ORCID Profile
0000-0002-0802-3499
Current Organisation
UNSW Sydney
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Publisher: Wiley
Date: 2006
DOI: 10.1002/MDS.21034
Abstract: The clinical distinction between Parkinson's disease (PD) with dementia (PDD) and dementia with Lewy bodies (DLB) is challenged by most neuropathological studies showing nearly identical changes in both conditions. We report an unusual case of PD evolving into a rapidly progressive dementia leading to death within 3 months that showed nearly all clinical features of DLB. At autopsy, numerous Lewy bodies and Lewy neurites were found in several areas of the brainstem, the limbic system, and the neocortex, consistent with pure DLB. This case demonstrates that Lewy body disease may exhibit a dramatic course without any coexisting pathology and exemplifies that PD, PDD, and DLB may sometimes represent sequential, yet overlapping, phenotypes of a same clinicopathological entity.
Publisher: Oxford University Press (OUP)
Date: 14-05-2012
Publisher: Wiley
Date: 03-1999
DOI: 10.1111/J.1699-0463.1999.TB01592.X
Abstract: We report a very uncommon case of endometrioid adenocarcinoma of the fallopian tube that mimicked, based on histology, a female adnexal tumor of probable Wolffian origin (FATPWO). We present our microscopic and immunohistochemical findings, and a review of the literature concerning these two entities. The differential diagnosis can be of great consequence, owing to the very different prognoses of the two tumors, and is based mainly on macroscopic appearance and immunohistochemical profile: epithelial membrane antigen (EMA) and CA125, generally lacking in FATPWO, are expressed in endometrioid adenocarcinoma, thus indicating the müllerian origin of this tumor.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-1998
Abstract: The immunosuppressive agent FK 506 is widely used in liver transplant patients. Neurotoxicity is a major complication of its use. We report progressive and irreversible neurologic complications occurring in a 39-year-old woman who underwent liver transplantation and was treated with FK 506. Neuropathologic examination revealed multiple vasculitic lesions. The possibility of an FK 506-mediated toxic effect on the cerebral vessels is suggested.
Publisher: Oxford University Press (OUP)
Date: 15-05-2201
Publisher: Wiley
Date: 18-12-2013
DOI: 10.1002/LARY.24518
Abstract: Chondrosarcoma of the larynx is a rare, low-grade malignancy in terms of histology and clinical behavior. We present an unusual case of laryngeal chondrosarcoma, which developed a large dedifferentiated component on recurrence after primary surgery. The diagnosis of dedifferentiation was suggested in view of the morphological and metabolic findings on hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) and was subsequently confirmed surgically. Whole-organ, slice-by-slice radiologic-histologic correlation revealed excellent delineation of the well-differentiated and dedifferentiated tumor components with PET/MRI. PET/MRI can provide additional functional information to supplement the morphological mapping and histopathology of these tumors.
Publisher: Springer Science and Business Media LLC
Date: 10-12-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2012
Publisher: Dustri-Verlgag Dr. Karl Feistle
Date: 11-2007
DOI: 10.5414/NPP26306
Abstract: Pilocytic astrocytoma (WHO Grade 1) is a low-grade glioma with a favorable prognosis most commonly diagnosed in patients aged below 20. It is the most common glioma in children, and cases discovered in elderly patients are rare. We report the highly unusual case of an 85-year-old man whose neurological signs included Parkinsonism, and in whom post mortem examination revealed a pilocytic astrocytoma of the brainstem. We also discuss the clinical, neuroradiological and neuropathological differential diagnosis.
