A Creutzfeldt-Jakob disease agent (Echigo-1 strain) recovered from brain tissue showing the 'panencephalopathic type' disease.

We used histologic evidence of degenerative changes in both the gray and white matter of the brain to diagnose a patient as having the panencephalopathic type of Creutzfeldt-Jakob disease (CJD). This type of CJD is relatively common in Japan, but not in North America or Europe. We recovered a transmissible pathogen (Echigo-1 strain) from an autopsy specimen of the patient's brain and passed it serially in Hartley guinea pigs. After a long latent period, it caused degenerative changes, mainly in the thalamic area of the guinea pig brain. On the 4th passage, a substrain emerged with a short latent period. When cross-transmitted to Golden Syrian hamsters, this substrain induced severe degeneration in both the thalamus and cerebral cortex. We compare our results with those for other experimental CJDs produced by other types of this disease.

Subclass of IgG antibody to GM1 epitope-bearing lipopolysaccharide of Campylobacter jejuni in patients with Guillain-Barré syndrome.

Sera of patients who develop Guillain-Barré syndrome (GBS) subsequent to Campylobacter jejuni enteritis frequently have IgG anti-GM1 antibody. Lipopolysaccharide (LPS) of C. jejuni isolated from a GBS patient has a GM1 ganglioside-like structure. IgG subclass distribution of the anti-GM1 antibody in GBS patients is mainly restricted to IgG1 and IgG3. Since IgG antibodies to bacterial polysaccharide generally are restricted to IgG2 subclass, some investigators have assumed that either the general rules for immune response to LPS are broken in the patients or an alternative antigen has yet to be identified. To clarify whether the LPS participates in the production of the anti-GM1 antibody, we investigated the subclass of IgG antibody to the LPS that bears GM1-like structure. The subclasses of IgG antibody to the LPS were restricted predominantly to IgG1 and IgG3. The GM1 epitope-bearing LPS may function in the production of the anti-GM1 antibody in patients with GBS subsequent to C. jejuni infection.

[Fundamental and clinical studies of PC-904 in pediatrics (author's transl)].

The following studies were carried out in pediatric patients. 1. Serum levels of PC-904 were examined in 3 patients by 1 hour intravenous infusion of 20 mg/kg, reaching the peak of 22.5 approximately 25.5 microgram/ml at the end of infusion. Half life was 37 approximately 48 minutes. 2. Investigated in only 1 patient, the urinary excretion rate was 12.9% (0 approximately 6 hours). 3. The effect of PC-904 on blood pressure was examined in 1 patient, and no effect was observed. 4. Clinical effects of PC-904 were examined in 9 patients; urinary tract infection (6 cases) and Salmonella enteritis (3 cases). The daily dose was 32.6 approximately 93.0 mg/kg. The overall clinical effectiveness was 66.7%. As to causative organisms E. coli, Klebsiella and Salmonella were isolated. The clinical effects by the organisms were 100%, 0%, and 66.7%, respectively. 5. Slight elevation of GOT and GPT and eosinophilia were observed in each one case but these abnormalities rapidly returned to pre-treatment levels when the administration was discontinued. No other side effects were noticed.

[Experience with cefuroxime in pediatric field (author's transl)].

Having resistance to beta-lactamase-producing strains and showing resistance to not only cephalosporin resistant strains of E. coli and Klebsiella but also to Citrobacter, Proteus and Enterobacter, Cefuroxime (CXM) was used in pediatric field for both fundamental and clinical studies. CXM was found to be a useful antibiotic in views of high clinical efficacy rate obtained and no side effect noted. As for the dose, the single dose of 25 mg/kg achieved sufficient blood levels. Also in view of good clinical effect, the dose of 25 mg/kg three or four times daily seems appropriate for treatment of children.

[Basic and clinical examinations of 6059-S in pediatrics (author's transl)].

1. MIC of 6059-S against 92 strains of clinically isolated bacteria were measured. The compound was active against most of Gram-negative rods, but was not active against Staphylococcus aureus. 2. 20 mg/kg of 6059-S (newly synthesized oxacephem antibiotics) was administered to the pediatric patients and its blood concentration was measured by agar well method using E. coli 7437 as a test organism. 3. The mean blood concentrations were maximum at 15 minutes after intravenous one-bolus injection. Maximum levels were 94.5 mcg/ml in the patients of below 5 years old and 98.7 mcg/ml above 6 years old. Their half-life of the blood levels were 95.4 and 110.6 minutes respectively. 4. The mean blood concentrations were highest at the end of the infusion in the cases of 60 minutes drip injection. Maximum levels were 85.0 mcg/ml in the patients of below 5 years old and 64.8 mcg/ml above 6 years old. 5. Clinical efficacy of 6059-S in 6 cases pyelonephritis, 2 cases of sepsis, 1 case of meningitis, 1 case of intraperitoneal abscess, 9 cases pneumonia and 2 case of tonsillitis was 100%. In the case of urinary tract infection, 4 patients were treated successfully by the administration of 20 mg/kg/day of 6059-S. Other bacterial infections were treated with 55 to 200 mg/kg/day. 6. 100% of the causative organisms were eliminated by 6059-S. They were E. coli, Klebsiella pneumoniae, Serratia marcescens, H. influenzae and beta-Streptococcus. 7. No remarkable side effect was noticed during administration.

