• Tuberculosis and Respiratory Diseases
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• v.64 no.1
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• pp.8-14
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• 2008

Background: Acinetobacter infections are difficult to treat as they often exhibit multiple resistance to the antibiotics that are currently available for the treatment of pneumonia. Colistin is active against gram-negative bacteria, including the multiple drug resistant (MDR) Acinetobacter species. However, intravenous administration of colistin was abandoned because of its nephrotoxicity and neurotoxicity. The aims of this study were to examine the efficacy and safety of colistin administered by aerosol in the treatment of pneumonia caused by MDR Acinetobacter baumannii. Methods: We retrospectively reviewed the medical records of patients admitted to the intensive care unit (ICU) from Dec. 2006 to Aug. 2007 who had been diagnosed as suffering from pneumonia due to MDR Acinetobacter baumannii and had been treated with nebulized colistin. Results: 31 patients received aerosolized colistin. The average duration of the treatment was $14{\pm}7$ days and the daily dose of ranged from 225 mg to 300 mg. All patients received concomitant intravenous antimicrobial agents. The average length of the stay in the ICU was $34{\pm}21$ days and in the hospital $58{\pm}52$ days. The overall microbiological eradication was observed in 25 patients (80.6%). 14 of these (56%) were cured, and 11 (44%) were infected with other microorganisms. The overall crude mortality of the ICU was 48%. Nephrotoxicity and significant bronchial constriction did not occur in any patient during neublized colistin treatment. Conclusion: Nebulized colistin may be a safe and effective option in the treatment of pneumonia due to MDR Acinetobacter baumannii. Its role in therapy warrants further investigation in comparative studies.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.975-991
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• 1997

Background : Many patients with isoniazid and rifampin-resistant pulmonary tuberculosis have organisms that are also resistant to other first-line drugs. Despite of aggressive retreatment chemotherapy, the results are often unsuccessful, with a failure rate approaching 40%. Recently, there has been a revival of resectional surgery for the treatment of multidrug-resistant pulmonary tuberculosis. Methods : A retrospective analyses of the case records and radiographic findings were done. Between January 1991 and December 1995, 14 human immunodeficiency virus (HIV)-seronegative patients with multidrug-resistant pulmonary tuberculosis were selected for resection to supplement chemotherapy. All patients had organisms resistant to many of the first-line drugs, including both isoniazid and rifampin. Results : Despite of aggressive therapy for median duration of 9.5 months, 12 of the 14 patients (86%) were still sputum smear and/or culture positive at the time of surgery. The disease was generally extensive. Although main lesions of the disease including thick-walled cavities were localized in one lung, lesser amounts of contralateral disease were demonstrated in 10 of 14 (71%). Types of surgery performed were pneumonectomy including extrapleural pneumonectomy in six patients, lobectomy or lobectomy plus in six patients, and segmentectomy in two patients. The resected lung appeared to have poor function ; preoperative perfusion lung scan showed only 4.8% of the total perfusion to the resected portion of the lung. There were no operative deaths. Two patients had major postoperative complications including empyema with bronchopleural fistula and prolonged air leak, respectively. Of the 14 patients, 13 (93%) remained sputum-culture-negative for M. tuberculosis for a median duration of 23 months and one remained continuously sputum smear and culture positive for M. tuberculosis. Conclusion : On the basis of comparison with historical controls, adjunctive resectional surgery appears to play a significant beneficial role in the management of patients with multidrug-resistant pulmonary tuberculosis if the disease is localized and there are adequate reserve in pulmonary function.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.210-222
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• 2000

