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)

Patients receiving phenytoin (PHT) may develop pseudolymphoma or, rare ly, malignant lymphoma. Previously, distinguishing the two diseases based solely on histopathology has been difficult. The recent introduction of molecular biologic techniques has provided a powerful tool to reassess this problem. A 17-year-old girl developed systemic lymphadenopathy after receiving PHT for 1 year for generalized tonic-clonic seizures (GTCS). Biopsy of a cervical lymph node showed diffuse proliferation of large lymphoid cells mimicking a large cell lymphoma. Immunophenotypic, immunoglobulin gene rearrangement, and cytogenic studies, however, showed polyclonal B-cell proliferation, consistent with PHT-induced pseudolymphoma. After PHT discontinuation, lymphadenopathy resolved in 1 month and no recurrence developed in the subsequent 10 months. Obtaining a history of drug use is crucial to recognizing this group of patients. Molecular biology and chromosome studies have become the definitive basis differentiating pseudolymphoma from malignant lymphoma in patients receiving chronic PHT therapy.
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PMID:Phenytoin-induced pseudolymphoma: reevaluation using modern molecular biology techniques. 860 15

Amplification of viral nucleic acids from the cerebrospinal fluid (CSF) has considerably improved the diagnosis of several acute, subacute and chronic viral infections of the nervous system. In herpes simplex virus (HSV) encephalitis (HSE) the polymerase chain reaction (PCR) has become the method of choice for the rapid, non invasive diagnosis. Other herpes virus associated diseases which can now be reliably diagnosed are encephalitis, ventriculoencephalitis, polymyeloradiculitis, myelitis and an inflammatory polyradiculoneuropathy caused by cytomegalovirus (CMV), HSV, varicella-zoster virus (VZV) or Epstein-Barr virus (EBV), EBV associated primary B-cell-lymphoma of the brain, acute aseptic meningitis in young adults allied with VZV, and meningoencephalitis with recurrent seizures due to human herpes virus type 6 (HHV-6). In AIDS patients, PCR has helped to differentiate lesions either due to the human immunodeficiency virus (HIV) itself or to opportunistic infections such as progressive multifocal leukoencephalopathy (PML) caused by JC virus (JCV) or CMV related complications. HIV can be detected early in the course of infection in the CSF and the amount of proviral DNA in CSF cells seems to be correlated with the severity and/or progression of neurological signs and symptoms. Acute epidemic aseptic meningitis caused by enterovirus infections can now be reliably diagnosed and typed by reverse transcriptase PCR (RT-PCR). Meningitis cases caused by vaccination with the Jeryl Lynn and Urabe vaccine strain of mumps virus have been identified using RT-PCR and sequencing of the amplified products (amplicon).
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PMID:Clinical implications of nucleic acid amplification methods for the diagnosis of viral infections of the nervous system. 879 10

Phenytoin is a hydantoin-type anticonvulsive agent used extensively for nearly sixty years in the prophylactic treatment of grand mal and psychomotor seizures. 2. Based upon somewhat contentious evidence of phenytoin-induced lymphoma in mice and upon epidemiologic evidence of an association between anticonvulsive therapy and lymphoma in epilepsy patients, the International Agency for Research on Cancer (IARC) has collectively regarded these data as limited evidence of carcinogenicity. 3. Two year carcinogenicity studies of standard bioassay design conducted in mice and rats yielded statistically significant increased incidence of hepatocellular adenomas in mice at phenytoin plasma concentrations approximating the therapeutic anticonvulsive range. Tumor incidence in rats was not affected. Previous carcinogenicity studies have found similar increases in hepatic tumor incidence in mice. 4. Phenytoin is a known enzyme inducer and shows tumor promoting activity in chemically initiated mouse liver. Evidence for genotoxicity is weak or equivocal, consequently phenytoin-induced liver tumors appear to occur through nongenotoxic mechanisms. 5. Finally, despite six decades of extensive therapeutic use and thorough epidemiologic evaluation, there is no evidence for an association between liver cancer and phenytoin therapy in epilepsy patients. Thus, hepatocellular neoplasia in phenytoin-treated rodents appears to be of little significance to man.
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PMID:Perspective on the carcinogenic potential of phenytoin based on rodent tumor bioassays and human epidemiological data. 884 24

A 20-month-old boy had an 8-week history of vomiting, lethargy, generalized muscle weakness, and seizures. There was no history or clinical signs of an underlying systemic disease or an immunodeficiency. Cerebrospinal fluid (CSF) had 99 nucleated cells/cu mm, malignant cells, high protein and normal glucose. CT and MRI scans showed diffuse meningeal enhancement around the brain and spinal cord, but no parenchymal involvement. Biopsy of the leptomeninges showed malignant cells with marked nuclear pleomorphism and prominent clear to eosinophilic cytoplasm. The immunohistochemical studies were positive for histiocyte-macrophage markers and were negative with T and B cells, Ki-1, neural and glial cell antibodies. Multiple tests revealed no other site of disease. The patient died 3 months after onset of treatment despite intensive i.v. and intrathecal chemotherapy. We have not found any other reported case of primary histiocytic leptomeningeal lymphoma in a young child.
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PMID:Primary leptomeningeal histiocytic lymphoma in a young child. 888 15