[Examination of blood levels and urinary excretion of cefmetazole in the mature and immature neonates (author's transl)].

1. Cefmetazole was administered to mature and immature neonates for the purpose of treatment and prophylaxis of infections, and the blood level was examined. The mean blood level (moni-trol I standard) of cefmetazole after a single administration, 20 mg/kg intravenously, were 63.9 mcg/ml in 0 to 3 days old neonates and 57.4 mcg/ml in 4 to 7 days old neonates after 30 minutes, and 24.2 mcg/ml and 12.4 mcg/ml, respectively, after 6 hours. 2. The mean half-life of the blood level was 5.42 hours in 0 to 3 days old neonates and 2.55 hours in 4 to 7 old neonates. 3. The urinary excretion was varied, but approximately 80% of the administered dose seemed to be excreted during 0 to 12 hours. 4. Cefmetazole is seemed to be clinically effective by a single dose of 20 mg/kg giving twice daily in every 12 hours in 0 to 3 days old neonates, a dose of 20 mg/kg giving three times daily in every 8 hours in 4 to 7 days old infants, and a single dose of 20 mg/kg giving 3 to 4 times in every 6 to 8 hours in older than 8 days old neonates.

[Basic and clinical examinations of CS-1170 in pediatrics (author's transl)].

1. CS-1170 was administered for the purpose of prophylaxis during cardiac catheterization in patients with heart disease, and its blood levels were measured. 2. The mean blood level (Moni-Trol I standard) after one intravenous shot of 20 mg/kg was 53.6 mcg/ml in catheterized children aged below 6 and 66.9 mcg/ml in catheterized children aged above 10 at 30 minutes, and 1.95 mcg/ml and 5.2 mcg/ml respectively at 6 hours. 3. The mean half life of the blood level was 1.09 hours in catheterized children aged below 6, 1.37 hours in catheterized children aged above 10, and 0.71 hours in infections children. 4. The urinary excretion seemed satisfactorily high although there was a great variation. 5. The clinical efficacy was 88.9%. 6. The bacteriological efficacy was 100% for E. coli, Klebsiella, Proteus mirabilis and Staphylococcus aureus and was 0% for Staphylococcus epidermidis. 7. Although GOT and GPT were elevated in one case as a side effect, they rapidly returned to normal after discontinuation of administration.

[Clinical investigation of cefadroxil in pediatric field (author's transl)].

(1) Cefadroxil powder for syrup was administered in 24 cases of respiratory tract infection and urinary tract infection, and the efficacy was obtained in 21 cases, effective ratio being 87.5%. (2) Clinical effect could be obtained satisfactorily at a daily dose of 10-15 mg/kg divided into 3 times after each meal. (3) As to the side effect, GOT and GPT rose in 1 case, and stomatitis in 1 case, though the patients returned to normal after discontinuation of the drug. (4) Haemophilus appeared by pharyngeal culture after administration of the drug, and attention should be paid on an alteration of pharyngeal flora.

[Fundamental and clinical evaluation of 9,3"-diacetylmidecamycin in pediatric field (author's transl)].

1. The dry syrup of MOM was administered orally to 17 patients mainly with heart diseases at doses of 10 mg/kg and 20 mg/kg. In 17 cases, the serum level was measured and in 4 cases, the urinary excretion rate including the metabolites of MOM. 2. The mean maximal concentrations were 0.54 mcg/ml at 30 minutes for the group of 10 mg/kg treatment and 0.33 mcg/ml at 1 hour for the group of 20 mg/kg treatment. The dose response was not observed obviously in both groups. 3. In each of the cases, the sum of excretion rates of metabolites in the 24-hour urine was about 1%. 4. MOM was administered clinically to 39 cases with respiratory tract infections and the overall efficacy rate was 85%. 5. In this study, 5 strains of S. pyogenes were isolated and the eradication rate was 60%. 6. Although severe side effects were not observed, gastrointestinal abnormalities like diarrhea and vomiting were seen in 3 cases. 7. Any pediatric patient did not refuse taking.

