• The Korean Journal of Pharmacology
• /
• v.16 no.2 s.27
• /
• pp.55-70
• /
• 1980

The pharmacological and microbiological studies of Cefoperazone (T-1551, Toyama Chemical Co., Japan) were conducted in vitro and in vivo. The studies included stability and physicochemical characteristics, antimicrobial activity, animal and human pharmacokinetics, animal pharmacodynamics and safety evaluation of Cefoperazone sodium for injection. 1) Stability and physicochemical characteristics. Sodium salt of cefoperazone for injection had a general appearance of white crystalline powder which contained 0.5% water, and of which melting point was $187.2^{\circ}C$. The pH's of 10% and 25% aqueous solutions were 5.03 ana 5.16 at $25^{\circ}C$. The preparations of cefoperazone did not contain any pyrogenic substances and did not liberate histamine in cats. The drug was highly compatible with common infusion solutions including 5% Dextrose solution and no significant potency decrease was observed in 5 hours after mixing. Powdered cefoperazone sodium contained in hermetically sealed and ligt-shielded container was highly stable at $4^circ}C{\sim}37^{\circ}C$ for 12 weeks. When stored at $4^{\circ}C$ the potency was retained almost completely for up to one year. 2) Antimicrobial activity against clinical isolates. Among the 230 clinical isolates included, Salmonella typhi was the most susceptible to cefoperazone, with 100% inhibition at MIC of ${\leq}0.5{\mu}g/ml$. Cefoperazone was also highly active against Streptococcus pyogenes(group A), Kletsiella pneumoniae, Staphylococcus aureus and Shigella flexneri, with 100% inhibition at $16{\mu}g/ml$ or less. More than 80% of Escherichia coli, Enterobacter aerogenes and Salmonella paratyphi was inhibited at ${\leq}16{\mu}/ml$, while Enterobacter cloaceae, Serratia marcescens and Pseudomonas aerogenosa were somewhat less sensitive to cefoperagone, with inhibitions of 60%, 55% and 35% respectively at the same MIC. 3) Animal pharmacokinetics Serum concentration, organ distritution and excretion of cefoperazone in rats were observed after single intramuscular injections at doses of 20 mg/kg and 50 mg/kg. The extent of protein binding to human plasma protein was also measured in vitro br equilibrium dialysis method. The mean Peak serum concentrations of $7.4{\mu}g/ml$ and $16.4{\mu}/ml$ were obtained at 30 min. after administration of cefoperazone at doses of 20 mg/kg and 50 mg/kg respectively. The tissue concentrations of cefoperazone measured at 30 and 60 min. were highest in kidney. And the concentrations of the drug in kidney, liver and small intestine were much higher than in blood. Urinary and fecal excretion over 24 hours after injetcion ranged form 12.5% to 15.0% in urine and from 19.6% to 25.0% in feces, indicating that the gastrointestinal system is more important than renal system for the excretion of cefoperazone. The extent of binding to human plasma protein measured by equilibrium dialysis was $76.3%{\sim}76.9%$, which was somewhat lower than the others utilizing centrifugal ultrafiltration method. 4) Animal pharmacodynamics Central nervous system : Effects of cefoperazone on the spontaneous movement and general behavioral patterns of rats, the pentobarbital sleeping time in mice and the body temperature in rabbits were observed. Single intraperitoneal injections at doses of $500{\sim}2,000mg/kg$ in rats did not affect the spontaneous movement ana the general behavioral patterns of the animal. Doses of $125{\sim}500mg/kg$ of cefoperazone injected intraperitonealy in mice neither increased nor decreased the pentobarbital-induced sleeping time. In rabbits the normal body temperature was maintained following the single intravenous injections of $125{\sim}2,000mg/kg$ dose. Respiratory and circulatory system: Respiration rate, blood pressure, heart rate and ECG of anesthetized rabbits were monitored for 3 hours following single intravenous injections of cefoperazone at doses of $125{\sim}2,000mg/kg$. The respiration rate decreased by $3{\sim}l7%$ at all the doses of cefoperazone administered. Blood pressure did not show any changes but slight decrease from 130/113 to 125/107 by the highest dose(2,000 mg/kg) injected in this experiment. The dosages of 1,000 and 2,000 mg/kg seemed to slightly decrease the heart rate, but it was not significantly different from the normal control. All the doses of cefoperazone injected were not associated with any abnormal changes in ECG findings throughout the monitering period. Autonomic nervous system and smooth muscle: Effects of cefoperazone on the automatic movement of rabbit isolated small intestine, large intestine, stomach and uterus were observed in vitro. The autonomic movement and tonus of intestinal smooth muscle increased at dose of $40{\mu}g/ml$ in small intestine and at 0.4 mg/ml in large intestine. However, in stomach and uterine smooth muscle the autonomic movement was slightly increased by the much higher doses of 5-10 mg/ml. Blood: In vitro osmotic fragility of rabbit RBC suspension was not affected by cefoperazone of $1{\sim}10mg/ml$. Doses of 7.5 and 10 mg/ml were associated with 11.8% and 15.3% prolongation of whole blood coagulation time. Liver and kidney function: When measured at 3 hours after single intravenous injections of cefoperaonze in rabbits, the values of serum GOT, GPT, Bilirubin, TTT, BUN and creatine were not significantly different from the normal control. 5) Safety evaluation Acute toxicity: The acute toxicity of cefoperazone was studied following intraperitoneal and intravenous injections to mice(A strain, 4 week old) and rats(Sprague-Dawler, 6 week old). The LD_(50)'s of intraperitonealy injected cefoperazone were 9.7g/kg in male mice, 9.6g/kg in female mice and over 15g/kg in both male and female rats. And when administered intravenously in rats, LD_(50)'s were 5.1g/kg in male and 5.0g/kg in female. Administrations of the high doses of the drug were associated with slight inhibition of spontaneous movement and convulsion. Atdominal transudate and intestinal hyperemia were observed in animals administered intraperitonealy. In rats receiving high doses of the drug intravenously rhinorrhea and pulmonary congestion and edema were also observed. Renal proximal tubular epithelial degeneration was found in animals dosing in high concentrations of cefoperazone. Subacute toxicity: Rats(Sprague-Dawley, 6 week old) dosing 0.5, 1.0 and 2.0 g/kg/day of cefoperazone intraperitonealy were observed for one month and sacrificed at 24 hours after the last dose. In animals with a high dose, slight inhibition of spontaneous movement was observed during the experimental period. Soft stool or diarrhea appeared at first or second week of the administration in rats receiving 2.0g/kg. Daily food consumption and weekly weight gain were similar to control during the administration. Urinalysis, blood chemistry and hematology after one month administration were not different from control either. Cecal enlargement, which is an expected effect of broad spectrum antibiotic altering the normal intestinal microbial flora, was observed. Intestinal or peritoneal congestion and peritonitis were found. These findings seemed to be attributed to the local irritation following prolonged intraperitoneal injections of hypertonic and acidic cefoperazone solution. Among the histopathologic findings renal proximal tubular epithelial degeneration was characteristic in rats receiving 1 and 2g/kg/day, which were 10 and 20 times higher than the maximal clinical dose (100 mg/kg) of the drug. 6) Human pharmacokinetics Serum concentrations and urinary excretion were determined following a single intravenous injection of 1g cefoperazone in eight healthy, male volunteers. Mean serum concentrations of 89.3, 61.3, 26.6, 12.3, 2.3, and $1.8{\mu}g/ml$ occured at 1,2,4,6,8 and 12 hours after injection respectively, and the biological half-life was 108 minutes. Urinary excretion over 24 hours after injection was up to 43.5% of administered dose.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.4
• /
• pp.729-741
• /
• 1997

