UCP1 deficiency increases susceptibility to diet-induced obesity with age.

Loss of nonshivering thermogenesis in mice by inactivation of the mitochondrial uncoupling protein gene (Ucp1-/- mice) causes increased sensitivity to cold and unexpected resistance to diet-induced obesity at a young age. To clarify the role of UCP1 in body weight regulation throughout life and influence of UCP1 deficiency on longevity, we longitudinally analyzed the phenotypes of Ucp1-/- mice maintained in a room at 23 degrees C. There was no difference in body weight and lifespan between genotypes under the standard chow diet condition, whereas the mutant mice developed obesity with age under the high-fat (HF) diet condition. Compared with Ucp1+/+ mice, Ucp1-/- mice showed increased expression of genes related to thermogenesis and fatty acid metabolism, such as beta3-adrenergic receptor, in adipose tissues of the 3-month-old mutants; however, the augmented expression was reduced in Ucp1+/+ mice in 11-month-old Ucp1-/- mice fed the HF diet. Likewise, the increased levels of UCP3 and cAMP-dependent protein kinase in the brown adipose tissue of Ucp1-/- mice given the standard diet were decreased significantly in that of Ucp1-/- mice fed the HF diet, which animals showed impaired norepinephrine-induced lipolysis in their adipose tissues. These results suggest profound attenuation of beta-adrenergic responsiveness and fatty acid utilization in Ucp1-/- mice fed the HF diet, bringing them to late-onset obesity. Our findings provide evidence that UCP1 is neither essential for body weight regulation nor for longevity under conditions of standard diet and normal housing temperature, but deficiency increases susceptibility to obesity with age in combination with HF diet.

Cloning, sequencing and mapping of a manganese superoxide dismutase gene of the nematode Caenorhabditis elegans.

We have cloned, sequenced and mapped a gene (sod-2) encoding manganese superoxide dismutase [EC 1.15.1.1] from the nematode Caenorhabditis elegans. The sod-2 was mapped to chromosome I by hybridization with a YAC polytene filter. The protein-coding region spans 1129 base pairs including 4 introns and encodes a protein of 221 amino acids (aa) (M(r) = 24536) of which the first 24 aa are the presumed mitochondorial-targeting signal peptide. The gene sequence of sod-2 was slightly different from an isoform, sod-3.

Self-induced photogenic epilepsy in infants.

We studied two infants with self-induced photogenic epilepsy and investigated their seizures with simultaneous EEG and videotape recording. A 2-year-old boy showed peculiar head-nodding behavior towards bright light before he manifested myoclonic absence or myoclonic seizures. A 14-month-old infant girl showed blinking in front of the television set before myoclonic jerks developed. Neither head nodding nor blinking was associated with paroxysmal discharges. We concluded that such preictal behavior was not part of the seizure.

Subclinical delta status in the newborn--an unfavorable prognostic sign.

A hitherto undescribed, unusual EEG abnormality invariably associated with a poor prognosis was reported and was called subclinical delta status. It consisted of continuous discharges of high voltage monomorphic or polymorphic delta activity occurring diffusely but often asynchronously in all leads, without sleep cycles. These discharges when monomorphic may be confused with respiratory artefacts, and when polymorphic they may be mistaken for part of the background activity. Four neonates with this abnormality all had intracranial bleeding and were mechanically ventilated because of frequent apneic attacks. Staring or deviation of the eyes was frequently observed during the EEG recording. A small dose of intravenous diazepam temporarily abolished this activity. Three infants died and the other survived with neurological sequelae.

EEG topography in porencephaly and arachnoid cyst.

With the topographic EEG mapping method, the correlation between the morphologic abnormality of the brain and its functional changes was investigated in 13 patients with porencephaly and arachnoid cyst verified by CT scan. The spatial distribution of the EEG activity was displayed in the delta, theta, alpha-1, alpha-2, beta-1, and beta-2 frequency bands. The abnormality of EEG topographic images (e.g., an increase of the power of delta activity and/or a decrease of the power of alpha activity in the involved side of the brain) was more marked in cases with porencephaly than those with arachnoid cyst, and in cases with mental retardation or paralysis than among those without.

