P2X7 receptor blockade reduces pyroptotic inflammation and promotes phagocytosis in Vibrio vulnificus infection.

Vibrio vulnificus, a gram-negative bacterium, causes serious wound infections and septicemia. Once it develops into early phase sepsis, hyperinflammatory immune responses result in poor prognosis in patients. The present study aimed to examine the possible underlying pathogenic mechanism and explore potential agents that could protect against V. vulnificus cytotoxicity. Here, we report that infection of mouse macrophages with V. vulnificus triggers antiphagocytic effects and pyroptotic inflammation via ATP-mediated purinergic P2X7 receptor (P2X7R) signaling. V. vulnificus promoted P2X7-dependent nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 translocation, modulating the expression of the inflammasome sensor NLR family pyrin domain containing 3 (NLRP3), adaptor apoptosis-associated speck-like protein containing a card (ASC), and pyroptotic protein gasdermin D (GSDMD) in mouse macrophages. V. vulnificus induced the NLRP3/caspase-1 inflammasome signaling complex expression that drives GSDMD transmembrane pore formation and secretion of interleukin (IL)-1ß, IL-18, and macrophage inflammatory protein-2 (MIP-2). This effect was blocked by P2X7R antagonists, indicating that the P2X7R mediates GSDMD-related pyroptotic inflammation in macrophages through the NF-κB/NLRP3/caspase-1 signaling pathway. Furthermore, blockade of P2X7R reduced V. vulnificus-colony-forming units in the spleen, immune cell infiltration into the skin and lung tissues, and serum concentrations of IL-1ß, IL-18, and MIP-2 in mice. These results indicate that P2X7R plays a vital role in mediating phagocytosis by macrophages and pyroptotic inflammation during V. vulnificus infection and provides new opportunities for therapeutic intervention in bacterial infections.

Combination therapy of iPSC-derived conditioned medium with ceftriaxone alleviates bacteria-induced lung injury by targeting the NLRP3 inflammasome.

The lung is the first and most frequent organ to fail among sepsis patients. The mortality rate of sepsis-related acute lung injury (ALI) is high. Despite appropriate antimicrobial therapy, no treatment strategies are available for sepsis-induced ALI. Stem cell-mediated paracrine signaling is a potential treatment method for various diseases. This study aimed to examine the effects of induced pluripotent stem cell-derived conditioned medium (iPSC-CM) combined with antibiotics on ALI in a rat model of Escherichia coli-induced sepsis. Rats were administered either iPSC-CM or the vehicle (saline) with antibiotics (ceftriaxone). After 72 h, liquid biopsy, bronchoalveolar lavage fluid (BALF), and tissues were harvested for analysis. Survival rates were observed for up to 3 days. Furthermore, we examined the effects of iPSC-CM on cytokine production, metalloproteinase 9 (MMP-9) expression, and NLRP3-ASC interaction in RAW264.7 cells stimulated with lipopolysaccharide/interferon-γ (LPS/IFN-γ). Combined treatment of iPSC-CM with antibiotics significantly improved survival in E. coli-infected rats (p = 0.0006). iPSC-CM ameliorated E. coli-induced infiltration of macrophages, reducing the number of cells in BALF, and suppressing interleukin (IL)-1ß, MIP-2, IL-6, and MMP-9 messenger RNA in lung sections. iPSC-CM treatment attenuated NLRP3 expression and inhibited NLRP3 inflammasome activation by disrupting NLRP3-mediated ASC complex formation in LPS/IFN-γ-primed RAW264.7 cells. This study reveals the mechanisms underlying iPSC-CM-conferred anti-inflammatory activity in ALI through the attenuation of macrophage recruitment to the lung, thus inactivating NLRP3 inflammasomes in macrophages. iPSC-CM therapy may be a useful adjuvant treatment to reduce sepsis-related mortality by ameliorating ALI.

Impact of statin on long-term outcome among patients with end-stage renal disease with acute myocardial infarction (AMI): a nationwide case-control study.

