Sakae Takanashi

Two-dimensional echocardiographic determinants of interventricular septal configurations in right or left ventricular overload

Configurations of interventricular septum (IVS) and left ventricle were evaluated in 60 normal subjects and in 68 patients with congenital heart disease using two-dimensional short axis cross-sectional echocardiography (2DE). Patients were divided into four groups; right ventricular (RV) pressure overload (n = 21), RV volume overload (n = 12), left ventricular (LV) pressure overload (n = 10), and LV volume overload (n = 25). The radii of curvature of the IVS (IVSr) and LV free wall (FWr) were calculated in end systole and end diastole. Measured IVSr was normalized by dividing IVSr by FWr (IVSr/FWr). End-systolic flattening of IVS was a specific finding in patients with RV pressure overload, since this pattern was not observed in other hemodynamic groups. Echocardiographic determinants of IVSr/FWr in end systole correlated well with RV peak systolic pressure/LV peak systolic pressure ratio (r = 0.878). There was also correlation between IVSr/FWr in end diastole and RV end-diastolic pressure/LV end-diastolic pressure ratio (r = 0.579). Thus, the evaluation of IVS configuration is a useful 2DE method of estimating relative RV systolic pressure in infants and children with congenital heart disease.

Long-term effectiveness and side effects of acetazolamide as an adjunct to other anticonvulsants in the treatment of refractory epilepsies

The long-term effectiveness of acetazolamide (AZA) and its side effects, especially the formation of renal calculi, were investigated in a prospective study when AZA was used as an adjunct to other antiepileptic drugs in the treatment of refractory epilepsies. The subjects comprised 37 patients aged from 1 to 17 years (mean age, 8 years and 1 month) whose seizures were hard to control with the use of two or more drugs among sodium valproate, carbamazepine and clonazepam. Thirty-two of the 37 patients were complicated with mental retardation. A daily dose of 10mg/kg of AZA was first administered and then the dosage was increased up to 20mg/kg based on the clinical response and side effects. The maintenance daily dosage of AZA (12.2+/-4.2mg/kg) produced a steady-state plasma concentration of 6.2+/-4.5 microg/ml. Among the 37 patients, complete seizure control for more than 3 years was obtained in four patients. Although there were no significant differences, all of the four patients were classified as having symptomatic localization-related epilepsies. Seizures recurred in five after complete remission for at least 6 months, and six showed >50% decrease in seizure frequency for more than 6 months after the introduction of AZA. Twenty-eight patients, who were taking AZA for 10 months to 14 years (mean, 6 years and 5 months), were examined for the formation of renal calculi. None of them showed evidence of renal calculi. This study reinforces the idea that AZA may be a useful adjunct drug in selected patients with refractory symptomatic localization-related epilepsies.

Influence of Concurrent Administration of Sodium Valproate on the Plasma Concentrations of Carbamazepine and Its Epoxide and Diol Metabolites

Sodium valproate (VPA) and carbamazepine (CBZ) are among the most widely used antiepileptic drugs and when administered together have been reported to present toxic side effects in some patients, despite the plasma levels of both VPA and CBZ remaining within the therapeutic range.8 l4 lB CBZ is extensively metabolized to the active metabolite carbamazepine1 0 , l l -epoxide (CBZ-E) and finally to the inactive 1 0 , l l dihydroxycarbamazepine ( C s Z H ) .l The high plasma concentration of CBZE may be responsible for the side effects.8 l4 l5 In the present study the influence of concurrently administered VPA on the steadystate plasma concentrations of CBZ, CBZ-E and its diol metabolite CBZ-H was investigated in patients receiving CBZ together with VPA, who attended our pediatric seizure clinic.

