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

Central nervous system (CNS) complications occur more frequently in cystic fibrosis (CF) patients than other lung transplant recipients. The purpose of this study was to compare CF patients with and without CNS complications following lung transplantation, to identify risk factors for CNS events. Records of 21 patients with CF who underwent lung transplant between 1991-1996 were reviewed. Data were collected on multiple variables, including: age at transplant; gender; cytomegalovirus (CMV) status; cholesterol and triglyceride levels; sinusitis; percent ideal body weight (IBW); body mass index (BMI); augmented immunosuppression, acute lung rejection episodes (ALR); cyclosporine doses; electrolytes; magnesium, blood urea nitrogen (BUN), and creatinine levels; and 6-month survival. CNS complications identified were seizures, severe headaches (HA), strokes, or confusional episodes. Eleven of 21 patients (52%) with CF had CNS events: eight had seizures, five HA, three strokes, and one confusional episode. There was no difference in age at transplant, pretransplant percent IBW or BMI, cholesterol and triglyceride levels, or number of ALR. CMV mismatch and clinical sinusitis had no effect. Cyclosporine doses did not differ between groups at 30 days, or 3 or 6 months posttransplant. Both BUN and creatinine concentrations showed a rise over time that did not differ between groups. Potassium levels were within normal limits for both groups. While sodium levels did not differ between groups pretransplant, or at 30 days or 6 months posttransplant, a decrease in sodium values was seen at the time of CNS events. There was no difference in 6-month survival. We could not identify any pre- or posttransplant risk factors that predicted CNS events. It is likely that cyclosporine toxicity is the major cause of CNS complications. Despite the high rate of CNS events, the overall prognosis was good, and 6-month survival was not affected.
 ...
PMID:Cystic fibrosis patients with and without central nervous system complications following lung transplantation. 1097 38

A rapid gas chromatographic method for the routine determination in serum of the new anticonvulsant drug topiramate (Topamax) (TOP) is described. The method involves extracting 0.50 mL of sample, previously adjusted to pH 9.5 with saturated borate buffer with ethyl acetate. One-microliter aliquots of the extract were injected into a 10-m x 0.53-mm i.d. x 0.5-microm 100% methyl silicone megabore capillary column connected to a nitrogen-phosphorus detector. The column temperature was initially at 170 degrees C for 0.1 min, then programmed at 10 degrees C/min to 240 degrees C, then 20 degrees C/min to 280 degrees C for 0.5 min. Under these conditions of the assay, the retention times of TOP and mepivicaine, internal standard, were 4.0 and 3.4 min, respectively. Quantitative determinations were performed with peak-height ratios of TOP to the internal standard. Calibration curves were linear from 2.5 to 150 mg/L TOP. The assay had a limit of quantitation of 2.5 mg/L. The overall within-run precision of the method yielded coefficients of variation (CV) of 3.9% at 10 mg/L (n = 10) and 3.1% at 100 mg/L (n = 10). The overall between-run precision calculated by three determinations on a single day for a week yielded CVs of 7.3% at 23 mg/L (n = 12) and 7.8% at 85 mg/L (n = 12). Common anticonvulsant and basic/neutral extractable drugs were found not to interfere with the assay. At present, no correlation has been demonstrated between trough plasma TOP concentrations and clinical efficacy. However, TOP values observed in our laboratory in serums from patients receiving adjunctive treatment for seizure disorders ranged from 2.5 to 35 mg/L.
 ...
PMID:Rapid gas chromatographic procedure for the determination of topiramate in serum. 1104 77

The discrimination of poisoning from other conditions is essential. When multiple patients with similar clinical findings are seen, deliberate poisoning should be considered along with the possibility of resulting from accidental food poisoning, infection, diseases resulting from extreme circumstances, and mass hysteria. The diagnosis of causal poisoning chemicals based on clinical findings is essential. Breath odors, findings of vomitus, skin color, body temperature, autonomic nervous system findings, and seizures are important physical findings. On the other hand, laboratory findings such as ECG abnormalities, metabolic acidosis, increased serum hepatic enzyme levels, and increased serum blood urea nitrogen and creatinine levels are also useful in obtaining the correct diagnosis. X-ray films are useful in demonstrating several types of radiopaque drugs in the stomach. Rapid tests are valuable in diagnosing poisoning caused by such chemicals as paraquat and cyanides. Therapeutic diagnoses obtained by administering competitive blockers of specific receptors are also valuable when benzodiazepine or opiate poisoning is suspected. The final diagnosis of the causal chemical should be based on both the clinical findings and analytical results.
 ...
PMID:[Diagnosis of acute poisoning]. 1121 55

