Synthesis and characterization of polyanhydride for local BCNU delivery carriers

p-Carboxyphenoxy propane (CPP) prepolymer consisting of 4 units and sebacic acid (SA) prepolymer consisting of about 10 units were synthesized by reacting CPP and SA in the presence of excess acetic anhydride, respectively. Polyanhydride, poly(CPP-SA) copolymers were copolymerized by a melt polycondensation process with a mixture of CPP and SA prepolymer. Copolymers of average molecular weight up to 110,000 g/mol were achieved. The crystallinity of poly(CPP-SA) copolymers was decreased by the addition of the CPP homopolymer segment to SA homopolymer. Poly(CPP-SA) copolymers gradually degraded for period of 10 days. No large difference of weight loss observed according to molecular weight variation of poly(CPP-SA) copolymers. BCNU release from wafers fabricated by poly(CPP-SA) showed a sustained release pattern with no initial burst and delay of drug release.     

Associations of serum TRAIL concentrations, anthropometric variables, and serum lipid parameters in healthy adults

To investigate the relationships of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), anthropometric variables, and lipid parameters, we measured serum TRAIL concentrations, body mass index (BMI), total body fat (TBF), and serum lipid profiles in 207 healthy adults. There were no significant differences in serum TRAIL concentrations between men and women, nor between elderly persons and middle-aged subjects. However, men with TBF 16.4 kg (75th per centile) exhibited significantly higher serum TRAIL concentrations than those with TBF 11.2 kg (25th per centile) (69.7 +/- 15.1 pg/ml vs 50.2 +/- 14.3 pg/ml, p < 0.05). Serum TRAIL concentration averaged 76.2 +/- 16.1 pg/ml in women with low-density lipoprotein cholesterol (LDL-C) 165 mg/dl (75th per centile), which was significantly above the values (53.1 +/- 12.9 pg/ml, p < 0.05) in those with LDL-C 117 mg/dl (25th per centile), although no differences were observed on the basis of TBF (75th percentile vs 25th percentile). Serum TRAIL concentrations correlated significantlywithTBF (r = 0.31, p < 0.05) and lean body mass (r = -0.26, p <0.05) in men and LDL-C (r = 0.32, p < 0.05) and total cholesterol (r = 0.21, p < 0.05) in women. In conclusion, serum TRAIL concentrations are associated with serum lipid levels and body adiposity in healthy adults, but are unrelated to a subject's age or gender.     

Identification of Bacillus anthracis by rpoB sequence analysis and multiplex PCR

Comparative sequence analysis was performed upon Bacillus anthracis and its closest relatives, B. cereus and B. thuringiensis. Portions of rpoB DNA from 10 strains of B. anthracis, 16 of B. cereus, 10 of B. thuringiensis, 1 of B. mycoides, and 1 of B. megaterium were amplified and sequenced. The determined rpoB sequences (318 bp) of the 10 B. anthracis strains, including five Korean isolates, were identical to those of Ames, Florida, Kruger B, and Western NA strains. Strains of the "B. cereus group" were separated into two subgroups, in which the B. anthracis strains formed a separate clade in the phylogenetic tree. However, B. cereus and B. thuringiensis could not be differentiated. Sequence analysis confirmed the five Korean isolates as B. anthracis. Based on the rpoB sequences determined in the present study, multiplex PCR generating either B. anthracis-specific amplicons (359 and 208 bp) or cap DNA (291 bp) in a virulence plasmid could be used for the rapid differential detection and identification of virulent B. anthracis.     

Hypertrophic obstructive cardiomyopathy with infundibular stenosis treated by alcohol ablation therapy

This report describes an uncommon case of hypertrophic obstructive cardiomyopathy (HOCM) accompanying infundibular stenosis of the right ventricle treated by alcohol ablation therapy, in a 28-yr-old male patient presenting with dyspnea on exertion. HOCM with infundibular stenosis was detected by echocardiogram and cardiac catheterization and patient has dynamic obstructions of both ventricular outflow tracts. We performed alcohol ablation therapy to improve clinical symptoms and to relieve dynamic obstructions of both ventricular outflow tracts. This is the first case in which HOCM with infundibular stenosis of the right ventricle was treated by alcohol ablation therapy.     

Use of convalescent plasma therapy in SARS patients in Hong Kong

In order to evaluate the efficacy of convalescent plasma therapy in the treatment of patients with severe acute respiratory syndrome (SARS), 80 SARS patients were given convalescent plasma at Prince of Wales Hospital, Hong Kong, between 20 March and 26 May 2003. Good outcome was defined as discharge by day 22 following the onset of SARS symptoms. Poor outcome was defined as death or hospitalization beyond 22 days. A higher day-22 discharge rate was observed among patients who were given convalescent plasma before day 14 of illness (58.3% vs 15.6%; P<0.001) and among those who were PCR positive and seronegative for coronavirus at the time of plasma infusion (66.7% vs 20%; P=0.001).     

