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Biomedical subjects

H J Reulen

Publications and source records attributed to H J Reulen.

At least 19 recordsLinked to original sources

Image guided interstitial laser thermotherapy: a canine model evaluated by magnetic resonance imaging and quantitative autoradiography.

OBJECTIVE: To determine the applicability and safety of a new canine model suitable for correlative magnetic resonance imaging (MRI) studies and morphological/pathophysiological examination over time after interstitial laser thermotherapy (ILTT) in brain tissue. MATERIAL AND METHODS: A laser fibre (Diode Laser 830 nm) with an integrated temperature feedback system was inserted into the right frontal white matter in 18 dogs using frameless navigation technique. MRI thermometry (phase mapping i.e. chemical shift of the proton resonance frequency) during interstitial heating was compared to simultaneously recorded interstitial fiberoptic temperature readings on the border of the lesion. To study brain capillary function in response to ILTT over time quantitative autoradiography was performed investigating the unidirectional blood-to-tissue transport of carbon-14-labelled alpha amino-isobutyric acid (transfer constant K of AIB) 12, 36 hours, 7, 14 days, 4 weeks and 3 months after ILTT. RESULTS: All laser procedures were well tolerated, laser and temperature fibres could be adequately placed in the right frontal lobe in all animals. In 5 animals MRI-based temperature quantification correlated strongly to invasive temperature measurements. In the remaining animals the temperature fibre was located in the area of susceptibility artifacts, therefore, no temperature correlation was possible. The laser lesions consisted of a central area of calcified necrosis which was surrounded by an area of reactive brain tissue with increased permeability. Quantitative autoradiography indicated a thin and spherical blood brain barrier lesion. The magnitude of K of AIB increased from 12 hours to 14 days after ILTT and decreased thereafter. The mean value of K of AIB was 19 times (2 times) that of normal white matter (cortex), respectively. CONCLUSION: ILTT causes transient, highly localised areas of increased capillary permeability surrounding the laser lesion. Phase contrast imaging for MRI thermomonitoring can currently not be used for reliable temperature readings in vivo. The suggested new canine model proved to be safe, accurate, easy to use, and provides clinical, radiographic, pathological and physiological correlations.

Aminoisobutyric Acids↗

Oedema formation in experimental photo-irradiation therapy of brain tumours using 5-ALA.

BACKGROUND: Five-aminolevulinic acid (5-ALA) induces the specific accumulation of photosensitising porphyrins in malignant gliomas and has been explored for photo-irradiation therapy of these tumours. However, information is unavailable on whether and to what extent this treatment modality may induce the formation of brain oedema, and how potential oedema might be treated. METHODS: Rats were implanted with C6 gliomas. Eight days later magnetic resonance images (MRI) were obtained. On day 9 rats received 100 mg 5-ALA/kg b.w. and were craniotomized for photo-irradiation of tumours 6 hours later (100 J/cm2, 635 nm argon-dye laser). Part of the animals was treated with daily dexamethasone injections (0.3 mg/kg), beginning 6 hours before phototherapy. 72 hours later, brains were removed and dissected according to tumour dimensions on pre-therapy MRI into "tumour", "brain around tumour" (BAT), residual cortex and basal ganglia, for measurements of water contents. Measurements were also performed in untreated animals with tumours, with or without steroid treatment and in control animals. An additional group of animals lacking tumours, with or without steroid treatment, underwent 5-ALA-phototherapy to determine effects on normal brain. RESULTS: C6 gliomas induced brain oedema, which responded to steroid treatment. 5-ALA-phototherapy resulted in additional oedema, which responded partly to steroids. 5-ALA-phototherapy of normal brain increased water content moderately in irradiated cortex. This oedema was also partly counteracted by steroids. CONCLUSIONS: Photo-irradiation therapy with 5-ALA induces oedema which is partly counteracted by steroid therapy. The possibility of steroid resistant oedema formation should be considered when planning human trials with this treatment modality.

Aminolevulinic Acid↗

Prospective documentation and analysis of the pre- and early clinical management in severe head injury in southern Bavaria at a population based level.