Background : We have recently reported that airway epithelial cells can produce RANTES and IL-8 in response to the stimulation of tubercle bacilli suggesting a certain role of airway epithelial cells in the pathogenesis of pulmonary tuberculosis. The pathogenesis of tuberculosis is determined by several factors including phagocytosis, immunological response of host, and virulence of tubercle bacilli. Interestingly, there have been reports suggesting that difference in immunological response of host according to the virulence of tubercle bacilli may be related with the pathogenesis of tuberculosis. We, therefore, studied the expressions and productions of RANTES and IL-8 in airway epithelial cells in response to tubercle bacilli(H37Rv, virulent strain and H37Ra, avirulent strain), in order to elucidate the possible pathophysiology of pulmonary tuberculosis. Methods : Peripheral blood monocytes were isolated from normal volunteers. Peripheral blood monocytes (PBM) were stimulated with LPS($10{\mu}g/ml$), H37Rv, or H37Ra($5{\times}10^5$ bacilli/well) along with normal control for 24 hours. A549 cells were stimulated with supernatants of cultured PBM for 24 hours. ELISA kit was used for the measurement of $TNF{\alpha}$ and IL-$1{\beta}$ production in supernatants of cultured PBM and for the measurement of RANTES and IL-8 in supernatants of cultured A549 cells. Northern blot analysis was used for the measurement of RANTES and IL-8 mRNA expression in cultured A549 cells. Results : $TNF{\alpha}$ and IL-$1{\beta}$ productions were increased in cultured PBM stimulated with LPS or tubercle bacilli(H37Rv or H37Ra) compared with the control. There was, however, no difference in $TNF{\alpha}$ and IL-$1{\beta}$ production between cultured PBM stimulated with H37Rv and H37Ra. RANTES and IL-8 expressions and productions were also increased in cultured A549 cells stimulated with LPS or tubercle bacilli compared with the control. RANTES and IL-8 mRNA expressions were significantly increased in cultured A549 cells stimulated with H37Ra-conditioned media(CM) compared with A549 cells stimulated with H37Rv-CM (p<0.05). However, there was no difference in RANTES and IL-8 productions between A549 cells stimulated with H37Rv-CM and H37Ra-CM. Conclusion : Airway epithelial cells can produce the potent chemokines such as RANTES and IL-8, in response to the stimulation of tubercle bacilli. These results suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis. However, the role of airway epithelial cells in the pathogenesis of tuberculosis according to the virulence of tubercle bacilli was not clear in this study.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.18 no.2
• /
• pp.22-27
• /
• 2014