A boy aged 3.5 years with post-diarrheal hemolytic-uremic syndrome (HUS) was referred to our hospital because of convulsion and stupor. He had been admitted to a regional hospital with a 3-day history of bloody diarrhea, colic abdominal pain and fever. Two days later, he had complained of generalized seizures and oliguria. On admission, he developed anuria, and serum blood nitrogen and creatinine increased to 56 mg/100 ml and 2.8 mg/100 ml, respectively. Platelets decreased to 42,000/microl. Under the diagnosis of HUS, a continuous hemodiafiltration treatment had to be instituted. Computed tomography of his head at hospital day 5 revealed abnormal low density area of infarction with edema in both the basal ganglia involving with the posterior limb of internal capsule. Serum titer of IgM antibody to Escherichia coli O157 showed positive value. Although his anuria and stupor persisted over 10 days, he recovered without serious complications. These clinical observations may indicate that patients with similar lesions do not necessarily have serious morbidity.
 ...
PMID:Thrombotic stroke in a child with diarrhea-associated hemolytic-uremic syndrome with a good recovery. 1132 Oct 53

Hyperammonemia associated with inherited disorders of amino acid and organic acid metabolism is usually manifested by irritability, somnolence, vomiting, seizures, and coma. Although the majority of these patients present in the newborn period, they may also present in childhood, adolescence, and adulthood with failure to thrive, persistent vomiting, developmental delay, or behavioral changes. Persistent hyperammonemia, if not treated rapidly, may cause irreversible neuronal damage. After the diagnosis of hyperammonemia is established in an acutely ill patient, certain diagnostic tests should be performed to differentiate between urea cycle defects and other causes of hyperammonemic encephalopathy. In a patient with a presumed inherited metabolic disorder, the aim of therapy should be to normalize blood ammonia levels. Recent experience has provided treatment guidelines that include minimizing endogenous ammonia production and protein catabolism, restricting nitrogen intake, administering substrates of the urea cycle, administering compounds that facilitate the removal of ammonia through alternative pathways, and, in severe cases, dialysis therapy. Initiation of dialysis in the encephalopathic patient with hyperammonemia is indicated if the ammonia blood level is greater than three to four times the upper limit of normal. Hemodialysis is the most effective treatment for rapidly reducing blood ammonia levels. Continuous hemofiltration and peritoneal dialysis are also effective modalities for reducing blood ammonia levels. An improved understanding of the metabolism of ammonia and neurological consequences of hyperammonemia will assist the nephrologist in providing optimal care for this high-risk patient population.
 ...
PMID:Hyperammonemia in urea cycle disorders: role of the nephrologist. 1132 92

Using N-(2,6-dimethyl)phenyl-2-piperidinecarboxamide (1) and N-(alpha-methylbenzyl)-2-piperidinecarboxamide (2) as structural leads, a variety of analogues were synthesised and evaluated for anticonvulsant activity in the MES test in mice. In the N-benzyl series, introduction of 3-Cl, 4-Cl, 3,4-Cl2, or 3-CF3 groups on the aromatic ring led to an increase in MES activity. Replacement of the alpha-methyl group by either i-Pr or benzyl groups enhanced MES activity with no increase in neurotoxicity. Substitution on the piperidine ring nitrogen led to a decrease in MES activity and neurotoxicity, while reduction of the amide carbonyl led to a complete loss of activity. Movement of the carboxamide group to either the 3- or 4-positions of the piperidine ring decreased MES activity and neurotoxicity. Incorporation of the piperidine ring into a tetrahydroisoquinoline or diazahydrinone nucleus led to increased neurotoxicity. In the N-(2,6-dimethyl)phenyl series, opening of the piperidine ring between the 1- and 6-positions gave the active norleucine derivative 75 (ED50=5.8 mgkg(-1), TD50 =36.4 mgkg(-1), PI=6.3). Replacement of the piperidine ring of 1 by cycloalkane (cyclohexane, cyclopentane, and cyclobutane) resulted in compounds with decreased MES activity and neurotoxicity, whereas replacement of the piperidine ring by a 4-pyridyl group led to a retention of MES activity with a comparable PI. Simplification of the 2-piperidinecarboxamide nucleus of 1 into a glycinecarboxamide nucleus led to about a six-fold decrease in MES activity. The 2,6-dimethylanilides were the most potent compounds in the MES test in each group of compounds evaluated, and compounds 50 and 75 should be useful leads in the development of agents for the treatment of tonic-clonic and partial seizures in man.
 ...
PMID:Synthesis and structure-activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores. 1133 5

