Epidemiological and clinical studies of West syndrome in Nagasaki Prefecture, Japan.

Recent advances in diagnostic and therapeutic techniques may have changed incidence and etiologies of West syndrome (WS). We performed a retrospective epidemiological study of WS that occurred in 47 children in Nagasaki Prefecture during a recent 10-year period from 1989 to 1998. The incidence of WS was 3.1/10,000 live births. Thirty-nine patients (83%) had symptomatic WS, in which the prenatal causes were most frequent, followed by low-birth weight (LBW) infants, perinatal and postnatal. Such high frequency of LBW may have been due to a relative increase in survivors of premature babies because of recent advances in perinatal care. The brain computerized tomography/magnetic resonance imaging performed in 41 patients revealed congenital brain malformation (10 patients), destructive brain disorders (13 patients), and no structural abnormalities (18 patients). The seizure outcome was worse in the symptomatic WS than in the cryptogenic WS. The developmental outcome was very poor in both symptomatic and cryptogenic WS. The mean developmental quotient (DQ) in all patients was 25, and only four patients (11%) had a normal DQ (>70). DQ was lower in patients with developmental delay before the onset of WS, symptomatic group, relapse and/or persistence of seizure. Developmental delay seen in WS patients seems to be related to the two major factors, that is, underlying brain abnormalities and the persistent seizures as a result of the former. Therefore, every effort should be made to control seizures, including medical and early surgical treatment, as well as prevention of brain damage through perinatal care.

[Clinical and bacteriological studies on hospital outbreak of Salmonella enteritidis food poisoning].

We experienced a hospital outbreak of salmonella food poisoning after ingestion of omelet which was the hospital evening meal on August 8, 1999. Total number of patients was sixty-two (Male 25: female 37) and the mean age was 52.1 years old. Salmonella Enteritidis was isolated from the stool in 59 cases. Twenty-one of them were associated with the immunosuppression (12 with malignancy, 6 with DM, one with nephrotic syndrome, one with chronic nephritis and one with allergic purpura). Clinical symptoms of the patients were composed of watery diarrhea (100%), fever (88.7%), abdominal pain (82.3%), nausea (45.2%) and vomiting (25.8%). The laboratory data revealed leukocytosis (15/47 = 31.9%), increased CRP (44/46 = 95.7%), elevated creatinin (1/37 = 2.7%) and hypokalemia (5/42 = 11.9%). MICs of 20 strains isolated in our laboratory almost coincided with each other indicating that the source of bacteria was probably the same. In vitro, S. Enteritidis were sensitive to OFLX, TFLX, FOM, most of PCs, CEPs, AGs but resistant to MPIPC, CAM, CLDM, VCM. Therefore we administered LVFX to 59 cases (alone in 45cases, combination with FOM in 6 cases), NFLX to two children and FMOX to one pregnant woman. Lactobacillus was administered to 28 cases (45.2%) and antidiarrhetics were given to 6 cases (9.7%). Finally all patients improved within two weeks. We suspect that the salmonella food poisoning was due to infected egg. The partially cooked omelet would permit the growth of a sufficient inoculum to cause disease. To prevent food poisoning, we have to be consistent in cooking the food well (at 75 degrees C, for more than 1 minute) and should not have omelets during the hot summer season.

[Epidemiological and clinical study of West syndrome in Nagasaki Prefecture, Japan].

To determine the occurrence, outcome, and prognostic factors of West syndrome (WS), we performed a retrospective epidemiological study of WS occurred in 47 children (26 boys and 21 girls) in Nagasaki prefecture during a recent 10-year period from 1989 to 1998. The incidence of WS was 3.1/10,000 live births. The mean age at onset of spasm is 6.3 months (range: 2 to 12 months). Thirty-nine patients (83%) had symptomatic WS, in which the prenatal causes (patients) were most frequent, followed by low-birth weight infants (patients), perinatal (patients) and postnatal (patients). The brain CT was performed in 37 patients, and revealed congenital brain malformations (9 patients), destructive brain disorders (12 patients), and no structural abnormalities (16 patients). The seizure outcome was worse in the symptomatic WS than in the cryptogenic WS; seizure/disappeared in 39% of the former and in 75% of the latter/developmental delay before the onset of WS, relapse of WS and persistence of seizures were associated with poor seizure outcomes. Among the remaining seizures at the time of this surveillance, a tonic seizure was most frequently observed, followed by the partial seizures. Lennox-Gastaut syndrome was observed in 2 patients only. Epileptic discharge in the latest interictal EEG were diffuse in 4.3%, focal or multifocal in 60.7%, and absent in 35%, suggesting that many patients with WS had cortical epileptogenic foci. The developmental outcome was very poor in both the symptomatic and cryptogenic WS. The mean DQ in all the patients was 25, and only 4 patients (11%) had a normal DQ (> 75). DQ was lower in patients with congenital brain malformations than in those with destructive brain disorders.

