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Biomedical subjects

A Okuno

Publications and source records attributed to A Okuno.

At least 109 records · Page 6Linked to original sources
PubMed1988

Treatment of hypopituitarism with recombinant somatropin for 1 year.

Twenty-five hypopituitary patients were treated with recombinant somatropin for 1 year at a dosage of 0.5 IU/kg/week. In previously untreated patients (n = 16), heights increased by between 4.5 and 10.2 cm, with a mean height velocity of 7.7 +/- 1.8 cm/year (mean +/- SD). In previously treated patients (n = 9), heights increased by between 3.9 and 7.6 cm, with a mean height velocity of 5.8 +/- 1.0 cm/year, similar to that observed during previous treatment with pituitary GH. Anti-GH antibodies were observed in two patients at a low titre. The antibodies disappeared in one patient during the treatment. These data indicate that recombinant somatropin has a growth promoting effect and low immunogenicity.

Adolescent↗
PubMed1987

Clinical trial with authentic recombinant somatropin in Japan.

Recombinant somatropin, produced by recombinant DNA technology, was administered by injection in daily doses of 8 IU to six healthy young volunteers. Daily injection for 4 days did not cause any significant change in the results of physical examination, blood count or urinalysis. Non-esterified fatty acid levels increased significantly from 0.45 +/- 0.16 to 1.08 +/- 0.12 mEq/litre (mean +/- SEM) at 4 hours after the first injection (p less than 0.001). Plasma IGF-1 levels increased from 0.80 +/- 0.14 units/ml to 1.72 +/- 0.50, 3.22 +/- 1.02, 3.17 +/- 1.20 and 3.63 +/- 0.78 units/ml at 24 hours after each daily injection for 4 days (p less than 0.001). Plasma hGH reached peak levels at 3 hours after intramuscular injection of recombinant somatropin, 4 IU, and this peak value was 57.3 +/- 2.8 ng/ml. A total of 21 patients with pituitary dwarfism were also treated with recombinant somatropin for 6 months at a dose of 0.5 IU/kg/week. Their heights increased by 2.2-5.0 cm during the 6 months of treatment, which was calculated to be equivalent to 4.4-10.0 cm/year with a mean growth rate of 7.4 +/- 0.4 cm/year. Anti-hGH antibody with a titre of 10 was observed in two patients at the end of 6 months of treatment.

Adolescent↗
PubMed1987

Urine growth hormone determinations compared with other methods in the assessment of growth hormone secretion.

Urinary excretion of hGH was studied in children with short stature using a sensitive sandwich enzyme immunoassay technique. Urinary hGH excretion, in terms of hGH: creatinine ratio, showed excellent correlation with the mean and peak hGH values during physiological and pharmacological tests. It seems that the urinary hGH levels reflect serum hGH profiles during the urine collection period. A border zone for the lower limits of normal hGH levels in the urine was 7.5-13.4 ng/g creatinine for the physiological test at night (from 2000 hours to 0600 hours) and 17.4-35.0 ng/g creatinine for the pharmacological tests. Assessment of hGH secretory status by the urinary hGH levels showed good agreement with the serum hGH response. Measurement of urinary hGH could be used as a diagnostic test for impaired hGH secretion, and the multiple blood drawing required in physiological and pharmacological tests might be replaced by urine sampling.

Child↗
PubMed1987

Treatment of pituitary dwarfism with authentic recombinant human growth hormone (SM-9500).

Twenty-one patients with pituitary dwarfism were treated with methionine-free hGH (r-hGH) for 6 months with a dosage of 0.5 IU/kg/week. The height of newly treated patients (N = 14), increased from 2.4 to 5.0 cm during treatment, which corresponded to from 4.8 to 10.0 cm with a mean of 8.1 +/- 0.5 cm/year. In switched patients (N = 7), height increased from 2.2 to 3.8 cm during the treatment, which corresponded to 4.4-7.6 cm with a mean of 6.1 +/- 0.5 cm/year, which was similar to that observed in previous treatment with pituitary extracted hGH (p-hGH). Anti-hGH antibody was observed in two patients (9.5%) at the end of 6 months of treatment with a titer of 10. These data indicate that r-hGH has a growth promoting effect and low antigenicity.

Adolescent↗
PubMed1987

Pharmacokinetics of methimazole in children and adolescents with Graves' disease. Studies on plasma and intrathyroidal concentrations.

Methimazole concentrations in plasma and in the thyroid glands were measured by means of high-performance liquid chromatography. Pharmacokinetics of methimazole were studied after a single oral dose (175 mumol/m2) in nine children and adolescent who were in the thyrotoxic state. Plasma levels of methimazole showed peak concentrations of 4.4 to 12.6 (median 9.2) mumol/l at 0.5 to 4 h after drug administration. Plasma half-life, area under the curve, and distribution volume ranged from 2.73 to 6.04 h, 32.8 to 77.9 mumol X l-1 X h-1, and 0.516 to 0.913 l/kg, respectively. These pharmacokinetic parameters showed a wide variation among the patients, but were quite reproducible in the same subject. Intrathyroidal concentrations of methimazole were measured in another nine subjects including four adolescents and five adults who underwent thyroidectomy. The drug concentrations in the thyroid glands ranged between 3.5 and 23.8 mumol/kg tissue and were far higher than those in the plasma obtained at the time of surgery. In this series of experiments, the dose of the drug varied from 76 to 319 mumol/m2, time after the last dose to surgery from 5 to 24 h, and the mode of drug administration from a single to three divided doses. Among these variable factors, only the daily dose of methimazole corrected by body surface area showed significant correlation with the intrathyroidal concentration, whereas the time after the last dose of the drug and the mode of drug administration did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Treatment of pituitary dwarfism with methionyl human growth hormone in Japan.

