• The Korean Journal of Physiology
• /
• v.18 no.1
• /
• pp.19-35
• /
• 1984

Since the first report of Drury and $Szent-Gy{\ddot{o}}rgyi$ in 1929, the inhibitory influences of adenosine on the heart have repeatedly been described by many investigators. These studies have shown that adenosine and adenine nucleotides have overall depressant effects, similar to those of acetylcholine. Heart beats become slow and weak. It is also well known that adenosine is a potent endogenous coronary vasodilator. Many investigations on the working mechanisms of adenosine have been focused mainly on the effects of the coronary blood flow. However, the cellular mechanisms underlying the inhibitory action of adenosine on sinus node are not well understood yet. Thus, this study was undertaken to examine the behavior of rabbit SA node under influence of adenosine. In these series of experiments three kinds of preparations were used: whole atrial pair, left atrial strip, and isolated SA node preparations. The electrical activity of SA node was recorded with conventional glass microelectrodes 30 to 50 $M{\Omega}$. The preparations were superfused with bicarbonate-buffered Tyrode solution of pH 7.35 and aerated with a gas mixture of $3%\;CO_2-97%\;O_2$ at $35^{\circ}C$. In whole atrial pair, adenosine suppressed sinoatrial rhythm in a dose-dependent manner. Effect of adenosine on atrial rate appeared at the concentration of $10^{-5}M$ and was enhanced in parallel with the increase in adenosine concentration. Inhibitory action of adenosine on pacemaker activity was more prominent in the preparation pretreated with norepinephrine, which can steepen the slope of pacemaker potential by increasing permeability of $Ca^{+2}$. Calcium ions in perfusate slowly produced a marked change in sinoatrial rhythm. Elevation of the calcium concentration from 0.3 to 8 mM increased the atrial rate from 132 to 174 beats/min, but over 10 mM $Ca^{+2}$ decreased. The inhibitory effect of adenosine on sinoatrial rhythm developed very rapidly. Atrial rate was recovered promptly from the adenosine-induced suppression by the addition of norepinephrine, but extra $Ca^{+2}$ was less suitable to restore the suppression of atrial rate. Adenosine suppressed also atrial contractility in the same dosage range that restricted pacemaker activity, even in the reserpinized preparation. In isolated SA node preparation, spontaneous firing rate of SA node at $35^{\circ}C$(mean{\pm}SEM, n=16) was $154{\pm}3.3\;beats/min. The parameters of action potentials were: maximum diastolic potential(MDP), $-73{\pm}1.7\;mV: overshoot(OS), $9{\pm}1.4\;mV: slope of pacemaker potential(SPP), $94{\pm}3.0\;mV/sec. Adenosine suppressed the firing rate of SA node in a dose-dependent manner. This inhibitory effect appeared at the concentration of $10^{-6}M$ and was in parallel with the increase in adenosine concentration. Changes in action potential by adenosine were dose-dependent increase of MDP and decrease of SPP until $10^{-4}M$. Above this concentration, however, the amplitude of action potential decreased markedly due to the simultaneous decrease of both MDP and OS. All these effects of adenosine were not affected by pretreatment of atropine and propranolol. Lowering extra $Ca^{2+}$ irom 2 mM to 0.3 mM resulted in a marked decrease of OS and SPP, but almost no change of MDP. However, increase of perfusate $Ca^{2+}$ from 2 mM to 6 or 8 mM produced a prominent decrease of MDP and a slight increase of OS and SPP. Dipyridamole(DPM), which is known to block the adenosine transport across the cell membrane, definately potentiated the action of adenosine. The results of this experiment suggest that adenosine suppressed pacemaker activity and atrial contractility simultaneously and directly, by decreasing $Ca^{2+}-permeability$ of nodal and atrial cell membranes.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.28 no.2
• /
• pp.95-110
• /
• 2006

