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)

We studied the effect of parenteral pulse cyclophosphamide therapy in nine patients with active systemic lupus erythematosus and severe central nervous system involvement. Seven patients had focal neurological deficits and/or seizures associated with abnormalities on cerebrospinal fluid analysis and/or magnetic resonance imaging. Two patients had organic brain syndrome with psychosis and normal cerebrospinal fluid and/or magnetic resonance imaging analysis. Six patients were unresponsive to treatment with high dose corticosteroid. Cyclophosphamide, 0.75-1.0 g/m2 body surface area, was administered intravenously every month for at least 2 months. Eight patients had a complete recovery or recovered with minor residuals. Cyclophosphamide was well tolerated with few side effects. We conclude that parenteral pulse cyclophosphamide is an effective adjunctive therapy for the management of patients with active systemic lupus erythematosus and central nervous system symptoms.
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PMID:Pulse cyclophosphamide for severe neuropsychiatric lupus. 180 42

A 35 year-old male was admitted to our hospital because of convulsive seizures. His parents are first cousins. No other members of his family have similar symptoms. He showed mental retardation since childhood. At age 14, he had generalized convulsive seizures that were intractable. Bilateral cataracts were found and extracted at age 18. He noticed bilateral swellings at Achilles tendons at around 25 years of age. Physical examination revealed bilateral swellings of Achilles tendons. Neurologically, he showed poor intellectual ability, hyperreflexia with positive Babinski's sign and cerebellar ataxia. Marked elevations of cholestanol level (53.84 micrograms/ml; normal: 2.71 +/- 0.81, n = 17) and cholestanol/cholesterol ratio (2.20%; normal: 0.16 +/- 0.05, n = 17) were detected in serum. EEG showed abnormal background activities with bursts of high voltage slow theta activities. MRI study showed high intensity lesions in globus pallidus and multiple lesions in white matter with long spin echo sequence. Oral administration of chenodeoxycholic acid improved EEG findings, serum cholestanol level and convulsive seizures. However, the MRI abnormalities remained unchanged, which suggested irreversible brain damage. We reviewed the previous reports of 144 cases of CTX. Fourteen cases had convulsive seizures. We stress that CTX is one the causes of symptomatic epilepsy.
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PMID:[A case of cerebrotendinous xanthomatosis with convulsive seizures]. 219 Jul 43

The lethal and non-lethal effects of L-buthionine-SR-Sulfoximine (BSO) with the sulfhydryl-dependent anticancer agents (SHDAA) were investigated in mice. The agents studied included carmustine (BCNU), cyclophosphamide (CTX), doxorubicin (DOX) and melphalan (LPAM). It was shown in normal mice that BSO is nontoxic when given IP or PO at a dose 5 g/kg. In pharmacodynamic studies with two different doses of BSO in CD-1 mice, the liver, kidney and heart demonstrated diurnal variations in thiol content and dose-dependent depression of tissue non-protein sulfhydryl (NPSH) levels. In acute lethal survival studies, mice treated with CTX and BSO exhibited increased lethality with seizures as a possible cause of death. This effect was not seen with BCNU, DOX and LPAM. Evaluations of organ-specific biochemical markers, showed slight elevations in LDH enzyme levels while bone marrow suppression was not enhanced using both in vivo spleen colony assay and in vitro colony forming unit myelotoxicity assays. These results show that the addition of BSO with SHDAA enhances the acute lethality of some agents such as CTX, and may also increase the non-myelosuppressive toxicities of other agents. It is recommended that BSO be used with caution in combination with SHDAA and that monitoring of hepatic enzymes be routinely performed.
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PMID:Lack of enhanced myelotoxicity with buthionine sulfoximine and sulfhydryl-dependent anticancer agents in mice. 382 7