Publisher: Springer Science and Business Media LLC
Date: 31-10-2015
Publisher: Wiley
Date: 15-11-2008
DOI: 10.1002/GLIA.20715
Abstract: T cell mediated immunotherapies are proposed for many cancers including malignant astrocytoma. As such therapies become more potent, but not necessarily more tumor-specific, the risk of collateral autoimmune damage to normal tissue increases. Tumors of the brain present significant challenges in this respect, as autoimmune destruction of brain tissue could have severe consequences. To investigate local immune reactivity toward a tumor-associated antigen in the brain, transgenic mice were generated that express a defined antigen (CW3 170-179) in astroglial cells. The resulting six transgenic mouse lines expressed the transgenic self-antigen in cells of the gastrointestinal tract and CNS compartments, or in the CNS alone. By challenging transgenic mice with tumor cells that express CW3, self/tumor-specific immune responses were visualized within a normal polyclonal T cell repertoire. A large expansion of the endogenous CW3 170-179-specific CD8 T cell population was observed in nontransgenic mice after both subcutaneous and intracerebral implantation of tumor cells. In contrast, CW3 170-179-specific immune responses were not observed in transgenic mice that exhibited extracerebral transgene expression. Importantly, in certain groups of mice in which transgene expression was restricted to the CNS, antigen-specific immune responses occurred when tumor was implanted subcutaneously, but not intracerebrally. This local immune tolerance in the brain was induced via peripheral (extrathymic) rather than central (thymic) tolerance mechanisms. Thus, this study highlights the role of regional immune regulation in the prevention of autoimmunity in the brain, and the potential impact of these mechanisms for brain tumor immunotherapy.
Publisher: Wiley
Date: 05-2006
DOI: 10.1002/PATH.1943
Abstract: Primary human brain tumours account for approximately 2% of all cancers. High levels of expression of vascular endothelial growth factor-A (VEGF-A), a potent angiogenic factor, are linked to poor prognosis. In contrast, the potential role in human brain tumour biology of newer VEGF family members, VEGF-C and VEGF-D, both of which are lymphangiogenic factors, is poorly understood. In the present study, the expression of all VEGFs (VEGF-A, -B, -C, and -D) and their receptors (VEGFR-1, -2, and -3) has been assessed in 39 primary human brain tumours. The well-established findings were confirmed with VEGF-A. Surprisingly, however, VEGF-C and VEGF-D, as well as VEGFR-3, were expressed in some tumour types such as haemangioblastomas and glioblastomas, despite their lack of lymphatic vessels. VEGF-C and VEGFR-3 transcripts were localized to the tumour palisade around necrotic areas in glioblastomas and were evenly distributed throughout haemangioblastomas. VEGF-C protein was localized by immunohistochemistry to the palisade layer in glioblastomas. More than 50% of VEGF-C-positive cells also expressed the intermediate-stage inflammatory macrophage marker CD163 however, a significant proportion of VEGF-C-positive cells were CD163-negative. These data demonstrate the presence of molecules, primarily described as regulators of lymphangiogenesis, in normal human brain and brain tumours that are devoid of lymphatics. Their localization in macrophages points to a role in tumour-associated inflammation.
Publisher: Springer Science and Business Media LLC
Date: 04-12-2008
DOI: 10.1007/S00117-008-1765-Z
Abstract: Cross-sectional imaging with CT, MRI and more recently PET CT plays an indispensable complementary role to endoscopy in the pretherapeutic diagnostic and staging of laryngeal neoplasms and in the evaluation of the operated or irradiated larynx. Adequate interpretation of the CT, PET CT and MR images requires a thorough knowledge of the patterns of submucosal spread and familiarity with the diagnostic signs of neoplastic invasion as seen with each modality. In addition, one should be aware of the implications of imaging for staging and treatment. Both CT and MR imaging are highly sensitive for the detection of neoplastic invasion of the preepiglottic and paraglottic spaces, subglottic region and cartilage. The high negative predictive value of both CT and MRI allows a relatively reliable exclusion of neoplasm cartilage invasion. The specificity of both CT and MRI is, however, moderately high and both methods may, therefore, overestimate the extent of tumor spread. However, recent investigations have shown that the specificity of MRI may be significantly improved by using new diagnostic criteria which allow differentiation of tumor from peritumoral inflammation in many instances. Both cross-sectional imaging methods also significantly improve the pretherapeutic staging accuracy of laryngeal tumors if used in addition to clinical examination and endoscopic biopsy. In the presence of a submucosal mass, CT and MRI play a key role for the diagnosis, as they may characterize the lesion, reliably depict its submucosal extent and guide the endoscopist to perform deep biopsies which allow the definitive histological diagnosis. Cross-sectional imaging also plays a key role in the evaluation of laryngoceles, recurrent laryngeal nerve paralysis and fractures.
