Forensic aspects of post-mortem histological detection of amniotic fluid embolism.

Amniotic fluid embolism (AFE) continues to be one of the most feared and devastating complications of pregnancy. A reliable diagnosis can be made only upon histological examination. A detection of AFE every now and then has a relevant implication on medico-legal aspects of intrapartum or post-partum maternal death.

Intratumoral homogeneity of MGMT promoter hypermethylation as demonstrated in serial stereotactic specimens from anaplastic astrocytomas and glioblastomas.

Hypermethylation of the DNA repair gene O(6)-methyl-guanine DNA methyltransferase (MGMT) has been linked to prolonged survival in glioblastoma patients treated with alkylating agents. It was aimed to analyze prospectively whether the MGMT status of malignant gliomas could be determined from small-sized stereotactic biopsies (maximum volume: 1 mm(3)). Special attention was directed towards the intratumoral distribution of the MGMT promoter methylation, the MGMT protein expression and potential correlations between both.

Tourniquet use in childhood: a harmless procedure?

Tourniquet ischemia is widely used in limb surgery in every age group. In adults, tourniquet-related deep vein thrombosis and pulmonary embolism are recognized complications of tourniquet use. In healthy children, tourniquet-associated alterations of blood clotting physiology are assumed to have no clinical impact.

Photodynamic therapy of prostate cancer by means of 5-aminolevulinic acid-induced protoporphyrin IX - in vivo experiments on the dunning rat tumor model.

Objective: In order to expand the use of photodynamic therapy (PDT) in the treatment of prostate carcinoma (PCA), the aim of this study was to evaluate PDT by means of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) in an in vivo tumor model.

Methods: The model used was the Dunning R3327 tumor. First of all, the pharmacokinetics and the localization of PPIX were obtained using fluorescence measurement techniques.

Endothelial cells but not epithelial cells or cardiomyocytes are partially replaced by donor cells after allogeneic bone marrow and stem cell transplantation.

Recent studies have convincingly demonstrated that adult bone marrow contains cells capable of differentiating into a variety of cell types. To investigate whether such bone marrow-derived cells participate on self-renewal and proliferation of nonhematopoietic tissues, we studied tissue obtained by autopsy from female recipients after sex-mismatched allogeneic bone marrow and stem cell transplantation for the presence of donor-derived cells. Epithelial, endothelial, and smooth muscle cells and hematopoietic cells were characterized by double-staining immunohistochemistry with a panel of antibodies and nonisotopic in situ hybridization with a Y-chromosome-specific probe.

Novel tumor antigens identified by autologous antibody screening of childhood medulloblastoma cDNA libraries.

Medulloblastoma is an embryonal childhood malignancy with poor prognosis. By screening 4 medulloblastoma cDNA expression libraries (SEREX) with autologous sera, 15 different antigens were identified. These antigens were encoded by 3 novel genes, genes of unknown function (KIAA0445, KIAA1853, KIAA0665, FLJ13942, HSPC213), a proto-oncogene (rab18), candidate tumor suppressor genes (BAP1, PRDM13) and genes encoding a motor protein (kinesin-2), a histone (H2A1.

Photoirradiation therapy of experimental malignant glioma with 5-aminolevulinic acid.

Object: Accumulation of protoporphyrin IX (PPIX) in malignant gliomas is induced by 5-aminolevulinic acid (5-ALA). Because PPIX is a potent photosensitizer, the authors sought to discover whether its accumulation might be exploited for use in photoirradiation therapy of experimental brain tumors, without injuring normal or edematous brain.

Methods: Thirty rats underwent craniotomy and were randomized to the following groups: 1) photoirradiation of cortex (200 J/cm2, 635-nm argon-dye laser); 2) photoirradiation of cortex (200 J/cm2) 6 hours after intravenous administration of 5-ALA (100 mg/kg body weight); 3) cortical cold injury for edema induction; 4) cortical cold injury with simultaneous administration of 5-ALA (100 mg/kg body weight) and photoirradiation of cortex (200 J/cm2) 6 hours later; or 5) irradiation of cortex (200 J/cm2) 6 hours after intravenous administration of Photofrin II (5 mg/kg body weight).

Surgery of lesions in the motor strip combining a stereotactically-guided mini-craniotomy with electrophysiological mapping of the motor cortex.

The removal of space-occupying lesions in the sensori-motor cortex carries a considerable risk of postoperative palsy. Therefore subcortical lesions located in the sensori-motor strip are often considered to be inoperable. Treatment options are stereotactic biopsy and radiosurgery beside radiological control examinations without surgery or surgery with a higher risk of postoperative deficits.

The risk of haemorrhage after image guided stereotactic biopsy of intra-axial brain tumours--a prospective study.

Objective: To analyze prospectively the frequency and the risk of symptomatic and asymptomatic haemorrhage after image guided stereotactic biopsy of intra-axial brain tumours.

Methods: The study was conducted within a time frame of 24 months (April 1998-April 2000). 326 patients (150 males, 176 females; mean age 56.

Cerebral involvement in graft-versus-host disease after murine bone marrow transplantation.

Neurologic manifestation of graft-versus-host disease (GvHD) after allogeneic bone marrow transplantation (BMT) has until now been limited to rare neuromuscular syndromes. Investigating cerebral findings using a murine BMT model, the authors found parenchymal lymphocytic inflammation, microglia activation, and mild cerebral angiitis-like changes in allogeneic transplanted animals but not in syngeneic controls. These findings suggest that cerebral involvement during GvHD may be a new neurologic complication after BMT.

Apoptosis in the basal ganglia of the developing human nervous system.

