Efficacy of carbamazepine for febrile seizures.
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Biomedical subjects
Publications and source records attributed to F Monaco.
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Thyroglobulin (Tg) biosynthesis and secretion have been studied in one case of undifferentiated small spindle cell human thyroid carcinoma. From tumor tissue were extracted 32 mg of soluble proteins per gram of wet tissue, compared with 54 mg from control gland; after ammonium sulfate fractionation, density gradient centrifugation, and immunoprecipitation, 1.3 mg of Tg per gram of wet tissue, compared with 31.2 mg from control, were purified. By incubating in vitro up to 3 hours tumor slices with tritiated leucine, galactose, and 125I, the rate of incorporation of leucine and galactose increased with time in tumor tissue. However 125I incorporation into soluble proteins from tumor, at 3 hours of incubation, was only 1.7% of control value. By density gradient centrifugation of labeled soluble proteins a well-separated component sedimenting in the 19S peak was identified. No radioiodine was detected in the 19S fraction which showed the immunoreactive properties of 19S and was poor in 127I and sialic acid. In the incubation medium of tumor were secreted 0.4 mg of 19S Tg per gram of wet tissue compared with 48 mg of tissue in the control gland. Thus the undifferentiated thyroid carcinoma synthesizes a protein with the physiochemical and immunologic properties of 19S Tg. The undifferentiation of thyroid cells does not affect the biochemical steps involved in the synthesis of Tg.
The behavior of the free fraction of valproic acid (VPA) was evaluated during long-term treatment of 24 children (9-18 months of age) with febrile convulsions. A series of relevant hematological parameters was monitored for the entire observation period (12 months). VPA plasma levels ranged from 54.3 +/- 26 to 66.6 +/- 32.8 micrograms/ml. The unbound fraction of the drug was determined in tears, which has been shown to be the best practical indicator of the free portion of an anticonvulsant drug, and ranged from 5.1 +/- 4.0 to 6.1 +/- 4.3 micrograms/ml. The tear/plasma ratio (and hence the free/total ratio) ranged from 9.3 to 9.7, in agreement with literature data. No significant variations of VPA plasma and tear levels, and therefore of the tear/plasma ratios, were ever observed. The hematological data revealed no significant alterations during the entire observation time, although some of the variables did fluctuate. Side effects were mild and temporary. The present report indicates that VPA has no particular toxic effect in young children treated for the prevention of febrile convulsions.
A 2-week open, randomized, crossover study was conducted in epileptic patients on chronic therapy, who took either carbamazepine (CBZ) 200 or CBZ 400 mg tablets. The oral dose was 1200 or 1600 mg/day, according to individual needs. There was no difference in absorption or steady-state levels between the two preparations. The new galenic preparation of CBZ will help the neurologist to reduce the number of tablets taken by severe epileptic patients, with no risk but only benefits for the subjects.
Sixty-two patients affected with subacute thyroiditis (SAT) were followed for a mean period of 14 months (range 1-40), by monitoring thyroid hormone levels in basal condition, pituitary TSH reserve, antithyroglobulin (TgAb) and antimicrosomal antibodies ( MsAb ), in order to study the natural course of the disease and to characterize its intermediate phase. In the first phase the mean serum iodothyronine levels were within normal limits, nevertheless elevated T3 and T4 levels were detected in 34 (54%) and 20 (32%) patients, respectively. The next phase was characterized by normal serum iodothyronine levels; TRH stimulation test, however, showed a significant increase of pituitary TSH reserve in 35 (56%) patients. All parameters reverted gradually towards normal in all but 3 patients, who showed overt permanent hypothyroidism. TgAb and MsAb were positive in the early stage in 15 (24%) and 40 (64%) patients, respectively, disappearing at the end of the follow-up period in all but one patient; this particular patient belonged to the group of 3 patients affected with permanent hypothyroidism. Our data indicate that the onset of SAT is characterized by transient hyperthyroidism and that transient subclinical hypothyroidism characterizes the next phase. TRH stimulation test is required for the diagnosis of the latter and for the identification of the few who develop permanent hypothyroidism.
A woman with peripheral neuropathy and cerebral atrophy, both secondary to a selective folic acid deficiency caused by severe gastrointestinal disturbances, was given folic acid replacement therapy, which improved her clinical, blood and neurophysiological status.
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The penetration of phenobarbital (PB) into cerebral tissue was determined in cats rendered epileptic by parenteral penicillin and in cats with focal penicillin-induced epilepsy. The results were compared with those from normal controls. In both kinds of experimental models of epilepsy, PB penetration was impaired, although a gradual and progressive accumulation of the drug in the brain tissue was observed in all three groups of cats (binding occurring from time 30 min on). Similar to the events with other substances, such as carbamazepine, the prolonged epileptic activity may have contributed to the impaired penetration of PB, because of severe metabolic alterations secondary to seizures. The present data confirm previous reports indicating that epileptic seizures alter the pharmacokinetics of drugs.