Isolated angiitis of the central nervous system (IAC) is an idiopatic, recurrent vasculitis confined to the CNS involving small blood vessels. We describe the clinical, angiographic, and neuropathological data in two patients with IAC and delineate the main clinical and neuropathological features in both cases as well as the importance of a complete autopsy for discovering subclinical vasculitic lesions outside the CNS. Patient 1 concerned a 40 year-old-man that evolved for the last three years, initially with focal seizures, headache, and neurological focal deficits, later on the left sided hemihyposthesia and preferentially left parieto-occipital dysfunctions. He presented an oligoclonal band in CSF with slight hyperproteinorraquia and 25 lymphocytes. A cerebral angiography was compatible with angiitis and a leptomeningeal/cerebral biopsy showed lymphocytic vasculitis in the leptomeningeal and intraparenchymatous cerebral small vessels. These results lead to start a treatment with Cyclophosphamide associated to high dose of steroids. The patient clearly improved and now is almost asymptomatic. Patient 2 concerned a 67 year-old-man that evolved for 4 years with encephalic ischemic lesions distributed and confined throughout the brain stem and cerebellum, temporary remissions occurred and the patient required high-dose steroids and Cyclophosphamide to improve. Conventional and MRI angiographies only suggested the diagnosis that was confirmed at autopsy. The patient died after a massive pulmonary thromboembolism and a complete necropsic study showed abundant lymphocytic infiltrates, without granulomatous lesions, in the intraparenchymatous and leptomeningeal cerebral small vessels specially at the brain stem and cerebellar level where many demyelinated greyish areas and few infarctions were to be seen. The inflammatory cells were, in both cases, predominantly CD4+ T lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Isolated angiitis of the central nervous system. Clinical and neuropathological study of 2 cases]. 748 77

It is known that stimulation of adenosine A1 receptors has a modulatory effect on the excitability of postsynaptic NMDA receptors. Conversely, acute stimulation of NMDA receptors results in release of adenosine via calcium-independent mechanisms. These findings indicate a close functional relationship between these receptors. It is, therefore, possible that chronic, low level stimulation of the NMDA receptor may have a negative impact on these modulatory processes. To investigate this possibility, we have subjected C57BL mice either to an acute injection of a N6-cyclopentyladenosine (CPA, 0.01 mg/kg) or deoxycoformycin (1 mg/kg) followed by a convulsant dose of N-methyl-D-aspartate (NMDA) (60 mg/kg) or to chronic, low level (20 mg/kg i.p. daily) exposure to NMDA for 8 weeks. One day after the last injection of NMDA, animals were injected either with a convulsant dose of NMDA alone, or with either CPA at 0.001 or 0.01 mg/kg, or with 1 mg/kg deoxycoformycin followed 15 min later by 60 mg/kg NMDA. Neither CPA nor deoxycoformycin were protective when NMDA was given acutely at 60 mg/kg. Chronic treatment with NMDA alone or chronic administration of NMDA followed by 0.001 mg/kg CPA had no significant effect on mortality following a convulsant dose of NMDA. However, when the chronic regimen of NMDA was followed by either 0.01 mg/kg CPA or 1 mg/kg deoxycoformycin, mortality was reduced to 10% (CPA), or eliminated completely (deoxycoformycin). Moreover, combination of chronic NMDA treatment with either CPA (both doses) or deoxycoformycin produced a significant improvement in other measures, i.e., seizure onset, intensity of neurological impairment, and extension of time to death.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic NMDA receptor stimulation: therapeutic implications of its effect on adenosine A1 receptors. 749 8

The purpose of this study was to evaluate the effects of the new anticonvulsant drug N-(2-amino-4-[fluorobenzylaminol-phenyl) carbamic acid ethyl ester (retigabine, D-23129, ASTA Medica, Dresden, Germany) on different patterns of epileptiform activity induced by 4-aminopyridine (4AP) in rat entorhinal cortex hippocampal slices. Application of 4AP (100 microM) induced in entorhinal cortex two different types of epileptiform activities; seizure-like events (SLE) and interictal epileptiform discharges (IED). Bicuculline (10 microM) changed 4AP-induced SLE and IED to recurrent epileptiform discharges (RED). IED were isolated after blockade of the SLE by glutamate receptor antagonists for alpha-amino-3-hydroxy-5-methylisoxazole4-proprionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors, i.e. 1,2,3,4 tetrahydro-6-nitro-2,3-dioxo-benzolflquinoxaline-7-sulfonamide (NBQX, 10 microM) and 2-amino-5-phosphonovaleric acid (APV, 30 microM). Anticonvulsant properties of retigabine were evaluated as effect on the frequency and amplitude of SLE, IED and RED. Retigabine suppressed all types of epileptiform events in a dose dependent and reversible manner. SLE were suppressed in 71.4 and 100% of slices by 5 and 10 microM, respectively. The frequency of IED was significantly reduced by 20 microM retigabine (40.9+/-24.5%) and IED were blocked completely by 50 microM retigabine. When IED were isolated by application of glutamate antagonists 20 microM retigabine was sufficient to block this activity completely. RED induced by combined application of bicuculline and 4AP were blocked in 71.4% of the tested slices with 100 microM retigabine. The frequency of the RED in the remaining slices was reduced by 96.1+/-6.1%. We conclude that retigabine acts on a large variety of different epileptiform activities in temporal lobe structures that are known to develop readily pharmacoresistant seizures.
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PMID:Effects of retigabine (D-23129) on different patterns of epileptiform activity induced by 4-aminopyridine in rat entorhinal cortex hippocampal slices. 993 48