Programmed cell death (PCD) plays a crucial role in the development of the central nervous system through controlling neuronal numbers and adequate synaptic connections. PCD has been considered to occur in the form of apoptosis. To examine how apoptosis occurs in the developing human brain, we performed a morphometric TUNEL study, using a commercially available kit (ApopTag Kit, Oncor Inc.

Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients.

Object: It has been established that 5-aminolevulinic acid (5-ALA) induces the accumulation of fluorescent porphyrins in glioblastoma multiforme (GBM), a phenomenon potentially exploitable to guide tumor resection. In this study the authors analyze the influence of fluorescence-guided resection on postoperative magnetic resonance (MR) imaging and survival in a series of patients who underwent surgery in the authors' department.

Methods: Fifty-two consecutive patients with GBM received oral doses of 5-ALA (20 mg/kg body weight) 3 hours before induction of anesthesia.

Primary diffuse leptomeningeal gliomatosis: unusual MRI with non-enhancing nodular lesions on the cerebellar surface and spinal leptomeningeal enhancement.

A 28 year old man presented with a 1 month history of symptoms of intracranial hypertension. Examination showed bilateral papilloedema and meningeal signs. Magnetic resonance imaging showed nodular lesions on the cerebellar and pontine surface and thickening of the thoracic spinal leptomeninges.

[Gliomatosis cerebri: two case reports with atypical clinical and neuroradiologic findings].

The diagnosis of the rare disease Gliomatosis cerebri requires the correlation of clinical, radiological, and pathological findings. We report on two patients with intravitally diagnosed gliomatosis cerebri. Due to the unusually high malignancy of the tumor cells, diagnosis was complicated by atypical findings such as gadolinium enhancement in MRI and raised intracranial pressure.

Angiitis of the central nervous system after allogeneic bone marrow transplantation?

Background And Purpose: There is only limited information about late neurological complications after bone marrow transplantation (BMT). The purpose of this study is to describe a cerebral angiitis-like syndrome after allogeneic BMT.

Methods: Clinical and diagnostic findings of 5 BMT patients with chronic graft versus host disease and neuropathological data of 1 patient were reported.

Inducible nitric oxide synthase: a possible key factor in the pathogenesis of chronic vasospasm after experimental subarachnoid hemorrhage.

Object: The role of nitric oxide (NO) in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH) is not well understood. Nitric oxide is a well-established vasodilatory substance; however, in SAH, NO may become a major source for the production of injurious free-radical species, leading to chronic cerebral vasospasm. Reactive overproduction of NO to counteract vascular narrowing might potentiate the detrimental effects of NO.

Clinical outcome of supratentorial astrocytoma WHO grade II.

Objective: There are divergent opinions about the prognostic value of the extent of surgery and of different histological subtypes in supratentorial astrocytomas WHO grade II.

Methods: We reviewed 75 consecutive patients (36 females, 39 males) with supratentorial astrocytomas WHO grade II (59 primary and 16 recurrent tumours) operated on between 1991 and 1995.

Results: Gross total resection could be achieved in 40 astrocytomas, subtotal resection (including biopsy) was performed in 35 cases.

Differential expression of MHC class II molecules by microglia and neoplastic astroglia: relevance for the escape of astrocytoma cells from immune surveillance.

There is increasing evidence that microglia serve as antigen presenters in the human CNS. Although the occurrence of MHC class II immunoreactive cells has been reported in astrocytic gliomas, the relative contribution of microglia to this cell population has not been studied in detail. Using computer-assisted image analysis, we have investigated the expression of MHC class II molecules and of the microglia/macrophage markers Ki-MIP, RCA-1, KP1 and iba1, in 97 astrocytic gliomas comprising all WHO grades to answer the question whether there is a correlation between tumour grade and the number of MHC class II positive microglia/macrophage profiles.

Microglia and the development of spongiform change in Creutzfeldt-Jakob disease.

Recent in vitro experiments suggest that neurotoxicity of the prion protein is dependent on the presence of microglia. We have studied 11 cases of Creutzfeldt-Jakob disease (CJD) using immunocytochemistry in combination with computerized image analysis to clarify the relationship between spongiform change and microglial activation. MHC class II-positive microglia were almost exclusively confined to cortical gray matter where the neuropil area occupied by these cells exceeded that of controls more than 350-fold.

Long-lasting perivascular accumulation of major histocompatibility complex class II-positive lipophages in the spinal cord of stroke patients: possible relevance for the immune privilege of the brain.

Six cases of middle cerebral artery occlusion are presented in which the cellular changes accompanying descending degeneration of the lateral corticospinal tract were studied at different time points (5 days-10 years) following the insult. Microglia and perivascular cells were found to ingest large amounts of myelin degradation products, while expressing high levels of major histocompatibility complex (MHC) class II molecules. Activation of perivascular macrophages, as indicated by increased class II expression, lasted for many years and appeared to follow down-regulation of both phagocytic activity and class II expression on parenchymal microglia.

[Tumor surgery of the speech cortex in local anesthesia. Neuropsychological and neurophysiological monitoring during operations in the dominant hemisphere].

We report on 30 cases where we have used cortical stimulation mapping to define the areas representing sensorimotor, language and speech functions under local anesthesia to facilitate resection of space-occupying lesions near these areas. Under the simplistic concept that Broca's area lies in the frontal operculum (inferior frontal gyrus) and that Wernicke's area is located in the posterior perisylvian area (superior temporal, angular and supramarginal gyri), we found language and speech function to be represented outside these areas in up to 4 stimulation sites of 15 patients. The results of cortical stimulation mapping were therefore essential to decide on the optimal access route to the lesions that were located subcortically and on the optimal resection plane in gliomas.