[Pharmacokinetic and clinical evaluation of cefozopran in newborn patients].

Pharmacokinetic and clinical evaluation of an injectable cephem antibiotics, cefozopran (SCE-2787, CZOP), was conducted in newborn patients and the following results were obtained: 1. Clinical results The clinical efficacy of CZOP was evaluated in one each patient with intrauterine infection and suspected septicemia. The efficacy was "excellent" in both patients. No clinically serious adverse drug reactions of signs and symptoms and abnormal alterations of the laboratory test values were recognized. 2. Pharmacokinetics CZOP was intravenously given to newborn patients at doses of 25.0, 20.0, and 18.75 mg/kg. The blood CZOP concentrations were 44.7 +/- 7.0 micrograms/ml (n = 3), 48.3 micrograms/ml and 48.2 micrograms/ml at one hour after administration, respectively. The elimination half life (T 1/2) was 4.22 +/- 1.17 hours (n = 3) in the patients given 25.0 mg/kg and 2.74 hours in the patient given 20.0 mg/kg. The urinary drug excretion rate was 44.5 +/- 8.7% and 31.3 +/- 9.7% of dose within 8 hours after administration of 25.0 mg/kg and 20.0 mg/kg, respectively.

[Clinical studies of S-1108, a new oral cephem, in pediatric patients].

Clinical studies of S-1108, a new oral cephem, in pediatric patients were conducted and results are summarized below. 1) Clinical effects of S-1108 against 18 cases of bacterial infections were excellent in 5 cases, good in 10 cases, fair in 1 case and poor in 2 cases, thus the clinical efficacy rates was 83.3%. 2) Bacteriological effects were evaluated in 16 strains. The elimination rate was 100%. 3) No adverse effects nor abnormal laboratory test results were observed in any of the cases.

[Pharmacokinetic and clinical studies on flomoxef in mature and premature infant].

Pharmacokinetic and clinical studies of flomoxef (FMOX) in neonates and premature infants were conducted, and the results obtained are summarized below. 1. Plasma concentrations of FMOX at 15 minutes after one shot intravenous injection of 20 mg/kg to 6 cases were in a rang of 33.0-69.9 micrograms/ml and half-lives (T 1/2's) were between 0.68 and 4.89 hours. The plasma concentration of FMOX at 15 minutes after one shot intravenous injection of 40 mg/kg to 1 case was 79.9 micrograms/ml and the half-life (T 1/2) was 2.45 hours. Drug concentrations in plasma upon 1-hour intravenous drip infusion were 71.1-114.0 micrograms/ml and T 1/2's were 1.64-3.41 hours. T 1/2 tended to be couse shorter as ages of babies increased. 2. Urinary excretion rates in the first 6 hours after one shot intravenous injection of FMOX 20 mg/kg to 1 case and 1-hour intravenous drip infusion of FMOX 40 mg/kg to 2 cases were 60.4%, and 27.2 and 55.3%, respectively. 3. Clinical effects of FMOX against 12 cases of bacterial infections were excellent in 6 cases, good in 5 cases and poor in 1 case, thus the clinical efficacy rate was 91.7%. FMOX was also given to 6 cases for prophylaxis and prophylactic effects were observed in all the cases. 4. No adverse effects were observed in the 21 cases examined, but elevations of S-GOT and S-GPT were found in 1 case. The abnormal laboratory test results were probably due to this drug.

Infantile cytochrome c oxidase deficiency with neonatal death.

A newborn male presented with severe respiratory insufficiency, generalized muscle weakness, and lactic acidemia. Immediately after admission, he was placed on a respirator because of respiratory arrest. He deteriorated rapidly and died 75 hours after birth. There was notable variation in fiber size and an increased number of type 2C fibers in the quadriceps femoris muscle obtained at autopsy; however, no ragged-red fibers were observed with modified Gomori trichrome staining. Markedly decreased cytochrome c oxidase activity was demonstrated in skeletal muscle by biochemical and histochemical studies, while cardiac muscle demonstrated normal cytochrome c oxidase activity. Mitochondrial myopathy should be considered in the differential diagnosis of patients with neonatal respiratory distress syndrome.

[Fundamental and clinical studies of flomoxef in the pediatric field].

