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)     

Ultrastructure of lentigo maligna in the oral cavity

A rare case of lentigo maligna in the oral cavity was investigated by light and electron microscopy. Cutaneous lentigo malignas often develop to malignant melanomas. However, the electron microscopic examination revealed that even though there were a large number of melanosomes, most of them were late stage and had membrane structure, and positive staining with HMB-45 was not recognized. From our findings, it is difficult to conclude that oral lentigo malignas develop malignant melanomas, and thus further studies are needed.     

A Combination of Speckled Lentiginous Nevus with Patch-type Blue Nevus

A peculiar case of “nevus on nevus” was reported. A 67-year-old man had had a pigmented lesion in the left hypochondrial area since birth. The clinicopathologic findings of the pigmented lesion revealed a combination of speckled lentiginous nevus and patch-type blue nevus. This case of “nevus on nevus” is not described under the term of combined nevus as is current in the literature; it was considered to be a subtype of the type II atypical blue nevus described by Kawamura.     

Select types of supporting cell in the inner ear express aquaporin-4 water channel protein

Aquaporins (AQPs) confer a high water permeability on cell membranes and play important parts in secretory and absorptive epithelia in kidney and other organs. Here we investigate whether AQPs are expressed in the sensory epithelia of the inner ear, where a precise volume regulation is crucial. By use of specific antibodies it was found that the inner ear contains AQP1 and 4 while being devoid of detectable levels of AQP2, 3 or 5. Immunofluorescence and postembedding immunogold labelling revealed a strictly non-epithelial distribution of AQP1, confirming previous data. In contrast, AQP4 protein and mRNA (visualized by in situ hybridization) were concentrated in select types of supporting cell, including Hensen's cells and inner sulcus cells. Immunogold particles signalling AQP4 were confined to the basolateral plasma membrane of Hensen's cells and to the basal plasma membrane of Claudius cells and inner sulcus cells. AQP4 was also found in supporting cells of the vestibular end organs, but was absent from transitional epithelial cells and dark cells. Strong labelling for AQP4 and AQP4-mRNA was associated with the central part of the cochlear and vestibular nerves. Hair cells were consistently unlabelled. Our findings indicate that AQP4 may facilitate osmotically driven water fluxes in the sensory epithelia of the inner ear and thus contribute to the volume and ion homeostasis at these sites.     

Right pneumonectomy syndrome: Report of two cases

We report herein the cases of two infants who developed right pneumonectomy syndrome, both of whom were born with gross C-type esophageal atresia (EA/TEF), and a hypoplastic right lung arising from the lower esophagus, being a bronchopulmonary foregut malformation (BPFM). Appropriate and well-timed treatments for a variety of sequelae primarily caused by the mediastinal shift must be considered after right pneumonectomy in early childhood.     

A case of a probable "cancer family syndrome" presenting four synchronous malignancies of the colon

A 72-year-old male was admitted because of right lower quadrant pain, Barium enema and total colonoscopy disclosed multiple colon cancers and sequentially, a subtotal colectomy was performed. The resected specimen demonstrated 3 advanced carcinomas and an adenomatous cancer with additional multiple polyps. Investigation of his family history revealed that his mother and his elder sister had died of uterine cancer, and that his elder brother, his nephew, and his niece had been operated on for colorectal cancer. We thus supposed a case of "Cancer Family Syndrome" presenting multiple neoplasms of the colon.     

Similarities between the relaxations induced by vasoactive intestinal peptide and by stimulation of the non-adrenergic non-cholinergic neurons in the rat stomach

