereas no local recurrence was found in low-grade (GI-Iia) and receptor positive tumors (p = 0.01). The multivariate analysis revealed maximal tumor diameter >/= 5 cm, four or more involved axillary lymph nodes and high-grade histopathology (GIIb-III) as independent predictors of poor local tumor control. CONCLUSION: In high-risk breast cancer patients postmastectomy irradiation with the electron-beam-rotation technique is an effective therapy, resulting in a 5-year local failure rate of 8%. Intensified local therapy needs further investigation in subgroups of patients with additional risk factors.     

Symptomatische infantile Polymyoklonie

Zusammenfassung Es wird über 2 Fälle von infantiler Polymyoklonie berichtet, bei denen gleichzeitig eine Meningoencephalitis bzw. ein Neuroblastom bestanden. Bei der infantilen Polymyoklonie (infantile myoklonische Encephalopathie) stehen neben ataktischen Bewegungsstörungen generalisierte myoklonische Zuckungen und ein Opsoklonus im Vordergrund. Während sich die Polymyoklonie bei der Meningoencephalitis spontan innerhalb von wenigen Wochen ohne Ausfälle zurückbildete, war bei dem Neuroblastom eine Behandlung mit ACTH erforderlich, um die neurologische Symptomatik zur Rückbildung zu bringen. ätiologisch kam für die Meningoencephalitis eine Viruserkrankung in Frage. Als Ursache der Polymyoklonie werden immunpathologische Reaktionen mit unterschiedlich starker funktioneller Schädigung bestimmter Kleinhirn-Hirnstamm-Strukturen diskutiert.

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Infantile polymyoclonic encephalopathy

The chief symptom of the so called infantile polymyoclonic encephalopathy is ataxia in combination with myoclonic jerks generalized as well as localized in the orbital muscles (opsoclonus; dancing eyes). 2 cases of infantile polymyoclonus are reported, one seen in the course of an acute meningoencephalitis which recovered spontaneously within a few weeks; the other occured with a neuroblastoma of the mediastinum. In this child the myoclonic symptoms did not disappear with the surgical removal of the tumour, followed by cytostatic treatment and radiation. Amelioration was seen after ACTH and Mogadan, but mild ataxia was still present after 6 months' treatment. 1 year later the motor symptoms had disappeared completely but the static and language development were retarded.The aetiology of infantile polymyoclonus is still unknown. Immuno-pathological reactions to different functional disturbances of certain cerebellar and brain stem structures are discussed.