Neurological symptoms of transient unsteadiness, dysarthria, dysphasia, dysbasia, transient monoor hemiparesis, hemiparesis, scintillating scotomas, amaurosis fugax, vertigo, dizziness, migraine accompaniments, syncope and seizures were the presenting manifestations of thrombocythemia in various myeloproliferative disorders. Erythromelalgia preceded or followed the neurologic ischemic attacks. The neurologic and ocular attacks usually had a sudden onset, lasted for a few seconds to several minutes and occurred independently or sequentially rather than simultaneously. This clinical syndrome is caused by platelet-mediated ischemic and thrombotic processes in the end-arterial microvasculature and reflects the existence of a platelet dependent and aspirin responsive arterial thrombophilia in thrombocythemia as novel disease entity, which confirms and elucidates Mitchell's hypothesis.
Leuk Lymphoma 1996 Sep
PMID:Atypical transient ischemic attacks in thrombocythemia of various myeloproliferative disorders. 895 74

Since its introduction in 1987, zidovudine monotherapy has been the treatment of choice for patients with HIV infection. Unfortunately it has been established that the beneficial effects of zidovudine are not sustained due to the development of resistant viral strains. This has led to the strategy of combination therapy, and in 1995 treatment with zidovudine plus didanosine, or zidovudine plus zalcitabine, was demonstrated to be more effective than zidovudine monotherapy in preventing disease progression and reducing mortality in patients with HIV disease. Recent work demonstrates an even greater antiviral effect from triple therapy with 2 nucleosides, zidovudine plus zalcitabine with the addition of saquinavir, a new protease inhibitor drug. The HIV protease enzyme is responsible for the post-translational processing of gag and gag-pol polyprotein precursors, and its inhibition by drugs such as saquinavir, ritonavir, indinavir and VX-478 results in the production of non-infectious virions. As resistance may also develop to the protease inhibitors they may be used in combination, and future strategies may well include quadruple therapy with 2 nucleoside analogues plus 2 protease inhibitors. Administration of protease inhibitors alone or in combination with other drugs does raise a number of important pharmacokinetic issues for patients with HIV disease. Some protease inhibitors (e.g. saquinavir) have kinetic profiles characterised by reduced absorption and a high first pass effect, resulting in poor bioavailability which may be improved by administrating with food. Physiological factors including achlorhydria, malabsorption and hepatic dysfunction may influence the bioavailability of protease inhibitors in HIV disease. Protease inhibitors are very highly bound to plasma proteins (> 98%), predominantly to alpha 1-acid glycoprotein. This may influence their antiviral activity in vitro and may also predispose to plasma protein displacement interactions. Such interactions are usually only of clinical relevance if the metabolism of the displaced drug is also inhibited. This is precisely the situation likely to pertain to the protease inhibitors, as ritonavir may displace other protease inhibitor drugs, such as saquinavir, from plasma proteins and inhibit their metabolism. Protease inhibitors are extensively metabolised by the cytochrome P450 (CYP) enzymes present in the liver and small intestine. In vitro studies suggest that the most influential CYP isoenzyme involved in the metabolism of the protease inhibitors is CYP3A, with the isoforms CYP2C9 and CYP2D6 also contributing. Ritonavir has an elimination half-life (t1/2 beta) of 3 hours, indinavir 2 hours and saquinavir between 7 and 12 hours. Renal elimination is not significant, with less than 5% of ritonavir and saquinavir excreted in the unchanged form. As patients with HIV disease are likely to be taking multiple prolonged drug regimens this may lead to drug interactions as a result of enzyme induction or inhibition. Recognised enzyme inducers of CYP3A, which are likely to be prescribed for patients with HIV disease, include rifampicin (rifampin) [treatment of pulmonary tuberculosis], rifabutin (treatment and prophylaxis of Mycobacterium avium complex), phenobarbital (phenobarbitone), phenytoin and carbamazepine (treatment of seizures secondary to cerebral toxoplasmosis or cerebral lymphoma). These drugs may reduce the plasma concentrations of the protease inhibitors and reduce their antiviral efficacy. If coadministered drugs are substrates for a common CYP enzyme, the elimination of one or both drugs may be impaired. Drugs which are metabolised by CYP3A and are likely to be used in the treatment of patients with HIV disease include the azole antifungals, macrolide antibiotics and dapsone; therefore, protease inhibitors may interact with these drugs. (ABSTRACT TRUNCATED)
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PMID:Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations. 908 59

