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)

Anticonvulsants are commonly used empirically to prevent seizures in patients receiving high-dose busulfan in preparation for bone marrow transplantation. This study evaluates the effects of two anticonvulsants with enzyme-inductive properties, phenytoin and phenobarbital, and an enzyme inducer without anticonvulsant properties, Aroclor 1254, on the myelotoxicity and acute neurotoxicity of busulfan in a murine model. To assess the neuroprotective effects of these agents, we studied the effects of a single dose of 100 mg/kg i.p. busulfan, previously shown in this model to be uniformly lethal due to neurotoxicity. A significantly greater proportion of mice survived when pretreated with phenytoin or phenobarbital as compared with Aroclor 1254 pretreatment or an untreated control group. Busulfan myelotoxicity was studied in another group of mice treated with 135-150 mg/kg given in divided doses over 6 days. The proportion of animals surviving the otherwise myeloablative effects of this regimen were significantly improved by Aroclor 1254, high-dose phenytoin, and phenobarbital pretreatment. We conclude that anticonvulsants offer protection from the acute neurotoxicity of busulfan. However, these enzyme-inducing agents may reduce the myelosuppressive effects as well. These results suggest that an inducible enzyme system such as microsomal or glutathione S-transferases plays an important role in busulfan metabolism, warranting concern over concomitant administration of agents that either induce or inhibit these enzymes.
Cancer Chemother Pharmacol 1990
PMID:The effect of hepatic enzyme inducers on busulfan neurotoxicity and myelotoxicity. 226 59

Acute changes in mental status (AMS) develop in children with cancer from a multitude of cancer- and treatment-related complications. To determine the incidence, etiology, and outcome of children with cancer who had AMS, the medical records of all children under 18 years of age with systemic cancer (excluding primary central nervous system tumors) who had AMS in our institution during the years 1981 through 1987 were reviewed. AMS developed in 89 of 815 children at risk (11%). The AMS was caused by seizures in 53 (60%), an encephalopathy in 24 (27%), and a stroke syndrome in 12 (13%). AMS occurred in 42 of 305 (14%) with leukemia, 16 of 139 (12%) with lymphoma, 14 of 136 (10%) with sarcoma, 10 of 104 (9%) with neuroblastoma, and 7 of 104 (5%) with other malignancies. Children with acute lymphocytic leukemia were more prone to having seizures (61%), while children with nonacute lymphocytic leukemia were almost equally likely to have encephalopathies, strokes, or seizures. Children with lymphoma were admitted for treatment most often with an encephalopathy (44%). Etiologies for AMS were evaluated vigorously, and one or more etiologies were identified in 80 of 89 (89%) patients. Dependent on the type of tumor, the anticancer treatment used and, timing during the course of illness AMS occurred, specific diagnoses were more likely. Neurologic morbidity and mortality were dependent on the cause of AMS. Children with seizures that were initially difficult to control were more likely to require long-term anticonvulsant therapy.
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PMID:Acute mental status changes in children with systemic cancer. 230 89

Recent research on the various biological indices of bipolar mood disorder reveals a complex framework for the understanding of this psychobiological disorder. Four major constructs emerge from the professional literature to form the basis of the current understanding of and approaches to bipolar disorder. The first construct is that of biological rhythms and mood disorders. From this perspective, time is considered as a biological dimension evidenced by biological rhythms. Disruption of certain internal circadian rhythms yields behavioral change and symptoms of psychobiological disequilibrium. Concepts inherent in this particular construct include sleep, effect of light on mood pattern, and possible biochemical indices of mood modulation such as melatonin or phenylethylamine. The second construct attempts to explore the linkage between biochemical brain function and aberrant mood behavior. This information bifurcates into two major categories: (1) effects of psychopharmacological substances on neurotransmitter synthesis and release; and (2) implications of dietary influences on neurotransmitter activity and the psychobiological ramifications of such activity on the clinical understanding of the behavioral disorder. An eclectic set of concepts form the third construct in the framework presented here. These concepts address other possible etiological or mitigating biological influences on bipolar mood states. Such influences include, but are not limited to, limbic seizure activity, neuroendocrine dysfunction, and organic substrates of bipolar states such as various malignancies. The final construct explores the role of genetics in either the predisposition to or the emergence of bipolar mood disordered states. This report will focus on a review of the aforementioned constructs, pointing to significant research and narrative professional publications. In addition, the presentation will address the application of the nursing process to psychobiological aspects of bipolar mood disorder, specifically circadian rhythmicity disturbance and dietary influences on neurotransmission.
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PMID:Psychobiological indices of bipolar mood disorder: future trends in nursing care. 231 96