BACKGROUND: Use of statin has been associated with reduced risk of cardiovascular diseases events and mortality. However, in patients with end-stage renal disease (ESRD), the protective effects of statin are controversial. To evaluate the impact of chronic statin use on clinical outcomes of patients with acute myocardial infarction (AMI) with ESRD. METHODS: We enrolled 8056 patients with ESRD who were initially diagnosed and admitted for first AMI from Taiwan's National Health Insurance Research Database. Of which, 2134 patients underwent statin therapy. We randomly selected and use age, sex, hypertension, diabetes mellitus (DM), peripheral vascular diseases (PVD), heart failure (HF), cerebrovascular accidents (CVA), chronic obstructive pulmonary disease, matched with the study group as controls (non-stain user). We compared the effects of statin use in term of all-cause death among patients with AMI with ESRD. RESULTS: Statin use resulted in a significantly higher survival rate in patients ith AMI with ESRD compared with non-statin users. After adjusted the comorbidities the male patients and patients with DM, PVD, HF and CVA had lower long-term survival rate (all p<0.001). Patients who underwent percutaneous coronary intervention (p<0.001), ACE inhibitors/angiotensin II receptor blockers (p<0.001), ß receptor blockers (p<0.001) and statin therapy (p=0.007) had better long-term survival rate. Patients with AMI with ESRD on statin therapy exhibited a significantly lower risk of mortality compared with non-statin users (p<0.0001). CONCLUSION: Among patients with ESRD with AMI, statin therapy was associated with reduced all-cause mortality.

Caffeic Acid Phenethyl Ester Rescues Pulmonary Arterial Hypertension through the Inhibition of AKT/ERK-Dependent PDGF/HIF-1α In Vitro and In Vivo.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial proliferation and remodeling, resulting in a specific increase in right ventricle systolic pressure (RVSP) and, ultimately right ventricular failure. Recent studies have demonstrated that caffeic acid phenethyl ester (CAPE) exerts a protective role in NF-κB-mediated inflammatory diseases. However, the effect of CAPE on PAH remains to be elucidated. In this study, monocrotaline (MCT) was used to establish PAH in rats. Two weeks after the induction of PAH by MCT, CAPE was administrated by intraperitoneal injection once a day for two weeks. Pulmonary hemodynamic measurements and pulmonary artery morphological assessments were examined. Our results showed that administration of CAPE significantly suppressed MCT-induced vascular remodeling by decreasing the HIF-1α expression and PDGF-BB production, and improved in vivo RV systolic performance in rats. Furthermore, CAPE inhibits hypoxia- and PDGF-BB-induced HIF-1α expression by decreasing the activation of the AKT/ERK pathway, which results in the inhibition of human pulmonary artery smooth muscle cells (hPASMCs) proliferation and prevention of cells resistant to apoptosis. Overall, our data suggest that HIF-1α is regarded as an alternative target for CAPE in addition to NF-κB, and may represent a promising therapeutic agent for the treatment of PAH diseases.

Dexamethasone Downregulates Expressions of 14-3-3ß and γ-Isoforms in Mice with Eosinophilic Meningitis Caused by Angiostrongylus cantonensis Infection.

Steroids are commonly used in patients with eosinophilic meningitis caused by A. cantonensis infections. The mechanism steroids act on eosinophilic meningitis remains unclear. In this mouse experiments, expressions of 14-3-3 isoform ß and γ proteins significantly increased in the CSF 2-3 weeks after the infection, but not increasedin the dexamethasone-treated group. Expression of 14-3-3 ß, γ, ε, and θ isoforms increased in brain meninges over the 3-week period after infection and decreased due to dexamethasone treatment. In conclusion, administration of dexamethasone in mice with eosinophilic meningitis decreased expressions of 14-3-3 isoform proteins in the CSF and in brain meninges.

The role of autonomic nervous system function in hypothermia-mediated sepsis protection.

OBJECTIVE: The objective of this study is to determine whether hypothermia will lessen decreases in heart rate variability and improve outcome in a rat model of sepsis. METHODS: Thirty-six male Sprague-Dawley rats were randomized into 3 groups: control, low sepsis, and high sepsis groups. These groups were each subdivided into a normothermia (37°C) (n = 6) and a hypothermia group (34°C) (n = 6). Cyclophosphamide (100 mg/kg) was administered 5 days before Staphylococcus aureus injection to produce conditions in which sepsis could be induced reliably. Hypothermic rats received temperature reduction for 1 hour post injection. Electrocardiogram was recorded before, after, and 1 day after staphylococcal injection, and the low frequency, high frequency (HF), and LF/HF ratio measurements of heart rate variability and the frequencies of arrhythmia were recorded. The effects of time, sepsis severity, and hypothermia on these variables were analyzed using a multivariate generalized estimation equation mode. RESULTS: Four deaths occurred in the normothermic group, and none, in the hypothermic group. Sepsis of both low and high severity increased low frequency and HF 1 day after sepsis induction. Hypothermia significantly decreased HF in low, but not high sepsis severity. CONCLUSIONS: Hypothermia decreased mortality in septic rats. The influence of hypothermia on HF depended on the severity of the sepsis.