Summary The characteristics of the non-adrenergic, noncholinergic inhibitory response of the rat stomach fundus to transmural nerve stimulation were compared with the relaxation induced by vasoactive intestinal polypeptide (VIP). Treatment with -chymotrypsin (5 U/ml) or VIP antiserum (1:200) significantly reduced the relaxation induced by transmural nerve stimulation at 30 Hz, indicating that the possible transmitter in the non-adrenergic, non-cholinergic nerves is a peptide and may be VIP or a closely related peptide. VIP was able to relax, fully and dose-dependently, the stomach fundus that had previously been constricted by treatment with 10^–6 M serotonin, and the IC₅₀ value for VIP was 2.4 × 10^–9 M. VIP elevated levels of cyclic AMP in a dose-dependent manner and the EC₅₀ value was 2.8 × 10^–9 M in the presence of 10^–6 M atropine and 10^–6 M guanethidine. The stomach fundus was relaxed by transmural nerve stimulation (30 Hz, 50 mA) and transmural nerve stimulation also caused production of cyclic AMP in the rat stomach in the presence of atropine and guanethidine. The basal level of cyclic AMP in the stomach was 8.7 ± 0.26 pmole/mg protein. When transmural nerve stimulation was applied for 5 min, the contraction of the stomach, induced by 10^–6 M serotonin, was inhibited by 54% in the presence of atropine and guanethidine and the level of cyclic AMP was increased to 13.0 ± 0.73 pmol/mg protein. Apamin inhibited the transmural nerve stimulation-induced relaxation and shifted the dose-response curve for VIP to the right. These results suggest that one of the putative neurotransmitter from non-adrenergic, non-cholinergic nerves in the rat stomach is VIP and that VIP-induced relaxation may be mediated by the production of cyclic AMP and by the opening of apamin-sensitive K⁺-channels.Send offprint requests to K. Kamata at the above address     

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)     

Radioallergosorbent test (RAST) for specific IgE antibody to lidocaine,procaine and methylparaben

Although anaphylactoid reactions to local anesthetics are well known, a radioallergosorbent test (RAST) to detect specific drug reagin (IgE) anti-body has not been developed. We established RAST for local anesthetics by using carboxylic acid derivatives of lidocaine, procaine and methylparaben. Serum samples were taken from 100 volunteers who were regarded to be nonallergic to the drugs used. Negative RAST values obtained from these volunteers were 1653 ± 254(SD) cpm (lidocaine), 2750 ± 264cpm (procaine), and 2805 ± 336cpm (methyl paraben).(Kokubu M, Oda K, Shinya N: Radioallergosorbent test (RAST) for specific IgE antibody to lidocaine, procaine and methylparaben. J Anesth 3: 74–79, 1989)     

Recent Trends in the Treatment and Prognosis of Adult Leukemia with Characteristics of Patients in Japan: Transition during the Fifteen Years from 1971 to 1985

Patients with acute (2,569) and chronic (957) leukemia diagnosedat 19 institutes took part in the study on the "MultidisciplinaryTreatment of Leukemia" between 1971 and 1985 and were investigatedretrospectively. By dividing the 15 years into three five-yearperiods, we were able to compare patient ratios in the differentperiods. The proportions of acute to chronic leukemia casesshowed no obvious change; however, the proportions of casesdiagnosed as acute lymphocytic leukemia in acute leukemia showeda significant increase. The main chemotherapeutic drugs usedduring the three time periods were cytarabine or its analogues,the anthracyclines, 6-mercaputopurine and prednisolone, againstacute myelogenous leukemia, and the vinca alkaloids, prednisoloneand the anthracyclines against acute lymphocytic leukemia. Therate of complete remission from acute myelogenous leukemia mademarked progress, from 45.1% during 1971–1975 to 62.3%during 1981–1985, but that of acute lymphocytic leukemiashowed no significant progress, being 65% during 1971–1975and 69.7% during 1981–1985. The durations of remission,however, and the survival times for patients with acute lymphocyticleukemia, as well as for those with acute myelogenous leukemia,became significantly longer over the three periods. Median survivaltimes from chronic myelocytic leukemia were 37–40 mo inall three periods, showing no progress. There was a better prognosisin cases of chronic myelocytic leukemia with, than without,Philadelphia chromosome. Except for a low incidence of chroniclymphocytic leukemia in Japan, adult leukemia patients' characteristicsand prognoses seem to be almost the same in Japan as in theU.S.A. and Europe.