The treatment for oral and maxillofacial carcinoma with chemotherapeutic agents is evaluated by many effective methods to reduce the tumor mass and cancer cell proliferation. However these chemotherapy have many serious side effects, such as bone marrow suppression, renal toxicity, G-I troubles. Therefore a possible approach to develop a clinically applicable chemotherapeutic agent is to screen anticancer activity of Taxol which is known to have very little side effect and have been used to breast cancer and ovarian carcinoma. Taxol is a new anti-microtubular anti-cancer agent extracted from the bark of the Pacific yew, Taxus brevifolia. Paclitaxel(Taxol) acts by promoting tubulin polymerization and over stabilizing microtubules agianst depolymerization. Despite the constant improvements of methods of the cancer treatment especially chemotherapy, the rate of cancer metastasis and recurrent are not decreased. Thus the investigation of new drug which have very little side effect and a possible clinically application continues to be a high priority. Considering that the Taxol have shown very effective chemotherapeutic agent with relatively low toxicity in many solid tumors, it deserves to evaluate its efficacy in oral squamous cell carcinoma. In this study, to investigate the in-vivo and in-vitro anti-cancer efficacy of Taxol in oral squamous cell carcinoma and lastly, the potency of Paclitaxel in the clinical application for oral cancer was evaluated. In vivo study, after HN22 cell line were xenografted in nude mice, the growth of tumor mass was observed, 3 mg/Kg taxol was injected intraperitoneally into nude mice containing tumor mass. The methods of these study were measurement of total volume of tumor mass, histopathologic study, immunohistochemical study, drug resistance assay, growth curve, MTT assay, flow cytometry, cDNA microarray in vivo and in vitro. The results were obtained as following. 1. The visual inspection of the experimental group showed that the volume of the tumor mass was slightly decreased but no significant difference with control group. 2. Ki-67 index was decreased at weeks 4 in experimental group. 3. Microscopic view of the xenografted tumor mass showed well differentiated squamous cell carcinoma and after Taxol injection, some necrotic tissue was seen weeks 4. 4. The growth curve of the tumor cells were decreased after 1day Taxol treatment. 5. According to the MTT assay, HN22 cell line showed relative drug resistancy above $5\;{\mu}g/ml$ concentrations of Taxol. 6. In drug resistance assay, the decrease of cell counts was seen relatively according to concentration. 7. In Flow cytometry, G2M phase cell arrests were seen in low concentration of the Taxol, while S phase cell arrests were seen in high concentration of the Taxol. 8. Using cDNA microarray technique, variable gene expression of ANGPTL4, TXNRD1, FAS, RRAGA, CTGF, CYCLINEA, P19, DUSP5, CEBPG, BTG1 were detacted in the oral squamous cell carcinoma cell after taxol treatment. In this study paclitaxel is effective against oral squamous cell carcinoma cell lines in vitro, but week effect was observed in vivo. So we need continuous study about anticancer effect of taxol in vivo in oral squamous cell carcinoma.

• Progress in Medical Physics
• /
• v.23 no.1
• /
• pp.48-53
• /
• 2012

The pencil beam convolution (PBC) algorithms in radiation treatment planning system have been widely used to calculate the radiation dose. A new photon dose calculation algorithm, referred to as the anisotropic analytical algorithm (AAA), was released for use by the Varian medical system. The aim of this paper was to investigate the difference in dose calculation between the AAA and PBC algorithm using the intensity modulated radiation therapy (IMRT) plan for lung cancer cases that were inhomogeneous in the low density. We quantitatively analyzed the differences in dose using the eclipse planning system (Varian Medical System, Palo Alto, CA) and I'mRT matirxx (IBA, Schwarzenbruck, Germany) equipment to compare the gamma evaluation. 11 patients with lung cancer at various sites were used in this study. We also used the TLD-100 (LiF) to measure the differences in dose between the calculated dose and measured dose in the Alderson Rando phantom. The maximum, mean, minimum dose for the normal tissue did not change significantly. But the volume of the PTV covered by the 95% isodose curve was decreased by 6% in the lung due to the difference in the algorithms. The difference dose between the calculated dose by the PBC algorithms and AAA algorithms and the measured dose with TLD-100 (LiF) in the Alderson Rando phantom was -4.6% and -2.7% respectively. Based on the results of this study, the treatment plan calculated using the AAA algorithms is more accurate in lung sites with a low density when compared to the treatment plan calculated using the PBC algorithms.