Intravascular malignant lymphomatosis (IML) is characterised by proliferation of tumoral cells within small vessels. Angiotropic large cell lymphoma commonly affects the central nervous system and the skin, although any organ may be involved. Few cases are diagnosed ante mortem. We report a new case of IML in a 62-year-old woman who presented with the main clinical features of central nervous system involvement: cerebrovascular events, epileptic seizures, subacute dementia and spinal cord syndrome. Cranial magnetic resonance imaging demonstrated increased periventricular signal on T2-weighted images. Diagnosis was established by brain biopsy. Despite corticosteroid and radiation therapy no improvement occurred and the patient died 14 months after the onset of the first symptoms.
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PMID:[Malignant endovascular large-cell lymphoma: disclosing central nervous system involvement confirmed by cerebral biopsy]. 924 49

Dural sinus thrombosis (DST) has been reported in association with cancer in both adults and children. We describe the seven patients seen with this complication in our centre between 1981 and 1995. Diagnosis was confirmed by either cerebral CT scanning, MRI or angiography. Median age was 13 years (range 8-15). Six patients were boys. Six children were being treated for non-Hodgkin lymphoma and one for neuroblastoma. Presenting symptoms were seizures and transient neurologic deficit, often preceded by headaches. The probable cause of DST was found in two cases. Tumour localisation in the central nervous system (CNS) probably caused DST in one patient who was treated for ki 1 lymphoma. Dehydration in combination with a poor general condition seemed to be the cause of DST in the patient with neuroblastoma. In five children with stage III or IV non-Hodgkin lymphoma (three lymphoblastic lymphoma; two Burkitt's lymphoma), etiology remained unknown. In these children, DST occurred early in the course of therapy. The median interval between start of chemotherapy and onset of symptoms was 19 days (range 8-40). No child had received L-asparaginase. Prognosis was favourable, with symptoms completely disappearing without therapy within 1 to 5 days. The incidence of DST in patients with advanced stage non-Hodgkin lymphoma during induction and consolidation was calculated to be below 3%. We conclude that DST is rarely diagnosed in children with cancer. Occurrence during the initial phase of therapy for non-Hodgkin lymphoma is associated with a benign prognosis.
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PMID:Dural sinus thrombosis in children with cancer. 1211 89

Liver transplantation is complicated by specific medical problems. Diabetes mellitus occurs in 4-20% of patients undergoing liver transplantation. Patients with primary sclerosing cholangitis and ulcerative colitis experience up to a 13% incidence of colon cancer after transplantation. Lymphomas occur in 1-3% of patients after transplantation and account for 57% of malignancies occurring in adult patients. Atraumatic bone fractures occur in 22-38% of patients and neurological complications, including seizures, headache, and neuropathy occur in 19-47% of patients following liver transplantation. Patients undergoing liver transplantation may experience recurrence of their primary liver disease: hepatitis B, hepatitis C, primary biliary cirrhosis, autoimmune hepatitis, or primary sclerosing cholangitis. In patients not receiving immunoprophylaxis after transplantation for chronic hepatitis B, recurrent hepatitis B is seen in up to 90% of patients. This can be markedly reduced with hyperimmune globulin immunoprophylaxis. Recurrent hepatitis C is seen in the majority of patients; current treatment modalities are inadequate. Recurrence of primary biliary cirrhosis or primary sclerosing cholangitis in the allograft is infrequent. Autoimmune hepatitis may recur in up to 26% of patients following liver transplantation. Primary disease recurrence in the allograft and preventive strategies are discussed.
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PMID:Medical problems occurring after orthotopic liver transplantation. 928 32

Empirical evidence in the clinical literature suggests that ionizing radiation influences human epileptic behavior. A group of patients with tumor-associated epilepsy, biopsy-proven malignancy, and primary antineoplastic treatment with ionizing radiation was selected to evaluate this observation. The antiepileptic effect of ionizing radiation was examined in 9 patients presenting with malignant cerebral tumor and medically refractory partial seizures during at least 2 months. Tissue diagnosis was obtained by stereotactic biopsy without further surgery. Histological categories included anaplastic astrocytoma (5 cases), glioblastoma (2), lymphoma (1), and metastatic non-small cell carcinoma of the lung (1). All patients had medically refractory simple partial seizures with or without secondary generalization with frequencies of 3/week to 8/day for 2-7 months before completion of therapy. Fractionated radiation therapy by parallel opposed fields was delivered with a cumulative dose range of 3,000-6,600 cGy. One patient also had 125I brachytherapy with implant removal after 6 months. Five patients had a seizure-free outcome for periods lasting 2-12 months, whereas the remainder experienced a reduction in frequency of greater than 75% during a follow-up period of 3 months to 6 years. One patient with a glioblastoma remained seizure-free for 3 months and experienced 2 generalized seizures during tumor progression and clinical deterioration but otherwise remained under good anticonvulsant control until his death after 1 year. This review of cases of partial seizures attributable to an unresected malignant cerebral tumor indicates that ionizing radiation may have a favorable effect upon medically refractory partial seizures with significant reduction or elimination of seizures. Moreover, the effect lasts beyond the immediate and early postradiation period. The therapy may thus also lessen the propensity for cerebral tissue towards later epileptogenicity that gives rise to a partial seizure disorder.
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PMID:Effect of ionizing radiation on partial seizures attributable to malignant cerebral tumors. 931 Oct 74


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