[Evaluation of cefotiam in pediatric field (author's transl)].

Studies on the antibacterial activity, absorption and excretion and also clinical investigation in the field of pediatrics have been carried out with cefotiam (SCE-963, CTM), a new cephalosporin antibiotic. 1) The MICs of CTM against the following clinical isolates were measured and compared with those of CEZ: S. aureus (81 strains), E. coli (27) and K. pneumoniae (27), with CTM being inferior by 1 tube in S. aureus, being superior by 2 to 3 tubes in E. coli and by about 2 - 3 tubes in K. pneumoniae. 2) Absorption and excretion. After intravenous one shot injection at dose levels of 10 mg/kg and 20 mg/kg, the peak in the serum concentration was shown in the 15-minute value with 18.1 and 36.6 mcg/ml for 10 mg/kg and 20 mg/kg, respectively. The half-life in ;the serum was 1.14 and 0.61 hours, respectively. In the case of 1-hour intravenous drip infusion at a dose level of 10 mg/kg, it was 14.3 mcg/ml, with 0.98-hour half-life in the serum. The recovery rates from the urine within 0 to 6 hours were 50.6% and 66.2% in the case of intravenous one shot injection at dose levels of 10 mg/kg and 20 mg/kg, respectively, with 71.1% in the case of the 1-hour intravenous drip infusion. 3) Two to 3 hours after intravenous one shot injection of CTM in H. influenzae-meningitis every 4 hours at a dose level of 62.5 mg/kg at one time, the cerebrospinal fluid concentration of CTM was only 2.12 to 10.0 mcg/ml, and this fact suggests that CTM is a useful cephalosporin for treating purulent meningitis. 4) CTM was administered in 19 clinical cases, with the results being: excellent in 4 out of 4 cases of bronchitis; excellent in 5 and good in 1 out of 6 cases of pneumonia; excellent in 3 cases of pyelitis; good in purulent parotitis, purulent meningitis and bacterial pericarditis; and excellent in peritonsillar abscess, purulent osteomyelitis and staphylococcal scalded skin syndrome (S.S.S.S.). No side effects have been observed in all cases. As for abnormal laboratory findings, 3 cases of eosinophilia were seen.

[A study on cefmetazole in the neonatal period (author's transl)].

The authors studied the antibacterial activity, absorption and excretion, and clinical use of cefmetazole in neonatal period, and obtained the following results. 1. The minimal inhibitory concentrations (MICs) of cefmetazole (CMZ) were measured, to compare with those of cefazolin (CEZ), for clinical isolates of S. aureus (31 strains), E. coli (29 strains) and K. pneumoniae (30 strains). On a cumulative percentage basis, 77% of S. aureus, 76% of E. coli and 90% of K. pneumoniae were inhibited by less than or equal to 3.13 microgram/ml of CMZ with a higher inoculum size. When compared with CEZ, MICs of CMZ were found to be superior or equal against E. coli, K. pneumoniae and some of S. aureus, but to be inferior against most of S. aureus. Most of strains which were resistant to CEZ were most sensitive to CMZ. These results suggest that CMZ is highly active against Gram-negative bacteria and is stable to beta-lactamase. 2. The serum concentration was measured in 7 neonates (5 approximately equal to 25 day-old) and 5 infants (1 approximately 3 month-old) after a single intravenous administration of 20 approximately 25 mg/kg of CMZ. The mean concentration in neonates was 68.3 microgram/ml at 1/2 hour postinjection, 57.0 microgram/ml at 1 hour, 35.4 microgram/ml at 2 hours, 18.1 microgram/ml at 2 hours, 18.1 microgram/ml at 4 hours and 9.5 microgram/ml at 6 hours. The mean half-life was 2.04 hours. The peak concentration of each neonate seemed to be related more to individual variation than to the days after birth. The mean concentration in infants was 60.7 microgram/ml at 1/2 hour, 42.8 microgram/ml at 1 hour, 22.2 microgram ml at 2 hours, 9.2 microgram/ml at 4 hours and 3.2 microgram/ml at 6 hours. The mean half-life was 1.31 hours. There was little difference in the mean peak concentration between neonates and infants, but the mean concentration after that were higher in neonates than infants. It was apparent that the half-life tends to be shortened in proportion to advanced age in days and months. 3. CMZ was administered clinically in 3 cases of acute bronchopneumonia. Its clinical effect was excellent or good in all of the cases. No adverse reaction or abnormal laboratory values were found.

