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Biomedical subjects

N De Tribolet

Publications and source records attributed to N De Tribolet.

At least 19 recordsLinked to original sources

Expression and localization of VEGF-C and VEGFR-3 in glioblastomas and haemangioblastomas.

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.

Biomarkers, Tumor↗

Double-lumen balloon microcatheter-assisted occlusion of cerebral vessels with coils: a technical note.

The purpose of this study was to describe a balloon-assisted double-lumen microcatheter technique to perform a controlled and tight coil packing of a vascular segment for vessel occlusion. This technique can be performed immediately after a test occlusion with the balloon kept in place and was, as illustrated in six cases, in our experience safe, straight forward to use and fast.

Adult↗

Fluorodeoxyuridine improves imaging of human glioblastoma xenografts with radiolabeled iododeoxyuridine.

Use of radiolabeled nucleotides for tumor imaging is hampered by rapid in vivo degradation and low DNA-incorporation rates. We evaluated whether blocking of thymidine (dThd) synthesis by 5-fluoro-2'-deoxyuridine (FdUrd) could improve scintigraphy with radio-dThd analogues, such as 5-iodo-2'-deoxyuridine (IdUrd). We first show in vitro that coincubation with FdUrd substantially increased incorporation of [125I]IdUrd and [3H]dThd in the three tested human glioblastoma lines. Flow cytometry analysis showed that a short coincubation with FdUrd (1 h) produces a signal increase per labeled cell. We then measured biodistribution 24 h after i.v. injection of [125I]IdUrd in nude mice s.c. xenografted with the three glioblastoma lines. Compared with animals given [125I]IdUrd alone, i.v. preadministration for 1 h of 10 mg/kg FdUrd increased the uptake of [125I]IdUrd in the three tumors 4.8-6.8-fold. Compatible with previous reports, there were no side effects in mice observed for 2 months after receiving such a treatment. The tumor uptake of [125I]IdUrd was increased < or =13.6-fold when FdUrd preadministration was stepwise reduced to 1.1 mg/kg. Uptake increases remained lower (between 1.7- and 5.8-fold) in normal proliferating tissues (i.e., bone marrow, spleen, and intestine) and negligible in quiescent tissues. DNA extraction showed that 72-80% of radioactivity in tumor and intestine was bound to DNA. Scintigraphy of xenografted mice was performed at different times after i.v. injection of 3.7 MBq [125I]IdUrd. Tumor detection was significantly improved after FdUrd preadministration while still equivocal after 24 h in mice given [125I]IdUrd alone. Furthermore, background activity could be greatly reduced by p.o. administration of KClO4 in addition to potassium iodide. We conclude that FdUrd preadministration may improve positron or single photon emission tomography with cell division tracers, such as radio-IdUrd and possibly other dThd analogues.

Animals↗

Diagnosis, treatment, and outcome of pituitary tumors and other abnormal intrasellar masses. Retrospective analysis of 353 patients.