Publisher: Elsevier BV
Date: 08-1999
DOI: 10.1016/S8756-3282(99)00140-4
Abstract: We report the pathological findings in cases of acrylic implants obtained by direct intratumoral injection of polymethyl-methacrylate (PMMA) and N-butyl-cyano-acrylate (NBCA). Direct intratumoral injection of acrylic implants was performed for a variety of primary and secondary bone lesions. These types of treatments have been used at our institution in the last 4 years for 40 vertebroplasty (PMMA) procedures and for nine bone lesions of other locations (PMMA, NBCA). Postmortem histology became available for 1 case of PMMA and for 5 cases with NBCA intratumoral acrylic implants. The pathological findings associated with PMMA and NBCA were evaluated and compared. PMMA exhibited a macroscopic and microscopic rim of tumor necrosis, 6 months after implantation. NBCA exhibited compressive effects on the nearby tumor tissue, however, without signs of significant necrosis outside the acrylic tumor cast. Tumor captured inside the acrylic cast showed extensive to near complete necrosis. Acrylic implants may lead to necrosis when injected directly in tumors. The necrotizing effect may extend beyond the limits of an implant in the case of PMMA. Such an extended effect of PMMA, when compared with NBCA, may be due to the variable toxicity of acrylic implants, including the different degrees of the exothermic reaction during polymerization.
Publisher: Wiley
Date: 05-03-2009
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.ULTRASMEDBIO.2013.08.012
Abstract: The aim of our study was to evaluate whether neo-vascularization of the carotid plaque can be accurately assessed by visual analysis of contrast-enhanced ultrasound images and whether these findings correlate with intensity-over-time curve analysis (ITC) and histopathology. Patients with ≥50% symptomatic or ≥60% asymptomatic stenosis according to European Carotid Surgery Trial criteria were included. Four investigators evaluated contrast enhancement visually (three grades), with positive agreement when three or more investigators were unanimous. ITC analysis of contrast enhancement was performed in the plaque and in the lumen. Histopathology (microvessel density with CD34 + staining) was completed when endarterectomy was performed. Visual grading (33 patients, inter-observer agreement = 94%) correlated significantly with ITC analysis (p = 0.03). Histopathology (n = 19) revealed a larger CD34 + area in patients with grade 1/2 versus grade 0 (p = 0.03). Visual analysis of neo-vascularization by means of contrast-enhanced ultrasound imaging is accurate and reproducible, with significant correlations with ITC and histopathology.
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2010
DOI: 10.1158/0008-5472.CAN-09-3074
Abstract: Immune infiltration of advanced human gliomas has been shown, but it is doubtful whether these immune cells affect tumor progression. It could be hypothesized that this infiltrate reflects recently recruited immune cells that are immediately overwhelmed by a high tumor burden. Alternatively, if there is earlier immune detection and infiltration of the tumor, the question arises as to when antitumor competency is lost. To address these issues, we analyzed a transgenic mouse model of spontaneous astrocytoma (GFAP-V12HA-ras mice), which allows the study of immune interactions with developing glioma, even at early asymptomatic stages. T cells, including a significant proportion of Tregs, are already present in the brain before symptoms develop, followed later by macrophages, natural killer cells, and dendritic cells. The effector potential of CD8 T-cells is defective, with the absence of granzyme B expression and low expression of IFN-γ, tumor necrosis factor, and interleukin 2. Overall, our results show an early defective endogenous immune response to gliomas, and local accumulation of immunosuppressive cells at the tumor site. Thus, the antiglioma response is not simply overwhelmed at advanced stages of tumor growth, but is counterbalanced by an inhibitory microenvironment from the outset. Nevertheless, we determined that effector molecule expression (granzyme B, IFN-γ) by brain-infiltrating CD8 T-cells could be enhanced, despite this unfavorable milieu, by strong immune stimuli. This potential to modulate the strong imbalance in local antiglioma immunity is encouraging for the development and optimization of future glioma immunotherapies. Cancer Res 70(12) 4829–39. ©2010 AACR.
