Effect of long term treatment with oxitropium bromide on airway secretion in chronic bronchitis and diffuse panbronchiolitis.

BACKGROUND--Anticholinergic bronchodilator drugs improve lung function in chronic bronchitis but less is known of their effects on the volume and physical properties of sputum in conditions associated with excessive airway secretions. This study examines the effects of the regular use of oxitropium bromide in such patients. METHODS--The study was conducted in a parallel, double blind, placebo controlled fashion. Patients were divided into two groups: the first group (n = 17) received oxitropium bromide from a metered dose inhaler (two puffs three times daily; 100 micrograms/puff) for eight weeks, and the second group (n = 16) received placebo. Lung function was measured as forced expiratory volume in one second (FEV1) and vital capacity. In evaluating airway secretion, daily amount of expectorated sputum, percentage solid composition, viscoelastic properties including elastic modulus and dynamic viscosity, and sputum microbiology were determined. RESULTS--Oxitropium bromide increased FEV1 and decreased the mean (SE) sputum production from 61(4) to 42(3) g/day after treatment, whereas placebo had no effect. Bacterial density and sputum flora were unchanged, but solid composition and elastic modulus increased from 2.52(0.43)% to 3.12(0.34)%, and 68(12) dyne/cm2, respectively, in the group taking oxitropium bromide. CONCLUSIONS--Regular treatment with oxitropium bromide not only improves airflow limitation but also reduces sputum production, probably through the inhibition of both mucus secretion and water transport, the latter component being predominant.     

Possible involvement of organic anion transporter 2 on the interaction of theophylline with erythromycin in the human liver.

Organic anion transporter 2 (Oat2 [SLC22A7]) is a multispecific organic anion transporter. Although several substrates of human Oat2 (hOat2) have been elucidated, a possible involvement of hOat2 in drug interaction is less defined. The purpose of this study was to investigate the interaction of theophylline with erythromycin mediated by hOat2 using a Xenopus laevis oocyte expression system. When expressed in Xenopus oocytes, hOat2 mediated the transport of theophylline and erythromycin. The finding indicates that the two compounds are novel substrates for hOat2. The apparent K(m) values for the uptake of hOat2 that mediated the transport of theophylline and erythromycin were 12.6 muM and 18.5 muM, respectively. The hOat2-mediated uptake of [(14)C]theophylline and [(14)C]erythromycin was cis-inhibited by adding erythromycin and theophylline, respectively. Our present findings suggest that hOat2 may, at least in part, be involved in the theophylline-erythromycin interaction in the human liver.     

Studies on the metabolic fate of 14C-rokitamycin. III. Transmigration to fetus or milk

Transmigration of 14C-radioactivity to fetus or milk were studied in 17-18 day-pregnant rats and mother rats on the 14th day after parturition after a single oral administration of 14C-rokitamycin (TMS-19-Q) at a dose of 200 mg/kg. The blood concentration of the drug in the mother reached a maximum level of 22.8 micrograms/ml at 2 hours after administration. Maximum concentrations of TMS-19-Q in placenta, ovary and uterus were attained in 2 hours, and were 28.9, 26.0 and 26.2 micrograms/g, respectively. The distribution to these tissues were considered good. The maximum concentration of TMS-19-Q in the amniotic fluid was attained in 2 hours, at a level of 5.4 micrograms/ml. The transmigration to the amniotic fluid was considered poor. The maximum concentration of the drug in the fetus was achieved in 2 hours at a level of 13.7 micrograms/g. Maximum concentrations of the drug in fetal liver and brain were attained in 4 hours, and were 32.8 and 11.4 micrograms/g, respectively. Whole body autoradiography was done when the radioactivity in maternal blood reached peak concentration. It was found that radioactivities in placenta and fetal membrane were similar to the radioactivity in maternal blood, while the radioactivity in fetal brain was considerably lower than that in maternal blood. Maximum concentrations were found at 1 hour in the blood and at 4 hours in the milk, and were 14.8 and 21.5 micrograms/ml, respectively. Transmigration to the milk was good.     

A Case of Glucagonoma with Liver Metastasis: Complete Response to Dacarbazine

Abstract: We report a case of glucagonoma syndrome with liver metastasis, who responded completely to dacarbazine chemotherapy. A 77-year-old woman complained of itching skin eruptions (diagnosed as necrolytic migratory erythema) and weight loss. She was found to have glucose intolerance, anemia, hypoproteinemia and hyperglucagonemia. Abdominal CT and celiac arteriography showed a hypervascular tumor in the pancreatic tail and a metastatic tumor in the left hepatic lobe. Immunohistochemical examination of the metastatic liver tumor obtained by laparoscopic biopsy revealed the tumor cells to be positive for glucagon. The patient was treated with 20 courses of 300 mg/day intravenous dacarbazine for 5 consecutive days followed by a 4 week drug-free interval. No major side effects were noted. Treatment resulted in disappearance of the skin lesions and correction of anemia, glucose intolerance, hypoproteinemia and hyperglucagonemia. Follow-up abdominal CT showed complete resolution of both the primary pancreatic tumor and the metastatic liver tumor. We suggest that dacarbazine be considered as the treatment of choice for metastatic glucagonoma.     

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.