The prevalence of Rett syndrome and infantile autism in Chikugo District, the southwestern area of Fukuoka prefecture, Japan.
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Biomedical subjects
Publications and source records attributed to F Yamashita.
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We report the results of ultrasonographic screening to determine the prevalence of renal abnormalities in children. This study was conducted simultaneously with a regular health check using portable realtime ultrasound equipment, from July 1988 to June 1989. Of 2920 three-year-old children resident in Kurume City, 2351 (80.5%) were screened. Abnormalities were detected in 11 (0.47%) of these, involving six cases of pelvic dilatation, three cases of unilateral renal agenesis, and two cases of a unilaterally small kidney. However, the simultaneous urinalysis of these 11 children did not disclose these abnormalities. Our results indicate that ultrasonography is an efficient tool for screening for a silent renal abnormality.
To establish a rationale of designing a drug targeting system using dextran conjugation, the disposition behaviour of dextran itself was investigated in mice. At a high dose (100 mg kg-1), [14C]dextran was retained in the blood circulation for a considerably long period. However, [14C]dextran rapidly disappeared from the plasma and accumulated in the liver (up to 60% of dose in 1 h) after a dose of 1 mg kg-1. Cellular localization of [14C]dextran in the liver following intravenous administration was examined and the contribution of parenchymal cells was demonstrated as well as the case of galactosylated bovine serum albumin (Gal-BSA). Pharmacokinetic analysis based on a physiological model including Michaelis-Menten type uptake mechanisms revealed that the Michaelis constant Km,l of [14C]dextran was 100 times greater than that of Gal-BSA. Coadministration of Gal-BSA delayed the hepatic uptake of [14C]dextran and the simulation based on the physiological model suggested that [14C]dextran was taken up by the same mechanism as Gal-BSA. These results suggested that dextran conjugation of a drug might lead to its undesirable accumulation in the liver at a low dose and an appropriate modification of dextran, such as carboxymethylation, would be required in such cases.
Wilson's disease is an autosomal recessive disorder characterized by an accumulation of a toxic amount of copper in the body. Triethylene tetramine dihydrochloride (trientine, 2HCl) is a new chelating agent that may be effective in the removal of excess copper but long-term efficacy has not yet been investigated. Here we report the use of trientine over more than 8 years in 2 patients with Wilson's disease who could not tolerate D-penicillamine. We found no significant side effect, except a decreased serum iron concentration without clinical symptoms of anemia. In annual examinations at a steady state, the serum copper levels remained below 20 micrograms/100 ml. The 24-hour urinary copper excretion was less than that found using D-penicillamine, while the basal copper excretion, after 5 days abstinence from trientine, was maintained below 100 micrograms/day. Both hepatic and neurological manifestations except bulbar symptoms were recovered without any initial deterioration.
A case of sclerosing hepatocellular carcinoma (SHCC) with hypercalcemia was reported. Clinical studies revealed a tumor at the liver hilum with invasion into the bile duct. Light microscopy of the tumor disclosed a moderately differentiated hepatocellular carcinoma (HCC) of the trabecular type with diffuse fibrous stroma. Abundant dense granules were observed in the cytoplasm of the tumor cells with electron microscopy. The elevated serum calcium (13.9 mg/dl) returned to the normal range after resection of the tumor.