MMP-10 from M1 macrophages promotes pulmonary vascular remodeling and pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by muscularized pulmonary blood vessels, leading to right heart hypertrophy and cardiac failure. However, state-of-the-art therapeutics fail to target the ongoing remodeling process. Here, this study shows that matrix metalloproteinases (MMP)-1 and MMP-10 levels are increased in the medial layer of vessel wall, serum, and M1-polarized macrophages from patients with PAH and the lungs of monocrotaline- and hypoxia-induced PAH rodent models. MMP-10 regulates the malignant phenotype of pulmonary artery smooth muscle cells (PASMCs). The overexpression of active MMP-10 promotes PASMC proliferation and migration via upregulation of cyclin D1 and proliferating cell nuclear antigen, suggesting that MMP-10 produced by infiltrating macrophages contributes to vascular remodeling. Furthermore, inhibition of STAT1 inhibits hypoxia-induced MMP-10 but not MMP-1 expression in M1-polarized macrophages from patients with PAH. In conclusion, circulating MMP-10 could be used as a potential targeted therapy for PAH.

Expression of matrix metalloproteinases and their tissue inhibitors in the serum and cerebrospinal fluid of patients with HIV-1 infection and syphilis or neurosyphilis.

The potential mechanisms for altered matrix metalloproteinase (MMP) or tissue inhibitors of matrix metalloproteinase (TIMP) function in patients with syphilis and HIV-1 co-infection (HIV-S) was unclear. To determine the expression of MMP-2, 9 and TIMP-1, 2, 4 in the serum and cerebrospinal fluid (CSF) of HIV-S patients, a total of 20 HIV-S patients and 8 controls were enrolled in a HIV-1 clinical cohort for diagnosis of neurosyphilis in Taiwan. Serum and CSF concentrations of MMP-2, 9, and TIMP-1, 2, 4 were determined by ELISA. Gelatin zymography was used to detect the expression of MMP-2 and MMP-9 in the CSF. Neurosyphilis was defined as a CSF white blood cell count ≥ 20 cells/µL or a reactive CSF Venereal Disease Research Laboratory (VDRL). All the patients with HIV-S were males. Most (85%) had sex with men (MSM) and serum rapid plasma reagin (RPR) titers of ≥ 1:32. The median age was 35 years (IQR 30-43). The median CD4 T cell counts at the time of the diagnosis of syphilis were 270 cells/µL (IQR 96-484). Ten patients (50%) had neurosyphilis based on a reactive CSF VDRL test (n=8) or increased CSF white cell counts ≥ 20/µL (n=2). The concentrations of CSF MMP-9, TIMP-1, and TIMP-2 were significantly higher in patients with HIV-S than the controls (P<0.05). The CSF TIMP-4 concentrations were significantly lower in those with HIV-S (452 pg/ml) than controls (3101 pg/ml), P<0001. There were no significant differences in serum concentrations between the groups. The only finding that distinguished HIV-1 patients with from those without neurosyphilis is a significant higher expression of CSF MMP-9. In conclusion, the MMP/TIMP system was found to be dysregulated in patients with HIV-S regardless of whether they met the laboratory definition of neurosyphilis. The CSF level of MMP-9 was the only measure that distinguished those with or without neurosyphilis.

The effects of lazaroid U-74389G in a rat sepsis model.

OBJECTIVE AND DESIGN: To examine the protective effects of a lazaroid, 21-aminosteroid U-74389G, in a rat septic shock model. MATERIALS OR SUBJECTS: Male Sprague-Dawley rats (n = 60) aged 6-8 months. TREATMENT: Groups were exposed to 500 cGy radiation followed by E. coli inoculation, and either placebo or lazaroid injection (10 mg/kg intraperitoneal) 5 days after irradiation. METHODS: Hemodynamic measurements, arterial blood gases, serum lactate, total antioxidative capacity, and cytokine levels were measured at specific time intervals. RESULTS: Treatment with the lazaroid U-74389G maintained cardiac output and mean aortic pressure. Lazaroid treatment also prevented the increase in serum lactate seen in placebo-treated rats. Cytokine serum levels in lazaroid-treated rats were not significantly different from those in placebo-treated rats at any time point. CONCLUSIONS: Lazaroid treatment of E. coli-inoculated septic animals lessens the hemodynamic deterioration seen in sepsis.