Publisher: Springer Science and Business Media LLC
Date: 07-08-2009
DOI: 10.1007/S00381-009-0968-6
Abstract: The association of a medulloblastoma and a syringomyelia has been already described in rare instances albeit without symptoms related to the syrinx. The case of a 23-year-old man operated in infancy for a medulloblastoma and then treated solely with adjuvant chemotherapy is reported. He was also operated in infancy for a scaphocephaly. With a very long time delay, he has developed a Chiari I and a symptomatic cervico-dorsal syringomyelia. The symptoms attributed to the syrinx consisted of a unilateral prurigo over the left arm which was so severe to lead to self-mutilation. Clinical and magnetic resonance imaging follow-up after cervico-dorsal decompression shows a significant improvement of the symptoms together with a reduction of the size of the syrinx. This case is discussed in the light of the presumed pathophysiology of the syrinx and its exceptional clinical presentation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-1999
DOI: 10.1097/00019606-199909000-00007
Abstract: A polymerase chain reaction (PCR) method, which lifies a fragment of the 16S ribosomal RNA (rRNA) gene present in all mycobacterial species, was developed and tested on 84 formalin-fixed paraffin-embedded tissue specimens from 51 patients with human immunodeficiency (HIV) infection. The PCR products were characterized either by sequencing or by hybridization with nonradioactive oligonucleotide probes specific for Mycobacterium tuberculosis complex, M. avium, or M. genavense. Sequencing was successful for 26 s les compared with the 45 s les for probe hybridization. The sensitivity of DNA lification compared with microscopic examination was 79.5%. A mixed infection was detected with M. genavense for only one patient who was infected with M. tuberculosis complex. In the group of 22 control patients, where no diagnosis of mycobacterial infection was made during life and no acid-fast bacteria were seen during the autopsy, four s les of one patient were positive by hybridization with the M. tuberculosis probe. This patient had a clinical history compatible with tuberculosis. This PCR method may be a powerful tool for the precise diagnosis of mycobacterial infections from histopathologic material, provided that several sections from the same specimen block are tested.
Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
Date: 05-2006
Publisher: Elsevier BV
Date: 09-1999
Publisher: Wiley
Date: 18-02-2014
Abstract: Parkinson's disease (PD) pathology spreads throughout the brain following a region-specific process predominantly affecting the substantia nigra (SN) pars compacta. SN exhibits a progressive loss of dopaminergic neurons responsible for the major cardinal motor symptoms, along with the occurrence of Lewy bodies in the surviving neurons. To gain new insights into the underlying pathogenic mechanisms in PD, we studied postmortem nigral tissues dissected from pathologically confirmed PD cases (n = 5) and neurologically intact controls (n = 8). Using a high-throughput shotgun proteomic strategy, we simultaneously identified 1795 proteins with concomitant quantitative data. To date, this represents the most extensive catalog of nigral proteins. Of them, 204 proteins displayed significant expression level changes in PD patients versus controls. These were involved in novel or known pathogenic processes including mitochondrial dysfunction, oxidative stress, or cytoskeleton impairment. We further characterized four candidates that might be relevant to PD pathogenesis. We confirmed the differential expression of ferritin-L and seipin by Western blot and demonstrated the neuronal localization of gamma glutamyl hydrolase and nebulette by immunohistochemistry. Our preliminary findings suggest a role for nebulette overexpression in PD neurodegeneration, through mechanisms that may involve cytoskeleton dynamics disruption. All MS data have been deposited in the ProteomeXchange with identifier PXD000427 (ataset/PXD000427).