Cefprozil (CFPZ), a newly developed cephalosporin in fine granular form, was administered to pediatric patients with skin and soft tissue infections. MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC), cloxacillin (MCIPC) against 53 clinical isolates of Staphylococcus aureus from these patients. An inoculum size of 10(6) CFU/ml was used in the MIC-determinations. CFPZ was given to 73 patients with ages ranging from 6 months to 10 years and 8 months and 71 cases were evaluable for clinical effects as follows; impetigo (65), Staphylococcal scalded skin syndrome (1), furuncle (1), subcutaneous abscess (3), and periproctal abscess (1). To study clinical efficacy, bacteriological effects and safety of this drug, a mean dose of 8.4 mg/kg with 3-4 daily dosages (57 cases of t.i.d. and 14 cases of q.i.d.) was administered for an average of 6 days. The results obtained are summarized as follows. 1. With regard to the 53 isolates of S. aureus, MICs of CFPZ against 52 strains (98.1%) ranged from 0.78 to 3.13 micrograms/ml. 45 strains (84.9%) were inhibited at 0.78 micrograms/ml. MIC90 of CFPZ was 1.56 micrograms/ml, but MIC against 1 strain of Methicillin-resistant S. aureus (MRSA) was 100 micrograms/ml. The MIC90 of CEX and CCL were 6.25 micrograms/ml and MIC of CEX and CCL against 1 MRSA strain were 200 and 100 micrograms/ml, respectively. The MIC90 of ABPC, DMPPC and MCIPC were 6.25, 3.13 and 0.39 micrograms/ml, respectively. CFPZ showed the second highest activity after MCIPC against S. aureus. 2. CFPZ showed very good clinical responses and clinical effects in 71 patients all of whom judged by doctors in charge as having "good" or better responses. 3. For impetigo patients, the evaluable cases by score 3, 5 and 7 days after administration of the drug were 52, 39 and 20 patients, respectively. The efficacy rates on these days were 90.4, 100 and 100%, respectively. The efficacy rate at a daily dose of 30.1-45.0 mg/kg on day 3 was 17.2% higher than that at 22.5-30.0 mg/kg, and the "excellent" response rate of 30.1-45.0 mg/kg group was 45.3% greater. Because of these results, it is expected that good clinical effects can be obtained at a daily dose of 22.5-30.0 mg/kg of CFPZ, but better responses can be expected at 30.1-45.0 mg/kg in 3-4 divided doses given for 5 days. 4. Bacteriological effects of CFPZ were determined against 60 strains of S. aureus.(ABSTRACT TRUNCATED AT 400 WORDS)
Cefprozil (CFPZ), a newly developed oral cephalosporin in a fine granular form for pediatric use, was administered to children with bacterial infections. MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC) and cloxacillin (MCIPC) against the following 84 strains isolated from cases to which CFPZ was administered; 55 strains of Gram-positive cocci (GPC) including 2 strains of Staphylococcus aureus, 49 strains of Streptococcus pyogenes, 4 strains of Streptococcus pneumoniae, and 29 strains of Gram-negative bacilli (GNB) including 10 strains of Haemophilus influenzae, 18 strains of Escherichia coli, and 1 strain of Proteus mirabilis. MIC determination of these strains was done with an inoculum size of 10(6) CFU/ml. In pharmacokinetic studies, serum concentrations, urinary concentrations and urinary recovery rates were investigated using bioassay and high-performance liquid chromatography (HPLC). CFPZ was orally administered 30 minutes before meals to 9 children with ages ranging from 7 years and 1 month to 12 years and 3 months. Three groups of 3 children were tested with doses of 4.0, 7.5 and 15.0 mg/kg, respectively. In addition to the above, clinical and bacteriological studies were performed in a total of 160 cases consisting of children with ages ranging 5 months to 12 years and 5 months. A mean dose of 8.6 mg/kg in 3-4 divided doses (130 cases of t.i.d. and 30 cases of q.i.d.) was administered for an average of 7 days. The 160 cases included 34 cases of pharyngitis, 5 cases of tonsillitis, 8 cases of acute bronchitis, 8 cases of pneumonia, 52 cases of scarlet fever, 4 cases of acute purulent otitis media, 47 cases of urinary tract infection, 1 case of purulent lymphadenitis and 1 case of posthitis. Adverse reactions and abnormal clinical laboratory test results were also examined in 166 cases, including 6 cases excluded from the evaluation of clinical efficacy. The results obtained are summarized as follows: 1. With regard to GPC, MICs of CFPZ against 2 strains of S. aureus were 0.78 or 1.56 micrograms/ml and CFPZ showed the second highest activity to MCIPC. MICs of CFPZ against 49 strains of S. pyogenes were all less than 0.025 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)
