Carlos Lam

Heme oxygenase-1 mediates the inhibitory actions of brazilin in RAW264.7 macrophages stimulated with lipopolysaccharide

Brazilin, the main constituent of Caesalpinia sappan L., is a natural red pigment that has been reported to possess anti-inflammatory properties. This study aimed to identify a novel anti-inflammatory mechanism of brazilin. We found that brazilin did not cause cytotoxicity below 300 microM, and activated heme oxygenase-1 (HO-1) protein synthesis in a concentration-dependent manner at 10-300 microM in RAW264.7 macrophages without affecting mRNA transcription of HO-1. Additionally, brazilin increased bilirubin production and HO-1 activity in RAW264.7 macrophages. In lipopolysaccharide (LPS)-stimulated macrophages, brazilin suppressed the release of nitric oxide (NO), prostaglandin E(2) (PGE(2)), interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha), and reduced the expression of inducible nitric oxide synthase (iNOS). A specific inhibitor of HO-1, Zn(II) protoporphyrin IX, blocked the suppression of NO production, cytokines release and iNOS expression by brazilin. These results suggest that brazilin possesses anti-inflammatory actions in macrophages and works through a novel mechanism involving the action of HO-1.

Carbapenemase-producing Gram-negative bacteria: current epidemics, antimicrobial susceptibility and treatment options

Carbapenemases, with versatile hydrolytic capacity against β-lactams, are now an important cause of resistance of Gram-negative bacteria. The genes encoding for the acquired carbapenemases are associated with a high potential for dissemination. In addition, infections due to Gram-negative bacteria with acquired carbapenemase production would lead to high clinical mortality rates. Of the acquired carbapenemases, Klebsiella pneumoniae carbapenemase (Ambler class A), Verona integron-encoded metallo-β-lactamase (Ambler class B), New Delhi metallo-β-lactamase (Ambler class B) and many OXA enzymes (OXA-23-like, OXA-24-like, OXA-48-like, OXA-58-like, class D) are considered to be responsible for the worldwide resistance epidemics. As compared with monotherapy with colistin or tigecycline, combination therapy has been shown to effectively lower case-fatality rates. However, development of new antibiotics is crucial in the present pandrug-resistant era.

Carbapenem susceptibilities and non-susceptibility concordance to different carbapenems amongst clinically important Gram-negative bacteria isolated from intensive care units in Taiwan: Results from the Surveillance of Multicentre Antimicrobial Resistance in Taiwan (SMART) in 2009

To investigate the in vitro susceptibilities to various carbapenems amongst clinical Gram-negative bacteria isolated from patients in intensive care units of ten major teaching hospitals in Taiwan in 2009, a survey was conducted to determine the minimum inhibitory concentrations (MICs) of ertapenem, imipenem, meropenem and doripenem against isolates of Enterobacteriaceae (n = 594), Pseudomonas aeruginosa (n = 185), Acinetobacter baumannii (n = 192) and Burkholderia cepacia (n = 23) using the agar dilution method. Susceptibilities were determined according to 2009, 2011 and 2012 MIC breakpoints recommended by the CLSI as well as 2012 MIC breakpoints recommended by EUCAST. Based on CLSI 2012 criteria, the ertapenem susceptible rate was 93%, 81%, 68% and 92% for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Serratia marcescens, respectively. All Proteus mirabilis and Morganella morganii isolates were susceptible to ertapenem; however, 64% of P. mirabilis and all M. morganii isolates were non-susceptible to imipenem. Meropenem and doripenem had better activities than imipenem against ertapenem-non-susceptible Enterobacteriaceae isolates. E. coli, K. pneumoniae and E. cloacae with ertapenem MICs≥4 mg/L were synchronously not susceptible to imipenem, meropenem and doripenem. Imipenem susceptibility was 65% and 29% for P. aeruginosa and A. baumannii, respectively. Additionally, P. aeruginosa and A. baumannii isolates with imipenem MICs≥8 mg/L were also not susceptible to meropenem and doripenem. These data provide a better understanding of choosing appropriate carbapenem agents to treat infections caused by ertapenem-non-susceptible Enterobacteriaceae as well as P. aeruginosa and A. baumannii isolates with imipenem MICs≥4 mg/L.