Background: Endothelin(ET) is the most potent vasoconstrictor and bronchoconstrictor. The plasma ET-1 level is elevated in patients with acute pulmonary thromboembolism(APTE). This finding suggest that ET-1 may be an important mediator in the cardiopulmonary derangement of APTE. But whether ET-1 is a pathogenic mediator or a simple marker of APTE is not known. The role of ET-1 in the pathogenesis of cardiopulmonary dysfunction in APTE(delete) was investigated through an evaluation of the effects of $ET_A$-receptor antagonist on APTE. The increase in local levels of preproET-1 mRNA and ET-1 peptide in the embolized lung was also demonstrated. Methods: In a canine autologous blood clot pulmonary embolism model, $ET_A$-receptor antagonist(10 mg/kg intravenously, n=6) was administered one hour after the onset of the embolism. Hemodynamic measurements, blood gas tensions and plasma levels of ET-1 immunoreactivity in this treatment group were compared with those in the control group(n=5). After the experiment., preproET-1 mRNA expression(using Northern blot analysis) and the distribution of ET-1(by immunohistochemical analysis) in the lung tissues were examined. Results: The increases in pulmonary arterial pressure and pulmonary vascular resistance of the treatment group were less than those of the control group. Decrease in cardiac output was also less in the treatment group. Complications such as systemic arterial hypotension and hypoxemia did not occur with the administration of $ET_A$-receptor antagonist The plasma level of ET-1 like(ED: what does 'like' mean?) immunoreactivity was increased after embolization in both groups but was significantly higher in the treatment group. The preproET-1 mRNA and ET-1 peptide expressions were increased in the embolized lung. Conclusion: ET-1 synthesis increases with embolization in the lung and may plays play an important role in the pathophysiology of cardiopulmonary derangement of APTE. Furthermore, $ET_A$-receptor antagonist attenuates cardiopulmonary alterations seen in APTE, suggesting a potential benefit of this therapy.

• Journal of Life Science
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• v.26 no.3
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• pp.376-386
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• 2016

Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.

• Journal of Preventive Medicine and Public Health
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• v.15 no.1
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• pp.145-151
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• 1982

Breslau's report on the two stillbirths induced by illuminating gas poisoning made many investigators explore the hazards. of carbon monoxide(CO) poisoning to pregnancy. The pregnant woman, her fetus, and the newborn infant have been identified to be particularly vulnerable to CO even in low concentration. Several factors, such as placental barrier, membrane resistance of maternal and fetal red blood cells etc., were considered to be related to the delayed elimination of CO from fetus. Slower elimination of CO from fetus than from mother was confirmed in several in vivo studies. But there are few studies which have confirmed the difference of carboxyhemoglobin (HbCO) dissociation in adult and fetal bloods. Author investigated the effects of hemoglobin itself on the elimination of CO from mother and fetus. By observing the difference of CO dissociation from adult and fetal hemoglobin at the various partial pressures of oxygen, the author tries to suggest the base of the proper treatment measure for the CO poisoning of pregnant woman and newborn infant. The results were as follows: 1. The total hemoglobin amounts of adults and fetal bloods were $16.1{\pm}0.50gm%\;and\;15.7{\pm}0.32gm%$, respectively. The fetal hemoglobin proportions in adult and fetal bloods were $1.2{\pm}0.15%\;and\;72.7{\pm}3.01%$, respectively. 2. Adult and fetal bloods saturated by CO to 100% HbCO were exposed to ambient air$(21%\;O_2),\;100%\;O_2\;and\;3\;ATAO_2$. After 30 minutes exposure, the HbCO saturations of adult blood were 96.7%, 70.9%, and 52.8%, respectively, and those of fetal blood were 98.5%, 76.1%, and 62.2%, respectively. HbCO dissociation was proportional to the partial pressure of oxygen and the most marked dissociation was shown under 3 ATA $O_2$, HbCO dissociation of fetal blood was slower than that of adult blood in all conditions. According to the above results, it is possible that CO poisoning make more serious damage to the fetus and newborn infant than to the adult due to the delayed dissociation of HbCO. Thus in the treatment of CO poisoning of pregnant woman and newborn infant, hyperbaric oxygen therapy seems to be the most eflective treatment measure, but the duration of hyperbaric oxygenation should be lengthened accordingly.

• Pediatric Infection and Vaccine
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• v.10 no.1
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• pp.81-86
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• 2003