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.CARPATH.2013.01.083
Abstract: Characterize the phenotypic features of smooth muscle cells (SMCs) in the wall of human saccular intracranial aneurysms (sIAs). We investigated by means of immunohistochemistry the expression of the cytoskeletal differentiation markers α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chains (SMMHCs), and smoothelin in 26 sIAs and 15 nonaneurysmal cerebral arteries. In addition, S100A4, a recently identified marker of dedifferentiated SMCs in atherosclerotic plaques, was also investigated. Six sIAs and 5 nonaneurysmal arteries were used for morphometric analysis. sIAs displayed a significant medial atrophy compared with nonaneurysmal cerebral arteries moreover, sIA SMCs showed marked decrease of α-SMA and SMMHCs expression and disappearance of smoothelin. Unexpectedly, S100A4 was strongly up-regulated in media SMCs of sIAs. In sIAs, media SMCs acquire a dedifferentiated phenotype and show de novo expression of S100A4, characteristic features of atherosclerotic plaque SMCs.
Publisher: Elsevier BV
Date: 05-1999
DOI: 10.1016/S0967-5868(99)90512-X
Abstract: Acute haemorrhagic presentation of a meningioma is an extremely rare event. In a review of the literature, 44 such cases were found and only eight of them presented with sudden onset of coma. The outcome in these eight cases was, with few exceptions, poor. We report the case of a 72-year-old woman who presented with sudden onset of coma due to a massive haemorrhage into a frontal meningioma. The diagnosis was suspected on the basis of a non-enhanced computed tomographic (CT) scan and considering the clinical status of the patient, emergency evacuation of the haematoma and complete macroscopic resection of the tumour was performed without further diagnostic procedures. The patient fully recovered. Clinical examination and contrast enhanced CT scan at 3 months follow-up were considered normal. The prognosis for haemorrhagic presenting meningiomas is poor especially for those presenting with acute onset of coma. The outcome seems to be improved with rapid decompression and tumour removal. We would like to stress the need to keep the diagnostic procedures to a minimum once a haemorrhagic decompensating meningioma is suspected despite the risks associated with an incomplete radiological work up before surgery. Complete or at least gross tumour removal at the time of emergency surgery seems to be associated with a better outcome and should be attempted in all patients, even those presenting with acute signs of herniation.
Publisher: Springer Science and Business Media LLC
Date: 15-08-2017
Publisher: Springer Science and Business Media LLC
Date: 23-08-1999
Abstract: Several plant-derived essential oils have been known for over a century to have epileptogenic properties. We report three healthy patients, two adults and one child, who suffered from an isolated generalized tonic-clonic seizure and a generalized tonic status, respectively, related to the absorption of several of these oils for therapeutic purposes. No other cause of epilepsy was found, and outcome was good in the two adult cases, but the course has been less favorable in the child. A survey of the literature shows essential oils of 11 plants to be powerful convulsants (eucalyptus, fennel, hyssop, pennyroyal, rosemary, sage, savin, tansy, thuja, turpentine, and wormwood) due to their content of highly reactive monoterpene ketones, such as c hor, pinoc hone, thujone, cineole, pulegone, sabinylacetate, and fenchone. Our three cases strongly support the concept of plant-related toxic seizure. Nowadays the wide use of these compounds in certain unconventional medicines makes this severe complication again possible.
Publisher: Springer Science and Business Media LLC
Date: 19-06-2007
DOI: 10.1007/S00401-007-0233-6
Abstract: The presence of Lewy bodies (LB) in autonomic structures of the central and peripheral nervous system in Parkinson's disease (PD) is well known and could explain clinical signs of pure autonomic failure (PAF) or dysphagia, frequently associated with the disorder. There are many neuropathological reports in the literature with detailed descriptions of PAF, however, LB dysphagia has thus far only been reported once. In the present study, we describe two cases of isolated dysphagia without extrapyramidal syndrome, diagnosed clinically as progressive supranuclear palsy and amyotrophic lateral sclerosis, where detailed neuropathological examination identified LBs in the dorsal vagal motor nuclei in the medulla. These findings confirm the existence of isolated LB dysphagia and emphasize the importance of detailed neuropathological and immunohistochemical examination in cases of dysphagia.