Meropenem (MEPM), a novel parenteral carbapenem antibiotic, was examined in a cooperative study involving 12 pediatric and 1 neonatologic facilities. The results are summarized as follows. 1. Antibacterial activity Antibacterial activity of MEPM against stock organisms including 31 strains of Streptococcus agalactiae, 14 of Listeria monocytogenes, 4 of Bordetella pertussis and 3 of Neisseria meningitidis ranged from 0.025 to 0.10 micrograms/ml in MIC90's, which were equal or lower than those of control drugs such as imipenem cefazolin, cefotiam, cefotaxime, ceftazidime and latamoxef. MICs against clinical isolates were as follows: In Gram-positive bacteria, MICs were 0.20 micrograms/ml to 6.25 micrograms/ml against 3 strains of Staphylococcus aureus, and 0.025 micrograms/ml or less against 4 of Streptococcus pneumoniae. In Gram-negative bacilli, MICs were 0.10 micrograms/ml to 0.20 micrograms/ml against 3 strains of Haemophilus influenzae and 0.78, 0.10 and 0.78 micrograms/ml, respectively, against one strain each of Enterobacter cloacae, Morganella morganii and Pseudomonas aeruginosa. MIC against 1 strain of Peptococcus saccharolyticus was < or = 0.025 micrograms/ml. 2. Pharmacokinetics Maximum plasma concentrations after intravenous infusion of MEPM over 30 minutes at doses of 10, 20 and 40 mg/kg, respectively, to 3 different groups of 3 children (total 9 cases) were observed at the completion of the treatment. Mean maximum concentrations in the 3 groups were 36.3, 69.5 and 129.8 micrograms/ml, respectively, exhibiting clear dose response. Mean plasma half lives in beta phase were 0.94, 0.86 and 0.94 hours, respectively, exhibiting no difference by doses, and this trend was observed also by HPLC. Urinary excretion rates in the first 6 hours after dose in the 10, 20 and 40 mg/kg groups were 67.3, 65.6 and 68.4%, respectively. Concentrations of MEPM in cerebrospinal fluid were determined in 2 cases of pyogenic meningitis. In 1 case, 500 mg (5.9 mg/kg) of MEPM was infused intravenously over 30 minutes and concentrations on Days 6, 8 and 15 observed at 190, 60 and 100 minutes after respective doses were 0.13, 0.10 micrograms/ml and less than the detection limit. Cerebrospinal fluid-plasma concentration ratio was determinable only on Day 8 and was 2.8%. In another case to which 250 mg (38.5 mg/kg) of MEPM was infused intravenously over 30 minutes, the concentration at Days 6, 7 and 10, 1 hour after the dose were less than the detection limit on day 6, and 2.04 and 2.62 micrograms/ml, respectively on days 7 and 10. 3. Clinical efficacy Clinical efficacies were evaluated in 49 cases and the efficacy rate was 93.9%.(ABSTRACT TRUNCATED AT 400 WORDS)
Streptococcus milleri (S. milleri) is found in healthy individuals in the mouth, nasopharynx, throat, vagina and in feces, and has been reported to be isolated from several infectious diseases in man, particularly from abscess in various parts of the body. We report two cases of severe infections due to S. milleri isolated from subdural abscess and pleural empyema. [Case 1] 13 year old boy who had been healthy until he was noticed to have meningeal signs and was diagnosed as left subdural abscess with siagonantritis by cranial CT scans. S. milleri was isolated from subdural abscess and maxillary sinus. [Case 2] 10 year old boy who had encephalitis and severe mental retardation after measles at 6 months of age. He had a fever, dyspnea and chest X-ray abnormalities and was diagnosed as right pleural empyema. Three strains of organism, S milleri, Bacteroides spp. and Fusobacterium nucleatum were isolated from the pleural effusion.
UNLABELLED: A study was undertaken to compare Pediatric Malignancy at Kurume (Japan) and Karachi (Pakistan) with reference to international data collected over the years, in order to identify essential differences between developed and developing conditions and factors influencing the etio-pathogenesis of pediatric cancer. The study was retrospective encompassing all types of cancer in children over a period of three years i-e 1988-1990. Essential factors related to present study were: 1. POPULATION: The population of Karachi is about 10 million while that of Kurume is only half a million. 2. Socio-economic conditions: The average socio-economic condition of people in Karachi is poor while in Kurume it appears to be good. 3. Educational status: Only 25% people in Karachi are educated beyond middle class while Kurume reveals a 100% education up to high school level. 4. Environmental conditions: The environmental conditions of Kurume and surrounding areas are very clean and free from pollution, sewage problems and traffic hazards. Karachi and its surroundings on the other hand pose very serious air and water industries! It was concluded that whereas genetic predisposition predominates, the environmental conditions, educational and socio-economic status of a society immensely influence the pattern and trends of pediatric carcinogenesis.