[Laboratory and clinical studies of cefoperazone in children (author's transl)].

Experimental and clinical studies on cefoperazone (CPZ), a new synthetic cephalosporin, were performed in the field of pediatrics. 1) The MICs of CPZ against 26 strains of S. aureus, 21 strains of E. coli, 20 strains of K. pneumoniae and 15 strains of H. influenzae which were clinically isolated were estimated and compared with those of CEZ and ABPC. Some strains were found to be high in the MIC of CPZ against S. aureus, E. coli and K. pneumoniae by original inoculation but 88% of S. aureus, 95% of E. coli, 95% of K. pneumoniae and 100% of H. influenzae were under 6.25 mcg/ml by 100 times dilution inoculation. The MIC of CPZ against S. aureus was inferior to CEZ and superior to ABPC, and that against E. coli, K. pneumoniae and H. influenzae was superior to CEZ and ABPC. 2) The serum concentration, urinary concentration and recovery rate from urine were measured in two healthy infants and one infant in the stage of convalescence from cholangiohepatitis after a single intravenous administration of 25 mg/kg of CPZ. The mean serum concentration in the two healthy infants was 88.0 mcg/ml at 30 minutes, 63.0 at 1 hour, 31.4 at 2 hours, 12.2 at 4 hours and 4.2 at 6 hours; the half-life was 1.29 hours, and the recovery rate from urine was 14.5%. 3) The clinical effect of CPZ was examined in 16 cases of acute lobar pneumonia or acute bronchopneumonia, 1 case of acute bronchitis and 4 cases of acute urinary tract infections. All of the cases responded effectively or markedly effectively. Among the causative bacteria in those cases, 2 strains of S. pneumoniae, 1 strain of S. faecalis, 1 strain of H. influenzae and 2 strains of E. coli and 1 strain of K. pneumoniae disappeared following the administration of CPZ. The bacteriological effect against 1 strain of P. aeruginosa was unknown, but clinical effectiveness was observed in this case. No clinical side effects were observed. Laboratory examination carried out before and after the administration revealed a rise of GOT and eosinophilia in each one case, but in both abnormality returned to normal after termination of therapy.

[Laboratory and clinical studies on cefoxitin in pediatric field (author's transl)].

Studies on antimicrobial activity, absorption and excretion and clinical use of cefoxitin in pediatric field were performed. 1. MIC of cefoxitin was compared with that of cefazolin and/or ampicillin for clinical isolates of Staphylococcus aureus (36 strains), Escherichia coli (35 strains), Klebsiella pneumoniae (34 strains) and Haemophilus influenzae (80 strains). MIC of cefoxitin against S. aureus was approximately 1-2 tubes higher than that of cefazolin. Many strains of E. coli and K. pneumoniae that showed high MIC to cefazolin were sensitive to cefoxitin. It is presumed that the results are due to the strong resistance of cefoxitin to beta-lactamase degradation. MIC of cefoxitin against H. influenzae was approximately 1-2 tubes lower than that of cefazolin, but approximately 4 tubes higher than that of ampicillin. 2. Serum level and urinary recovery rate of cefoxitin after one shot i.v. injection of 25 mg/kg were examined. The serum mean levels were 33.8 microgram/ml at 1/2 hour, 7.0 microgram/ml at 1 hour and 2.9 microgram/ml at 2 hours after the injection, respectively, and the drug was not detected in serum at 4 and 6 hours after the injection. The mean half-life of serum level was 27.1 minutes. The mean urinary recovery rate within 6 hours after injection was 96.0% and most of the drug were excreted into urine within 2 hours after the injection. 3. In order to evaluate clinical response, bacteriological response and side effects, cefoxitin was applied to 19 cases, i.e., 12 cases of either acute lobar pneumonia or acute bronchopneumonia, 2 cases of acute pyelitis, 1 case each of acute bronchitis, acute purulent tonsillitis, acute purulent arthritis, acute orbital phlegmon and acute buccal abscess. As for clinical response, the overall efficacy rate (the percentage of cases showed excellent and good efficacy) was 88.9%. As for bacteriological response, among the 13 strains which were determined or supposed to be causative organisms, i.e., 6 strains of Streptococcus pneumoniae, 2 strains of H. influenzae and 1 strain each of streptococcus pyogenes, alpha-Streptococcus, Enterococcus, E. coli and Neisseria sp., all strains were disappeared except for Enterococcus which was reduced by the treatment with cefoxitin. No side effect was observed in any case. Abnormalities of laboratory findings were observed in 3 cases, i.e., 1 case each of reduction of RBC and Hb, elevation of GOT and GPT and elevation of GPT, but all of them returned to normal following completion of the dosage term.