Treatment of patients suffering from severe head injury is so far restricted to general procedures, whereas specific pharmacological agents of neuroprotection including hypothermia have not been found to improve the outcome in clinical trials. Albeit effective, symptomatic measures of the preclinical rescue of patients (i.e. stabilization or reestablishment of the circulatory and respiratory system) or of the early clinical care (e.g. prompt diagnosis and treatment of an intracranial space occupying mass, maintenance of a competent circulatory and respiratory system, and others) by and large constitute the current treatment based on considerable organizational and logistical efforts. These and other components of the head injury treatment are certainly worthwhile of a systematic analysis as to their efficacy or remaining deficiencies, respectively. Deficits could be associated with delays of providing preclinical rescue procedures (e.g. until intubation of the patient or administration of fluid). Delays could also be associated in the hospital with the diagnostic establishment of intracranial lesions requiring prompt neurosurgical intervention. By support of the Federal Ministry of Education and Research and under the auspices of the Forschungsverbund Neurotraumatology, University of Munich, a prospective system analysis was carried out on major aspects of the pre- and early clinical management at a population based level in patients with traumatic brain injury. Documentation of pertinent data was made from August 1998 to July 1999 covering a catchment area of Southern Bavaria (5.6 mio inhabitants). Altogether 528 cases identified to suffer from severe head injury (GCS < or = 8 or deteriorating to that level within 48 hrs) were enrolled following admission to the hospital and establishment of the diagnosis. Further, patients dying on the scene or during transport to the hospital were also documented, particularly as to the frequency of severe head injury as underlying cause of mortality. The analysis included also cases with additional peripheral trauma (polytrauma). The efficacy of the logistics and organization of the management was studied by documentation of prognosis-relevant time intervals, as for example until arrival of the rescue squad at the scene of an accident, until intubation and administration of fluid, or upon hospital admission until establishment of the CT-diagnosis and commencement of surgery or transfer to the intensive care unit, respectively. The severity of cases studied in the present analysis is evident from a mortality of far above 40% of cases admitted to the hospital, which was increased by about 20% when including prehospital mortality. The outcome data notwithstanding, the emerging results demonstrate a high efficacy of the pre- and early clinical management, as indicated by a prompt arrival of the rescue squad at the scene, a competent prehospital and early clinical management and care, indicative of a low rate of avoidable complications. It is tentatively concluded on the basis of these findings that the patient prognosis is increasingly determined by the manifestations of primary brain damage vs. the development of secondary complications.

Craniocerebral Trauma↗

Internal regulations and general guidelines of a neurosurgical department and training programme.

It is strongly recommended that general guidelines and internal regulations be laid down in written form by the department. The guidelines regulate the general workflow and related trainee duties and responsibilities, education and research, special procedures for particular diseases and conditions (standards of care). Regarding general workflow of the department, the following items should be laid down once in written form: time table of department, working hours, admission procedures, medical records directives, responsibilities on wards and in the emergency unit, patient information, discharge procedures, outpatient consultations, call schedule and on-call duty plan, as well as week-end and holiday regulations for rounds on wards and ICU. Regarding education and research, the following items should be written down: conferences and teaching rounds, policies on presentations and publications, policies regarding meetings and courses, research leave and vacation plan. The written definition of standards of care is still considered optional in neurosurgery at the present time.

Certification↗

Intralesional radioimmunotherapy in the treatment of malignant glioma: clinical and experimental findings.

In the last two decades radioimmunotherapy has been used as an additional treatment option for malignant glioma in several centers. More than 400 patients have been reported, who were treated in the framework of different studies. Most of them received labelled antibodies to tenascin, an extracellular matrix-glycoprotein, which is expressed in high amounts in malignant gliomas. We report side effects and survival time of 46 patients, treated after surgical resection and conventional radiotherapy with intralesionally injected labelled (131-Iodine) antibodies to tenascin. Despite the fact, that many treatments have been performed, little is known about the distribution properties of labelled antibodies after injection in the tumour cavity. For an optimal effect labelled antibodies should be able to reach tumour cells, which have migrated into the surrounding tissue. We investigated the propagation velocity and area of distribution of labelled antibodies and their considerably smaller fragments after the injection in C6-gliomas of Wistar rats. Propagation increased with time and was significantly greater after injection of labelled fragments than after injection of labelled antibodies. According to our results labelled fragments might be better able to reach distant tumour cells in the peritumoural tissue of malignant gliomas than labelled antibodies.

Administration, Topical↗

Fluorescence-guided resections of malignant gliomas--an overview.

