Preoperative plasma N-terminal pro-brain natriuretic peptide concentration and perioperative cardiovascular risk in elderly patients.

BACKGROUND: The prediction of perioperative cardiovascular complications is important in the medical management of patients undergoing noncardiac surgery. Several indices have been developed, but a simpler, more practical and accurate method is needed. The purpose of this study was to determine whether the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration before operation can be used to predict perioperative cardiovascular complications in elderly patients undergoing noncardiac surgery. METHODS AND RESULTS: The study group comprised 279 patients older than 60 years who were scheduled for elective surgery. The plasma NT-proBNP concentration, clinical cardiac indices and left ventricular ejection fraction were measured prior to operation. The postoperative cardiac outcomes were followed and predictors for postoperative cardiac risk were identified. Cardiovascular complications occurred in 25 patients (9.0%). Age, the incidence of prior ischemic heart disease or congestive heart failure, and the plasma NT-proBNP concentration were significantly higher in patients with perioperative cardiovascular complications than in those without. Using receiver operating characteristic analysis to predict perioperative cardiovascular events, a cut-off value of 201 pg/ml was identified as the optimal predictor of perioperative complications, showing a sensitivity of 80.0% and specificity of 81.1%. Multivariate analysis revealed that NT-proBNP >201 pg/ml (odds ratio (OR) 7.6, 95% confidence interval (CI) 2.2-26.6, p=0.003) and revised cardiac index > or =2 (OR 6.3, 95% CI 1.7-23.8, p=0.007) were independent predictors for perioperative cardiovascular complications. CONCLUSIONS: Elevated NT-proBNP levels are independently associated with an increase in the risk of perioperative cardiovascular complications in elderly patients undergoing noncardiac and nonvascular operations.     

Gastrokine 1 functions as a tumor suppressor by inhibition of epithelial–mesenchymal transition in gastric cancers

Purpose  

Gastrokine 1 (GKN1) plays an important role in the gastric mucosal defense mechanism and also acts as a functional gastric tumor suppressor. The specific aim of this study was to determine the molecular mechanisms underlying GKN1 tumor suppressor activity in the progression of gastric cancers.     

Self-assembled nanoparticles containing hydrophobically modified glycol chitosan for gene delivery.

A self-assembled nanoparticle was prepared using a hydrophobically modified glycol chitosan for gene delivery. A primary amine of glycol chitosan was modified with 5beta-cholanic acid to prepare a hydrophobically modified glycol chitosan (HGC). The modified chitosan spontaneously formed DNA nanoparticles by a hydrophobic interaction between HGC and hydrophobized DNA. As the HGC content increased, the encapsulation efficiencies of DNA increased while the size of HGC nanoparticles decreased. Upon increasing HGC contents, HGC nanoparticle became less cytotoxic. The increased HGC contents also facilitated endocytic uptakes of HGC nanoparticles by COS-1 cells, which were confirmed by a confocal microscopy. The HGC nanoparticles showed increasing in vitro transfection efficiencies in the presence serum. In vivo results also showed that the HGC nanoparticles had superior transfection efficiencies to naked DNA and a commercialized transfection agent. The HGC nanoparticles composed of hydrophobized DNA and hydrophobically modified glycol chitosan played a significant role in enhancing transfection efficiencies in vitro as well as in vivo.     

Characterization of antimicrobial resistance and class 1 integrons found in Escherichia coli isolates from humans and animals in Korea

OBJECTIVES: Antimicrobial resistance and class 1 integrons found in Escherichia coli isolates from humans and animals in Korea were characterized. METHODS: E. coli isolates were examined for susceptibility to antimicrobial agents. Integrase genes were amplified. Gene cassette regions for classes 1 and 2 integrons were amplified and sequenced. Conjugal transfer and Southern hybridization were performed to determine the genetic localization of class 1 integrons. The clonal relationship of E. coli isolates carrying an identical cassette array was analysed by PFGE. RESULTS: Commensal E. coli isolates from animals were highly resistant to commonly used antimicrobial agents such as tetracycline, sulfamethoxazole, streptomycin, ampicillin and carbenicillin. Integrons were most prevalent in commensal E. coli isolates from poultry (44%), followed by clinical isolates from humans (33%), commensal isolates from swine (23%) and humans (13%). dfrA17-aadA5, dfrA12-orfF-aadA2 and aadA1 were found most frequently in E. coli isolates from humans, poultry and swine, respectively. Class 1 integrons were mostly located in conjugative plasmids. E. coli isolates carrying an identical cassette array were phylogenetically unrelated. CONCLUSIONS: The use of antibiotics is strongly associated with antimicrobial resistance. E. coli isolates from different sources may select a specific gene cassette by antibiotic selective pressure, which results in differences in class 1 integrons. The horizontal transfer of class 1 integrons through conjugative plasmids seems to be responsible for wide dissemination of a particular type of class 1 integron.     