[Evaluation of cefroxadine in the field of pediatrics (author's transl)].

Basic and clinical evaluations of a new oral cephalosporin cefroxadine (CXD) in pediatric fields were investigated, and the following results were obtained. 1. MICs of CXD against various bacteria were compared with those of cephalexin (CEX). MIC peaks of CXD against clinically isolated S. aureus (22 strains), S. pyogenes (25), S. pneumoniae (8), H. influenzae (23), and E. coli (23) in pediatric fields, were 1.56, 0.2, 1.56, 25 approximately 50 and 6 .25 microgram/ml, respectively in the inoculum size of 10(8) cells/ml, and they were 1.56, less than 0.1, 0.78, 25 and 6.25 microgram/ml respectively in the inoculum size of 10(6) cells/ml. In comparison with CEX, MIC peaks of CXD against S. aureus, S. pyogenes, H. influenzae and E. coli were almost the same with those of the former, it was, however, better by 1 approximately 2 tubes than that of CEX against S. pneumoniae. 2. CXD in the form of dry syrup was administered orally at a dose of either 10 mg/kg or 20 mg/kg to 5 children, and the serum levels and the urinary excretion were evaluated. In the case of 3 children who were administered a dose of 10 mg/kg the mean serum levels were 11.9 microgram/ml after 30 minutes, 13.7 microgram/ml after 1 hour, 4.7 microgram/ml after 2 hours, 0.7 microgram/ml after 4 hours, and 0.3 microgram/ml after 6 hours, while those 2 children who were administered a dose of 20 mg/kg, they were 15.1, 28.5, 12.5, 2.0 and 0.9 microgram/ml respectively. The mean periods of half-life in serum were 0.87 hour in the case of 10 mg/kg and 0.94 hour in the case of 20 mg/kg. The mean excretion rates were 83.8% in the case of 10 mg/kg and 59.8% in the case 20 mg/kg. 3. CXD dry syrup was administered to 31 children with various bacterial infections i.e. acute pharyngitis (15 cases), acute purulent tonsillitis (10 cases), acute bronchitis (4 cases) and 1 case each of acute pyelonephritis and acute purulent cervical lymphadenitis, and the clinical and bacteriological responses and side effect were investigated. The clinical response was either excellent or good in all of the cases. Out of the S. pyogenes (20 strains), S. aureus (1), S. pneumoniae (2), E. coli (1) and H. influenzae (1), bacteriological eradication was observed in all strains with the exception of 1 strain each in S. pyogenes and H. influenzae in which reduction was observed. No side effects and abnormal laboratory findings were observed.

[Laboratory and clinical studies on 6059-S in children (author's transl)].