Sixty-two patients with pituitary dwarfism were treated with three different preparations of methionyl hGH (m-hGH) for 3 to 14 months. They were given 0.5 IU/kg/week intramuscularly. The growth rate during treatment with the three different preparations was the same for each and increased from 3.5 +/- 0.9 to 8.2 +/- 1.7 cm/year. A high incidence of hGH antibody formation was observed following the treatment, but the titer of antibody was decreased according to the purity of m-hGH preparations. At the end of 12 month treatment with a highly purified preparation (Somatonorm III), 76.2% of the patients had hGH antibody. However, the presence of antibodies did not affect the growth rate except in one patient. No clinical or laboratory side-effects were observed following the treatment with m-hGH. Thus, m-hGH was considered to be useful for the treatment of GH deficient children.

Adolescent↗
PubMed1985

Neuropathologic study in the heterozygotes of X-linked brindled mutant mouse.

The clinical and morphological features were studied in female heterozygotes of the sex-linked brindled mutant mice, which are an appropriate animal model for human Menkes' kinky hair disease (MKHD). Clinically, female heterozygotes presented phenotypical variety. In these heterozygotes, we distinguished the unique group of mice, which showed mottled white and dark brown fur and curly whiskers. We designated this unique group "heterozygote, variant type", in contrast to the remaining group--"heterozygote, usual type"--, of which the fur was mottled dark and light brown, and the whiskers were straight. Ultrastructurally, various degrees of mitochondrial changes, from an almost normal appearance of the mitochondria to similar to those of the hemizygotes, were observed. Furthermore we noticed that, in the heterozygotes, there were positive correlations between this morphological spectrum and those phenotypical varieties. These findings were interpreted as a possible subclinical copper deficiency in the heterozygotes, and the morphological alterations in heterozygotes were probably due to X-chromosome inactivation according to Lyon's hypothesis. The presence, however, of clinical and morphological varieties in the heterozygotes leads us to the hypothesis that the inactivation rate is not necessarily the same for all carriers. Moreover, it can be speculated that pathologic changes similar to those in heterozygotes may be present in the female carriers of human MKHD.

Animals↗
PubMed1985

Pathochemical study of a case of hereditary cerebral degenerative disease--lipopigment accumulation and peroxidase deficiency in brain.

Ultrastructural study of autoptic cerebral tissue from a patient with hereditary degenerative disease of the nervous system revealed lipofuscin-like bodies and variable sized osmiophilic granular masses in neurons. Autofluorescent granules were also found in neurons. Biochemical study demonstrated a deficiency of diaminobenzidine peroxidase and the accumulation of lipopigment in cerebral tissue.

Brain↗
PubMed1985

Placental transfer of lidocaine and elimination from newborns following obstetrical epidural and pudendal anesthesia.

Following local anesthetic use, maternal and umbilical serum levels of lidocaine were determined at delivery by means of a gas-chromatography-mass-spectrometry technique in 13 cases. In six cases, where delivery was performed by cesarean section, lidocaine was used for epidural analgesia. The dose given averaged 4.0 +/- 1.7 mg/kg, and the time between analgesia and delivery was 22.0 +/- 4.5 minutes. The mean umbilical serum level of lidocaine was 1.19 +/- 0.79 micrograms/ml and that of the maternal serum was 2.18 +/- 1.25 micrograms/ml. The fetal to maternal ratio was 0.52 +/- 0.18. Lidocaine levels of neonatal plasma were followed at 3, 6, 12, and 24 hours after delivery, and the mean half-life was found to be 6.7 +/- 1.3 hours. In the other seven cases, lidocaine was given in normal vaginal delivery for pudendal nerve block, and the dose was as small as 0.79 +/- 0.06 mg/kg. The mean umbilical and maternal serum concentrations of lidocaine were 0.064 +/- 0.039 micrograms/ml and 0.143 +/- 0.071 micrograms/ml, respectively, and the ratio was 0.45 +/- 0.16. Lidocaine given to the mothers crossed to the fetuses readily and resulted in neonatal plasma levels that were half those of the mothers'. The elimination of lidocaine from the newborn after birth was prolonged so that it might prevent the adaptation of the infant to postnatal circumstances. Viewed from the standpoint of infant care, anesthetics at delivery should be given to the mother only when the benefit obtained by their use outweighs any possible disadvantages.

Anesthesia, Epidural↗
PubMed1984

[An improved method for plasma methimazole assay and its clinical application].