Purpose There is the recent PET/CT scan in tendency that use low dose to reduce patient's exposure along with development of equipments. We diminished $^{18}F$-FDG dose of patient to reduce patient's exposure after setting up GE Discovery 690 PET/CT scanner (GE Healthcare, Milwaukee, USA) establishment at this hospital in 2011. Accordingly, We evaluate acquisition time per proper bed by change of infusion dose to maintain quality of image of PET/CT scanner. Materials and Methods We inserted Air, Teflon, hot cylinder in NEMA NU2-1994 phantom and maintained radioactivity concentration based on the ratio 4:1 of hot cylinder and back ground activity and increased hot cylinder's concentration to 3, 4.3, 5.5, 6.7 MBq/kg, after acquisition image as increase acquisition time per bed to 30 seconds, 1 minute, 1 minute 30 seconds, 2 minute, 2 minutes 30 seconds, 3 minutes, 3 minutes 30 seconds, 4 minutes, 4 minutes 30 seconds, 5 minutes, 5 minutes 30 seconds, 10 minutes, 20 minutes, and 30 minutes, ROI was set up on hot cylinder and back radioactivity region. We computated standard deviation of Signal to Noise Ratio (SNR) and BKG (Background), compared with hot cylinder's concentration and change by acquisition time per bed, after measured Standard Uptake Value maximum ($SUV_{max}$). Also, we compared each standard deviation of $SUV_{max}$, SNR, BKG following in change of inspection waiting time (15minutes and 1 hour) by using 4.3 MBq phantom. Results The radioactive concentration per unit mass was increased to 3, 4.3, 5.5, 6.7 MBqs. And when we increased time/bed of each concentration from 1 minute 30 seconds to 30 minutes, we found that the $SUV_{max}$ of hot cylinder acquisition time per bed changed seriously according to each radioactive concentration in up to 18.3 to at least 7.3 from 30 seconds to 2 minutes. On the other side, that displayed changelessly at least 5.6 in up to 8 from 2 minutes 30 seconds to 30 minutes. SNR by radioactive change per unit mass was fixed to up to 0.49 in at least 0.41 in 3 MBqs and accroding as acquisition time per bed increased, rose to up to 0.59, 0.54 in each at least 0.23, 0.39 in 4.3 MBqs and in 5.5 MBqs. It was high to up to 0.59 from 30 seconds in radioactivity concentration 6.7 MBqs, but kept fixed from 0.43 to 0.53. Standard deviation of BKG (Background) was low from 0.38 to 0.06 in 3 MBqs and from 2 minutes 30 seconds after, low from 0.38 to 0 in 4.3 MBqs and 5.5 MBqs from 1 minute 30 seconds after, low from 0.33 to 0.05 in 6.7 MBqs at all section from 30 seconds to 30 minutes. In result that was changed the inspection waiting time to 15 minutes and 1 hour by 4.3 MBq phantoms, $SUV_{max}$ represented each other fixed values from 2 minutes 30 seconds of acquisition time per bed and SNR shown similar values from 1 minute 30 seconds. Conclusion As shown in the above, when we increased radioactive concentration per unit mass by 3, 4.3, 5.5, 6.7 MBqs, the values of $SUV_{max}$ and SNR was kept changelessly each other more than 2 minutes 30 seconds of acquisition time per bed. In the same way, in the change of inspection waiting time (15 minutes and 1 hour), we could find that the values of $SUV_{max}$ and SNR was kept changelessly each other more than 2 minutes 30 seconds of acquisition time per bed. In the result of this NEMA NU2-1994 phantom experiment, we found that the minimum acquisition time per bed was 2 minutes 30 seconds for evaluating values of fixed $SUV_{max}$ and SNR even in change of inserting radioactive concentration. However, this acquisition time can be different according to features and qualities of equipment.

