Pharmacokinetics of clarithromycin granule and tablet in children

It has been known that clarithromycin (TE-031, A-56268), a new macrolide antibiotic (ML), achieves higher concentrations in blood, is better excreted into urine and is better distributed into various tissues than conventional MLs. We investigated the pharmacokinetics of TE-031 in children upon oral administration of the drug in the following method. TE-031 granular preparation with a potency of 100 mg/g was given to 6 boys (5 years 4 months-14 years 0 month) with dose levels of 5 mg/kg and 10 mg/kg for each 3 boys. A tablet preparation with each tablet containing 50 mg of TE-031 was administered to 4 boys and 2 girls (8 years 5 months-11 years 6 months) with dose level of 2 tablets (i.e., 100 mg) and 3 tablets (i.e., 150 mg) for each 3 children. All administrations were done at 30 minutes before meal. Then, to conduct a cross-over test, the granule preparation was given orally to the 3 children mentioned above who was given 2 tablets and the 1 of 3 cases that were given 3 tablets at the same dose levels (100 mg and 150 mg) respectively. A bioassay was used to determine concentrations in blood of active antibiotic compounds and an high performance liquid chromatography (HPLC) was used to determine unchanged TE-031 and its main metabolite, M-5. Urinary concentrations of active antibiotic compounds were also determined by the bioassay and the HPLC was used to determine concentrations and proportions of unchanged TE-031 and its metabolites, M-1, M-4, M-5, M-6 and M-7 to figure out the urinary recovery rate in the first 6 hours. The results of these experiments are summarized as follows. 1. As was mentioned above, TE-031 was administered orally to 2 groups of children at dose levels of 5 mg/kg and 10 mg/kg, respectively. Mean serum levels of total active antibiotic compounds reached their maximum in 1 and 2 hours for the 5 mg/kg and the 10 mg/kg dosage groups, respectively, at 1.28 and 3.62 micrograms/ml, respectively. Mean half lives of serum concentrations in the 2 groups were quite similar, with values of at 2.1 and 2.0 hours, respectively. Mean serum concentrations of unchanged TE-031 determined by the HPLC method reached their peaks in 1 hour after administration in either of the 5 and 10 mg/kg dosage groups at peak levels of 0.65 micrograms/ml and 2.67 micrograms/ml, respectively. Thus, dose-response relationships were observed with TE-031 and M-5.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetics of amikacin in children and neonates

To evaluate pharmacokinetics of amikacin (AMK), one of the aminoglycoside antibiotics, children with ages from 2 days to 11 years were treated with various doses by various administration routes, and both plasma and urinary levels of AMK were determined. The following is a summary of the results obtained: 1. Of 6 children, three were treated with 2.0 mg/kg of AMK by a 30-minute intravenous drip infusion, and the other 3 with 4.0 mg/kg by a 60-minute. Peaks of average plasma levels were observed at the ends of the infusions in both cases, and their levels were 9.23 and 13.67 micrograms/ml, respectively, showing a dose-dependency. Both half-lives and areas under plasma concentration-time curves (AUCs) were similar to those of adults. However, the volume of distribution (Vd) showed a lower value than that of adults. Peaks of average urine levels were 149.3 micrograms/ml with 2.0 mg/kg in 0-2 hours after the start of the infusion and 223.3 micrograms/ml with 4.0 mg/kg in 2-4 hours. Average urinary recovery rates within 6 hours after the start of the infusion were 95.4% with 2.0 mg/kg and 85.7% with 4.0 mg/kg. These recoveries were equal to or higher than that of adults. 2. When 3.0, 4.0 and 6.0 mg/kg of AMK were administered to 3 groups of mature or premature babies by intramuscular injection, average peak levels of AMK in plasma were 6.26, 8.61 and 12.60 micrograms/ml, respectively, at 30 minutes after the injection, showing dose-dependency. In these groups, the younger the day age after birth was, the longer the half-life became. The AUCs were larger as the half-life became longer. The Vd was larger than that in the intravenous drip infusion group, but, any particular was not observed. Average peak levels of AMK in urine were 78.83 micrograms/ml at 4-6 hours with a dose level of 3.0 mg/kg, 99.17 micrograms/ml at 2-4 hours with 4.0 mg/kg and 139.20 micrograms/ml at 0-2 hours with 6.0 mg/kg. Average urinary recovery rates within 6 hours were 36.57% with 3.0 mg/kg, 34.67% with 4.0 mg/kg and 43.77% with 6.0 mg/kg. These recovery rates were markedly lower than those observed in adults and children. One of the causes of this low recovery is that mature and premature babies have immature renal functions. 3. When 3.0 mg/kg of AMK was administered to three premature babies by a 30-minute intravenous drip infusion, the average peak plasma levels was 7.61 micrograms/ml at the end of the drip infusion.(ABSTRACT TRUNCATED AT 400 WORDS)     

Idiopathic mediastinal fibrosis: Report of a case

(Received for publication on Nov. 14, 1996; accepted on May 12, 1997)     

Thyroplasty Type I with Ceramic Shim

Abstract: To prevent side effects from a silicone shim in Isshiki thyroplasty type I, we used a ceramic shim in 10 patients with unilateral recurrent laryngeal nerve paralysis. No published reports have described the use of ceramic in this type of surgery. According to the degree of glottic insufficiency, ceramic shims of various heights were inserted into the fenestration made in the thyroid ala. All patients experienced subjective improvement of voice postoperatively. Laryngoscopies in most cases showed that glottic insufficiency improved postoperatively. In the postoperative examination, the maximum phonation time improved an average of 3.7 s, and the mean flow rate improved an average of 331 ml/s. We have analyzed the relationship of these improvements to the degree of glottic insufficiency and have compared our results with those of other investigators.     