• Progress in Medical Physics
• /
• v.19 no.2
• /
• pp.131-138
• /
• 2008

We evaluated on the calculation accuracy of treatment planning system (TPS) with phantom having convex and concave surface. The TPS is Eclipse (Varian, USA) using both algorithms AAA and PBC for photon dose calculations. PBC algorithms have three corrections of Batho, modified Batho (M-Batho), and equivalent TAR (E-TAR). The field sizes were $10{\times}10\;cm^2$ and $20{\times}20\;cm^2$, and MLC-shaped fields for these fields. We measured doses at three depths 5, 10 and 15cm in phantom of SSD=90cm in the condition of inserted farmer chamber. For given conditions, we have calculated dose with these algorithms and compared them with measured doses. In AAA the calculated doses (dose/MU) were agreed to measured doses within ${\pm}1%$ in flat and convex surface and were under estimated with -1.9% maximum in concave surface. In PBC the calculated doses were over estimated with +1.7% and +4.1% respectively in flat and convex surface and the differences were from -3.1% to +2.1% in concave surface. In comparison of criteria from AAPM and IAEA reports, and statistical analysis for these results, it is found that the AAA's results are in good agreement with measured values and the M-Batho's results are generally good agreed with measured values among PBC algorithms.

• Clinical and Experimental Pediatrics
• /
• v.51 no.9
• /
• pp.971-976
• /
• 2008

Purpose : Surveillance for detecting and managing latent tuberculosis infection (LTBI) is a key component of tuberculosis control. The classic surveillance tool, the tuberculin skin test (TST), may have some limitations when used in the Bacillus Calmette-$Gu{\acute{e}}rin$ (BCG)-vaccinated population. The object was to perform a blood test $QuantiFERON^{(R)}$-TB Gold In Tube (QFT-G IT) based on the detection of interferon-$\gamma$ ($IFN-{\gamma}$) released by T cells in response to Mycobacterium tuberculosis-specific antigens, and to compare the efficacy of this new diagnostic tool for LTBI with that of TST. Methods : For six months, between October 1, 2006 and April 30, 2007, data were collected from 111 patients under 15 years of age at Severance Children's Hospital. TST and QFT-G IT tests were performed with children with or without contact histories of tuberculosis. In addition to these tests, we examined comparative data from 29 adults who had tuberculosis, to detect false negative rates in the QFT-G IT method. Results : Thirty-three children had household contact histories. In this group, 15% and 42% of cases were found to be positive using the QFT-G IT assay and TST, respectively. Agreement was low between these two tests (${\kappa}=0.39$). In the adult active tuberculosis group, the QFT-G IT false negative rate defined as a positive culture and a negative QFT-G IT result was 12.5%. Conclusion : In diagnosing LTBI in children, the usefulness of a whole-blood $IFN-{\gamma}$ assay employing TB-specific antigens will be revealed only by examining additional longitudinal clinical data; this study serves as a starting point in that process.

