Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human microvessels were isolated and cultured from non-neoplastic cerebral tissue specimens resected for the treatment of seizure disorders and from malignant glial tumors. After 1-2 weeks, cobblestone patterned plaques of cells were isolated and cultured from these microvessels. Cell lines positive for Factor VIII antigen and negative for glial fibrillary acidic protein were designated as endothelium. Endothelium from both tissue sources produced gamma-glutamyl transpeptidase in response to glial cell conditioned media. Tumor derived microvessel endothelium had decreased longevity in culture when compared to normal microvessel endothelium. Tumor derived endothelium also formed less extensive intercellular junctional complexes in vitro. The isolation and characterization of human cerebral microvessel endothelium derived from non-neoplastic tissue and glial tumors may lead to a further understanding of the role of endothelium in tumor growth and vascular permeability alterations.
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PMID:Human cerebral endothelium: isolation and characterization of cells derived from microvessels of non-neoplastic and malignant glial tissue. 211 73

Results of initial clinical trials of brain tumor chemotherapy after osmotic blood-brain barrier disruption are promising. In general, the procedure is well tolerated. The major complication has been seizures. In this report, data are presented which indicate that the etiology of these seizures is related to the use of contrast agent (meglumine iothalamate) to monitor barrier modification. A series of 19 patients underwent a total of 85 barrier modification procedures. Documentation of barrier disruption was monitored by contrast-enhanced computed tomographic (CT) scanning, radionuclide brain scanning, or a combination of both techniques. In 56 procedures (19 patients) monitored by enhanced CT, seizures occurred a total of 10 times in eight patients. Twenty-three barrier modification procedures (in nine of these 19 patients) documented by nuclear brain scans alone, however, resulted in only one focal motor seizure in each of two patients. In eight of the 19 patients who had seizures after barrier disruption and enhanced CT scan, four subsequently had repeat procedures monitored by radionuclide scan alone. In only one of these patients was further seizure activity noted; a single focal motor seizure was observed. Clearly, the radionuclide brain scan does not have the sensitivity and spatial resolution of enhanced CT, but at present it appears safer to monitor barrier modification by this method and to follow tumor growth between barrier modifications by enhanced CT. Four illustrative cases showing methods, problems, and promising results are presented.
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PMID:Osmotic blood-brain barrier modification: clinical documentation by enhanced CT scanning and/or radionuclide brain scanning. 641 31

The purpose of this investigation was to determine whether paraplegia induced by neoplastic cord compression affects the pharmacodynamics of phenobarbital general anesthesia or of pentylenetetrazol (PTZ)-induced convulsions. Paraplegic rats harboring a thoracolumbar epidural tumor, or an identical hindlimb tumor mass, received an i.v. infusion of phenobarbital until the onset of anesthesia. At that point, the phenobarbital concentrations in the CSF and serum were measured. Similarly, PTZ was infused until the onset of maximal seizures. It was found that changes related to systemic tumor growth and newly developed paraplegia due to neoplastic spinal cord compression did not attenuate the pharmacodynamics of phenobarbital. However, sustained paraplegia of 4 days' duration reduced CNS sensitivity to the hypnotic action of the barbiturate as evidenced by the higher cerebrospinal fluid phenobarbital concentration required to induce anesthesia (170 +/- 31 vs 125 +/- 20 mg/L; P < 0.05). On the other hand, sustained paraplegia did not affect brain threshold concentration for PTZ-induced seizures.
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PMID:Pharmacodynamics of phenobarbital anesthesia and pentylenetetrazol-induced maximal seizures in a rat model of neoplastic spinal cord compression. 805 11