Fundamental and clinical studies of flomoxef (FMOX, 6315-S) were conducted and the obtained results are summarized as follows. For the pharmacokinetic investigation, FMOX at 10 or 20 mg/kg was administered by intravenous drip infusion over 30 minutes. In the 10 mg/kg group, the maximum blood concentration was reached just after completion of the drip infusion with the mean concentration of 30.3 +/- 4.5 micrograms/ml, and the mean half-life was 0.734 +/- 0.196 hour. The 6-hour urinary excretion rate was 72.3%. In the 20 mg/kg group, which also showed the peak concentration immediately after completion of the drip infusion, the mean peak blood concentration was 54.3 +/- 9.7 micrograms/ml and the mean half-life was 0.628 +/- 0.185 hour. The 6-hour urinary excretion rate was 69.3%. The urinary recovery tended to be lower in children than in adults. Between 10 mg/kg and 20 mg/kg, a definite correlation was observed between dose levels and blood concentrations. In the clinical investigation conducted with a total of 30 patients (22 with respiratory tract infection, 3 with lymphadenitis, 2 each with urinary tract infection and cellulitis, and 1 with acute osteomyelitis), FMOX was found to be excellent in 14 cases, good in 9, fair in 1, poor in 1, and not evaluable in 5. The efficacy rate was, therefore, 92.0%. In the bacteriological evaluation, 8 out of 12 clinically isolated strains were eradicated, 2 unchanged and 2 unknown. The elimination rate was 80.0%. Regarding side effects, no abnormal clinical symptoms were observed. As abnormal laboratory values, eosinophilia, prolongation of APTT, increased platelet count, and a slight elevation of GOT were observed.

[Clinical investigation of ceftizoxime sodium suppositories in pediatric infections].

Ceftizoxime suppository (CZX-S) was given to 6 patients, with the following results. The peak serum concentration of CZX was 1.8-7.5 micrograms/ml at 30 minutes after dosing of CZX-S with 9.6-16.7 mg/kg. The antibacterial activity of CZX revealed that the drug can be expected to be effective sufficiently. The overall effect of CZX-S was "markedly improved" in 1 and "moderately improved" in 3 of the 4 patients with pneumonia and "markedly improved" in 1 and "slightly improved" in 1 of the 2 with UTI. CZX-S caused a slight increase in frequency of defecation in 2 of the 6 patients. There were no abnormal findings of symptoms or laboratory test values which were ascribable to side effects.

[Clinical evaluation of aspoxicillin in children].

Aspoxicillin (ASPC), a new semisynthetic penicillin, was administered to a total of 13 children with respiratory tract and other various infections. Respiratory tract infections in 7 of 13 children were treated with ASPC intravenously, 64 to 144 mg/kg/day t.d.s. or q.i.d. The other 6 patients with various types of infections were also treated with the combination of ASPC and other antibiotics. Their clinical and laboratory data were evaluated only for adverse reactions. Concentration of ASPC level in serum and urine was determined after 60 minutes intravenous drip infusion of 20 mg/kg/dose of ASPC dissolved with the solution of solita T3 in 3 children. The half-life of ASPC was 0.76 to 2.31 hours and urinary excretion rate was 53.0% in first 6 hours. The effectiveness rate in respiratory tract infections was 100%. Clinical side effects were not recognized except loose stool in 1 case. The increase and decrease of platelet counts and the elevation of GPT were encountered 3 of 13 cases.

[Clinical evaluation of cefminox in children].

In a total of 13 children with infections, ranging in age from 1 month to 6 years, cefminox (CMNX, MT-141), a new antibiotic of cephem group, was administered 14 times and its absorption, excretion, clinical results and safety were determined. Following intravenous drip infusion of CMNX, high blood level was achieved, with half-life of about 1 hour (0.77 to 1.13 hours). The urinary recovery rate was approximately 80% within the first 6 hours after completion of administration. Clinical results were rated as effective in 8 out of 12 assessable cases (66.7%). In any of the cases treated no side effects developed nor any abnormal changes in laboratory finding were observed. From these results, CMNX is considered to be a new antibiotic useful and safe for use in the field of pediatrics.

[Studies on absorption and excretion of cyclacillin granules (vastcillin granules 'Takeda') (author's transl)].

Vastcillin granules 'Takeda', a cyclacillin (AC-PC) preparation for children were orally administered to nine children at a single dose of 10 mg/kg and its blood concentrations and urinary excretion were studied. From the results obtained, the following conclusions were obtained as to clinical dose and indications. (1) Absorption of AC-PC of Vastcillin granules is excellent . At 15 minutes after administration, 9.3 mcg/ml of AC-PC blood level was attained and its peak appeared 30 minutes after administration. The mean peak level was 17.6 mcg/ml.