• Pediatric Infection and Vaccine
• /
• v.17 no.2
• /
• pp.83-90
• /
• 2010

Purpose : Although the incidence of polymicrobial bloodstream infection (PBSI) has increased, only a few studies have so far focused on children. Therefore, in an effort to prevent more serious situations in pediatric patients, we analyzed the clinical features, organisms, and laboratory results of PBSI. Methods : We performed a retrospective review of the case records of 97 patients with polymicrobial bloodstream infection in the Severance hospital, from 2001 to 2008. Using t-test and chi-square test, we analyzed the underlying medical conditions, clinical characteristics, organisms, and laboratory results of those patients. Results : Annual incidence of polymicrobial bloodstream infection increased from 1.4 % in 2001 to 10.9% in 2008 in pediatric patients. Immunocompromised hemato-oncological malignancy was found in 31 (31.9%) patients, and was the most common underlying medical condition; cardiovascular disease was found in 15 patients (15.4%), neurologic disease in 10 patients (10.3%), and so on. Gram positive organisms were recovered in 143 cases and gram negative organisms were recovered in 101 cases of PBSI. Staphylococcus epidermidis was the most common organism. Factors affecting mortality included underlying medical disease, immune status, nosocomial infection, and central catheter-related infection, for which the rate of mortality showed a greater increase (P<0.05). Conclusion : Due to the close connection between PBSI and fatal conditions or high mortality, it requires more aggressive management. Compared with previous studies, we discovered that immunocompromised hemato-oncological malignancy was the most common underlying medical condition and that frequency of gram-positive bacteria and fungus isolated has increased.

• Pediatric Infection and Vaccine
• /
• v.17 no.2
• /
• pp.122-129
• /
• 2010

Purpose : Enteroviral infection is a common viral illness in children. We undertook this study in attempt to comprehend the epidemiologic and clinical features of enteroviral infections, particularly EV71 in children. Methods : We enrolled 63 children with enteroviral infection at Severance Children's Hospital in Seoul between May and August 2009. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed from stool or cerebrospinal fluid samples, which were then tested for enteroviral infection. Viral isolation and serotype identification also were performed by RT-PCR. Results : A total of 63 patients with clinical diagnosis of enteroviral infections were enrolled; of those, 38 (60%) were positive for enterovirus. The mean age of the patients was 2 years and 7 months and the sex ratio of male to female was 0.9 :1. Their clincal manifestations included aseptic meningitis (21 cases, 55%), HFMD (16 cases, 42%), herpangina (5 cases, 13%), neonatal fever (2 cases, 5%), encephalitis (1 case, 3%), and myocarditis (1 case, 3%). Serotypes of isolated enteroviruses were EV71 (8 cases, 21%), coxsackievirus B1 (8 cases, 21%), coxsackievirus A16 (2 cases, 6%), coxsakievirus A2 (1 case, 3%), coxsakievirus A5 (1 case, 3%), and echovirus 9 (1 case, 3%). Clinical symptoms of EV71 infection included HFMD (5 cases, 63%), aseptic meningitis (3 cases, 38%), encephalitis (1 case, 13%), and myocarditis (1 case, 13%). A positive rate of C-reactive protein in EV71 was higher than those in other enterviral infections. However, there was no statistically significant difference in other laboratory findings. Conclusion : We reported on identified enteroviruses, including EV71, during a period of 3 months in the summer of 2009. In this study, EV71 infection frequently occurred in male and clinical manifestation caused by EV71 was a more severe disease than that due to other enterviral infections. There is a need for continuous surveillance of enteroviral infection and its clinical manifestations for diagnosis and treatment of enteroviral infection.