Arsenic, vinyl chloride, viral hepatitis, and hepatic angiosarcoma: a hospital-based study and review of literature in Taiwan.

BACKGROUND: Hepatic angiosarcoma (HAS) is a rare type of liver cancer that is often fatal, and arsenic and vinyl chloride monomer (VCM) are two major causal agents. Whereas Taiwan is an endemic area of liver cancer, epidemiologic data on HAS are limited. We reviewed the cases observed at a teaching hospital to evaluate the roles of VCM, arsenic, and viral hepatitis in the occurrence of HAS. METHODS: We reviewed the medical records of patients with pathological proof of HAS from January 2000 to August 2010 at a teaching hospital which is adjacent to the major VCM processing area in Taiwan and nearby an endemic area of arsenic exposure from drinking water. We also conducted a literature review and included all patients of HAS reported in Taiwan. RESULTS: Six male and three female cases aged from 56 to 83 years (64.6 ± 8.2 years) were identified at the hospital. The differences in clinical features between men and women were not statistically significant. None of them had exposure to VCM or arsenic in drinking water. Two had evidence of hepatitis C infection, but none had evidence of hepatitis B infection. Five male and four female cases aged 30 to 82 years (58.6 ± 15.5 years) were identified in the literature, including two with arsenic exposure and one with chronic hepatitis B infection. CONCLUSIONS: HAS is rare in Taiwan, and we found no evidence supporting a major role of VCM, arsenic in drinking water, or viral hepatitis in its occurrence.

Non-nosocomial healthcare-associated infective endocarditis in Taiwan: an underrecognized disease with poor outcome.

BACKGROUND: Non-nosocomial healthcare-associated infective endocarditis (NNHCA-IE) is a new category of IE of increasing importance. This study described the clinical and microbiological characteristics and outcome of NNHCA-IE in Taiwan. METHODS: A retrospective study was conducted of all patients with IE admitted to the Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan over a five-year period from July 2004 to July 2009. The clinical and microbiological features of NNHCA-IE were compared to those of community-acquired and nosocomial IE. Predictors for in-hospital death were determined. RESULTS: Two-hundred episodes of confirmed IE occurred during the study period. These included 148 (74%) community-acquired, 30 (15%) non-nosocomial healthcare-associated, and 22 (11%) nosocomial healthcare-associated IE. Staphylococcus aureus was the most frequent pathogen. Patients with NNHCA-IE compared to community-acquired IE, were older (median age, 67 vs. 44, years, p < 0.001), had more MRSA (43.3% vs. 9.5%, p < 0.001), more comorbidity conditions (median Charlson comorbidity index [interquartile range], 4[2-6] vs. 0[0-1], p < 0.001), a higher in-hospital mortality (50.0% vs. 17.6%, p < 0.001) and were less frequently recognized by clinicians on admission (16.7% vs. 47.7%, p = 0.002). The overall in-hospital mortality rate for all patients with IE was 25%. Shock was the strongest risk factor for in-hospital death (odds ratio 7.8, 95% confidence interval 2.4-25.2, p < 0.001). CONCLUSIONS: NNHCA-IE is underrecognized and carries a high mortality rate. Early recognition is crucial to provide optimal management and improve outcome.

Dual trajectories of loneliness and depression and their baseline correlates over a 14-year follow-up period in older adults: Results from a nationally representative sample in Taiwan.