[Clinical and fundamental studies on intravenous drip infusion of gentamicin in the pediatric field. Pediatric study group of gentamicin].

A multiclinic study of gentamicin (GM) given by intravenous drip infusion was carried out by the Gentamicin Pediatric Study Group. The results are summarized as follows: 1. Upon intravenous drip infusion of GM at a dose range of 2.0-2.5 mg/kg over a period of 0.5-1 hour, therapeutically effective serum concentrations of 4-12 micrograms/ml were obtained. These values are similar to reported values in previous studies using GM intramuscular injection. 2. High urinary concentrations were observed up to 6 hours after administration, and the urinary recovery rate was approximately 60%. 3. Of a total of 142 cases collected, 117 cases were evaluated. Efficacy rates by diseases were: 100% in pneumonia (30/30), 98.3% in urinary tract infections (59/60), and 92.3% in other infections (skin and soft tissue) (12/13), with an overall efficacy rate of 94.9% (including 77 "excellent" cases). 4. Bacteriological examinations showed high eradication rates with the use of GM; i.e., 80% with Staphylococcus aureus (8/10), 60% with Pseudomonas aeruginosa (3/5), 100% with Haemophilus influenzae (7/7) and 97.8% with Escherichia coli (44/45), achieving an overall eradication rate of 92.4%. In mixed infections, the eradication rate was 85.7% (6/7). 5. No ototoxicity, nephrotoxicity or allergic reactions was observed. Abnormal laboratory findings observed were: GOT elevation in 3.1% of cases, GPT elevation in 3.9%, platelet increase in 1.5% and eosinophil increase in 0.8%, thus an overall rate of the appearance of abnormality was 5.6%. The above results indicate that an intravenous drip infusion of GM is a useful method for treating infections in pediatrics.

[Fundamental and clinical studies of cefotiam in the field of pediatrics (author's transl)].

The fundamental and clinical studies on cefotiam (CTM) were performed in the field of pediatrics, and the following results were obtained: 1. The peak MIC's of CTM against Gram negative rods such as E. coli, Klebsiella, Salmonella, Proteus were 1.56 mcg/ml. The MIC distribution against S. aureus was almost equal to the conventional cephalosporin antibiotics. The MICs against P. pseudomonas and Serratia were over 400 mcg/ml. 2. The mean serum levels of CTM after bolus intravenous injection of 25 mg/kg were 59.9 mcg/ml after 15 min., 30.0 mcg/ml after 30 min., 15.6 mcg/ml after 1 hour. 3. Administration of CTM to 6 pediatric patients produced the clinical responses which were good in all 6 cases and the bacterial effects of eradication in 3 cases and superinfection in the 2 cases in the 5 cases from whom the organism were isolated. No side effect was observed. From the above results, it is considered that a bolus injection of CTM 25 mg/kg t.i.d. to q.i.d. is a safe and useful treatment for pediatric cases.

[Pharmacokinetics study on gentamicin intravenous drip infusion in children].

Pharmacokinetics of gentamicin in children after intravenous infusion over 60 minutes were compared with that after intramuscular injection. 1. Mean measured peak serum levels after intravenous infusion of 2.5 mg/kg and intramuscular injection of 2.0 mg/kg were 6.1 micrograms/ml at termination of infusion and 6.5 micrograms/ml at 30 or 60 minutes after injection, respectively. Older children showed higher serum levels. 2. There was no difference in serum half-life between both modes of administration. 3. The AUC after intravenous infusion was slightly larger than that after intramuscular injection. 4. It was suggested that the efficacy and safety of the treatment by intravenous infusion in children are comparable to that by the intramuscular injection, and optimum single dose is 1.5--2.5 mg/kg.

[Study of cefroxadine in pediatrics regarding clinical efficacy and serum levels (author's transl)].

Basic and clinical evaluations of cefroxadine were carried out in children, and the following results were obtained. 1. Cefroxadine 20 mg/kg was administered to 9 children with heart disease for the prophylaxis against infections before undergoing cardiocatheterization and cardioangiography, and serum levels were determined. Peak levels reached after 30 minutes in 4 of the 9 cases, with a mean peak level of 22.5 mcg/ml and after 1 hour in 5 cases, with a mean peak level of 16.2 mcg/ml. Half life was 3.1 hours in the former group in a 6-hour blood sampling (1.04 hours in a 2-hour sampling) while in the latter group it was 1.37 hours. 2. Clinical responses were evaluated in 56 children comprising 23 cases of pharyngitis, 8 of tonsillitis, 13 of scarlet fever, 10 of urinary tract infections and 2 of impetigo. Fifty of these cases had excellent and good responses showing a efficacy rate of 89.3%. 3. From 42 of the cases, 43 strains were isolated as causative organisms. Major organisms included 27 strains of S. pyogenes, 9 of E. coli and 3 of S. aureus. As for bacteriological responses, all strains were eradicated. 4. No severe side effects were observed except for diarrhea of 1 cases and eosinophilia of 2 cases. Furthermore, no children refused to take cefroxadine dry syrup.

