Pharmacokinetic Study of Isoniazid and Rifampicin in Healthy Korean Volunteers / 결핵

BACKGROUND: Isoniazid(INH) and rifampicin(RFP) are potent antituberculous drugs which have made tuberculous disease become decreasing. In Korea, prescribed doses of INH and RFP have been different from those recommended by American Thoracic Society. In fact they were determined by clinical experience rather than by scientific basis. Even there has been. few reports about pharmacokintic parameters of INH and RFP in healthy Koreans. METHOD: Oral pharmacokinetics of INH were studied in 22 healthy native Koreans after administration of 300mg and 400mg of INH to each same person successively at least 2 weeks apart. After an overnight fast, subjects received medication and blood samples were drawn at scheduled times over a 24-hour period. Urine college lion was also done for 24 hours. Pharmacokinetics of RFP were studied in 20 subjects in a same fashion with 450mg and 600mg of RFP. Plasma and urinary concentrations of INH and RFP were determined by high-performance liquid chromatography(HPLC). RESULTS: Time to reach peak serum concentration (Tmax) of INH was 1.05α0.34 hrs at 300mg dose and 0.98α0.59 hrs at 400mg dose. Half-life was 2.49α0.88 hrs and 2.80α0.75 hrs, respectively. They were not different significantly(p>0.05) Peak serum concentration(Cmax) after administration of 400mg of INH was 7.14α 1.95mcg/mL which was significantly higher than Cmax (4.37α1.28mcg/mL) by 300mg of INH(p0.05). Cmax after administration of 600mg of RFP was 13.61 α3.43mcg/mL which was significantly higher than Cmax(10.12α2.25mcg/mL) by 450mg of RFP(p<0.01). CLtot of RFP at 450mg dose was 7.60α1.34mL/hr. At 600mg dose it was 7.05α 1.20mL/hr which was significantly lower(p<0.05) than by 450mg dose. While CLr was not different among two groups, CLnr at 600mg dose(5.36α1.20mL/hr) was significantly lower than CLnr(6.19α 1.56mL/hr) by 450mg dose(p<0.01). CONCLUSION: Considering Cmax and CLnr, 300mg, of INH and 450mg RFP might be sufficient doses for the treatment of tuberculosis in Koreans. But it remains to be clarified in the patients with tuberculosis.

Adhesion-induced generation of oxygen free radical from human alveolar macrophages and its mechanisms / 결핵

BACKGROUND: Neutrophils or monocytes separated in vitro by the adherence to plastic surface are known to be activated by surface adherence itself and subsequent experimental data might be altered by surface adherence. In the process of surface adherence, adhesion molecules have a clear role in intracellular signal pathway of cellular activation. Human alveolar macrophages(HAM) are frequently purified by the adherence procedure after bronchoalveolar lavage. But the experimental data of many reports about alveolar macrophages have ignored the possibility of adhesion-induced cellular activation. METHOD: Bronchoalveolar lavage was performed in the person whose lung of either side was confirmed to be normal by chest CT. With the measurement of hydrogen peroxide release from adherent HAM to plastic surface and non-adherent HAM with or without additional stimulation of phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP), we observed the effect of the adherence to plastic surface. We also evaluated the effect of various biological surfaces on adhesion-induced activation of HAM. Then, to define the intracellular pathway of signal transduction, pretreatment with cycloheximide, pertussis toxin and anti-CD 11/CD18 monoclonal antibody was done and we measured hydrogen peroxide in the culture supernatant of HAM. RESULTS: 1) The adherence itself to plastic surface directly stimulated hydrogen peroxide release from human alveolar macrophages and chemical stimuli such as phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine(fMLP) colud not increase hydrogen peroxide release in these adherent macrophages which is already activated. 2) PMA activated human alveolar macrophages irrespective of the state of adhesion. However, fMLP stimulated the release of hydrogen peroxide from the adherent macrophages, but not from the non-adherent macrophages. 3) HAM adherent to A549 cell(type II alveolar epithelium-like human cell line) monolayer released more hydrogen peroxide in response to both PMA and fMLP. This adherence-dependent effect of fMLP was blocked by pretreatment of macrophages with cycloheximide, pertussis toxin and anti-CD18 monoclonal antibody. CONCLUSION: These results suggest that the stimulatory effect of PMA and fMLP can not be found in adherent macrophage because of the activation of human alveolar macrophage by the adherence to plastic surface and the cells adhered to biologic surface such as alveolar epithelial cells are appropriately responsive to these stimuli. It is also likely that the effect of fMLP on the adherent macrophage requires new protein synthesis via G protein pathway and is dependent on the adhesion between alveolar macrophages and alveolar epithelial cells by virtue of CD11/CD18 adhesion molecules.

Two cases of bronchial leiomyoma resectedby Nd-YAG laser under flexible bronchoscopy / 결핵

The leiomyoma of the bronchus is a very rare benign tumor in the lower respiratory tract. Though classical treatment of the branchial leiomyoma is surgical resection, bronchoscopic tumor resection has been recently applied to selected cases. We experienced two cases of bronchial leiomyomas which were successfully resected under flexible bronchoscopy using Nd-YAG laser and bronchial snare. We speculated that bronchoscopic resection of the bronchial leiomyoma would be an effective and safe way of treatment, and more technical developments should follow.

Bilateral Hyperintense Basal Ganglia on T1-weighted Image

PURPOSE: Bilateral high signal intensity in basal ganglia on Tl-weighted images is unusual. the purpose of this study is to describe the pattern of high signal intensity and underlying disease. METHODS AND MATERIALS: During the last three years, 8 patients showed bilateral high signal intensity in basal ganglia on Tl-weighted image, as compared with cerebral white matter. Authors analized the images and underlying causes retrospectively. Of 8 patients, 5 were male and 3 were female. The age ranged from 15 days to 79 years. All patient were examined by a 0.5T superconductive MRI. Images were obtained by spin echo multislice technique. RESULTS: Underlying causes were 4 cases of hepatopathy, 2 cases of calcium metabolism disorder, and one case each of neurofibromatosis and hypoxic brain injury. These process were bilateral in all cases and usually symmetric. In all cases the hyperintense areas were generally homogenous without mass effect or edema, although somewhat nodular appearence was seen in neurofibromatosis. Lesions were located in the globus pallidus and internal capsule in hepatopathy and neurofibromatosis, head of the caudate nucleus in disorder of calcum metabolism, and the globus pallidus in hypoxic brain injury. CONCLUSION: Although this study is limited by its patient population, bilateral hyperintense basal ganglia is associated with various disease entities. On analysis of hyperintense basal ganglia lesion, the knowledge of clinical information improved diagnostic accuracy.