A double-blind controlled trial was performed on 6 patients affected with Steinert's disease in order to evaluate the efficacy of two different dosages of diphenylhydantoin (PHT, 200 and 300 mg/day) and carbamazepine (CBZ, 600 and 800 mg/day) on the myotonic afterdischarge. Both dosages of PHT and CBZ induced a significant improvement of myotonia. For PHT a trend towards decreased efficacy is pointed out at toxic or at high dosages.
Peripheral nerve function was evaluated in 30 epileptic patients on chronic therapy with carbamazepine (CBZ) and 20 healthy controls. The electrophysiological data indicated a mild progressive reduction of both motor and sensory conduction velocity in the patients on long-term treatment with the drug. The impairment of nerve function paralleled the duration of therapy (i.e. 1 through 3 years). CBZ plasma levels were constantly within the therapeutic range. Folic acid levels were below normal in about 50% of the subjects. In the absence of other evidence, the hypothesis cannot be excluded that folate deficiency may have played some role in the development of the peripheral nerve dysfunction.
The CO2 measured by a heated skin surface electrode is greater than arterial CO2. In this study we (1) determined the magnitude of this difference retrospectively, (2) adjusted the calibration of the heated transcutaneous CO2 electrode to reflect this difference, and (3) tested the validity of the calibration procedure prospectively. The retrospective study consisted of 252 simultaneous arterial and transcutaneous measurements on 38 infants and children (age range, 1 day to 6 yr). A linear regression analysis showed PtcCO2 = 1.61 X PaCO2 - 0.01 mmHg, r = 0.90 (p less than 0.0001). Because the intercept was virtually zero, we subsequently changed the calibration procedure by dividing the transcutaneous electrode reading by 1.61. The prospective study consisted of 269 more simultaneous arterial and transcutaneous measurements from 57 consecutive infants and children (age range, 1 day to 18 yr) using this calibration procedure. Regression analysis showed PtcCO2 = 1.02 X PaCO2 - 2.3 mmHg, r = 0.96 (p less than 0.0001). Thus, we found that the transcutaneous CO2 electrode, using this technique, reliably predicted the arterial CO2.
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The transcutaneous partial pressures of carbon dioxide (PtcCO2) and oxygen (PtcO2) were measured with heated electrodes in 18 hemodynamically stable pediatric ICU patients and these data were compared to simultaneously measured arterial oxygen and carbon dioxide tensions. There was a significant degree of correlation (p less than 0.001) between the skin surface CO2 and O2 and their corresponding arterial tensions. These data defined values for PtcCO2 and PtcO2 indices in the pediatric patient without cardiovascular complications as PtcCO2 index = 1.6 +/- 0.2 and the PtcO2 index = 0.84 +/- 0.18 (PtcCO2 index = PtcCO2/PaCO2 and PtcO2 index = PtcO2/PaO2). The authors found the monitoring of skin surface gases a reliable technique to monitor arterial gas tension in hemodynamically stable patients.
Phenobarbital (PB), diphenylhydantoin (PHT) and carbamazepine (CBZ) levels were determined in spiked rat brain homogenates by means of the EMIT assay, and these were compared with results obtained by high-pressure liquid chromatography (HPLC). The extraction procedure of the three drugs was identical for both methods, with minor modifications for EMIT (no addition of internal standard; reconstitution with the buffer used in routine plasma level analysis). Correlation coefficients between the data obtained by EMIT and HPLC were extremely good (PB, 0.90-0.98; PHT, 0.92-0.98; CBZ, 0.93-0.99). The results indicate that the EMIT system can detect PB, PHT, and CBZ in brain tissue with good accuracy, although HPLC remains the most accurate and proven method available for research purposes.
Carbamazepine (CBZ) was determined by EMIT assay in plasma, cerebrospinal fluid (CSF), and brain samples of cats after administration of the drug (40 mg/kg, i.p.). Plasma and CSF levels increase in a parallel manner from time 0 to 90 min after completion of injection, indicating a passive transport from one body fluid to the other. Brain levels reach a steady state at 15 min, with no significant difference being found between the concentrations at 15, 30, 60, and 90 min postinjection; this indicates that substantial early binding occurs in the brain. Since peak CSF concentrations occur at 90 min, concomitant with those for plasma, while brain levels are already high at 15 min, it is likely that CBZ enters the two compartments by independent mechanisms.