Purpose : Streptococcus pneumoniae remains a leading cause of meningitis, sepsis, pneumonia, and otitis media in children worldwide. Emergence of drug-resistant organism has substantially complicated the therapy of these infections. This study was conducted to determine the clinical features and changing patterns of antibiotic-resistant rates of Streptococcus pneumoniae. Methods : We have retrospectively examined 306 cases of culture proven patients who were admitted to the Department of Pediatrics, Severance hospital, from the year 1991 to year 2000. The type of culture specimen used, presence of penicillin resistance, characteristics according to various presenting diseases and their prevailing year were also examined. Results : The mean age of cases was 7.9 year and the ratio of male to female was 1.6 : 1. The main age group of pneumococcal infection was under 2 years(42%). Systemic infections associated with pneumococci were sepsis(19.3%) and meningitis(9.5%), while local infections presented as pneumonia(29.2%), otitis media(19.3%), exudative tonsillitis(13.3%), and sinusitis(9.2%) in the order of frequency. Seasonal variation was seen in the incidence of pneumococcal infection: high incidence of infection was seen in Spring(Mar.~Apr; 32%), while the incidence was low during summer(Aug.~Sep.; 6%). Penicillin-resistant rate of pneumococci was steadily on the increase since the year 1991(65%) to year 2000(84%). Conclusion : Antibiotic-resistant pneumococci increased during the past decade. For effective prevention of pneumococcal infections, national survey of pneumococcal infections and expanded use of pneumococcal vaccination would be needed.

• Clinical and Experimental Pediatrics
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• v.48 no.6
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• pp.619-623
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• 2005

Purpose : Bacteremia in immunocompromised pediatric cancer patients can lead to high morbidity and mortality, if not treated early and properly. The incidence and antibiotic sensitivities to common pathogens of bacteremia in pediatric cancer patients are liable to change, according to region and time. We investigated the causative organisms and antibiotic sensitivities of bacteremia in pediatric cancer patients to assess the adequacy of empiric antimicrobial therapy. Methods : From September 1995 to August 2003, we retrospectively evaluated 58 episodes in 39 pediatric cancer patients with bacteremia treated at the Pediatric Department of Yeungnam University Hospital. We investigated and analyzed the causative organisms and the antibiotic sensitivity test results by reviewing the records of the microbiologically proven positive blood culture results. Results : The incidence of bacteremia in pediatric cancer patients in this study was 5.7 percent (58 episodes out of 1,022 occasions of blood cultures). Gram-positive organisms were isolated more often than gram-negative organisms (63.8 percent vs 36.2 percent) in the following order : Staphylococcus epidermidis (37.9 percent), Staphylococcus aureus (17.3 percent), Escherichia coli (12 percent), Streptococcus (8.6 percent), Enterobacter (6.9 percent), Klesiella (6.9 percent), Serratia (3.5 percent), Acinetobacter (3.5 percent), Proteus (1.7 percent) and Morganella morganii (1.7 percent). In antibiotic sensitivity tests, only six of 37 isolates (16 percent) of gram positive bacteria were sensitive to penicillin and 15 of 37 isolates (40 percent) were sensitive to oxacillin. All except one Staphylococcus aureus were sensitive to vancomycin and all except one Staphylococcus epidermidis were sensitive to teicoplanin among 37 isolates of gram positive bacteria. In the case of gram negative bacteria, two of 21 isolates (10 percent) and four of 21 isolates (19 percent) were sensitive to cefotaxime and ceftazidime, respectively. Only six of 21 isolates (29 percent) were sensitive to aminoglycoside, but all 21 isolates (100 percent) were sensitive to imipenem. All seven isolates tested after the year 2000 were sensitive to meropenem. Conclusion : In conclusion, we should choose the proper antimicrobials in treating pediatric cancer patients with suspected bacteremia, reflecting the increasing episodes of gram positive bacteremia and polymicrobial resistance of gram positive and negative organisms.

• Clinical and Experimental Pediatrics
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• v.45 no.6
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• pp.754-763
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• 2002

Purpose : The incidence of type 2 diabetes in children and adolescents has been reported to increase recently. The aim of this study is to investigate the clinical features of type 2 diabetes developing during childhood and adolescent period. Methods : The medical records of 33 patients with type 2 diabetes were reviewed. We analysed clinical manifestations, demographic data, and modes and responses of treatment. Results : Age at diagnosis was $13.4{\pm}1.8$ years. Seventy percent of patients revealed pubertal signs at diagnosis. Half of the patients had BMI more than $25kg/m^2$. Seventy-three percent of patients had family history of type 2 diabetes. Acanthosis nigricans were found in 18% of patients. Nineteen(57.6%) patients were diagnosed incidentally by random urine or blood glucose test without any typical diabetic symptom or sign. The modes of therapy to control hyperglycemia were insulin alone(75.8%), oral hypoglycemic agents alone(9.1%), insulin and oral hypoglycemia agents(9.1%), and only diet with exercise(6%). At the time of investigation, 45.5% of patients were not using insulin. The typical diabetic symptoms at diagnosis were more prevalent in patients who required insulin for more than two years than patients who did not(P<0.05). Conclusion : The development of type 2 diabetes in children and adolescents is possibly related to puberty, obesity, family history, and defects in insulin secretion rather than insulin resistance. Many children and adolescents with type 2 diabetes required insulin initially and some of them could discontinue. More than half of the patients were diagnosed as diabetes without any typical symptom or sign, which might be one of the predictive factors of the prolonged insulin requirement.