• Journal of Preventive Medicine and Public Health
• /
• v.30 no.1 s.56
• /
• pp.45-59
• /
• 1997

It has been known that there is a tracking phenomenon in the level of serum lipids. However, no study has been performed to examine the change and tracking of serum lipids in Korean adolescents. The purpose of this study is to examine the changes of serum lipids in Korean adolescents from 12 to 16 years of age, and to examine whether or not there is a tracking phenomenon in serum lipids level during the period. In 1992 serum lipids(total cholesterol(TC), triglyceride(TG), LDL cholesterol(LDL-C), HDL cholesterol(HDL-C)) were measured in 318 males, 365 females who were 12 years of age in Kangwha county, Korea. These participants have been followed up to 1996 and serum lipids level were examined in 1994 and 1996. Among the participants 162 males and 147 females completed all three examinations in fasting state. To examine the effect of eliminating adolescents with incomplete data, we compared serum lipids, blood pressure and anthropometric measures at baseline between adolescents with complete follow-up and adolescents who were withdrawn. To examine the change of serum lipids we compared mean values of serum lipids according to age in males and females. Repeated analysis of variance was used to test the change according to age. We used three methods to examine the existence of tracking. First, we analyzed the trends in serum lipids over 4-year period within quartile groups formed on the basis of the first-year serum lipids level to see whether or not the relative ranking of the mean serum lipids among the quartile groups remained in the same group for 4-year period. Second, we quantified the degree of tracking by calculating Spearman's rank correlation coefficient between every tests. Third, the persistence extreme quartile method was used. This method divides the population into quartile groups according to the initial level of blood lipids and then calculates the percent of the subjects who stayed in the same group at follow-up measurement. The decreases in levels were noted during 4 years for TC, LDL-C, primarily for boys. The level of HDL-C decreased between baseline and first follow-up for both sexes. Tracking, as measured by both correlation coefficients and persistence extreme quartiles, was evident for all of the lipids. The correlation coefficients of TC between baseline and 4 years later in boys and girls were 0.55 and 0.68, respectively. And the corresponding values for HDL-C were 0.58 and 0.69. More than 50% of adolescents who belonged to the highest quartile group in TC, HDL-C and LDL-C at the baseline were remained at the same group at the examination performed 2 years later for both sexes. The probabilities of remaining at the same group were more than 35% when examined 4 years later. The tracking phenomenon of TG was less evident compared with the other lipids. Percents of girls who stayed at the same group 2 years later and 4 years later were 42.9% and 25.7%, respectively. It was evident that serum lipid levels tracked in Korean adolescents. Researches with longer follow-up would be needed in the future to investigate the long-term change of lipids from adolescents to adults.

• Radiation Oncology Journal
• /
• v.25 no.1
• /
• pp.16-25
• /
• 2007

[ $\underline{Purpose}$ ]: Breast conserving surgery (BCS) followed by chemotherapy (CTx.) and radiation therapy (RT) is widely performed for the treatment of early breast cancer. This retrospective study was undertaken to evaluate our interim results in terms of failure patterns, survival and relative risk factors. $\underline{Materials\;and\;Methods}$: From January 1999 through December 2003, 129 patients diagnosed with invasive breast cancer and treated with BCS followed by RT were subject to retrospective review. The median age of the patients was 45 years (age distribution, $27{\sim}76$ years). The proportions of patients according to their tumor, nodes, and metastases (TNM) stage were 65 (50.4%) in stage I, 41 (31.7%) in stage IIa, 13 (10.1%) in stage IIb, 9 (7.0%) in stage III, and 1 patient (0.8%) in stage IIIc. For 32 patients (24.8%), axillary node metastasis was found after dissection. BCS consisted of quadrantectomy in 115 patients (89.1%) and lumpectomy in 14 patients (10.6%). Axillary node dissection at axillary level I and II was performed for 120 patients (93%). For 7 patients (5.4%), only sentinel node dissection was performed with BCS. For 2 patients (1.6%) axillary dissection of any type was not performed. Postoperative RT was given with 6 MV X-rays. A tumor dose of 50.4 Gy was delivered to the entire breast area using a tangential field with a wedge compensator. An aditional dose of $9{\sim}16\;Gy$ was given to the primary tumor bed areas with electron beams. In 30 patients (23.3%), RT was delivered to the supraclavicular node. Most patients had adjuvant CTx. with $4{\sim}6$ cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimens. The median follow-up period was 50 months (range: $17{\sim}93$ months). $\underline{Results}$: The actuarial 5 year survival rate (5Y-OSR) was 96.9%, and the 5 year disease free survival rate (5Y-DFSR) was 93.7%. Local recurrences were noted in 2 patients (true: 2, regional node: 1) as the first sign of recurrence at a mean time of 29.3 months after surgery. Five patients developed distant metastases as the first sign of recurrence at $6{\sim}33$ months (mean 21 months). Sites of distant metastatic sites were bone in 3 patients, liver in 1 patient and systemic lesions in 1 patient. Among the patients with distant metastatic sites, two patients died at 17 and 25 months during the follow-up period. According to stage, the 5Y-OSR was 95.5%, 100%, 84.6%, and 100% for stage I, IIa, IIb, and III respectively. The 5Y-DFSR was 96.8%, 92.7%, 76.9%, and 100% for stage I, IIa, IIb, and III respectively. Stage was the only risk factor for local recurrence based on univariate analysis. Ten stage III patients included in this analysis had a primary tumor size of less than 3 cm and had more than 4 axillary lymph node metastases. The 10 stage III patients received not only breast RT but also received posterior axillary boost RT to the supraclavicular node. During the median 53.3 months follow-up period, no any local or distant failure was found. Complications were asymptomatic radiation pneumonitis in 10 patients, symptomatic pneumonitis in 1 patient and lymphedema in 8 patients. $\underline{Conclusion}$: Although our follow up period is short, we had excellent local control and survival results and reaffirmed that BCS followed by RT and CTx. appears to be an adequate treatment method. These results also provide evidence that distant failure occurs earlier and more frequent as compared with local failure. Further studies and a longer follow-up period are needed to assess the effectiveness of BCS followed by RT for the patients with less than a 3 cm primary tumor and more than 4 axillary node metastases.