Radical resections of contrast-enhancing tumour in patients with malignant gliomas may be pertinent for survival but are often difficult to achieve due to uncertainties in distinguishing tumour margins intra-operatively. In this respect a number of novel methods are being examined which aim at enhancing resections. Among these methods, resections that exploit the accumulation of fluorescent porphyrins within malignant glioma tissue in response to exogenous administration of a metabolic percursor, 5-aminolevulinic acid, may offer particular advantages. This article summarises the clinical background and current status of 5-ALA drug development for fluorescence-guided resections of malignant gliomas and analyses the available literature with regard to possible mechanisms that govern the highly specific accumulation of fluorescent porphyrins in malignant glioma tissue in response to 5-ALA administration.

Aminolevulinic Acid↗

Locoregional radioimmunotherapy in selected patients with malignant glioma: experiences, side effects and survival times.

UNLABELLED: Prognosis of malignant glioma is very unfavourable mainly due to minimal tumour remnants in the peritumoural tissue. Intralesionally applied radioimmunotherapy is a possible therapeutical option with the potential to improve survival of patients with malignant glioma. We investigated side effects and survival after surgery, conventional radiotherapy and additional radioimmunotherapy with labelled tenascin-antibodies in patients with malignant glioma. METHODS: Since 1995, 37 patients were treated with radioimmunotherapy after resection and radiotherapy of a malignant glioma. Patients received antibodies labelled with yttrium-90 and iodine-131 in different doses into the tumour cavity via a previously implanted ommaya-reservoir. Treatment was applied in up to 8 cycles (mean 2.96 cycles) in time intervals of 6-8 weeks. Mean age was 46 years, histology was anaplastic astrocytoma in 13 patients and glioblastoma in 24 patients. RESULTS: For the whole group median survival time has not yet been reached. For glioblastoma the median survival time is 17 months, 5-year survival probability for anaplastic astrocytoma is 85% approximately. Quality of life was acceptable. Acute side effects following treatment were headache, seizures and worsening of pre-existing neurological symptoms. Late side effects were skin necrosis and, in 1 case, a delayed aphasia probably due to a vascular lesion. CONCLUSION: Radioimmunotherapy prolonged survival time in a selected group of patients with malignant gliomas as compared to a historical control group. Patients with anaplastic astrocytomas seem to have more benefit from this therapy than patients with glioblastomas.

Adult↗

Basic research vs. applied research.

Research rotation is an important component in the education of a neurosurgical resident. The selection of the area of research is essential. There are many arguments in favour of selecting research projects to be close to the individual trainee's clinical interest. Studies far away from the individual's clinical interest in most cases are less productive and will not be pursued later. There are also many advantages if a cooperation is planned with other institutions. The programme director or staff members play an important role in the selection of the research project, of an appropriate laboratory or institution, and in the process of financing a research rotation.

Curriculum↗

[Initial experiences with adjuvant locoregional radioimmunotherapy using 131I-labeled monoclonal antibodies against tenascin (BC-4) for treatment of glioma (WHO III and IV)].

AIM: None of the established treatments (surgery, radiotherapy, chemotherapy) for malignant glioma has improved its very poor prognosis. Adjuvant locoregional radio-immunotherapy (RIT) represents a new therapeutic approach. We present our initial experience with this therapeutic tool with respect to adverse effects, biokinetics and clinical follow-up. METHODS: Following surgery and radiotherapy, 12 patients with glioma (4, WHO stage III; 8, WHO stage IV) underwent 1-5 RIT-cycles (average dose 1100 MBq 131labelled monoclonal BC-4 antibodies) at six week intervals. Follow-up included serial FDG-PET and MRI investigations. Evaluation of biokinetics included whole body scans, together with analysis of blood, urine and fluid from the tumor cavity. RESULTS: Following RIT, four patients experienced temporary seizures, which, in one case, were associated with temporary aphasia. Eight patients developed HAMA (human anti-mouse antibodies) during follow-up. Mean biologic half-life of the radiopharmaceutical in the resection cavity was 3.9 d (range: 1.0-10.2 d) and remained stable intraindividually during further RIT-cycles. The antibody/radionuclide conjugate remained stable in the tumor cavity for at least 5 d. Median survival presently stands at 18.5 months compared to 9.7 months in a historical patient group (n = 89) undergoing conventional therapeutic strategies. Five patients show no signs of recurrence. In three patients with post-surgical evidence of residual tumor, one patient showed partial remission, one stable disease, and one progressive disease during RIT. Four patients without evidence of residual tumor mass at the beginning of RIT developed recurrence during therapy. CONCLUSIONS: Initial experience demonstrates that locoregional RIT is a well tolerated treatment modality that may represent a promising new approach in the management of patients with malignant glioma. Advantages of local application include passage of the blood-brain barrier, high concentration of activity within the resection cavity and low systemic toxicity.