• Pediatric Infection and Vaccine
• /
• v.15 no.1
• /
• pp.45-51
• /
• 2008

Purpose : Better understanding of the epidemiology of Streptococcus pneumoniae affects preventive and therapeutic strategies for children with otitis media. This study was undertaken to examine the prevalence of pneumococcal serotypes causing otitis media in children. Methods : Pneumococcal isolates obtained from the ear discharge of children with otitis media between January 2001 and December 2006 were characterized by serotyping and antibiotic susceptibility testing. Results : There were 54 pneumococcal isolates from 54 children with otitis media. The median age of patients was 13 months, and the proportion of children <5 years old was 81%. The predominant serotypes, in order of decreasing frequency, were 19A (44%), 19F(28%), 6B (7%), 6A (4%), 9V (4%), and 1 (4%); 23 isolates (43%) belonged to types included in the heptavalent pneumococcal conjugate vaccine (PCV7). The proportion of serotype 19A and 19F accounted for 72% of overall pneumococcal isolates, which accounted for 84% of pneumococcal isolates from otorrhea of children <5 years old (vs 20% in children ${\geq}5$ years old, P<0.001). All serotypes isolated from 3 vaccinees of PCV7 were 19A. There was no significant diminution in otitis media caused by pneumococcal vaccine serotypes after the introduction of PCV7. The frequency of nonsusceptibility to penicillin, erythromycin, and trimethoprim-sulfamethoxazole was higher in serotype 19A than in other non-vaccine serotypes, respectively. The frequency of multiple drug resistance was 96% in serotype 19A, compared with 29% in other non-vaccine serotypes (P=0.001). Conclusion : 19A was the most common pneumococcal serotype causing otitis media and represented a large proportion of strains with multiple drug resistance in children younger than 5 years of age.

• Clinical and Experimental Pediatrics
• /
• v.50 no.2
• /
• pp.182-189
• /
• 2007

Purpose : The primary purpose of this study was to evaluate the growth and neuropsychologic function following treatments for pediatric hematologic and oncologic diseases. Healthy monozygotic twins served as ideal controls for comparison to exclude possible confounding factors. Methods : Seven children treated with various hematologic and oncologic diseases were included in the study: acute lymphoblastic leukemia (ALL; n=2), Diamond-Blackfan anemia twins (n=2), and aplastic anemia (n=3). The median age at the diagnosis was 5.2 (0.3-15) years. The median duration of follow-up was 7.2 (4.9-10) years. Controls were healthy monozygotic twins. Growth was measured and the percentile channels were evaluated sequentially for patients. The K-WISC III was applied and compared in 5 pairs of patients and controls. Results : Similar growth profiles were noted for the twins. The percentiles at diagnosis was 3-10 in 3, 25-50 in 2, and 50-75 in 2 cases. All patients stayed in their growth percentiles through follow-up, except for 1 patient who became obese. For IQ tests, the mean behavioral, verbal and full scale IQ scores of patients were 88.0, 93.8, and 89.8, respectively, and those from their corresponding controls were 92.2, 97.0, and 91.7 (P>0.05). However, 2 children who were treated for ALL had lower IQ scores. Conclusion : Similar growth profiles were observed in the monozygotic twins in terms of height and weight. The IQ scores of patients were similar to those of monozygotic twins. However, prophylactic CNS-directed therapy for leukemia might adversely affect the IQ scores. A further prospective study on larger number of twins is warranted.

• Radiation Oncology Journal
• /
• v.18 no.2
• /
• pp.127-132
• /
• 2000

Purpose : To determine if the tumor intersitial fluid pressure (TIFP) and/or its change in patients with metastatic Iymph node in head and neck area can predict radiotherapy outcome. Materials and Methods : In 26 biopsy Proven metastatic Iymph node Patients in head and neck area with accessible by direct inspection and palpation, and of sufficient thickness (>1 cm) to permit accurate needle placement, we measured TIFP at cervical Iymph node before and during radiotherapy. Tumor size was measured clinically and radiologically. Results : The mean preradiotherapy TIFP was 24.7 mmHg. Preradiotherapy TIFP had marginally significant relationship with tumor size (p=0.06). Preradiotherapy TIFP significantly decreased when tumor size decreased (p=0.009). Preradiotherapy TIFP was not different between complete response group and group with partial or less response (p=0.75). Radiotherapy outcome was not different between group with above and group with below than average TIFP (p=0.229). TIFP decreased 36mmHg in complete response group and 29.7 mmHg in group with partial or less response. Conclusion :The mean TIFP was elevated with 24.7 mmHg. Preradiotherapy TIFP had marginally significant relationship with tumor size (p=0.06). TIFP decreased 36 mmHg in complete response group and 29.7 mmHg in group with partial or less respone but there was no statistically significant relationship in two groups.