• Korean Journal of Fisheries and Aquatic Sciences
• /
• v.15 no.1
• /
• pp.1-25
• /
• 1982

Limnological study on the physico-chemical properties and biological characteristics of the Lake Ok-Jeong was made from May 1980 to August 1981. For the planktonic organisms in the lake, species composition, seasonal change and diurnal vertical distribution based on the monthly plankton samples were investigated in conjunction with the physico-chemical properties of the body of water in the lake. Analysis of temperature revealed that there were three distinctive periods in terms of vertical mixing of the water column. During the winter season (November-March) the vertical column was completely mixed, and no temperature gradient was observed. In February temperature of the whole column from the surface to the bottom was $3.5^{\circ}C$, which was the minimum value. With seasonal warming in spring, surface water forms thermoclines at the depth of 0-10 m from April to June. In summer (July-October) the surface mixing layer was deepened to form a strong thermocline at the depth of 15-25 m. At this time surface water reached up to $28.2^{\circ}C$ in August, accompanied by a significant increase in the temperature of bottom layer. Maximum bottom temperature was $r5^{\circ}C$ which occurred in September, thus showing that this lake keeps a significant turbulence Aehgh the hypolimnial layer. As autumn cooling proceeded summer stratification was destroyed from the end of October resulting in vertical mixing. In surface layer seasonal changes of pH were within the range from 6.8 in January to 9.0 in guutuost. Thighest value observed in August was mainly due to the photosynthetic activity of the phytoplankton. In the surface layer DO was always saturated throughout the year. Particularly in winter (January-April) the surface water was oversaturated (Max. 15.2 ppm in March). Vertical variation of DO was not remarkable, and bottom water was fairly well oxygenated. Transparency was closely related to the phytoplankton bloom. The highest value (4.6 m) was recorded in February when the primary production was low. During summer transparency decreased hand the lowest value (0.9 m) was recorded in August. It is mainly due to the dense blooming of gnabaena spiroides var. crassa in the surface layer. A. The amount of inorganic matters (Ca, Mg, Fe) reveals that Lake Ok-Jeong is classified as a soft-water lake. The amount of Cl, $NO_3-N$ and COD in 1981 was slightly higher than those in 1980. Heavy metals (Zn, Cu, Pb, Cd and Hg) were not detectable throughout the study period. During the study period 107 species of planktonic organisms representing 72 genera were identified. They include 12 species of Cyanophyta, 19 species of Bacillariophyta, 23 species of Chlorophyta, 14 species of Protozoa, 29 species of Rotifera, 4 species of Cladocera and 6 species of Copepoda. Bimodal blooming of phytoplankton was observed. A large blooming ($1,504\times10^3\;cells/l$ in October) was observed from July to October; a small blooming was present ($236\times10^3\;cells/l$ in February) from January to April. The dominant phytoplankton species include Melosira granulata, Anabaena spiroides, Asterionella gracillima and Microcystis aeruginota, which were classified into three seasonal groups : summer group, winter group and the whole year group. The sumner group includes Melosira granulate and Anabaena spiroides ; the winter group includes Asterionella gracillima and Synedra acus, S. ulna: the whole year group includes Microtystis aeruginosa and Ankistrodesmus falcatus. It is noted that M. granulate tends to aggregate in the bottom layer from January to August. The dominant zooplankters were Thermocpclops taihokuensis, Difflugia corona, Bosmina longirostris, Bosminopsis deitersi, Keratelle quadrata and Asplanchna priodonta. A single peak of zooplankton growth was observed and maximum zooplankton occurrence was present in July. Diurnal vertical migration was revealed by Microcystis aeruginosa, M. incerta, Anabaena spiroides, Melosira granulata, and Bosmina longirostris. Of these, M. granulata descends to the bottom and forms aggregation after sunset. B. longirostris shows fairly typical nocturnal migration. They ascends to the surface after sunset and disperse in the whole water column during night. Foully one species of fish representing 31 genera were collected. Of these 13 species including Pseudoperilnmpus uyekii and Coreoleuciscus splendidus were indigenous species of Korean inland waters. The indicator species of water quality determination include Microcystis aeruginosa, Melosira granulata, Asterionelta gracillima, Brachionus calyciflorus, Filinia longiseta, Conochiloides natans, Asplanchna priodonta, Difflugia corona, Eudorina elegans, Ceratium hirundinella, Bosmina longirostris, Bosminopsis deitersi, Heliodiaptomus kikuchii and Thermocyclops taihokuensis. These species have been known the indicator groups which are commonly found in the eutrophic lakes. Based on these planktonic indicators Lake Ok-Jeong can be classified into an eutrophic lake.