Relationship between the distribution of cefepime minimum inhibitory concentrations and detection of extended-spectrum β-lactamase production among clinically important Enterobacteriaceae isolates obtained from patients in intensive care units in Taiwan: Results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART) in 2007

BACKGROUND The data on susceptibility of important cephalosporins against four Enterobacteriaceae members producing potential extended-spectrum β-lactamase (ESBL) collected from Taiwanese intensive care units are lacking. METHODS Minimum inhibitory concentrations (MICs) of cefotaxime, ceftazidime, and cefepime were determined using agar dilution method, against Escherichia coli (n = 344), Klebsiella pneumoniae (n = 359), Enterobacter cloacae (n = 103), and Proteus mirabilis (n = 78). Susceptibilities of these isolates to three cephalosporins were assessed according to MIC breakpoints recommended by the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2013. The double-disk synergy test using disks containing cefepime (30 μg) with or without clavulanate (10 μg) was applied to confirm production of ESBL for isolates with cephalosporin MIC ≥ 2 μg/mL. RESULTS A total of 175 isolates were verified as ESBL producers. The rates of cefepime susceptibility among the ESBL-producing isolates, according to CLSI (EUCAST) criteria, were 56.7% (22.4%) for E. coli, 61.3% (12.0%) for K. pneumoniae, 57.9% (31.6%) for E. cloacae, and 71.4% (7.1%) for P. mirabilis. Using different cefepime MIC breakpoints (MICs ≥ 16 μg/mL recommended by CLSI criteria and ≥ 2 μg/mL by EUCAST criteria) to define nonsusceptibility, we found that both criteria were poorer at predicting ESBL producers among K. pneumoniae and E. cloacae than among the other two species. In addition, we also found that the cefepime MIC level of 1.0 μg/mL best distinguished non-ESBL- from ESBL-producing K. pneumoniae and E. cloacae. CONCLUSION To detect ESBLs, CLSI should revise the cefepime MIC breakpoint against Enterobacteriaceae.

Comorbidity as an Independent Risk Factor in Patients With Cancer An 8-Year Population-Based Study

This study determined the prevalence of medical conditions in patients with cancer and their impact on outcome. We evaluated a cohort of 37 411 patients diagnosed with cancer between 2000 and 2008 in Taiwan, collecting the cancer diagnosis and chronic disease diagnoses. The severity of the comorbid condition was correlated with the cancer diagnosis and outcome. Overall, 71.9% of the study population had 1 or more comorbid conditions. Patients with none (n = 10 508), 1 (n = 8881), 2 (n = 6583), and 3 or more (n = 11 439) comorbid conditions had mortality rates of 11.49%, 15.99%, 19.61%, and 29.39%, respectively. Older patients with comorbid conditions had a significantly higher chance of death. Dementia, heart disease, or cerebrovascular diseases were associated with the highest mortality. Cancer patients with comorbid conditions have a significantly higher risk of death. Prevention and better medical management of comorbid conditions is likely to result in improved outcomes for patients with cancer.

The effect of various types of motorcycle helmets on cervical spine injury in head injury patients: a multicenter study in Taiwan.

Introduction. The relationship between cervical spine injury (CSI) and helmet in head injury (HI) patients following motorcycle crashes is crucial. Controversy still exists; therefore we evaluated the effect of various types of helmets on CSI in HI patients following motorcycle crashes and researched the mechanism of this effect. Patients and Methods. A total of 5225 patients of motorcycle crashes between 2000 and 2009 were extracted from the Head Injury Registry in Taiwan. These patients were divided into case and control groups according to the presence of concomitant CSI. Helmet use and types were separately compared between the two groups and the odds ratio of CSI was obtained by using multiple logistic regression analysis. Results. We observed that 173 (3.3%) of the HI patients were associated with CSI. The HI patients using a helmet (odds ratio (OR) = 0.31, 95% confidence interval (CI) = 0.19−0.49), full-coverage helmet (0.19, 0.10−0.36), and partial-coverage helmet (0.35, 0.21−0.56) exhibited a significantly decreased rate of CSI compared with those without a helmet. Conclusion. Wearing full-coverage and partial-coverage helmets significantly reduced the risk of CSI among HI patients following motorcycle crashes. This effect may be due to the smooth surface and hard padding materials of helmet.