An improved method for plasma methimazole assay using high performance liquid chromatography is described. The plasma samples were treated with sodium bisulfite and ammonium sulfate prior to extraction with chloroform. This pretreatment of the samples raised the extraction coefficient to 90%, while simple extraction yielded only 55%. The minimal detection limit was 0.02 microgram/ml, and the coefficient of variation at the level of 0.2 and 1.0 microgram/ml was less than 5%. Pharmacokinetics of methimazole was studied after a single oral dose (20 mg/m2) in six subjects including two healthy adults and four thyrotoxic children. Plasma levels of methimazole showed a peak concentration of 1.03 +/- 0.25 microgram/ml approximately one hour after the drug administration. Plasma half-life, area under the curve and distribution volume were 4.56 +/- 0.71 hr, 7.05 +/- 0.95 microgram/ml X hr, and 630 +/- 110 ml/kg respectively.

Adolescent↗
PubMed1983

Neuropathologic changes in suckling and weanling rats with pyrithiamine-induced thiamine deficiency.

Pregnant and nursing Wistar rats were fed a thiamine-deficient diet, and their offspring were injected daily with pyrithiamine. The pathologic lesions in the suckling rats were examined at different times of development. There were distinct changes at 22 days of age, by which time the rats are weaned, and the morphogenesis of the cerebellum is almost completed. Before 22 days of age, there were no pathologic changes except for scattered petechial hemorrhages in the brain. After 22 days of age, acute pathologic changes were observed, in decreasing order of severity, in the vestibular nuclei, inferior olivary nuclei, mammillary body, periventricular gray matter, thalamus, and quadrigeminal plates. The initial changes were swelling of post-synaptic dendrites and distension of the periaxonal space of myelinated axons in the parenchyma and ring-shaped hemorrhages in the perivascular space. Pyrithiamine injections into the offspring of rats fed a thiamine-deficient diet probably induce disturbance of the electrolyte permeability of the neuronal excitable membrane, resulting in swelling of this element. These changes were followed by the filtration of erythrocytes and plasma into the parenchyma and astrocytic swelling, which may be a secondary effect of neuronal changes on the brain vascular permeability.

Age Factors↗
PubMed1983

[Comprehensive evaluation of cefotetan in pediatrics].

Fundamental and clinical studies on cefotetan (CTT), a new cephamycin antibiotic, were carried out under a joint study programme in pediatric field, and the following results were obtained. Pharmacokinetic study In 20 pediatric patients with normal renal function, weighing 15 to 48 kg, CTT was injected intravenously at 20 mg/kg in 3 to 5 minutes. The mean blood concentration of CTT was 215.6 micrograms/ml at 15 minutes after the end of injection, 90.7 micrograms/ml at 1 hour, 57.2 micrograms/ml at 2 hours, 33.9 micrograms/ml at 4 hours and 10.2 micrograms/ml at 8 hours. The half-life of the drug in the beta-phase, computed from the mean blood concentrations up to 8 hours postdosing, was 2.61 hours. The peak of the mean urinary excretion of cefotetan appeared in 0 to 2 hours after the injection and 36.5% of the dose was recovered in the urine. The mean excretion at 0 to 8 hours was 68.1%. Clinical study Clinical effects of CTT was evaluated in 285 patients with 287 diseases, since 1 patient had both pneumonia and erysipelas, and another both pneumonia and acute otitis media. Daily dosage of CTT ranged from 15 to 123 mg/kg, and 266 patients (93.3%) received the drug either 2 or 3 times daily. The clinical response was seen in 83.3% of the 6 cases with sepsis, 89.3% of the 122 cases with pneumonia with or without pyothorax, 96.2% of the 52 cases with either acute bronchitis or tonsillitis, 92.5% of the 67 cases with urinary tract infection and 92.5% of the 40 cases with other infections. The causative organisms were detected in 160 patients and the rate of complete disappearance was 80.6%. Out of 310 patients, side effects were seen in 9 cases, diarrhea in 8 (2.6%) and rash in 1 (0.3%). Abnormal clinical laboratory findings were seen in 24 cases, elevation of serum transaminases in 19 (7.8%), elevation of TTT and LDH in 1 (0.4%) and eosinophilia in 4 (1.6%). None of these cases showed serious side effects or abnormal clinical laboratory findings. From the above results, it is concluded that CTT is one of the useful drug for treatment of infections in pediatric field.

Adolescent↗
PubMed1983

[Clinical results of cefpiramide therapy in infections of children].

Twenty-one pediatric patients with moderate or severe infections were treated with cefpiramide (CPM). The drug was given intravenously in a dose of 10 approximately 52.3 mg per kg at 8 approximately 12 hourly interval. All 7 patients with urinary tract infection, 4 with bacterial enteritis and 4 out of 7 patients with lower respiratory tract infections responded satisfactory, but 2 patients with either Serratia marcescens septicemia or H. influenzae meningitis not responded to treatment. Over all response rate was 71.4 percent. There was no change in test of liver and renal function. CPM appears to be effective and well-tolerated antibiotics for the treatment of pediatric patients with various infections.

Age Factors↗