Primary CNS malignancies are responsible for approximately 12,000 deaths annually in the United States. There has been little change in the outcome for adults with malignant brain tumors over the past few decades, despite improvements in surgical techniques and advances in radiation therapy. These tumors are uniformly fatal one to two years after diagnosis. The morbidity and mortality of this disease arise from the effects of a locally invasive, non-metastasizing lesion. The patients may suffer from seizures, paralysis, incoordination, aphasia, confusion, memory loss, sensory deficits or visual loss, depending on the regions of the brain affected. In addition, they usually require large doses of corticosteroids early and late in their illness, and may experience disabling side effects of this treatment, such as edema, proximal myopathy, diabetes, fungal infections or deep vein thrombosis. Few patients in the older age group are able to work after the diagnosis. Most of the patients are incapable of self-care for several months before death. The localized transfer of new genes into cancer cells potentially permits the expression of proteins with specific biologic functions that may provide a means to alter the biology of tumor growth through a variety of mechanisms including increasing tumor immunogenicity, inducing the local expression of toxic agents, and sensitization of tumors to chemotherapeutic agents. Gene therapy with the transfer of the drug susceptibility gene Herpes virus thymidine kinase (HSV-TK) has shown promise in a number of animal models, including CNS tumors. This study will evaluate the use of adenovirus-mediated transfer of the HSV-TK gene into primary human brain tumors followed by systemic treatment with ganciclovir. The goals of this phase I study are to evaluate the overall safety and efficacy of this treatment and to gain insight into the parameters that may limit the general applicability of this approach. In this phase I study, patients with recurrent gliomas will receive stereotactic-guided injections of the virus into the brain tumor, followed by intravenous ganciclovir for 14 days. Patients eligible to undergo a palliative debulking procedure will receive the same treatment followed by resection on day 7. At the time of resection a second dose of virus will be administered intra-operatively into the residual, unresectable portion of the tumor, and intravenous ganciclovir will be continued for additional 14 days. Tissue removed at the time of resection will be analyzed for evidence of adenovirus infection, thymidine kinase expression and signs of inflammation. The size and metabolic activity of all tumors will be followed by volumetric MRI scans and Position Emission Tomography Scans, respectively. Patients will be enrolled in groups of three, with each group receiving successively larger doses of adenovirus. This study will quantify the toxicity of this therapy, and provide evidence as to the duration of transgene expression and virus induced inflammation.
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PMID:Treatment of advanced CNS malignancies with the recombinant adenovirus H5.010RSVTK: a phase I trial. 884 6

Angiomyolipomas can occur sporadically or in association with tuberous sclerosis complex (TSC). TSC is an autosomal dominant disorder characterized by seizures, mental retardation, and benign tumors of the brain, heart, kidney, and skin. Angiomyolipomas are more common in women than in men, suggesting a possible hormonal influence on tumor growth. In this study, 35 angiomyolipomas from 23 patients were immunostained with antibodies to estrogen receptor (ER) and progesterone receptor (PR). Eleven angiomyolipomas (31%) contained clusters of PR-immunoreactive smooth muscle cells. None contained ER-immunoreactive cells. Of the 21 tumors from patients with TSC, 11 (48%) were PR immunoreactive. All of the PR-immunoreactive angiomyolipomas were from women younger than 50 years of age, and all except one of these women had TSC. This study suggests that hormonal factors play a role in the pathogenesis of TSC-associated angiomyolipomas.
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PMID:Frequent progesterone receptor immunoreactivity in tuberous sclerosis-associated renal angiomyolipomas. 968 88

A patient with seizures and a contrast-enhancing temporal lesion after radiation therapy for a chondrosarcoma of the nasal septum is described. To differentiate between radiation necrosis and recurrent tumor, thallium-201 (201Tl) SPECT was used. 201Tl SPECT revealed high local accumulation suggesting tumor growth; however, pathologic examination demonstrated focal necrosis with reactive changes but without tumor. The 201Tl SPECT findings in this patient demonstrate a possible diagnostic pitfall in differentiating recurrent tumor from radiation necrosis.
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PMID:Bilateral temporal lobe necrosis after radiotherapy: confounding SPECT results. 978 54

This is a rare case of concomitant bihemispheric cerebral ganglioglioma and hemangioma in an 18-month-old child. There were two identical processes; a combination of ganglioglioma and hemangioma was located in the parieto-occipital region of both cerebral hemispheres. The child underwent diagnostic computed tomographic and magnetic resonance imaging examinations for seizures and right-sided facial palsy, which showed the bilateral presence of parieto-occipital, oval, well-demarcated, subcortically located processes. A biparieto-occipital craniotomy was carried out and two well-demarcated abnormalities were observed and both were removed in toto. Two years after the operation, the boy had normal psychomotor development and remained free from seizures with no therapy required. Repeat magnetic resonance imaging showed no tumor recurrence. Gangliogliomas are relatively uncommon tumors in childhood, located in the supratentorial compartment and usually associated with seizures. Histopathologic and immunohistochemical analysis of the two processes found in our patient showed them to be a ganglioglioma and a hemangioma, confirming the dysontogenetic origin of these alterations and the association between malformations and tumor growth. The combination of ganglioglioma and hemangioma, especially bilateral presentation of two such identical processes in a young child, is very rare and was not found in the recent literature.
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PMID:Concomitant bihemispheric cerebral ganglioglioma and hemangioma in an 18-month-old child: case report. 1080 91