Evaluation of nicotine,cotinine, thiocyanate,carboxyhemoglobin, and expired carbon monoxide as biochemical tobacco smoke uptake parameters

Summary In a cross-sectional study on 236 individuals in Japan (174 males, 62 females; 149 smokers, 87 non-smokers) plasma nicotine (pnic), cotinine (pcot) and thiocyanate (pSCN), urinary creatinine ratios of nicotine (unic), cotinine (ucot) and thiocyanate (uSCN) as well as carboxyhemoglobin (COHb) and expired carbon monoxide (COex) were determined. All tobacco smoke uptake parameters (TSUP) were significantly elevated in smokers as compared to non-smokers. The discriminant power (smokers vs non-smokers) rank in the following order: ucot pcot unic > pSCN COHb pnic > COex uSCN. All parameters except for pnic are significantly correlated with the self-reported number of cigarettes smoked per day. The reason for the poor correlation of pnic with daily cigarette consumption is the short half-life of pnic coupled with the arbitrary time of blood drawing in relation to the last time of smoking.Dr. Muranaka, the chief author of this paper, was the director of our hospital. He died suddenly on 18 April 1986. This article is therefore the last monument to be planned and achieved under the late Dr. Muranaka's direction.     

Coronary artery reoperation utilizing "free" gastroepiploic artery

A 57-year-old female underwent coronary artery bypass reoperation successfully by utilizing the free gastroepiploic artery (GEA) graft in combination with the in situ left internal mammary artery (IMA) graft. The left IMA was anastomosed to the left anterior descending artery and the "free" GEA was anastomosed to the left IMA proximally and to the first diagonal branch distally. The patient recovered well with a disappearance of angina. Postoperative angiogram at 6 weeks showed good patency of both grafts and improvement of left ventricular contraction was obtained. Thus, GEA can be utilized not only as an "in situ" graft, but also as a "free" graft, effectively.     

A new closed-system using partially frozen injectate for thermodilution cardiac output determinations

The FI (partially frozen injectate) system, a new closed-system devised by the authors for thermodilution cardiac output determinations, has two major features: 1) it needs no ice-filled receptacle to keep injectate cold because it uses partially frozen injectate, and 2) it can go without monitoring the injectate temperatures during the whole process of cardiac output determinations. The author evaluated the accuracy and reproducibility of cardiac output determinations with the FI system in 10 critically ill patients, as compared with another closed-system (which is commercially available) and the standard open method. The injectate temperatures in the FI system were also measured in vitro. The mean injectate temperature in the FI system was 0.71 ± 0.26°C and 80% of the injectate temperatures were lower than 1.0°C. Even when no monitoring of injectate temperatures was made, the predicated error in the calculated cardiac output resulted as low as 2% with the FI system. The mean cardiac output values were not statistically different between the FI system and the other two systems.(Maruta H, Usuda Y, Okutsu Y et al.: A new closed-system using partially frozen injectate for thermodilution cardiac output determinations. J Anesth 3: 35–39, 1989)     

Prevalence of depressive symptoms in a Japanese occupational setting: a preliminary study.

We measured the prevalence of depressive symptoms in 2,190 Japanese tax office workers using the Japanese version of the Center for Epidemiologic Studies Depression Scale (CES-D). Score distribution by sex was more symmetrical and the mean score of each sex was higher than in the United States population. A high level of depressive symptoms was found in 15.2 percent of males and 10.6 percent of females by controlling for age and marital status. Males aged 50 years and over had more depressive symptoms than other male age groups. Perceived stress, related both to family life and the workplace, was associated with a high level of depressive symptoms. "Long-distance marriage" ("business bachelorhood"), peculiar to Japanese occupations, had little influence on depressive symptomatology.     

Influence of ascending noradrenergic fibers on the neurotensin-like immunoreactive perikarya and evidence of direct projection of ascending neurotensin-like immunoreactive fibers in the rat central nucleus of the amygdala

The influence of ascending noradrenergic neuronal input on the neurotensin (NT)-like immunoreactive neuronal perikarya located in the dorsal part of the central nucleus of the amygdala (CNA) was examined using fluorescence histochemistry and peroxidase-antiperoxidase (PAP) immunocytochemistry. Unilateral hemitransection of the ascending noradrenergic pathway by injection of 6-hydroxydopamine into the caudal mesencephalon just rostral to the locus coeruleus caused a marked depletion of immunoreactivity in NT-like immunoreactive neuronal perikarya in the CNA. Ascending noradrenergic neuronal input, therefore, is considered to facilitate production of NT-like immunoreactive substances in neuronal perikarya and to influence on the functional role of the amygdaloid complex. In addition, we obtained evidence of unilateral direct ascending projections of NT-like immunoreactive neurons into the CNA since the disappearance of NT-like immunoreactive processes occurred mainly in the ventral part of the CNA after surgical hemitransection of the ascending neuronal pathway that interrupts the ascending NT-like immunoreactive pathway arising from the neurons in the brain stem.