The synthesis and pharmacological profile of a series of neuroprotective adenosine agonists are described. Novel A(1) agonists with potent central nervous system effects and diminished influence on the cardiovascular system are reported and compared to selected reference adenosine agonists. The novel compounds featured are derived structurally from two key lead structures: 2-chloro-N-(1-phenoxy-2-propyl)adenosine (NNC 21-0041, 9) and 2-chloro-N-(1-piperidinyl)adenosine (NNC 90-1515, 4). The agonists are characterized in terms of their in vitro profiles, both binding and functional, and in vivo activity in relevant animal models. Neuroprotective properties assessed after postischemic dosing in a Mongolian gerbil severe temporary forebrain ischemia paradigm, using hippocampal CA1 damage endpoints, and the efficacy of these agonists in an A(1) functional assay show similarities to some reference adenosine agonists. However, the new compounds we describe exhibit diminished cardiovascular effects in both anesthetized and awake rats when compared to reference A(1) agonists such as (R)-phenylisopropyladenosine (R-PIA, 5), N-cyclopentyladenosine (CPA, 2), 4, N-[(1S,trans)-2-hydroxycyclopentyl]adenosine (GR 79236, 26), N-cyclohexyl-2'-O-methyladenosine (SDZ WAG 994, 27), and N-[(2-methylphenyl)methyl]adenosine (Metrifudil, 28). In mouse permanent middle cerebral artery occlusion focal ischemia, 2-chloro-N-[(R)-[(2-benzothiazolyl)thio]-2-propyl]adenosine (NNC 21-0136, 12) exhibited significant neuroprotection at the remarkably low total intraperitoneal dose of 0.1 mg/kg, a dose at which no cardiovascular effects are observed in conscious rats. The novel agonists described inhibit 6, 7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate-induced seizures, and in mouse locomotor activity higher doses are required to reach ED(50) values than for reference A(1) agonists. We conclude that two of the novel adenosine derivatives revealed herein, 12 and 5'-deoxy-5'-chloro-N-[4-(phenylthio)-1-piperidinyl]adenosine (NNC 21-0147, 13), representatives of a new series of P(1) ligands, reinforce the fact that novel selective adenosine A(1) agonists have potential in the treatment of cerebral ischemia in humans.
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PMID:N-substituted adenosines as novel neuroprotective A(1) agonists with diminished hypotensive effects. 1047 79

Lymphomatoid granulomatosis (LYG)/angiocentric immunoproliferative lesions (AIL) consist of angiocentric and angiodestructive lymphoreticular proliferation predominantly involving the lungs and other extranodal sites, such as the central nervous system (CNS). This clinical entity is considered as a B cell process related to Epstein-Barr virus (EBV) infection and EBV positive diffuse large B-cell lymphoma. The CNS is involved in 20% of cases of LYG, but initial involvement is rare. In cases without pulmonary symptoms, diagnosis may be difficult. We report a rare case involving initial progression of CNS symptoms followed by a pulmonary abnormality.A 14-year-old girl suffered from high fever, ataxic gait and paraparesis. MRI revealed diffuse T2 high signals with multiple gadolinium enhancements in the cerebellum, brain stem and cerebral white matter. Her symptoms briefly improved after steroid therapy, but ataxia gradually progressed. Dyspnea due to pulmonary interstitial involvement appeared when she was 18 years old. Steroid therapy proved effective for respiratory symptoms. At 20 years old she suffered from disseminated intravascular coagulopathy (DIC) and hemophagocytic syndrome (HPS) with respiratory symptoms and repeated seizures. Her symptoms improved after the administration of cyclophosphamide. Mild hemiparesis and gait disturbance appeared when she was 22 years old. MRI revealed new lesions at the basal ganglia and subcortical white matter, brain atrophy and diffuse T2 high intensity of cerebral white matter. Cyclophosphamide was effective and there has been no recurrence of symptoms in the last 5 years. We reviewed the non-tumorous LYG/AIL involving the CNS, and discussed the clinical features, MRI imaging and diagnosis of the LYG/AIL.
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PMID:A case of lymphomatoid granulomatosis/angiocentric immunoproliferative lesion with long clinical course and diffuse brain involvement. 1287 57