Adult↗

[Normal pressure hydrocephalus--from clinical picture to diagnosis. Help by early shunt placement].

Normal pressure hydrocephalus (NPH), which may either be idiopathic or occur secondarily, is responsible for approximately 6% of the cases of dementional syndromes in the elderly. Although its diagnosis still remains a problem, every attempt should be made to identify patients with clinical symptoms arising from NPH, since the placement of a shunt can result in a much improved quality of life. Candidates for surgical treatment must be selected with care, since the transient peri-operative morbidity may be as high as 7%.

Cerebrospinal Fluid Shunts↗

[Brain protective interstitial laser thermotherapy. Therapy of brain tumors without secondary damage].

The purpose of interstitial radiosurgery is to deliver a necrotizing dose of heat to an accurately defined focal area without damaging adjacent healthy brain tissue. To achieve this, heat at a temperature of 60-100 degrees C is applied via a laser fiber placed stereotactically in the center of the tumor. With the aid of thermosensitive magnetic resonance imaging (MRI), not only can the heat distribution within and around the tumor be measured during treatment, but also the extent of the lesion produced assessed. Interstitial laser thermotherapy (ILTT) performed under MRI monitoring, could become an important interdisciplinary minimally invasive treatment option for patients with brain tumors. Experimental data on the biological effects of interstitial laser therapy on normal brain tissue are not yet available, and only preliminary clinical studies investigating the effects of laser energy on brain tumors have so far been carried out. This overview presents a description of our own initial results, discusses the present state of our knowledge and current possibilities and limitations of this new treatment modality.

Brain↗

Local immunotherapy of glioma patients with a combination of 2 bispecific antibody fragments and resting autologous lymphocytes: evidence for in situ t-cell activation and therapeutic efficacy.

After adoptive transfer of pre-activated lymphocytes into the operation cavity of glioma patients, tumor regression and improved survival have been reported in some patients. Results were most impressive when bispecific antibodies with tumor x CD3 specificity were also applied. In this study, we attempted to avoid time-consuming pre-activation procedures for adoptively transferred cells by using a combination of bispecific antibodies directed to the EGF receptor (EGFR) on tumor cells and to CD3 and CD28 on T cells. Eleven patients with high-grade malignant glioma received 3 injections of 2 bispecific antibody fragments (EGFR x CD3 and EGFR x CD28) together with freshly isolated autologous lymphocytes via an Ommaya reservoir. Intracavitary fluid aspirated during immunotherapy was examined for markers of T-cell activation. Increased levels of soluble IL-2 receptor and TNF-alpha were detected in the intracavitary fluid of all patients tested. Two of the 11 treated patients experienced a beneficial response to therapy as defined by a transient contrast enhancement in subsequent MRI scans and prolonged survival. Side effects were transient and consisted of fever, nausea, headache and aggravation of pre-existing neurologic deficits. These adverse effects were most likely due to the antibody construct containing anti-CD3 specificity. Two patients developed cerebral edema and required steroid treatment.

Adult↗

Performance in picture naming and word comprehension: evidence for common neuronal substrates from intraoperative language mapping.

Correlations of naming ability and performance in the Token Test are known from aphasia; however, the mechanisms underlying these correlations are unclear. Naming tasks are commonly used in intraoperative mapping for identification of cortical areas involved in language processing. In the present study, we measured performance in an elementary Token Test task, i.e., single word comprehension, during electrical stimulation of cortical sites at which this stimulation previously had disturbed the naming process. It was found that at about half of the sites at which naming could be disturbed electrical stimulation also led to disturbances in Token Test performance, indicating that there are common neural structures critical for performance in both tasks. These findings are discussed in terms of a multilayered semantic network in which the level of the simultaneous binding of features into concepts and the level of units that are organized with respect to semantic relations may be disturbed separately.

Adult↗

The semi-annual residency rotation summary: a means to assess the quality of neurosurgical training.

The periodic evaluation of the progress made by the trainees is an adequate means for quality control of a training programme. The combination of the Neurosurgical Log-book and the new Evaluation Sheet allows a comprehensive assessment of the knowledge, progress, as well as the personal and professional development of the individual resident. Upcoming problems can be recognised at an early time point and be corrected immediately. With such periodic supervision the quality of training will improve with time and with experience.

Clinical Competence↗