Laboratory and clinical studies were performed on 6059-S in the field of pediatrics, a new semi-synthetic 1-oxacephem antibiotic, and results were as follows. 1. MICs of 6059-S were compared with those of cefazolin (CEZ) and cefmetazole (CMZ) on 31 strains of S. aureus, 29 strains of E. coli, 30 strains of K. pneumoniae and 16 strains of P. aeruginosa. With the inoculum size of 10(8) cells/ml an 10(6) cells/ml, the peak of distribution of MICs were S. aureus 6.25, 3.13 micrograms/ml, E. coli 0.2, 0.1 micrograms/ml, K. pneumoniae 0.2, 0.05 micrograms/ml and P. aeruginosa 12.5, 6.25 micrograms/ml, respectively. MICs 6059-S against S. aureus was more less 2 to 3 tubes than CEZ and CMZ, but against E. coli and K. pneunoniae were more higher than 3 to 4 tubes than CEZ and CMZ. 2. The serum concentrations and urinary recovery rate of 6059-S were measured in 5 pediatric patients. 6059-S was given 20 mg/kg by an intravenous injection to 2 cases or a 30 minutes intravenous drip infusion to 3 cases. The mean concentration of the former were 64.3, 44.3, 26.8, 11.7 and 5.0 micrograms/ml at 0.5, 1, 2, 4 and 6 hours, and T 1/2 was 1.51 hours. The urinary recovery rates was 75.0% within 6 hours after the injections. The mean concentration of the latter were 65.3, 86.3, 63.0, 40.3, 17.8 and 8.9 micrograms/ml at 0.25, 0.5, 1, 2, 4 and 6 hours, and T 1/2 was 1.63 hours. The urinary recovery rates was 52.1% within 6 hours after the injection. 3. Eleven cases with acute pneumonia, 1 case with acute bronchitis, 3 cases with acute purulent tonsillitis, 1 case with acute purulent parotitis and 1 case subcutaneous abscess were treated with 6059-S by intravenous injection. All cases were above effective clinically. Five strains of H. influenzae, 3 strains of S. pneumoniae, 2 strains of S. pyogenes and 1 strain of S. aureus were eradicated in all strains. No clinical adverse reaction and abnormal laboratory findings were noted.

[Pharmacokinetic and clinical studies of cefuzonam in pediatrics].

Pharmacokinetic and clinical studies were conducted to evaluate cefuzonam (L-105, CZON), a new cephem type antibiotic, in the pediatric field. A total of 9 pediatric patients (2-14 years) was treated with intravenous injection of CZON: 4 cases with one shot of 20 mg/kg, 2 cases with one shot of 40 mg/kg and 3 cases with drip infusion over 1 hour of 40 mg/kg. CZON concentrations in serum and the excretion in urine were determined. Mean serum concentrations of CZON after one shot intravenous injection of 20 mg/kg were 49.0, 22.7, 9.03, 2.13, 0.37, and 0.09 micrograms/ml at 15, 30 minutes, 1, 2, 4 and 6 hours, respectively. With 40 mg/kg one shot intravenous injections, mean serum concentrations were 117.5, 68.0, 26.2, 8.80, 0.63 and 0.19 micrograms/ml at 15, 30 minutes, 1, 2, 4 and 6 hours, respectively. With 40 mg/kg intravenous drip infusions over 1 hour, mean concentrations were 57.1, 78.8, 12.9, 1.12 and 0.23 micrograms/ml at 30 minutes, 1, 2, 4 and 6 hours, respectively. Mean half-lives were 0.69 hour for 20 mg/kg one shot injections, 0.44 hour for 40 mg/kg one shot injections, and 0.58 hour for 40 mg/kg 1 hour drip infusions. Urinary recovery rates in 6 hour after administration were 70.8% (mean) for the 20 mg/kg one shot injection, 44.1% (1 case) for the 40 mg/kg one shot injection, and 60.0% (mean) for the 40 mg/kg 1 hour drip infusion. CZON was administered in 26 cases of pediatric infections, and the clinical efficacy, antibacterial activity, and side effects were evaluated. Of the 26 cases 2 were excluded for the reason of not having bacterial infection, and the remaining 24 cases were assessed. Included in the 24 cases were 16 cases of acute pneumonia, 2 cases of acute purulent lymphadenitis, and 1 case each of acute bronchitis, acute purulent otitis media, acute apical periodontitis, staphylococcal scalded skin syndrome (SSSS), acute pyelonephritis, and acute enteritis. Clinical efficacy evaluation showed 19 excellent cases and 5 good cases, with an efficacy rate of 100%. Bacteriologically, Staphylococcus aureus 1 strain, Streptococcus pneumoniae 1 strain, beta-Streptococcus 1 strain, Haemophilus influenzae 10 strains, Haemophilus parainfluenzae 1 strain, Proteus mirabilis 1 strain, and Campylobacter jejuni 1 strain were determined or assumed as pathogens, but all of them were eradicated.(ABSTRACT TRUNCATED AT 400 WORDS)