We reviewed the clinical features, essential laboratory data, pituitary imaging findings (computerized tomography and magnetic resonance imaging), management, and outcome of 353 consecutive patients with the presumptive diagnosis of pituitary tumor investigated from January 1984 through December 1997 at University Hospital, Lausanne, Switzerland. In 18 cases primary empty sella turcica was diagnosed, and in 13 cases of pseudacromegaly there were no endocrine abnormalities. The remaining 322 patients disclosed abnormal pituitary masses, including 275 pituitary adenomas, 18 craniopharyngiomas, 6 cases of primary pituitary hyperplasia, 6 intrasellar meningiomas, 6 cases of distant metastases, 4 intrasellar cysts, 2 chordomas, 1 primary lymphoma, and 1 astrocytoma. Biologic data and immunohistochemical analysis of the excised tissues demonstrated that prolactinomas and nonsecreting adenomas (NSAs) were the most frequent pituitary tumors (40% and 39%, respectively), followed by somatotropic adenomas with acromegaly (11%) and Cushing disease (6%). In contrast with the vast majority of NSAs, which significantly expressed glycoprotein hormones in tissue without secreting them, there was a small group of glycoprotein hormone-secreting adenomas (2%), which had a more severe clinical course after surgery. Thirty-eight pituitary masses were incidentally discovered, most of them NSAs. The expansion of pituitary adenomas into the right cavernous sinus was twice as frequent as to the left cavernous sinus. For the differential diagnosis of hyperprolactinemia, basal prolactin (PRL) levels above 85 micrograms/L, in the absence of renal failure and PRL-enhancing drugs, and a PRL increment of less than 30% after thyrotropin-releasing hormone (TRH) accurately ruled out functional hyperprolactinemia due to NSA, and were typical of prolactinomas. For screening and follow-up of acromegaly, basal growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, as well as the paradoxical GH response to TRH (present in 2/3 acromegalic patients), could be used as convenient tools, but the most accurate test for diagnosis and prediction of outcome after therapy was GH (lack of) suppression during oral glucose tolerance test. In Cushing disease, single evening plasma cortisol was as good as the overnight dexamethasone suppression test for screening, and a combined dexamethasoneovine corticotropin-releasing hormone (oCRH) test was as accurate as the long dexamethasone suppression test to confirm the diagnosis. Bilateral inferior petrosal sinus catheterization coupled with oCRH test confirmed the pituitary origin of excess adrenocorticotropic hormone (ACTH) in all patients, including those with normal pituitary on magnetic resonance imaging (50% of the cases). However, this procedure failed to predict tumor localization correctly within the pituitary in 21% of patients. Pituitary cysts, meningiomas, and craniopharyngiomas with an intrasellar component were correctly diagnosed based on pituitary imaging in 75%, 67%, and 44% of cases, respectively. The remainder, as well as the cases of pituitary hyperplasia, metastases, and other less frequent pathologies, were initially diagnosed as NSAs or as masses of unknown nature. When surgery was indicated, pituitary adenomas and other intrasellar masses were operated on by the transsphenoidal route, with the exception of 100% of meningiomas, 83% of craniopharyngiomas, and 10% of NSAs, which were operated on by the transcranial route. Favorable late surgical outcome of prolactinomas could be predicted by a restored PRL response to TRH. However, dopamine agonist (DA) therapy, usually resulting in satisfactory control of PRL levels and in tumor shrinkage, progressively displaced surgery as primary treatment for prolactinomas throughout the study period. After full-term pregnancy, the size of prolactinoma decreased in 7 of 9 patients, and PRL was normal in 2. Surgery was the first treatment for NSAs, with a tumor rela

Acromegaly↗

Predicting chemoresistance in human malignant glioma cells: the role of molecular genetic analyses.

Less than 30% of malignant gliomas respond to adjuvant chemotherapy. Here, we asked whether alterations in the p53 and RB pathways and the expression of six BCL-2 family proteins predicted acute cytotoxicity and clonogenic cell death induced by BCNU, vincristine, cytarabine, teniposide, doxorubicin, camptothecin or beta-lapachone in 12 human malignant glioma cell lines. Neither wild-type p53 status, nor p53 protein accumulation, nor p21 or MDM-2 levels, nor differential expression of BCL-2 family proteins predicted drug sensitivity, except for an association of BAX with higher beta-lapachone sensitivity in acute cytotoxicity assays. p16 protein expression was associated with high doubling time and chemoresistance. We conclude that some important molecular changes, which are involved in the development of gliomas and attributed a role in regulating vulnerability to apoptosis, may not determine the response to chemotherapy in these tumors.

Antineoplastic Agents↗

Focalized external radiotherapy for resected solitary brain metastasis: does the dogma stand?

PURPOSE: To investigate whether whole brain irradiation might be replaced by focalized irradiation after resection of a single brain metastasis in patients where extracranial tumor control is deemed to be obtained. PATIENTS AND METHODS: Twelve patients were introduced in a phase I/II prospective study of conformal postoperative external irradiation after resection of a solitary brain metastasis. The radiation treatment consisted of 50.4 Gy (1.8 Gy per fraction, five fractions per week). The planning target volume consisted of the tumor bed and a 2 cm safety margin. All treatments were optimized with head immobilization, dedicated tomodensitometry and computer assisted three-dimensional treatment planning. RESULTS: The median survival was 7.2 months (range 2.4-50.4 months). Eleven of the 12 patients died. Eight of the 12 patients presented intracranial recurrence and seven died as a consequence of intracranial tumor progression. CONCLUSIONS: Focalized external irradiation cannot serve as a reasonable alternative to whole brain radiotherapy (WBRT) even for patients with apparently one single resected brain metastasis. The dogma of 'one metastasis = multiple metastases' seems to be confirmed.