Characterization of erythromycin-resistant Streptococcus pneumoniae in Korea, and In Vitro activity of telithromycin against erythromycin-resistant Streptococcus pneumoniae

To characterize the phenotypes and genotypes of erythromycin-resistant clinical isolates of Streptococcus pneumoniae in Korea and to evaluate the in vitro activity of telithromycin against these erythromycin-resistant isolates, we tested a total of 676 isolates of S. pneumoniae collected from 1997 to 2002 in a tertiary hospital in Seoul, Republic of Korea. MICs for erythromycin and telithromycin were determined by the agar dilution method. The macrolide resistance phenotypes of erythromycin-resistant isolates were determined by the erythromycin- clindamycin-rokitamycin triple disk (ECRTD) and MIC induction tests, whereas their macrolide resistance genotypes were determined by PCR for the erm(B), erm(A), subclass erm(TR), and mef genes. To discriminate between mef(A) and mef(E), PCR-restriction fragment length polymorphism (RFLP) analyses were performed. Of the 676 S. pneumoniae isolates, 459 (67.9%) were resistant to erythromycin. Of the 459 erythromycin-resistant isolates, 343 (74.7%) were assigned to the cMLS phenotype, 48 (10.4%) to the iMcLS phenotype, 4 (0.9%) to the iMLS phenotype, and 64 (14.0%) to the M phenotype. The erm(B) gene was detected in 251 (54.6%) isolates, the mef gene was detected in 64 (14.0%), and both the erm(B) and mef genes were detected in 144 (31.4%) isolates. All of the mef genes detected were identified as mef(E). Of the 459 erythromycin- resistant isolates, all but one were susceptible to telithromycin. The MIC(50)/MIC(90) to telithromycin of isolates carrying erm(B), mef(E), and both genes was 0.06/0.5 microg/ml, 0.03/0.125 microg/ml, and 0.5/1.0 microg/ml, respectively. Although the MICs of telithromycin for the erythromycin-resistant isolates varied according to genotype, telithromycin was very active against these erythromycin-resistant S. pneumoniae.     

The effect of passive smoking on asthma symptoms,atopy,and airway hyperresponsiveness in schoolchildren

Passive smoking is a major cause of respiratory morbidity, and is associated with increased bronchial responsiveness in children. To evaluate the effect of smoking by a parent on asthma symptoms, atopy, and airway hyperresponsiveness (AHR), we conducted a cross-sectional survey of 503 schoolchildren that involved questionnaires, spirometry, allergy testing, and a bronchial challenge test. If the PC20 methacholine was less than 16 mg/mL, the subject was considered to have AHR. The prevalence of a parent who smoked was 68.7%. The prevalence of AHR was 45.0%. The sensitization rate to common inhalant allergens was 32.6%. Nasal symptoms such as rhinorrhea, sneezing, nasal itching, and nasal obstruction were present in 42.7%. Asthma symptoms such as cough and wheezing were present in 55.4%. The asthma symptoms were significantly more prevalent in children who had a parent who smoked than in those whose parents did not. The nasal symptoms, atopy, and AHR did not differ according to whether a parent smoked. In a multiple logistic regression model, the asthma symptoms and atopy were independently associated with AHR, when adjusted for confounding variables. Passive smoking contributed to asthma symptoms in schoolchildren and was not an independent risk factor of airway hyperresponsiveness in an epidemiological survey.     

Molecular and genetic characterizations of five pathogenic and two non-pathogenic monoclonal antiphospholipid antibodies

Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by thrombosis, recurrent fetal loss and thrombocytopenia. Antiphospholipid antibodies, detected by enzyme-linked immunoabsorbent assays (aCL) and/or in vitro blood clotting assays (LAC) are strongly associated with APS. Both the molecular structures used by pathogenic antiphospholipid antibodies and the genetic mechanisms leading to their production are unknown. We describe here the variable region genes of seven IgG antiphospholipid antibodies derived from two APS patients. Of these, five are pathogenic as defined in a mouse model of thrombosis and two are not. Analyses of the expressed variable region genes show no preferential V gene usage. However, similar to anti-DNA antibodies, pathogenic antiphospholipid antibodies contain an increased number of arginine residues in the third complimentarity-determining region (CDR3) of their H chains. The increased accumulation of arginine residues in the V(H) CDR3 may act to enhance antigen binding, promote disease and point to the importance of the H chain in the pathogenic potential of certain antiphospholipid antibodies.     

Synergic in-vitro activity of imipenem and sulbactam against Acinetobacter baumannii

The interaction between sulbactam and imipenem was evaluated with four clinical isolates of Acinetobacter baumannii, including two isolates resistant to imipenem, one of which produced IMP-1 metallo-beta-lactamase. Two isolates (one of which was imipenem-resistant) were sulbactam-resistant by undefined mechanisms. MICs were determined by standard broth microdilution methods. Time-kill assays with imipenem and sulbactam, alone or in combination at 0.5 x MIC and 1 x MIC, showed a synergic effect in all four isolates of A. baumannii after incubation for 0, 4, 8 and > 24 h at 35 degrees C.