Recently we were able to stain bone canaliculi using the decalcified bone tissues, according to a modified method of the Bodian staining method, which is commonly used for staining the nerve fibers with silver impregnation of protargol. The bone tissues from normal rabbits, rats, and humans were decalcified with buffered EDTA solution after 10% formalin fixation. The tissues were embedded in paraffin and were sliced at 4 microns then the sections were attached to the gelatin-coated glass slides. These sections were treated first with potassium dichromate followed by 2% protargol solution containing copper. After gold chrolide treatment, they were immersed in oxalic acid. Both the lacunae and canaliculi of osteocytes were stained black in sharp contrast to bone matrix of red purple. Using the present staining method, the bone canaliculi were clearly detectable in fine details without producing apparent artificial damage of soft tissues. The canaliculi showed also markedly complex fine structures. By combining the present staining method with eosin or toluidine blue staining, we were able to recognize even immature osteocytes in enchondral ossification at growth cartilage with fine bone canaliculi. From these results, we conclude that the present method is very useful in histopathological studies of the lacuna-canalicular system of osteocytes in the decalcified bone tissues.
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UNLABELLED: Cefamandole (sodium salt) was administered to total 32 cases of bacterial infectious diseases of children, and in 3 cases, there were investigated of these absorption and excretion. The results are as follows; 1. Blood levels: Cefamandole was given intravenous dose of 25 mg/kg to 3 children. The blood level of 15 minutes after intravenous injection was 140.4 micrograms/ml in average, and 0.3 micrograms/ml in average at 4 hours after intravenous injection. T 1/2 was 13.9 minutes. 2. Urinary concentration: Within 6 hours after intravenous injection, 51.8% of the drug was recovered in average from the urine and the urinary concentration reached to 3,050 micrograms/ml in average (0 approximately 2 hours), 1,262 micrograms/ml in average (2 approximately 4 hours), 41 micrograms/ml in average (4 approximately 6 hours) after injection. 3. CLINICAL RESULTS: The drug was given 109 mg/kg/day (t.i.d. or q.i.d.) by intravenous route. The duration of administration was 11 days in average. The overall efficacy rate was 97%. In bacteriological results, excellent in 2, failure in 1, out of 3 strains. As side effects vascular pain was observed in 3 cases at the intravenous injection, and eosinophilia in 2 cases.
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PC-904 was administered to 24 patients: urinary tract infections (7 cases), bronchitis (2 cases), pneumonia (3 cases), brain abscess (1 case), septicemia and the suspected cases (10 cases), and buttock abscess (1 case). The daily dosage varied from 60 to 223.4 mg/kg and averaged 86.9 mg/kg. The drug was administered three times a day by 1-hour drip infusion, and the duration of the treatment averaged 11 days. Clinical results were obtained as excellent responses in 5 cases, good in 13, poor in 4, and unknown in 2, giving 75% of the clinical effectiveness. Bacteriological responses were excellent in 7, good in 2, poor in 2, and unknown in 13, and the overall effectiveness was evaluated as excellent in 2, good in 17, and unknown in 5. Antibacterial activities against clinically isolated bacteria were examined. MIC values of PC-904 were over 100 mg/ml 1 strain of E. coli and 2 strains of Klebsiella, however excellent sensitivities were observed in 3 strains of Ps. aeruginosa and MIC values varied 1.56 to 3.12 microgram/ml at 10(8) of inoculum size and 0.78 to 1.56 microgram/ml at 10(8). As to side effects, diarrhea was observed in 1 case, rash in 2, lowering ob blood pressure in 2, elevation of GOT in 1, and elevation of LDH in 2. Abnormal elevations of GOT (10 cases), GPT (5 cases), A1-P (1 case), LDH (7 cases), and BUN (1 case) were noticed in other patients, but it was considered to be due to underlying diseases.
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Incidence of spontaneous tumors was examined in 77 male and 73 female SD-JCL rats reared throughout their lifespan of 5 to 36 months. Total tumor incidences were 60% and 95% for males and females, respectively. The sex difference was mostly attributable to a high incidence of mammary tumor in females. The pituitary tumor was found in 30% of males and 66% of females aged 5 to 36 months while islet cell tumor of the pancreas and thyroid tumor occurred later and the incidence of latter was particularly high in rats lived more than 2 years. Myeloid leukemia appeared to occur as early as 5 months of age.