• Nuclear Medicine and Molecular Imaging
• /
• v.41 no.1
• /
• pp.30-41
• /
• 2007

Purpose: Bone metastasis in breast cancer patients are usually assessed by conventional Tc-99m methylene diphosphonate whole-body bone scan, which has a high sensitivity but a poor specificity. However, positron emission tomography with $^{18}F-2-deoxyglucose$ (FDG-PET) can offer superior spatial resolution and improved specificity. FDG-PET/CT can offer more information to assess bone metastasis than PET alone, by giving a anatomical information of non-enhanced CT image. We attempted to evaluate the usefulness of FDG-PET/CT for detecting bone metastasis in breast cancer and to compare FDG-PET/CT results with bone scan findings. Materials and Methods: The study group comprised 157 women patients (range: $28{\sim}78$ years old, $mean{\pm}SD=49.5{\pm}8.5$) with biopsy-proven breast cancer who underwent bone scan and FDG-PET/CT within 1 week interval. The final diagnosis of bone metastasis was established by histopathological findings, radiological correlation, or clinical follow-up. Bone scan was acquired over 4 hours after administration of 740 MBq Tc-99m MDP. Bone scan image was interpreted as normal, low, intermediate or high probability for osseous metastasis. FDG PET/CT was performed after 6 hours fasting. 370 MBq F-18 FDG was administered intravenously 1 hour before imaging. PET data was obtained by 3D mode and CT data, used as transmission correction database, was acquired during shallow respiration. PET images were evaluated by visual interpretation, and quantification of FDG accumulation in bone lesion was performed by maximal SUV(SUVmax) and relative SUV(SUVrel). Results: Six patients(4.4%) showed metastatic bone lesions. Four(66.6%) of 6 patients with osseous metastasis was detected by bone scan and all 6 patients(100%) were detected by PET/CT. A total of 135 bone lesions found on either FDG-PET or bone scan were consist of 108 osseous metastatic lesion and 27 benign bone lesions. Osseous metastatic lesion had higher SUVmax and SUVrel compared to benign bone lesion($4.79{\pm}3.32$ vs $1.45{\pm}0.44$, p=0.000, $3.08{\pm}2.85$ vs $0.30{\pm}0.43$, p=0.000). Among 108 osseous metastatic lesions, 76 lesions showed as abnormal uptake on bone scan, and 76 lesions also showed as increased FDG uptake on PET/CT scan. There was good agreement between FDG uptake and abnormal bone scan finding (Kendall tau-b : 0.689, p=0.000). Lesion showed increased bone tracer uptake had higher SUVmax and SUVrel compared to lesion showed no abnormal bone scan finding ($6.03{\pm}3.12$ vs $1.09{\pm}1.49$, p=0.000, $4.76{\pm}3.31$ vs $1.29{\pm}0.92$, p=0.000). The order of frequency of osseous metastatic site was vertebra, pelvis, rib, skull, sternum, scapula, femur, clavicle, and humerus. Metastatic lesion on skull had highest SUVmax and metastatic lesion on rib had highest SUVrel. Osteosclerotic metastatic lesion had lowest SUVmax and SUVrel. Conclusion: These results suggest that FDG-PET/CT is more sensitive to detect breast cancer patients with osseous metastasis. CT scan must be reviewed cautiously skeleton with bone window, because osteosclerotic metastatic lesion did not showed abnormal FDG accumulation frequently.