Adult↗

Gene therapy for amyotrophic lateral sclerosis (ALS) using a polymer encapsulated xenogenic cell line engineered to secrete hCNTF.

The gene therapy approach presented in this protocol employs a polymer encapsulated, xenogenic, transfected cell line to release human ciliary neurotrophic factor (hCNTF) for the treatment of Amyotrophic Lateral Sclerosis (ALS). A tethered device, containing around 10(6) genetically modified cells surrounded by a semipermeable membrane, is implanted intrathecally; it provides for slow continuous release of hCNTF at a rate of 0.25 to 1.0 micrograms/24 hours. The semipermeable membrane prevents immunologic rejection of the cells and interposes a physical, virally impermeable barrier between cells and host. Moreover, the device and the cells it contains may be retrieved in the event of side effects. A vector containing the human CNTF gene was transfected into a line of baby hamster kidney cells (BHK) with calcium phosphate using a dihydrofolate reductase-based selection vector with a SV40 promoter and contains a HSV-tk killer gene. hCNTF is a potent neurotrophic factor which may have utility for the treatment of ALS. Systemic delivery of hCNTF in humans has been frustrated by peripheral side effects, the molecule's short half life, and its inability to cross the blood-brain barrier. The gene therapy approach described in this protocol is expected to mitigate such difficulties by local intrathecal delivery of a known quantity of continuously-synthesized hCNTF from a retrievable implant.

Amyotrophic Lateral Sclerosis↗

Klüver-Bucy syndrome after left anterior temporal resection.

A 70-year-old right-handed woman developed a complete Klüver-Bucy syndrome including psychic blindness, aberrant sexual behavior, hypermetamorphosis, aphasia and visual agnosia following left anterior temporal lobectomy for an anaplasic oligodendroglioma. MRI showed no argument for a contralateral ischemic infarct, tumoral growth or white matter damage. Thus the possibility that a unilateral anterior temporal lesion can cause the whole picture of Klüver-Bucy syndrome must therefore be considered.

Affect↗

Visual outcome after transsphenoidal surgery for pituitary adenomas.

We have reviewed the records of 53 patients with visual impairment secondary to pituitary macroadenomas and studied the visual outcome after surgery. After transsphenoidal procedures visual field defects improved in 89% of the patients and visual acuity improved in 82%. There were 13 cases of acute symptomatic intratumoural haemorrhage (pituitary apoplexy) in this series. After surgery, visual defects improved in all these cases even when the delay between the onset of symptoms and surgery was long.

Adenoma↗

Distribution of GABA-containing neurons in human frontal cortex: a quantitative immunocytochemical study.

Fresh biopsy specimens of human cerebral cortex were collected from patients suffering from deep-seated tumors requiring resection. GABAergic neurons were revealed in 50-microns-thick sections, for pre-embedding, and 1-micron-thick sections, for post-embedding GABA immunocytochemistry. In both thick and thin sections, the reaction product was found in neuronal cell bodies and in small profiles in the neuropil. In both preparations, GABA-containing somata were distributed evenly throughout the depth of the cortex. As best appreciated in the thicker sections, GABA-immunoreactive neurons belonged to a variety of morphological cell types with multipolar, bitufted or bipolar, and horizontal dendritic arbors. In the semi-thin sections sampled in the frontal cortex, the proportion of these neurons could be accurately evaluated and was found to be 21.2% +/- 4.8% of all cortical neurons. The average size of GABA-immunoreactive neurons was, in each layer, smaller than that of immunonegative neurons. The average soma size of both neuronal populations, immunoreactive and immunonegative for GABA, increased with depth. The comparison between the rat, cat, macaque monkey, and human GABAergic interneurons revealed similarities among primate brains, contrasting with the parameters (morphology, size, density) measured in rodents. These data are pertinent to the involvement of the GABAergic neurons in the shaping of receptive-field properties of cortical neurons in healthy brains and in pathologies involving the impairment of inhibitory neurotransmission.