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.AMJOTO.2009.08.001
Abstract: Submandibular gland sarcoidosis is rare and little is known about its clinical presentation besides the usual neck swelling. The aim of the study was to extract clinical knowledge on submandibular sarcoidosis from the literature. A systematic review was performed using a search in Medline with the key-words "sarcoidosis," "submandibular," "submaxillary." Forty-six articles fitting the search criteria were found, whereas 31 had to be excluded because they did not report submandibular gland sarcoidosis. Twenty cases of submandibular gland sarcoidosis were considered suitable for analysis. Almost all reported cases concerned female patients. In some cases submandibular gland's swelling is the first and only manifestation of the disease. Sarcoidosis should be considered in the differential diagnosis of all progressive and painless swellings of the submandibular gland, especially in women. Rarely, it may be the first manifestation of the disease.
Publisher: Wiley
Date: 30-09-2010
DOI: 10.1002/GLIA.20941
Abstract: Brain invasion is a biological hallmark of glioma that contributes to its aggressiveness and limits the potential of surgery and irradiation. Deregulated expression of adhesion molecules on glioma cells is thought to contribute to this process. Junctional adhesion molecules (JAMs) include several IgSF members involved in leukocyte trafficking, angiogenesis, and cell polarity. They are expressed mainly by endothelial cells, white blood cells, and platelets. Here, we report JAM-C expression by human gliomas, but not by their normal cellular counterpart. This expression correlates with the expression of genes involved in cytoskeleton remodeling and cell migration. These genes, identified by a transcriptomic approach, include poliovirus receptor and cystein-rich 61, both known to promote glioma invasion, as well as actin filament associated protein, a c-Src binding partner. Gliomas also aberrantly express JAM-B, a high affinity JAM-C ligand. Their interaction activates the c-Src proto-oncogene, a central upstream molecule in the pathways regulating cell migration and invasion. In the tumor microenvironment, this co-expression may thus promote glioma invasion through paracrine stimuli from both tumor cells and endothelial cells. Accordingly, JAM-C/B blocking antibodies impair in vivo glioma growth and invasion, highlighting the potential of JAM-C and JAM-B as new targets for the treatment of human gliomas.
Publisher: American Medical Association (AMA)
Date: 03-2010
Publisher: Wiley
Date: 11-05-2012
Publisher: Springer Science and Business Media LLC
Date: 14-02-2003
DOI: 10.1007/S00401-003-0681-6
Abstract: Malignant transformation of human gliomas is accompanied by extensive proliferation of stromal blood vessels. Recent data suggest mesenchymal transdifferentiation of neoplastic cells in various human cancers, including colon and breast cancer as well as gliosarcoma. In this study, we have analyzed proliferating stromal blood vessels in glioblastoma multiforme for the presence of mutations in the tumor suppressor gene TP53. Using tissue arrays derived from glioblastoma specimens, cases with significant immunohistochemical p53 accumulation were selected for molecular genetic detection of TP53 mutations in exons 5 to 8. None of the tumors included in this series displayed properties of gliosarcoma. Proliferating glomeruloid stromal vessels were isolated by laser microdissection from paraffin sections. In six cases, single-strand conformation polymorphism analysis for mutations of the TP53 gene in stromal blood vessels compared with adjacent tumor cells and subsequent DNA sequencing of the resulting DNA fragments were carried out. Glioblastoma cells of these cases exhibited TP53 mutations in exons 5, 7 and 8. None of these tumors showed TP53 mutations in microdissected s les from glomeruloid vessels. The absence of TP53 mutations in vascular stromal components of glioblastoma multiforme supports the hypothesis that microvascular proliferations originate from the tumor stroma and are not derived from transdifferentiated glioblastoma cells.