• Journal of Preventive Medicine and Public Health
• /
• v.31 no.1 s.60
• /
• pp.112-126
• /
• 1998

To investigate the effectiveness of the interventions in working environment and personal hygiene for the occupational exposure to the lead, the blood zinc protoporphyrin (ZPP) concentrations of 131 workers (100 exposed subjects and 31 controls) of a newly established battery factory were analyzed. They were measured in every 3 months up to 18 months. Ai. lead concentration (Pb-A) of the workplaces was also checked for 3 times in 6 months interval from August 1987. Environmental intervention included the local exhaust ventilation and vacuum cleaning of the floor. Intervention of the personal hygiene included the daily change of clothes, compulsory shower after work and hand washing before meal, prohibition of cigarette smoking and food consumption at the work site and wearing mask. Mean blood ZPP concentration of the controls was $16.45{\pm}4.83{\mu}g/d\ell$ at the preemployment examination and slightly increased to $17.77{\pm}5.59{\mu}g/d\ell$ after 6 months. Mean blood ZPP concentration of the exposed subjects who were employed before the factory was in operation (Group A) was $17.36{\pm}5.20{\mu}g/d\ell$ on employment and it was increased to $23.00{\pm}13.06{\mu}g/d\ell$ after 3 months. The blood ZPP concentration was increased to $27.25{\pm}6.40{\mu}g/d\ell$ on 6 months (p<0.01) after the employment which was 1 month after the initiation of intervention program. It did not increase thereafter and ranged between $25.48{\mu}g/d\ell$ and $26.61{\mu}g/d\ell$ in the subsequent 4 results. Mean blood ZPP concentration of the exposed subjects who were employed after the factory had been in operation but before the intervention program was initiated (Group B) was $14.34{\pm}6.10{\mu}g/d\ell$ on employment and it was increased to $28.97{\pm}7.14{\mu}g/d\ell$ (p<0.01) in 3 months later(1 month after the intervention). The values of subsequent 4 tests were maintained between $26.96{\mu}g/d\ell$and $27.96{\mu}g/d\ell$. Mean blood ZPP concentration of the exposed subjects who were employed after intervention program had been started (Group C) was$21.34{\pm}5.25{\mu}g/d\ell$ on employment and it was gradually increased to $23.37{\pm}3.86{\mu}g/d\ell$ (p<0.01) after 3 months, $23.93{\pm}3.64{\mu}g/d\ell$ after 6 months, $25.50{\pm}3.01{\mu}g/d\ell$ after 9 months, and $25.50{\pm}3.10{\mu}g/d\ell$ after 12 months. Workplaces were classified into 4 parts according to Pb-A. The Pb-A of part I, the highest areas, were $0.365mg/m^3$, and after the intervention the levels were decreased to $0.216mg/m^3$ and$0.208mg/m^3$ in follow-up test. The Pb-A of part II which was resulted in lowe. value than part I was decreased from $0.232mg/m^3$ to $0.148mg/m^3$, and $0.120mg/m^3$ after the intervention. The Pb-A of part III was tested after the intervention and resulted in $0.124mg/m^3$ in January 1988 and $0.181mg/m^3$ in August 1988. The Pb-A of part IV was also tested after the intervention and resulted in $0.110mg/m^3$ in August 1988. There was no consistent relationship between Pb-A and blood ZPP concentration. The blood ZPP concentration of the group A and B workers in the part of the highest Pb-A were lower than those of the workers in the parts of lower Pb-A. The blood ZPP concentration of the workers in the part of the lowest Pb-A increased more rapidly. The blood ZPP concentration of the group C workers was the highest in part III. These findings suggest that the intervention in personal hygiene is more effective than environmental intervention, and it should be carried out from the first day of employment and to both the exposed subjects, blue color workers and the controls, white color workers.

• Journal of Sericultural and Entomological Science
• /
• v.25 no.2
• /
• pp.1-31
• /
• 1984