Adult↗

Dissecting aneurysm of the posterior inferior cerebellar artery.

Dissecting aneurysms of the posterior inferior cerebellar artery are an uncommon cause of stroke in the vertebrobasilar system, but they may also present with subarachnoid bleeding into the posterior fossa in 70% of the cases. Neither magnetic resonance imaging nor vertebral angiography show specific signs. Treatment should be neurosurgical to prevent rebleeding, although few cases have been reported. The authors report a tenth case and the literature is reviewed.

Adult↗

[Relaxation and protection of the brain on the operating table].

Cerebral protection combines techniques aimed 1) to avoid death of neurones which sustained primary ischemic of traumatic insults and 2) to prevent secondary insults to the brain. The chemical brain retractor concept includes the use of a total intravenous anesthesia technique, mild hypocapnia and mannitol with strict monitoring and maintenance of the global cerebral homeostasis. This contributes to decrease brain volume and intracranial pressure and allows the best possible access to the operating site, while avoiding excessive pressure under the surgical brain retractors. Neuronal protection is based on a better understanding of the biological basis of secondary brain damage; therapeutic or prophylactic techniques include the use of specific pharmacological agents, hypothermia, hemodilution and maintenance of an elevated cerebral perfusion pressure. In short, although the favourable effects of such techniques are nor easy to demonstrate in man, their use in today's clinical practice, in association with the concept of the chemical brain retractor, is an effective way to prevent ischemic cerebral insults during neurosurgical procedures.

Anesthesia, Intravenous↗

L-dopa resistant parkinsonism in an adult woman with a cyst in the posterior fossa.

We report a case of a woman with L-Dopa resistant asymmetrical parkinsonism with a posterior fossa cyst compressing the lower brainstem on MR. She did not show improvement in any of her symptoms after cysto-cardiac derivation. It was not possible to delineate if this was a case of a new malformative syndrome or the coincidence of two different disorders.

Adult↗

Morphology and distribution of neuropeptide-containing neurons in human cerebral cortex.

Biopsies of human cerebral cortex were fixed by immersion and immunostained for the detection of neuropeptides in neuronal cell bodies and axons. Four neuropeptides (neuropeptide Y, somatostatin, , substance P and cholecystokinin) were visualized in a series of adjacent sections. All populations of immunoreactive neurons had a morphology characteristic of interneurons, with variations in dendritic arborizations and laminar distribution. The cholecystokinin-immunoreactive neurons were most numerous in the supragranular layers, whereas neurons containing the other three peptides occurred mainly in infragranular layers, or even in neurons populating the subcortical white matter. Quantitatively, each population of neuropeptide-containing neurons accounted for 1.4-2.5% of the total neuronal population. The distribution of these neurons varied slightly between cytoarchitectonic divisions, with substance P- and somatostatin-immunoreactive neurons dominating in the temporal lobe and cholecystokinin-immunoreactive neurons in the frontal lobe. Neuropeptide Y-immunoreactive neurons dominated in the gray matter of the frontal half of the hemisphere and in the subcortical white matter of the caudal half of the hemisphere. Furthermore, co-existence of neuropeptide Y or substance P immunoreactivity within somatostatin-immunoreactive neurons could be demonstrated using double labeling immunofluorescence techniques. The axonal plexuses immunoreactive for neuropeptide Y, somatostatin, or substance P were distributed in all layers, with a strong predominance of horizontally oriented fibers in layer I, a moderate plexus of randomly oriented fibers in the supra- and infragranular layers, and a slightly weaker innervation of layer IV. Immunoreactive axons formed, in addition, complex terminal arbors, mostly in older subjects, suggesting that they resulted from an as yet undefined aging process. The present study underlines several aspects of the organization of the neuropeptide-containing neurons of the human cerebral cortex, which are of particular interest in the light of the involvement of these neurons in several neurodegenerative diseases.

Axons↗