Publisher: Elsevier BV
Date: 2004
DOI: 10.1016/J.NEUROSCIENCE.2003.10.012
Abstract: In the brain, the efflux transporter P-glycoprotein (Pgp) is predominantly located on the luminal membrane of endothelial cells lining brain microvessels and forming the blood-brain barrier. Many lipophilic drugs, including antiepileptic drugs, are potential substrates for Pgp. Overexpression of Pgp in endothelial cells of the blood-brain barrier has been determined in patients with drug resistant forms of epilepsy such as temporal lobe epilepsy and rodent models of temporal lobe epilepsy and suggested to lead to reduced penetration of antiepileptic drugs into the brain. Expression of Pgp after seizures has also been described in astrocytes, whereas it is not clear whether neurons can express Pgp. In the present study, Pgp expression was studied by immunohistochemistry in rats 24 h after a status epilepticus induced by either pilocarpine or kainate, widely used models of temporal lobe epilepsy. Unexpectedly, in addition to endothelial Pgp staining, intense Pgp staining was found in neurons in the CA3c/CA4 sectors and hilus of the hippoc us formation, but not in other brain regions examined. The neuronal Pgp staining was confirmed by two different Pgp antibodies. Double immunolabeling and confocal microscopy showed that Pgp was colocalized with the neuronal marker neuronal nuclear antigen, but not with the glial marker glial fibrillary acidic protein. No neuronal Pgp staining was seen in control rats. The expression of Pgp in neurons after limbic seizures was substantiated by determining Pgp encoding genes (mdr1a, mdr1b) in neurons by real time quantitative RT-PCR. Increased Pgp expression in hippoc al neurons is likely to affect the action of drugs with intraneuronal targets and, in view of recent evidence from other cell types, could be associated with prevention of apoptosis which is involved in neuronal damage developing after seizures such as produced by pilocarpine.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2002
DOI: 10.1097/00001756-200507130-00010
Abstract: Immunosuppressive soluble factors such as transforming growth factor beta and cell surface molecules such as FasL may contribute to the immune evasion of malignant glioma. B7 homolog 1 is a member of the B7 family of costimulatory molecules implicated in the negative regulation of T cell immune responses. Here, we show that human glioma cell lines express B7 homolog 1 protein that reduces interferon-gamma production by activated T cells. The expression of B7 homolog 1 in vivo was demonstrated in a large series of human glioma s les, with a significant correlation between the level of B7 homolog 1 expression and the tumor grade. Overall, our data suggest that B7 homolog 1 may be involved in the immune evasion of glioma and encourage the blockade of this pathway in future immunotherapies.
Publisher: Radiological Society of North America (RSNA)
Date: 09-2015
Abstract: Interpreting imaging studies of the irradiated neck constitutes a challenge because of radiation therapy-induced tissue alterations, the variable appearances of recurrent tumors, and functional and metabolic phenomena that mimic disease. Therefore, morphologic magnetic resonance (MR) imaging, diffusion-weighted (DW) imaging, positron emission tomography with computed tomography (PET/CT), and software fusion of PET and MR imaging data sets are increasingly used to facilitate diagnosis in clinical practice. Because MR imaging and PET often yield complementary information, PET/MR imaging holds promise to facilitate differentiation of tumor recurrence from radiation therapy-induced changes and complications. This review focuses on clinical applications of DW and PET/MR imaging in the irradiated neck and discusses the added value of multiparametric imaging to solve diagnostic dilemmas. Radiologists should understand key features of radiation therapy-induced tissue alterations and potential complications seen at DW and PET/MR imaging, including edema, fibrosis, scar tissue, soft-tissue necrosis, bone and cartilage necrosis, cranial nerve palsy, and radiation therapy-induced arteriosclerosis, brain necrosis, and thyroid disorders. DW and PET/MR imaging also play a complementary role in detection of residual and recurrent disease. Interpretation pitfalls due to technical, functional, and metabolic phenomena should be recognized and avoided. Familiarity with DW and PET/MR imaging features of expected findings, potential complications, and treatment failure after radiation therapy increases diagnostic confidence when interpreting images of the irradiated neck. Online supplemental material is available for this article.