On the basis of the SAR of a series of known gamma-aminobutyric acid (GABA) uptake inhibitors, including 4 (SKF 89976), new tricyclic analogues have been prepared. These novel compounds are derivatives of nipecotic acid, guvacine, and homo-beta-proline, substituted at the nitrogen of these amino acids by various lipophilic moieties such as (10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)alkoxyalkyl or (10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)alkoxyalkyl. The in vitro values for inhibition of [(3)H]-GABA uptake in rat synaptosomes was determined for each compound in this new series, and it was found that several of the novel compounds showed a high potency comparable with that of the reference compounds 4, 5 (tiagabine), and 6 (CI-966). Several of the novel compounds were also evaluated for their ability in vivo to inhibit clonic seizures induced by a 15 mg/kg (ip) dose of methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). One compound, (R)-1-(2-(2-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)ethoxy)ethyl)-3-piperidinecarboxylic acid (23), was selected for further biological investigations and showed a protective index comparable to or slightly better than that of the recently launched anticonvulsant product 5 ((R)-1-(4,4-bis(3-methyl-2-thienyl)-3-butenyl)-3-piperidinecarboxylic acid).
 ...
PMID:Synthesis of novel gamma-aminobutyric acid (GABA) uptake inhibitors. 5.(1) Preparation and structure-activity studies of tricyclic analogues of known GABA uptake inhibitors. 1140 52

Recreational scuba diving has become a popular sport in the United States, with almost 9 million certified divers. When severe diving injury occurs, the nervous system is frequently involved. In dive-related barotrauma, compressed or expanding gas within the ears, sinuses and lungs causes various forms of neurologic injury. Otic barotrauma often induces pain, vertigo and hearing loss. In pulmonary barotrauma of ascent, lung damage can precipitate arterial gas embolism, causing blockage of cerebral blood vessels and alterations of consciousness, seizures and focal neurologic deficits. In patients with decompression sickness, the vestibular system, spinal cord and brain are affected by the formation of nitrogen bubbles. Common signs and symptoms include vertigo, thoracic myelopathy with leg weakness, confusion, headache and hemiparesis. Other diving-related neurologic complications include headache and oxygen toxicity.
 ...
PMID:Neurologic complications of scuba diving. 1141 73

Clobazam (CLB) is a new antiepileptic drug that is the first 1,5-benzodiazepine (BZP) having nitrogen atoms in the 1 and 5 positions of the heterocyclic ring, whose chemical structure was designed to give it a different pharmacological profile from that of 1,4-BZPs. Although CLB has a Ki value of 2,130 nM and thus has a lower affinity for the BZP receptor than 1,4-BZPs, it had the selectivity to omega 2 receptor contributing to anticonvulsive actions compared with omega 1 receptor in relation to other CNS activities such as sedation. CLB had a wide spectrum of anticonvulsive actions against seizures in several animal models induced by chemical convulsants and maximal electroshock. CLB reduced both seizure stage and afterdischarge duration in a dose-dependent manner in amygdala or hippocampal kindled rats. Usefulness of an anticonvulsant is generally assessed by quoting the protective index (PI) in the ratio of TD50 to ED50. As the PI for CLB was greater than that for 1,4-BZPs, it suggested that CLB was superior to 1,4-BZPs in tolerability while showing anticonvulsive actions. In clinical studies, CLB was used as an adjunctive treatment in patients with refractory epilepsies. From both experimental and clinical observations, CLB was proven to possess a wide spectrum of activity, high effectiveness and good tolerability in several types of epilepsies.
 ...
PMID:[A pharmacological profile of clobazam (Mystan), a new antiepileptic drug]. 1153 Jun 81

Guanidinoacetate methyltransferase (GAMT) deficiency (McKusick 601240), an inborn error of creatine biosynthesis, is characterized by creatine depletion and accumulation of guanidinoacetate (GAA) in the brain. Treatment by oral creatine supplementation had no effect on the intractable seizures. Based on the possible role of GAA as an epileptogenic agent, we evaluated a dietary treatment with arginine restriction and ornithine supplementation in order to achieve reduction of GAA. In an 8-year-old Kurdish girl with GAMT deficiency arginine intake was restricted to 15 mg/kg/day (0.4 g natural protein/kg/day) and ornithine was supplemented with 100 mg/kg/day over a period of 14 months. The diet was enriched with 0.4 g/kg/day of arginine-free essential amino acid mixture and creatine treatment remained unchanged (1.1 g/kg/day). Guanidino compounds in blood, urine, and CSF were measured by means of cation-exchange chromatography. The combination of arginine restriction and ornithine supplementation led to a substantial and permanent decrease of arginine without disturbance of nitrogen detoxification. Formation of GAA was effectively reduced after 4 weeks of treatment and sustained thereafter. Biochemical effects were accompanied by a marked clinical improvement. Distinctly reduced epileptogenic activities in electroencephalography accompanied by almost complete disappearance of seizures demonstrates the positive effect of GAA reduction. This indicates for the first time that GAA may exert an important epileptogenic potential in man. Arginine restriction in combination with ornithine supplementation represents a new and rationale therapeutic approach in GAMT deficiency.
 ...
PMID:Improving treatment of guanidinoacetate methyltransferase deficiency: reduction of guanidinoacetic acid in body fluids by arginine restriction and ornithine supplementation. 1174 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>