[Studies on imipenem/cilastatin sodium in the field of pediatrics].

Pharmacokinetic and clinical studies on imipenem (MK-0787)/cilastatin sodium (MK-0791), a combined drug of carbapenem antibiotics (MK-0787) and renal depeptidase inhibitor (MK-0791) in a 1:1 ratio, were performed in the field of pediatrics. Absorption and excretion Serum levels and urinary excretion of MK-0787/MK-0791 were determined in 7 children aged 4 to 11 years. Four cases were administered with a single dose of MK-0787/MK-0791 at 10 mg/10 mg/kg by intravenous drip infusion and the other 3 cases were given a single dose of 20 mg/20 mg/kg. Serum concentrations of MK-0787 reached their peaks at the end of drip infusion where the mean level was 17.5 +/- 1.0 micrograms/ml for the group given 10 mg/10 mg/kg, and 43.6 +/- 2.1 micrograms/ml for the group given 20 mg/20 mg/kg. Concentrations decreased with half-lives of 0.82 +/- 0.10 hour and 0.74 +/- 0.04 hour for the low and high doses, respectively, and serum levels at 6 hours after administration were 0.3 +/- 0.1 microgram/ml and 0.4 +/- 0.1 microgram/ml, respectively. Peak concentrations of MK-0791 were 22.6 +/- 4.8 micrograms/ml in the 10 mg/10 mg/kg group and 52.9 +/- 4.7 micrograms/ml in the 20 mg/20 mg/kg group at the end of the drip infusion. Half-lives were 0.56 +/- 0.17 hour and 0.46 +/- 0.11 hour for the 2 doses, respectively while MK-0791 levels were below detection limit at 6 hours after administration. Mean urinary recovery rates in 6 hours after administration were 54.0 +/- 15.3% and 49.3 +/- 7.8% for MK-0787 and MK-0791, respectively, in the group of 10 mg/10 mg/kg, and 62.0 +/- 7.4% and 65.3 +/- 9.2%, respectively, in the group of 20 mg/20 mg/kg. These results showed that pharmacokinetics of MK-0787 and MK-0791 in children were similar to that in adults. Clinical study MK-0787/MK-0791 was used for treatment in a total of 22 pediatric patients to evaluate clinical effectiveness, bacteriological efficacy and adverse reactions. Each of patients was treated 3 or 4 times per day at a single dose of 11.4-22.8 mg/kg (of MK-0787). Duration of treatment ranged from 2.5 to 18 days and total doses ranged from 1.36 to 19.92 g. Clinical efficacy in cases including 2 with acute purulent tonsillitis, 1 with acute purulent otitis media, 9 with acute pneumonia, 1 with pythorax, 3 with acute purulent lymphadenitis, and 6 with acute pyelonephritis were judged excellent in 20 cases and good in 2 cases; an efficacy rate of 100%.(ABSTRACT TRUNCATED AT 400 WORDS)

[Fundamental and clinical evaluations of ceftazidime in neonates].