Slowed conduction velocity of the median sensory nerve across the carpal tunnel in normal adults

OBJECTIVE: To examine the difference of using onset or peak latency in the segmental conduction study of the median nerve in normal adults without carpal tunnel syndrome. DESIGN: We investigated 60 hands of 30 young healthy adults (15 men and 15 women; mean age, 27.1 yrs; range, 18-36 yrs). We performed the mid-palm segmental conduction study using antidromic and orthodromic techniques in the median sensory nerves of the second and third digits and the onset and peak latencies of the proximal (wrist-palm) and distal (palm-digit) segments were measured. The distoproximal latency ratios were compared between onset and peak latencies and were compared with the ratios of the superficial radial sensory nerve. RESULTS: Distoproximal peak latency ratios in the median and superficial radial sensory nerves were always >1.0 in both the antidromic and orthodromic conduction studies. However, distoproximal onset latency ratios in the median sensory nerve were >1.0 in only 35% and 21.7% of second digits and in only 25% and 11.7% of third digits in orthodromic and antidromic studies, respectively (P < 0.05). The results of distoproximal onset latency ratios in the superficial radial sensory nerve were 93.3% in the orthodromic study and 86.7% in the antidromic study (P < 0.05). CONCLUSION: Prolongation of onset latency across the carpal tunnel during segmental conduction study of the median sensory nerve was common in healthy adults. When comparing proximal and distal segments for diagnosis of carpal tunnel syndrome, using onset latency as a diagnostic variable may cause greater reporting of false positives.     

Efficacy and safety of standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg in primary hypertension: A randomized,double-blind,active-controlled,multicenter phase 3 trial

The authors evaluated the efficacy, safety, and characteristics of patients who respond well to standard dose triple combination therapy including chlorthalidone 25 mg with telmisartan 80 mg plus amlodipine 5 mg in hypertensive patients. This is a multicenter, double-blind, active-controlled, phase 3, randomized trial. Patients are randomized to triple combination (telmisartan 40 mg/amlodipine 5 mg/chlorthalidone 12.5 mg, TEL/AML/CHTD group) or dual combination (telmisartan 40 mg/amlodipine 5 mg, TEL/AML group) treatment and then dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. The primary endpoint is the change of mean sitting systolic blood pressure (MSSBP) at week 8. A Target BP achievement rate, a response rate, and the safety endpoints are also evaluated. Total 374 patients (mean age = 60.9 ± 10.7 years, male = 78.3%) were randomized to the study. The baseline MSSBPs/diastolic BPs were 149.9 ± 12.2/88.5 ± 10.4 mm Hg. After 8 weeks treatment, the change of MSSBPs at week 8 are −19.1 ± 14.9 mm Hg (TEL/AML/CHTD) and −11.4 ± 14.7 mm Hg (TEL/AML) (p < .0001). The achievement rates of target BP (53.8% vs. 37.8%, p = .0017) and responder rate (54.8% vs. 35.6%, p = .0001) at week 8 were significantly higher in TEL/AML/CHTD. There are no serious adverse event and no one discontinued medication due to adverse event. Among the TEL 80/AML5/CHTD25mg treatment group, patients of female or age ≥ 65 years old showed higher rate of target BP achievement than relatively young male. (61.4 vs. 46.8%, p = .042) Our study showed standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg is efficacious and safe in treatment of primary hypertension. Target BP achievement with triple therapy would be facilitated in female or old age.     

The effect of age and calorie restriction on HIF-1-responsive genes in aged liver

Hypoxia inducible factor-1 (HIF-1) regulates transactivation of several genes in response to hypoxia condition. We explore hepatic HIF-1 responsive gene regulation during aging and the age-related changes of the HIF-1 related gene activation in young and old rats. Results indicate that the aging process induces the activation of HIF-1, which is accompanied by increased HIF-1 DNA binding. This increased binding activity is accompanied by the increase of HIF-1-dependent genes, heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), erythropoietin (EPO), and inducible nitric oxide synthase (iNOS), which all showed remarkable up-regulation during aging process. In contrast, the increased HIF-1 related gene expression was effectively blunted by the anti-oxidative action of calorie restriction in aged rat liver. We propose that age-related HIF-1 binding activity may well be influenced by the increased pro-oxidative conditions of aged animals, which up-regulate HIF-1-dependent gene expression.Min Ju Kang and Hyon Jeen Kim Contributed equally to this work