In the "minimal change" nephrotic syndrome (MCNS), steroids induce remissions in most cases (93% in children and 81% in adults). Response occurs in an average time of 11 days in children but may take up to 16 weeks in adults. The dose of prednisone is 60 mg/m(2)/day (maximum 80 mg/day) given usually for 4 weeks and then reduced to 40 mg/m(2) on alternate days for a few weeks. The medication may be discontinued abruptly at the end of the course of treatment. Children who do not respond to prednisone should be biopsied. Those whose biopsy shows minimal changes may have a remission with more prolonged alternate day treatment, or may need cyclophosphamide or cyclosporine. Relapses of nephrotic syndrome are common and usually respond to steroids given daily until remission, then on alternate days for 4 weeks. In adults prednisone on alternate days for 1 year after the presenting attack decreases the risk of relapse. Toxicity is a problem only in steroid-dependent patients who may require other drugs. Cyclophosphamide (2-3 mg/kg/day) and chlorambucil (0.15 mg/kg/day) for 8-12 weeks induce long-term remissions in 25-70% of children and are also beneficial in adults. The effectiveness of cyclophosphamide in steroid-resistant MCNS is limited to bringing about a faster remission. In children with MCNS who are initially steroid-responsive and later become resistant, cyclophosphamide usually induces a remission and restores steroid responsiveness. The toxicity of cyclophosphamide and chlorambucil in MCNS has generally been mild and reversible. It includes bone marrow depression, hemorrhagic cystitis, some hair loss, infertility and, extremely rarely, oncogenesis. The risk of gonadal toxicity is minimized with total doses below 200 mg/kg for cyclophosphamide and 7-10 mg/kg for chlorambucil. Seizures have been reported in 8% of children treated with chlorambucil. Cyclosporine (6 mg/kg/day initially) produces complete remissions in 85% of children and 79% of adults with steroid dependence and in 67% of children and 61% of adults with steroid resistance. Levamisole may be helpful in steroid-dependent cases, but data about its efficacy are conflicting. Cyclosporine and levamisole usually do not induce permanent remissions.
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PMID:Pharmacological treatment of nephrotic syndrome. 1297 5

Prenatal morphine exposure on gestation days 11-18 alters bicuculline-induced seizures in rats during development and in adulthood. Adult, morphine-exposed male progeny exhibit an increased latency to bicuculline seizures, which can be reversed by administration of the opioid receptor antagonist naloxone. In chronically morphine-treated adult mice, cholera toxin B (CTX-B) can reverse the effects of chronic morphine administration. Therefore, the present study investigated whether prenatally morphine-exposed rats show a similar response to CTX-B as chronically morphine-treated adult rodents. Prenatally morphine-, saline- and unexposed male progeny were tested for seizure susceptibility with a 7.5-mg/kg intraperitoneal injection of bicuculline in adulthood. CTX-B or saline was injected subcutaneously at 24, 12, and 0.5 h before bicuculline injection. CTX-B decreased the occurrence of bicuculline-induced seizures in both prenatally saline- and morphine-exposed but not unexposed rats. Furthermore, three, but not one, saline injections administered at 12-h intervals prior to bicuculline administration reversed the increase in seizure latency in prenatally morphine-exposed adult males, suggesting an altered responsiveness of the stress system. The present study demonstrates that CTX-B can decrease the occurrence of bicuculline seizures in prenatally stressed rats and that increased seizure latencies in prenatally morphine-exposed male rats may be related to stress responses.
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PMID:Cholera toxin B decreases bicuculline seizures in prenatally morphine- and saline-exposed male rats. 1500 61


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