An association between central nervous system neoplasm and pregnancy is uncommon although its frequency is underestimated. The most commonly observed tumors are acoustic neuromas, meningiomas and gliomas. The interactions between these tumors and pregnancy is not well known : Pregnancy could affect tumor growth by : - activating tumor growth by stimulating receptors; - increasing the peritumoral edema; - favoring immunotolerance due to pregnancy. Steroid hormone receptors and their therapeutic significance are described here, focusing particularly in meningiomas. Central nervous system tumors do not effect the progress of pregnancy per se but do the therapeutic implications. The clinical aspects are the same as in non-pregnant women. MRI appears to be the most adapted imaging technique. Neurosurgical guidelines are also described, with emphasis on symptomatic therapeutics, especially for seizure. Attitudes concerning the nature of the tumor and time of pregnancy are then discussed. The obstetrical attitude should be therapeutic abortion or delivery, with cesarean if necessary. Prognosis is getting better for the child and mother alike, but still remains poor.
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PMID:[Tumors of the neuraxis and neuraxial sheaths during pregnancy (excluding tumors of the sellar region)]. 1084 48

Aicardi syndrome is an X-linked dominant disorder primarily defined by the triad of corpus callosum agenesis, infantile spasms and a pathognomonic lacunar chorioretinopathy. Papillomas of the choroid plexus have been reported in affected patients. We report an Aicardi syndrome patient who had three separate choroid plexus papillomas and associated hydrocephalus. A dizygotic twin was unaffected. Staged resection of the tumors was safely accomplished, with improvement in seizure control. Imaging between procedures revealed rapid tumor growth.
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PMID:Three choroid plexus papillomas in a patient with Aicardi syndrome. A case report. 1112 40

Somatostatin (SRIF, somatotropin release inhibiting factor), discovered for its inhibitory action on growth hormone (GH) secretion from pituitary, is an abundant neuropeptide. Two forms, SRIF14 and SRIF28 exist. Recently, a second family of peptides with very similar sequences and features was described; the cortistatins (CST), CST17 and CST29 which are brain selective. The five cloned SRIF receptors (sst1-5) belong to the G-protein coupled/ heptathelical receptor family. Structural and operational features distinguish two classes of receptors; SRIF1 - sst2/sst3/sst5 (high affinity for octreotide or seglitide) and SRIF2 = sst1/sst4(very low affinitty for the aforementioned ligands). The affinity of SRIF receptors for somatostatins and cortistatins is equally high, and it is not clear whether selective receptors do exist for one or the other of the peptides. Several radiologlands label all SRIF receptors, e.g., [125]LTT-SRIF28' [l25I]CGP23996, [125]Tyr10cortistatin or [125I]Tyr11SRIF14. In contrast, [125I]Tyr3octreotide, [125I]BIM23027, [125I]MK678 or [125I]D-Trp8SRIF14 label predominantly SRIF1 sites, especially sst2 and possibly sst5 receptors. In brain, [125I]Tyr3octreotide binding equates with sst2 receptor mRNA distribution. Native SRIF2receptors can be labeled with [125I]SRIF14 in the presence of high NaCl in brain (sst1) or lung (sst4) tissue. Short cyclic or linear peptide analogs show selectivity for sst2/sst5 (octreotide, lanreotide, BIM 23027), sst1 (CH-275), sst3 (sst3-ODN-8), or sst5 receptors (BIM 23268); although claims for selectivity have not always been confirmed. Beta peptides ith affinity for SRIF receptors are also reported. The general lack of SRIF receptor antagonists is unique for peptide receptors, although CYN 154806 is a selective and potent sst2 antagonist. Nonpeptide ligands are still rare, although a number of molecules have been reported with selectivity and potency for sst1 (L 757,519), sst2 (L 779,976), sst3 (L 796,778), sst4 (NNC 26-9100, L 803,087) or sst1/sst5 receptors (L 817,018). Such molecules are essential to establish the role of SRIF receptors, e.g., sst1 in hypothalamic glutamate currents: sst2 in inhibiting release of GH, glucagon, TSH, gastric acid secretion, pain, seizures and tumor growth, and sst5 in vascular remodeling and inhibition of insulin and GH release.
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PMID:Drug design at peptide receptors: somatostatin receptor ligands. 1193 45


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