Evaluations of ceftazidime (CAZ) in a few different categories were carried out in neonates. Single doses of 20 mg/kg of CAZ were administered to 8 neonates (day-age range: 1-26) and 3 infants (day-age range: 45-119) by bolus intravenous injection. Mean serum concentrations of CAZ at 15, 30 min., 1, 2, 4 hours and 6 hours were 51.6 +/- 9.2, 48.1 +/- 8.7, 47.9 +/- 7.8, 38.2 +/- 6.5, 20.2 +/- 4.0 micrograms/ml, and 15.3 +/- 5.8 micrograms/ml, respectively, in the neonates, and 51.1 +/- 10.3, 44.7 +/- 6.8, 35.5 +/- 4.1, 21.4 +/- 2.0, 8.6 +/- 1.0 micrograms/ml and 3.5 +/- 0.8 micrograms/ml, respectively, in the infants. Mean half-lives of CAZ in serum were 2.87 +/- 0.77 hours in the neonates and 1.39 +/- 0.10 hours in the infants, and mean urinary recovery rates in the first 6 hours were 60.5 +/- 16.0%, and 76.8 +/- 39.6% in the neonates and the infants, respectively. When individual differences are taken into consideration, no significant difference exists among 30-minute serum concentrations of neonates of different day-ages, and these concentrations were not significantly different from those in infants and older children. Half-lives of CAZ in sera decreased rapidly with the advances of the day-ages of the neonates, and the half-life at an age of 1-month should be similar to that in older children. The CAZ was administered to 2 cases of suspected sepsis, 7 of acute pneumonia, 1 of acute pyelonephritis, 1 of cellulitis, and 2 of idiopathic respiratory distress syndrome, and clinical efficacies were excellent in all the cases except for 2 cases excluded from the assessment. S. pyogenes (1), E. coli (1) and S. aureus (1) suspected as causative organisms were eradicated by the treatment with CAZ. Neither clinical adverse effects nor abnormal laboratory findings were observed in any case. From the above results, CAZ is considered to be an antibiotic with high efficacy and safety in the treatment of neonates.

[Fundamental and clinical studies on ceftizoxime in pediatric field (author's transl)].

Fundamental and clinical studies of ceftizoxime, a new cephalosporin antibiotic, in children led to the following results. 1. Ceftizoxime compared favorably with cefazolin (CEZ) and cefmetazole (CMZ) for in vitro activity against clinically isolated strains of Staphylococcus aureus (31 strains), Escherichia coli (29), Klebsiella pneumoniae (30) and Pseudomonas aeruginosa (16). While somewhat less active against S. aureus than CEZ and CMZ, ceftizoxime was far more active than these 2 cephalosporin antibiotics against the test strains of E. coli and K. pneumoniae, which included strains resistant to the 2 drugs. Ceftizoxime was not particularly active against Ps. aeruginosa, but this seeming disadvantage was offset by the absolute ineffectiveness of the 2 reference drugs on this obstinate organism. 2. The time course of mean serum ceftizoxime levels in 3 pediatric patients of 5--10 years old given a single intravenous dose of 20 mg/kg was as follows: 45.4 micrograms/ml at 15 minutes, 40.4 micrograms/ml at 30 minutes, 22.1 micrograms/ml at 1 hour, 10.4 micrograms/ml at 2 hours, 2.9 micrograms/ml at 4 hours and 0.9 microgram/ml at 6 hours. The mean serum half life was 1.12 hours. The mean urinary levels of ceftizoxime at serial 2-hour collection intervals were as follows: 2,477 micrograms/ml for 1--2 hours, 1,235 micrograms/ml for 2--4 hours and 462 micrograms/ml for 4--6 hours. The mean urinary recovery up to 6 hours was 61.0%. 3. The clinical response of 28 children with infection to ceftizoxime treatment was 'excellent' in 22 children, 'good' in 4, and 'poor' in 2. These children comprised 11 with acute pneumonia, 3 with acute bronchitis, 4 with acute pyelonephritis, 2 each with acute purulent arthritis and acute enterocolitis, and 1 each with acute purulent tonsillitis, acute purulent lymphadenitis, furunculosis, subcutaneous abscess, subdural abscess and sepsis. The overall rate of effectiveness was 92.9%. Successfully eradicated strains in the bacteriological sense consisted of 4 strains each of H. influenzae and E. coli, 1 strain each of P. morganii, S. pneumoniae and S. pyogenes, 1 of the 2 strains of S. enteritidis, and 1 of the 3 strains of S. aureus. The overall rate of bacteriological effectiveness was 81.3%. No clinical side effects were observed. Changes in laboratory test findings included slightly and transiently elevated GOT and GPT in 1 child and GOT alone in another child.