Flacherie, as one of the most prevalent silkworm diseases, causes severe economic damage to sericultural industry and its pathogens have been proved to be flacherie virus (FV) and densonucleosis virus (DNV). Multiplications of the viruses in the larvae of the silkworm, Bombyx mori, were studied by the sucrose density gradient centrifugation and electron microscopy. The quantitative and qualitative changes of nucleic acids and proteins were investigated from the midgut and hemolymph in the silkworm larvae infected separately with FV and DNV. The histopathological changes of epithelial cells of infected midgut also were examined by an electron microscope. 1. Purified fractions of FV or DNV in a sucrose density gradient centrifugation yielded one homogenous and sharp peak without a shoulder, suggesting no heterogenous materials in the preparation. Electron microscopy also revealed that FV and DNV were spherical particles, 27nm and 21nm in diameter, respectively. 2. Silkworm larvae showed a decrease in body weight on the 6th day and in midgut weight on the 3rd day after inoculation with FV or DNV. 3. DNA content was higher in the midgut when infected with FV or DNV, but the hemolymph of the infected larvae showed no difference during first 6 days after inoculation, after which DNA concentration declined rapidly. 4. RNA synthesis of silkworm larvae infected separately with FV and DNV was stimulated in the midgut, but RNA content was reduced in the hemolymph at the early stage of virus multiplication. At the late stage of virus multiplication, however, it was extremely reduced in both midgut and hemolymph. 5. The concentration of protein in the midgut and hemolymph of silkworm larvae infected separately with FV and DNV showed no difference from that of the healthy larvae at the early stage of virus multiplication, but it was significantly reduced at the late stage of virus multiplication. 6. There was no difference in the electrophoretic patterns of RNAs extracted from the midgut of healthy or virus-infected larvae. 7. The electrophoresis of proteins extracted from the midgut infected with FV or DNV, when carried out on the 1st and 5th day after virus inoculation, showed no difference from that of the healthy larvae. But, there was an additional band with medium motility in the proteins on the 8th day after virus inoculation, while a band with low mobility shown in the proteins of healthy larvae disappeared in the infected larvae. However, a band with high mobility in the healthy larvae was separated into two fractions in the infected larvae. 8. The electrophoretic pattern of hemolymph proteins of the silkworm larvae infected separately with FV and DNV was similar to that of the healthy larvae, but the concentration of hemolymph proteins in the infected larvae was lower than that of the healthy larvae at the late stage. 9. Two types of inclusion bodies were shown by the double staining of pyronin-methyl green in the columnar cell of the midgut on the 8th day after FV inoculation. 10. Electron microscopy of the infected midgut revealed that the 'cytoplasmic wall' of the goblet cell thickened on the 5th day after FV inoculation and several types of the cytopathogenic structures, such as virus$.$specific vesicles, virus particles, linear structures, tubular structures, and high electron-dense matrices were observed in the cytoplasm of the goblet cell. The virus particles were also observed in the microvilli and the structures similar to spherical virus particles were observed around the virus-specific vesicles, suggesting the virus assembly in the cytoplasm. 11. Fluorescence micrograph of the infected midgut stained with acridine orange showed that the nucleus, the site of DNV multiplication in the columnar cell, enlarged on the 5th day after virus inoculation. 12. Electron microscopic examination of DNV infected midgut revealed that the nucleolus of the columnar cell was broken into granules and those granules dispersed into apical region of the nucleus on the 5th day after virus inoculation. On the 8th day after inoculation, it was also observed that the nucleus of the columnar cell was full with the high electron-dense virogenic stroma which were similar to virus particles. These facts suggest that the virogenic stroma were the sites of virus assembly in the process of DNV multiplication.

• Korean Journal of Veterinary Research
• /
• v.9 no.1
• /
• pp.23-62
• /
• 1969

Throughout the studies the following experimental results were obtained and are summarized: 1. Multiplication of agents in primary cell cultures of both GF classical and CR-64 acute strain of Marek's disease infected chicken kidneys was accompanied by the formation of distinct transformed cell foci. This characteristic nature of cell transformation was passaged regularly by addition of dispersed cell from infected cultures to normal chicken kidney cell cultures, and also transferred was the nature of cell transformation to normal chick-embryo liver and neuroglial cell cultures. No cytopathic changes were noticed in inoculated chick-embryo fibroblast cultures. 2. The same cytopathic effects were noticed in normal kidney cell monolayers after the inoculation of whole blood and huffy coat cells derived from both forms of Marek's disease infected chickens. In these cases, however, the number of transformed cell foci appearing was far less than that of uninoculated monolayers prepared directly from the kidneys of Marek's disease infected chickens. 3. The change in cell culture IS regarded as a specific cell transformation focus induced by an oncogenic virus rather than it plaque in slowly progressing cytopathic effect by non-oncogenic viruses, and it is quite similar to RSV focus in chick-embryo fibroblasts in many respects. 4. The infective agent (cell transformable) were extremely cell-associated and could not be separated in an infective state from cells under the experimental conditions. 5. The focus assay of these agents was valid as shown by the high degree of linear correlation (r=0.97 and 0.99) between the relative infected cell concentration (in inoculum) and the transformed cell foci counted. 6. No differences were observed between the GF classical strain and the CR-64 acute strain of Marek's disease as far as cell culture behavior. 7. Characterization of the isolates by physical and chemical treatments, development of internuclear inclusions in Infected cells, and nucleic acid typing by differential stainings and cytochemical treatments indicated that the natures of these cell transformation agents closely resemble to those described fer the group B herpes viruses. 8. Susceptible chicks inoculated with infected kidney tissue culture cells developed specific lesions of Marek's disease, and in a case of prolonged observation after inoculation (5 weeks) the birds developed clinical symptoms and gross lesions of Marek's disease. Kidney cell cultures prepared from those inoculated birds and sacrificed showed a superior recovery of cell transformation property by formation of distinct foci. 9. Electron microscopic study of infected kidney culture cells (GF agent) by negative staining technique revealed virus particles furnishing the properties of herpes viruses. The particle was measured about $100m{\mu}$ and, so far, no herpes virus envelop has been seen from these preparations. 10. No relationship of both isolates to avian leukosis/sarcoma group viruses and PPLO was observed.