The Long-Term Effectiveness of Clonazepam Therapy in the Control of Partial Seizures in Children Difficult to Control with Carbamazepine Monotherapy

The group of patients comprised 28 children aged from 3 to 15 (mean, 9 years and 2 months) with any type of partial seizures, whose seizures were not completely controlled by CBZ monotherapy, in spite of maintaining the plasma levels above 7 pg/ml within the range of therapeutic levels. NO patients showed evidence of mental retardation or other associated neuropsychiatric handicaps (Table 1 ) . A daily dose of 0.025-0.05 mg/kg of CZP was introduced and the dosage was increased to the initial maintenance daily dose of 0.1 mg/kg, if the patient was tolerating. If toxicity developed, the dosage was main-

Long-term prognosis of West syndrome treated with the combination of ACTH and clonazepam

tion. Her developmental milestones were normal. She had two episodes of febrile convulsions between 1 and 2 years of age. Her family history revealed that her 29-year-old aunt suffered from frequent dystonic attacks from 8 years of age. At the age of 8, the patient began to have brief dystonic attacks induced by sudden movements. The attacks were always stereotyped and mainly involved the right side of her body. Immediately before the attacks, she felt ‘numbness’ in her right upper limb and trunk. She gradually bent her head with the right arm extended backwards and her face grimacing. During the attacks, her consciousness was clear. The duration of the attacks ranged from 5 to 10 s. The frequency of the attacks ranged from 10 to 20 times per day. Neurological examination on admission revealed no abnormalities. Blood chemistry, brain computed tomography and magnetic resonance imaging were normal. Interictal EEG revealed mild slow-wave dysrhythmia in awake records but no abnormalities in sleep records. EEG recorded with a telemeter during attacks showed two diffuse 4 Hz spike and wave bursts lasting for 4 s followed by muscle contraction artifacts. The patient was treated with 120 mg (4 mg/kg) of carbamazepine. There is now almost complete control of the attacks. Discussion: There are two possible explanations for the pathophysiology of PKC: an epileptogenic or an extrapyramida1 tract disorder. In this case, we suspect that the PKC is related to the epileptogenic mechanism.

The effect of concurrent rectal administration of an antipyretic on the rectal absorption of diazeppam suppositories: a pharmacokinetic study in children with febrile convulsions

Benign epilepsy of children with complex partial seizures following febrile convulsions Kazuyoshi Watanabe, Izumi Takahashi, Tamiko Negoro, Kosaburo Aso and Kiyokuni Miura (Department of Pediatrics, Nagoya University School of Medicine, Nagoya, Japan) This study was presented for discussion to the meeting by invitation of the meeting organizer, although the study is already published as an original article in Seizure 1993;2:57-61.

Probability of developing epilepsies after starting intermittent therapy with rectal diazepam suppositories for prevention of recurrent febrile convulsions

CBZ-H. The daily dose of CBZ in 26 patients receiving CBZ together with VPA (mean age: 12 years, 9 months) and that in the other 71 patients receiving CBZ alone (mean: 9 years, 1 month) were 11.0 + 3.0 mg/kg and 11.0 + 4.0 mg/kg, respectively. The daily dose of VPA in the patients treated with CBZ and VPA was 22.1 + 6.3 mg/kg. The plasma levels of CBZ and its metabolites were measured by means of high-performance liquid chromatography, and those of VPA by TDX ®. The plasma concentrations of CBZ, CBZ-E, and CBZ-H in patients treated with both CBZ and VPA were 7.46 + 1.82 ~tg/ml, 1.93 + 0.91 ktg/ml, and 1.47 _+ 0.59 ~tg/ml; those in patients treated solely with CBZ were 7.43 + 2.07 Ixg/ml, 1.28 + 0.55 ktg/ml, and 1.74 _+ 0.63 Bg/ml, respectively. It is evident that the mean plasma levels of CBZ-E and CBZ-E/CBZ ratio were significantly higher in the patients treated with CBZ and VPA than in those treated with CBZ alone. Conversely, the plasma CBZ-H/CBZ-E ratio was significantly lower in the former group than in the latter group. The plasma concentration in the group of patients treated with both CBZ and VPA was 75.81 + 15.57 ~g/ml. It has been shown that the concurrent administration of VPA raises the plasma CBZ-E level, while the plasma CBZ level remains unaltered. Our study indicates that VPA impairs the elimination of CBZ-E by inhibiting its conversion to CBZ-H. The high plasma concentration of CBZ-E may be responsible for toxic side effects in some patients.