[Pharmacokinetic and clinical studies on cefmenoxime in neonates and infants].

Pharmacokinetic and clinical studies on cefmenoxime (CMX) in neonates and infants were conducted. 1. CMX 20 mg/kg was administered by intravenous bolus injection to 6 neonates (with ages 2 to 20 days) and 5 infants (with ages 36 to 107 days) and its serum concentration and urinary excretion rates were determined. In the neonates, serum concentrations of CMX after intravenous administration reached peak levels of 48.2 to 90.7 micrograms/ml (mean 70.4 +/- 14.3 micrograms/ml) in 1/4 hour, then declined with half-lives of 1.27 to 5.19 hours (mean 2.28 +/- 1.56 hours), and were 3.6 to 16.9 micrograms/ml (mean 8.3 +/- 6.0 micrograms/ml) at 6 hours. In the infants, serum concentrations at 1/4 hour were 67.5 to 111.0 micrograms/ml (mean 95.5 +/- 18.0 micrograms/ml); half-lives were 0.64 to 0.94 hour (mean 0.81 +/- 0.13 hour); and the serum concentrations at 6 hours were 0.2 to 1.1 micrograms/ml (mean 0.7 +/- 0.4 micrograms/ml). Mean peak serum concentrations in the neonates tended to be lower than those in the infants, but higher than those in children. Regarding the age differences of serum concentrations due to age in the neonates, their peak levels tended to be lower in younger ones. Half-lives were shorter in older subjects and, in early infancy, approached values observed in children. Urinary recovery rates in the first 6 hours after intravenous administration ranged from 43.6 to 87.5% (mean 61.6 +/- 14.6%) in the neonates and from 52.1 to 90.8% (mean 78.0 +/- 15.1%) in the infants. Thus, recovery rates were high even in younger subjects and tended to be higher in older subjects. 2. CMX was administered to 27 neonates and 4 infants to investigate its clinical effect, bacteriological effect and side effects. Clinical efficacy ratings of the drug in 19 neonate cases that could be evaluated (1 with purulent meningitis, 2 with suspected septicemia, 1 with acute bronchitis, 12 with acute pneumonia, 1 with impetigo, 1 with periumbilical abscess and 1 with acute pyelonephritis) were "excellent" in 14 cases, "good" in 4, and "poor" in 1. The efficacy rate covering "excellent" and "good" was 94.7%. In 4 infants (2 with acute pneumonia, 1 with periumbilical abscess and 1 with acute pyelonephritis), "excellent" was obtained in 2 cases and "good" in 2 cases. Thus, all the cases showed "good" or higher ratings. Bacteriologically, 1 strain of Staphylococcus aureus and 3 strains of Escherichia coli in neonates were eradicated while, in infants, 1 strain of S. aureus persisted but 1 of E. coli was eradicated.(ABSTRACT TRUNCATED AT 400 WORDS)

REM sleep prevents sudden infant death syndrome.

Near-miss events were observed to occur in indeterminate sleep in a preterm infant reaching term at 6 weeks after birth. Moreover, prolonged sleep apnea and periodic respiration were frequently encountered in non-REM sleep. In view of the observation that pathologic sleep apnea occurs in non-REM sleep and the apparently contradictory findings of respiratory depression and more frequent apneas during REM sleep, apneic episodes during REM sleep were analysed in relation to phasic REM events. The frequent occurrence of respiratory pauses in REM burst-free periods of REM sleep suggests that tonic REM mechanisms inhibit respiratory neurons, while phasic REM mechanisms are facilitatory and protect an infant from prolonged sleep apnea.