Of 77 patients with supratentorial Grades I and II astrocytoma diagnosed from January 1975 to December 1984, 66 were treated with postoperative radiation therapy. The patients received a tumor dose of 5000 to 5500 cGy in 180 cGy fractions, five fractions per week, over 5.5 to 6 weeks. Overall actuarial survival at 2, 5, and 10 years was 71%, 55%, and 43%, respectively. Progression-free survival at 2, 5, and 10 years was 69%, 50%, and 39%, respectively. Survival for patients receiving postoperative radiation therapy in the range of 4500 to 5900 cGy was 78% and 66% at 2 and 5 years, respectively. Quality of life was determined at two points in time: 1 to 2 years postoperatively, and at last follow-up (2-12 years postoperatively). The occurrence of mental retardation was specifically addressed in long-term survivors, and was observed in 50% of children. Overall, however, 80% of short-term survivors and 67% of long-term survivors were intellectually and physically intact, without major neurologic deficit. Specific prognostic factors were assessed by multivariate analysis. Improved survival was observed with young patients, females, normal preoperative mental status, surgical resection (versus biopsy alone), involvement of only one lobe with tumor, and a history of preoperative seizures. A weighted prognostic factor score derived from these observations permits a clinically useful assessment of risk for individual patients.
Cancer 1990 Jul 01
PMID:Low-grade cerebral astrocytomas. Survival and quality of life after radiation therapy. 235 9

Busulfan is known to be neurotoxic in animals and humans, but its acute neurotoxicity remains poorly characterized in children. We report here a retrospective study of 123 children (median age, 6.5 years) receiving high-dose busulfan in combined chemotherapy before bone marrow transplantation for malignant solid tumors, brain tumors excluded. Busulfan was given p.o., every 6 hours for 16 doses over 4 days. Two total doses were consecutively used: 16 mg/kg, then 600 mg/m2. The dose calculation on the basis of body surface area results in higher doses in young children than in older patients (16 to 28 mg/kg). Ninety-six patients were not given anticonvulsive prophylaxis; 7 (7.5%) developed seizures during the 4 days of the busulfan course or within 24 h after the last dosing. When the total busulfan dose was taken into account, there was a significant difference in terms of neurotoxicity incidence among patients under 16 mg/kg (1 of 57, 1.7%) and patients under 600 mg/m2 (6 of 39, 15.4%) (P less than 0.02). Twenty-seven patients were given a 600-mg/m2 busulfan total dose with continuous i.v. infusion of clonazepam; none had any neurological symptoms. Busulfan levels were measured by a gas chromatographic-mass spectrometry assay in the plasma and cerebrospinal fluid of 9 children without central nervous system disease under 600 mg/m2 busulfan with clonazepam:busulfan cerebrospinal fluid:plasma ratio was 1.39. This was significantly different (P less than 0.02) from the cerebrospinal fluid:plasma ratio previously defined in children receiving a 16-mg/kg total dose of busulfan. This study shows that busulfan neurotoxicity is dose-dependent in children and efficiently prevented by clonazepam. A busulfan dose calculated on the basis of body surface area, resulting in higher doses in young children, was followed by increased neurotoxicity, close to neurotoxicity incidence observed in adults. Since plasma pharmacokinetic studies showed a faster busulfan clearance in children than in adults, this new dose may approximate more closely the adult systemic exposure obtained after the usual 16-mg/kg total dose, with potential inferences in terms of anticancer or myeloablative effects. The busulfan dose in children and infants undergoing bone marrow transplantation should be reconsidered on the basis of pharmacokinetic studies.
Cancer Res 1990 Oct 01
PMID:Dose-dependent neurotoxicity of high-dose busulfan in children: a clinical and pharmacological study. 240 Sep 86

Ifosfamide/mesna was given to 97 patients who had malignant solid tumors diagnosed before they were 21 years of age. Patients received 1.6 g/m2 ifosfamide daily x 5, given i.v. over 15 min, followed by 400 mg/m2 i.v. mesna at 15 min and 4 and 6 h after ifosfamide. Responses were noted in patients with osteosarcoma, Ewing's sarcoma, rhabdomyosarcoma and other soft-tissue sarcomas, rhabdoid tumor, neuroblastoma, Wilms' tumor, primitive neuroectodermal tumor, retinoblastoma, germ-cell tumors, and B-cell lymphoma. Toxicity included mild to moderate nausea and vomiting, transient, reversible myelosuppression, transient elevations of serum blood urea nitrogen (BUN) and creatinine and liver enzymes, infections, and self-limiting neurotoxicity characterized by changes in mental status, motor dysfunction, cranial nerve palsy, cerebellar dysfunction, and seizures. Neurotoxic symptoms were generally seen in patients who had previously received cisplatin. Ifosfamide is an important alkylating agent that should be combined with other agents in phase II and III trials. Alternate dose schedules should also be investigated.
Cancer Chemother Pharmacol 1989
PMID:Ifosfamide in pediatric malignant solid tumors. 250 57