[Basic and clinical studies on cefmenoxime in pediatric field].

Basic and clinical studies were made on cefmenoxime (CMX) in pediatric field, and the following results were obtained. 1. The antibacterial activity of CMX against clinically isolated and maintained strains was examined. CMX had stronger antibacterial activity than CEZ against Escherichia coli, Salmonella, Klebsiella pneumoniae, Proteus mirabilis, Serratia marcescens and Pseudomonas aeruginosa, but CEZ had stronger antibacterial activity against Staphylococcus aureus. 2. The blood concentrations of CMX, 0.5, 1, 2, 4 and 6 hours after a one-shot intravenous injection of 20 mg/kg of CMX were 33.6, 15.1, 4.5, 2.5 and 0.6 mcg/ml, respectively, with the half-life of 1.04 hours. 3. The blood concentrations of CMX, 0.5, 1, 2, 4 and 6 hours after a 1-hour intravenous drip infusion of 20 mg/kg of CMX were 32.0, 55.2, 8.4, 4.2 and 1.0 mcg/ml, respectively, with the half-lite of 0.96 hour. 4. A complete or partial clinical response to therapy with CMX was obtained in all 10 children with infectious diseases. 5. Bacteriological examination made on 3 patients showed that all bacteria had been eradicated, and that therapy was effective. The bacteria were E. coli in 2 patients and Proteus mirabilis in 1 patient. 6. The side effects produced were neutropenia, eosinophilia and skin eruption in 1 patient, and diarrhea in 1 patient.

[The experimental and clinical studies on cefsulodin in the pediatric field].

A new cephalosporin cefsulodin (CFS) was studied basically and clinically and the following results were obtained. 1. The serum levels of 25 mg/kg of CFS administered intravenously were 39.5 mcg/ml after 30 minutes, 22.6 mcg/ml after 1 hour, 11.6 mcg/ml after 2 hours, 6.0 mcg/ml after 4 hours and 2.1 mcg/ml after 6 hours. The half life from serum was 84 minutes. 2. Clinical response on 4 cases of Pseudomonas aeruginosa infections were all good. 3. The slight elevations of GOT, GPT were observed by the drug administrations in 1 case. From the above results, CFS was effective drug to P. aeruginosa infections by intravenous administration of 25 mg/kg of CFS.

[Fundamental and clinical studies of cefotaxime in neonates and immature infants].

Cefotaxime (CTX) was used in the treatment and prophylaxis of infections in neonates and immature infants. The following results were obtained. 1. Mean serum concentrations (bioassay) 30 minutes after a single intravenous injection of about 20 mg/kg of CTX were 44.5 mcg/ml in neonates and 47.2 mcg/ml in immature infants aged 0-3 days, 45.8 mcg/ml in neonates and 56.4 mcg/ml in an immature infant aged 4-7 days and 40.6 mcg/ml in neonates and 38.1 mcg/ml in immature infants aged 8 or more days. Six hour values were respectively 10.9 mcg/ml, 17.0 mcg/ml, 4.6 mcg/ml, 13.4 mcg/ml, 3.8 mcg/ml and 2.7 mcg/ml. 2. Mean serum concentration half-lives were 3.0 hours in neonates and 3.2 hours in immature infants aged 0-3 days, 1.8 hours in neonates and 3.2 hours in an immature infant aged 4-7 days, and 1.5 hours in neonates and 1.6 hours in immature infants aged 8 or more days. 3. Urinary recovery rates were 0.8-78.0% for 0-6 hours after treatment. 4. Adequate clinical efficacy can be expected by the intravenous injection of CTX in doses of 20 mg/kg 2 times daily, every 12 hours, in neonates and immature infants aged 0-3 days, 20 mg/kg 3 times daily, every 8 hours, in neonates and immature infants aged 4-7 days, and 20 mg/kg 3 to 4 times daily, every 6-8 hours, in neonates and immature infants aged 8 or more days. 5. The clinical efficacy of CTX was good in all 4 cases of sepsis (including suspected case), excellent in 1 case of urinary tract infection, and good in all 4 cases of fever of unknown origin for a cure rate of 100%. 6. Adverse reactions were not noted in any cases.