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.NEUCHI.2013.04.001
Abstract: We report a rare case of renal carcinoma metastasis involving a lumbar nerve root. Metastases to nerve roots are rare occurrences, and to our knowledge, only six cases have been reported so far in the literature. The patient in this report presented with weakness in the right lower limb and intractable pain irradiating along the L5 dermatome. MRI findings revealed a right-sided L5 nerve root mass, suggestive of a schwannoma, involving the spinal ganglion and its extraforaminal region. Complete macroscopic resection of this mass was performed, and histopathologic analysis confirmed the lesion to be a metastasis of a renal clear cell carcinoma. Local radiotherapy was given and tyrosine kinase inhibitors administered. At 5 months, the patient was pain-free and his right limb weakness had completely resolved. A tumoral recurrence could be observed on the control MRI 5 months after surgery. This report presents the first case of a patient with a renal clear cell carcinoma metastasis to a L5 nerve root, as well as a brief review of previous cases of metastases to peripheral nerve roots.
Publisher: Mary Ann Liebert Inc
Date: 06-2013
Abstract: Anatomopathological studies that described the immediate causes of death of patients with advanced cancer were first published approximately 20 years ago. Our objective was to analyze if causes of death changed with a wider use of broad spectrum antibiotics and prophylactic anticoagulation. We conducted a retrospective study of all patients with an advanced cancer hospitalized in the Division of Palliative Medicine at the University Hospital Geneva from 2004 to 2010 who had an autopsy. Two hundred forty patients were included (130 men, mean age: 74±13). Main causes of death discovered at the autopsy were pulmonary infection (n=131 55%), advanced cancer (n=39 16%), pulmonary infection together with pulmonary embolism (PE) (n=27 12%), PE alone (n=22 9%), cardiac complications (n=19 5%) and others (n=2 1%). In a logistic regression model, with adjusting for age, gender, main diagnosis, comorbidities, blood count, corticosteroids, and antibiotics, there were no independent factors associated with pulmonary infection at autopsy. In a similar model, with adjusting for age, gender, main diagnosis, comorbidities, and anticoagulation, the only independent factor associated with PE at autopsy was the history of thrombo-embolic disease and therapeutic anticoagulation. The results of this retrospective study demonstrate that causes of death did not change with the modification of our practice. The high rate of pulmonary infection and embolism in this population, including in patients who received broad spectrum and prophylactic anticoagulation should encourage us to pursue other prospective studies to actually demonstrate the benefit of these treatments in this population.
Publisher: Oxford University Press (OUP)
Date: 02-07-2010
Publisher: Elsevier BV
Date: 1998
DOI: 10.1016/S0344-0338(98)80062-9
Abstract: We describe the case of a 27 year-old woman presenting with acute abdominal pain due to torsion of a right ovarian cyst. Histopathological examination of the excised lesion revealed a mature cystic ovarian teratoma consisting primarily of a highly organized cerebellar component, an exceedingly rare finding. The possibility of a malignant neuroepithelial tumor arising from immature precursor cells within this neural tissue justifies complete excision of such lesions.
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.EJRAD.2008.03.027
Abstract: The purpose of this article is to review currently used imaging protocols for the evaluation of pathologic conditions of the larynx and hypopharynx, to describe key anatomic structures in the larynx and hypopharynx that are relevant to tumor spread and to discuss the clinical role of Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and PET CT in the pretherapeutic workup and posttherapeutic follow-up of patients with squamous cell carcinoma of this region. A detailed discussion of the characteristic neoplastic submucosal invasion patterns, including extension to the preepiglottic space, paraglottic space and laryngeal cartilages and the implications of imaging for tumor staging and treatment planning is provided. The present article also reviews less common tumors of this region, such as chondrosarcoma, lymphoma, minor salivary gland tumors and lipoma. As the majority of non-neoplastic conditions do not require imaging the role of CT and MRI is discussed in some particular situations, such as to delineate cysts and laryngoceles, abscess formation in inflammatory conditions, to evaluate laryngeal and hypopharyngeal involvement in granulomatous and autoimmune diseases, and to evaluate the extent of laryngeal fractures due to severe blunt trauma.
Publisher: BMJ
Date: 28-08-2013
No related grants have been discovered for Karim Burkhardt.