• Pediatric Infection and Vaccine
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• v.21 no.2
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• pp.129-138
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• 2014

Purpose: Streptococcus pyogenes is an important cause of invasive diseases in children. We aimed to describe the clinical characteristics of invasive infections due to S. pyogenes in children in Korea. Methods: A retrospective study of children under 18 years of age with invasive infections due to S. pyogenes at Seoul National University Children's Hospital between March 1992 and December 2012, and Seoul National University Bundang Hospital between March 2003 and December 2012 was conducted. Demographic factors, clinical characteristics, laboratory findings, treatment, mortality and morbidity of all patients were reviewed. Results: A total of 30 among 36 cases identified as invasive disease due to S. pyogenes were available for review. There was a predominance for male subjects (male:female=2.75:1). The median age was 50 months (range 12 days to 15 years) and 53.3% were under 5 years of age. Skin and soft tissue infections (9/30, 30.0%), bacteremia without identified focus (4/30, 13.3%) and bone and joint infections (6/30, 20.0%) were the most frequent clinical presentations. Streptococcal toxic shock syndrome (3/30, 10.0%) pulmonary, abdomen and central nervous system infections (2/30, 6.7%) were also seen. There was a peak in number of patients in year 2012 (9/30, 30.0%). There were no cases of mortality. Erythromycin and clindamycin resistance rates were low by 3.8% and 7.5%, respectively. Conclusion: We studied the clinical presentations of invasive infections due to S. pyogenes during the past 20 years in Korean children. The findings of this study help us understand the characteristics of the disease, enhancing early recognition and prompting adequate antibiotic therapy which is important in reducing morbidity and mortality.

• Journal of Yeungnam Medical Science
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• v.25 no.1
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• pp.31-40
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• 2008

Background/Aims : Entecavir is a synthetic nucleoside analogue, cyclopentyl guanine nucleoside, which has a potent antiviral effect and the least viral breakthrough in hepatitis B virus (HBV) replication. Entecavir has been available in Korea since 2007 but there are few reports on its effects. The aim of this study was to evaluate the virological response (VR) and biochemical response (BR) to entecavir in HBV patients at 3, 6 and 9 months after treatment with entecavir. Materials and Methods : Thirty-three chronic hepatitis B patients who took entecavir for at least 9 months were enrolled. We investigated VR and BR by retrospectively reviewing medical records. Patients who satisfied the following criteria were chosen: 1) initial alanine aminotransferase (ALT) levels = 1.5upper limit of normal (ULN) and 2) initial HBV DNA levels = $5\;log_{10}\;copies/ml$. We measured ALT levels every 3 months until month 9. HBV DNA was measured every 2 or 3 months by polymerase chain reaction (PCR) method. Results : Most patients taking entecavir showed good BR (ALT < 40 IU/L). The BR rates were 61%, 73% and 67% at months 3, 6 and 9, respectively. VR (HBV DNA < $5\;log_{10}\;copies/ml$ or 2 log lower than initial HBV DNA) rates were 82%, 91% and 91% at months 3, 6 and 9, respectively. Undetectable HBV DNA (HBV DNA < 4 log10 copies/ml) rates were 49%, 73% and 85% at months 3, 6 and 9, respectively. Two patients presented with virological breakthrough without adverse effects until month 9. Conclusions : Entecavir showed good BR and VR from month 3 and these effects continued through the 9-month observation period. This suggests that entecavir is also a good choice for the first line treatment of chronic hepatitis B (CHB). Further studies are needed to determine the long-term efficacy and drug resistance of entecavir in Korean CHB patients.