Cisplatin (DDP) is a chemotherapeutic agent that has shown efficacy against primary CNS malignancies. Intra-arterial (IA) administration of DDP to patients with brain tumors should produce higher peak levels of drug than intravenous (IV) administration of an identical dose and reduce systemic toxicity. Twelve patients with malignant glioma were entered into the study. All had failed irradiation, 11 had failed IA BCNU. Each patient received IA DDP, 58-100 mg/m2, into the internal carotid artery at four to six week intervals. One of 12 patients had a partial response of 6 months. The remaining 11 patients had progressive disease or severe complications. Toxicity included seizures in four patients, weakness and/or aphasia in four patients, coma in two patients, and visual deterioration in two patients. IA DDP has very limited efficacy in patients with malignant gliomas after failure of nitrosoureas and is associated with an unacceptable level of toxicity. IA DDP may be more effective when used as initial chemotherapy of malignant gliomas.
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PMID:Intra-arterial cisplatin for the treatment of malignant gliomas. 254 32

From 1980 to 1987, 162 consecutive children with soft tissue and osseous sarcoma were reviewed to determine the frequency and types of neurologic complications seen. Neurologic complications occurred in 43 of 162 (26.5%) patients. Children with poorly differentiated sarcomas and rhabdomyosarcoma were more likely to have neurologic complications, which occurred in 39% of patients at risk. The types of complications seen included: metastatic spinal cord compression (11%); symptomatic peripheral neuropathy (10%); intracranial metastatic disease (7.5%); seizures (6%); and acute and chronic methotrexate-related neurologic dysfunction (2.5%). Spinal cord compression frequently occurred early in disease whereas brain metastases was almost always a late finding. Symptomatic peripheral neuropathy occurred primarily in children with rhabdomyosarcoma and Ewing's sarcoma. The advent of increasingly successful therapies for children with sarcoma and the frequency of severe neurologic complications indicate that a heightened level of surveillance for neurologic compromise is required.
Cancer 1989 Dec 15
PMID:Neurologic complications in children with soft tissue and osseous sarcoma. 255 41

Lambert-Eaton myasthenic syndrome is characterized by muscle weakness, hyporeflexia, and autonomic dysfunction, which result from impaired release of acetylcholine from cholinergic nerve terminals. It is frequently associated with cancer, it is autoimmune-mediated, and treatment has been unsatisfactory. 3,4-Diaminopyridine enhances the release of acetylcholine. In this prospective, double-blind, placebo-controlled crossover study of 12 patients with Lambert-Eaton myasthenic syndrome (7 of whom had cancer), 3,4-diaminopyridine in doses up to 100 mg per day was effective in treating both the motor and the autonomic deficits of the syndrome. Muscle strength increased from an average of 70 percent of normal to 81 percent of normal in the upper extremities, and from 45 to 65 percent of normal in the lower extremities. The amplitudes of compound-muscle-action potentials nearly doubled, increasing from an average of 2.9 mV to 5.0 mV in the arm and from 1.6 mV to 3.1 mV in the leg. Autonomic symptoms were relieved. One patient had a seizure after 10 months of treatment, but other side effects from the drug were minimal and dose-related. We conclude that 3,4-diaminopyridine, either alone or in conjunction with other therapies, may be useful in the treatment of Lambert-Eaton myasthenic syndrome.
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PMID:3,4-Diaminopyridine in the treatment of Lambert-Eaton myasthenic syndrome. 258 57

One hundred forty-seven cancer patients were treated with intravenously administered ciprofloxacin, 200 mg every eight hours, as initial therapy for febrile episodes. Thirty patients (20 percent) were neutropenic (less than 1,000 neutrophils/mm3) at the onset of infection. The overall clinical response rate was 78 percent, 73 percent for neutropenic patients and 79 percent for patients with adequate neutrophil counts. Favorable responses were observed in 19 of 25 patients with bacteremia, 29 of 44 patients with pneumonia, 16 of 18 patients with skin and soft-tissue infection, nine of nine patients with urinary tract infection, 10 of 11 patients with upper respiratory infection, and 26 of 34 patients with fever of undetermined origin. Gram-negative infections were associated with a response rate of 94 percent, gram-positive infections with a response rate of 75 percent, and polymicrobial infections with a response rate of 82 percent. Resistance to ciprofloxacin did not develop and no superinfections were seen. Toxicity was minor except in one patient, in whom a seizure developed. Intravenously administered ciprofloxacin is effective and safe therapy for many infections in cancer patients.
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PMID:Intravenous ciprofloxacin for infections in cancer patients. 258 75


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