Influence of a 100-km ultra-marathon on hepatitis B carrier runners.

This study compares the serological markers between runners who are hepatitis B virus carries (HBVc) and runners who are non-HBVc in a 100-km ultra-marathon race. Blood samples of 8 HBVc and 18 non-HBVc runners were drawn 1 week before, immediately following, and 24 h after the race. Samples were analyzed and compared between the 2 groups for liver function tests, muscle damage markers and oxidative stress cytokines. For HBVc runners, HBV-DNA (hepatitis B virus-deoxyribonucleic acid) levels were also evaluated for virus reactivation. The results demonstrate a statistically significant increase in both immediate and 24-h post-race values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), compared with pre-race values. No statistically significant difference was observed between the 2 groups for the values of AST, LDH, CK, hs-CRP, IL-6 and TNF-α either before or after the race. There was also no statistically significant change in the levels of HBV-DNA in HBVc runners. These findings suggest that HBVc runners do not have higher risks of liver function impairment, muscle breakdown and inflammatory response compared to non-HBVc runners in such endurance races.

Whether intravenous contrast is necessary for CT diagnosis of acute appendicitis in adult ED patients

RATIONALE AND OBJECTIVES To assess the necessity of intravenous contrast medium for abdominopelvic computed tomography (CT) diagnosis of acute appendicitis (APP) among adult patients with right lower quadrant (RLQ) abdominal pain at emergency department (ED). MATERIALS AND METHODS ED patients with clinical suspicion of APP from RLQ pain for a period of 8 months were enrolled retrospectively. Both pre- and postintravenous contrast-enhanced CT scans were performed for these patients. The visibility of vermiform appendix and specific CT findings of APP were recorded separately for noncontrast CT (NCT) and contrast-enhanced CT (CCT) images without knowledge of the patients identity and final diagnosis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of CT diagnosis for APP were compared between the two groups. The ease of identifying appendix was also compared. RESULTS Forty-two (42.0%) of the 100 patients (55 males, 45 females; age range, 16-90 years; mean age, 49.3 years) were APP. There was no significant difference for the visibility of appendix (94% vs. 91%; P = .589) and radiological characters between the CCT and NCT groups. There were significant differences between the two groups for sensitivity (100% vs. 90.5%; P = .036), specificity (94.8% vs. 100%; P = .038), PPV (93.3% vs. 100%; P = .021), NPV (100% vs. 93.5%; P = .021), but no significant difference for accuracy (97% vs. 96%; P = 1). The appendix was easier to detect on CCT than NCT images (P = .013). CONCLUSION The diagnostic sensitivity of CCT was significantly better than that of NCT. Intravenous contrast administration could also make doctors easier in indentifying appendixes.

Emphysematous cholecystitis complicating liver abscess due to Clostridium baratii infection

Clostridium baratii bacteremia is a rare but severe anaerobic infection. Its major clinical features are neurological presentation, and significant risk factors include hemodialysis, intestinal disease or malignancy. We describe a case of emphysematous cholecystitis complicated by a liver abscess due to C baratii infection in a healthy adult without neurological manifestation.

An old lady with anterior chest pain and unilateral facial flushing

Harlequin syndrome is rare and typically characterized by asymmetric flushing and sweating. Although it is usually considered idiopathic, literature review shows that it may be caused by lesion over lung apex or after central venous catheterization in the internal jugular vein. We present a 74-year-old woman who had been experiencing recurrent chest pain and right shoulder pain since 2 weeks ago. The tentative diagnosis was made by the emergency physician (EP) as acute coronary syndrome. The patient was given nitroglycerin treatment. Twelve hours later, the patient developed another episode of chest pain. The electrocardiogram and cardiac enzyme study results were, however, both normal. Further evaluation showed intermittent flushing over the left side of her face, as well as right-eye ptosis. A chest computed tomography (CT) was conducted, under the suspicion of Harlequin syndrome in combination with Horner syndrome, to derive the diagnosis of a right lung apex tumor. This case showed that history taking and physical examination are very important in the emergency department. It is particularly vital to observe the microchanges in the patients symptoms and signs. It is also imperative to reassess the patient whose symptoms fail to improve under treatment, to look for other underlying lesions.