AIMS: To explore the codevelopment between loneliness and depression in older adults, and to identify its potential baseline individual, family and extrafamilial correlates. BACKGROUND: The number of older adults around the world has steadily increased over the last decades. Later life is a particularly vulnerable life stage due to multiple unfavourable conditions, and mental health in this stage appears to become an inescapable issue. Previous research has found the cross-sectional association between loneliness and depression, but their codevelopment has been understudied. Therefore, exploring the codevelopment and its correlates has significant implications for prevention and healthcare professionals. DESIGN: A longitudinal follow-up study. METHODS: The study used nationally representative data over a 14-year follow-up period from the Taiwan Longitudinal Study on Ageing focused on Taiwanese aged 60 years and above (n = 4049). Group-based trajectory modelling, group-based dual-trajectory modelling and multinomial logistic regression were the primary analytical methods. RESULTS: We identified three distinct dual trajectories of loneliness and depression: longitudinal low-frequency lonely depressed (29.3%), longitudinal moderate-frequency lonely depressed (59.4%) and longitudinal high-frequency lonely depressed (11.3%). After considering several demographic and background characteristics, difficulty in physical functioning, number of physical symptoms and diseases, sleep quality and number of child deaths were found to be significantly associated. CONCLUSION: Across the three identified dual-trajectory groups, they all showed a stable loneliness frequency pattern over time; however, the moderate-frequency group and high-frequency group both had a trajectory of increasing depression. It seems that depression tends to change over time in a worsening direction, especially for those with a certain frequency of loneliness. Furthermore, differences in individual and family correlates were found across the groups. IMPLICATIONS FOR PRACTICE: Interventions focusing on the specific factors may help hinder coexisting loneliness and depression, and have implications for developing health promotion strategies and chronic disease care plans.

Kikuchi-Fujimoto disease: an amazing response to hydroxychloroquine.

Kikuchi-Fujimoto disease is a benign and self-limited disorder. The common clinical features are fever and cervical lymphadenitis. A 9-year-old girl with fever and cervical lymphadenitis was admitted because of persistent symptoms. A cervical lymph node biopsy showed the characteristic features of Kikuchi-Fujimoto disease. Herein, we will discuss the clinical features, diagnosis, and treatment of Kikuchi-Fujimoto disease and highlight the dramatic response when a patient was treated with hydroxychloroquine.

Effects of epinephrine on heart rate variability and cytokines in a rat sepsis model.

Catecholamines have both anti-inflammatory and vasoactive properties. A decreased cardiac response to catecholamines has been associated with a high risk of death in sepsis and septic shock. The aim of this study was to investigate the effects of epinephrine (EPI) on heart rate variability (HRV) and autonomic balance, as well as cytokine levels, in a rat sepsis model. Thirty-six male Sprague-Dawley rats were assigned to 4 experimental groups and 2 control groups of 6 rats each. The rats in the experimental groups were inoculated with a lipopolysaccharide (LPS, endotoxin) to establish a sepsis model. Group A received only LPS; group B received LPS, antecedent EPI and the nonselective ß-blocker propranolol; group C received LPS and antecedent EPI; and group D received LPS, antecedent EPI and the selective ß1-blocker esmolol. One control group received EPI and the other received saline placebo. Heart rate variability (HRV) was analyzed and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) levels were measured. Measurements were carried out at baseline, at 0 hour after EPI infusion, and at 0.5, 2, and 4 hours after LPS inoculation. There were significant differences in HRV and cytokine levels between the groups, indicating that LPS infusion caused autonomic imbalance. Antecedent EPI significantly decreased the level of TNF-α in group C compared with group A in which TNF-α level peaked at 2 hours and then declined. Propranolol (group B) but not esmolol (group D) administration resulted in elevated TNF-α levels, comparable to those observed in group A. In conclusion, antecedent administration of EPI in a rat sepsis model inhibits the production of TNF-α possibly via the ß2-adrenoceptor.

Predictors of septic metastatic infection and mortality among patients with Klebsiella pneumoniae liver abscess.

BACKGROUND: Primary liver abscess caused by Klebsiella pneumoniae is an infection that is emerging worldwide and that is associated with severe morbidity and considerable mortality. METHODS: A retrospective analysis of 110 episodes of primary liver abscess caused by K. pneumoniae that required hospitalization during 2001-2002 was conducted to identify predictors of metastatic infection, mortality, and the efficacy of first-generation cephalosporins and percutaneous drainage. The potential role of Klebsiella rmpA and magA genes was also evaluated. RESULTS: The study included 59 men and 51 women, with a mean age of 61.8 years. Diabetes was noted in 67 patients (60.9%). Metastatic infection occurred in 17 patients (15.5%), with meningitis accounting for 11 patients (64.7%) and endophthalmitis accounting for 4 patients (23.5%). The overall mortality rate was 10.0% (11 patients). Most of the severe complications occurred within the first 3 days after hospital admission. Ninety-two patients (83.6%) received treatment with cefazolin for >3 days. Four patients (4.3%) of the group who received cefazolin had metastatic infection, 1 patient (1.1%) experienced septic shock, and 3 (3.3%) experienced acute respiratory failure. Five (5.4%) of those 92 patients died. Multivariable analysis revealed that rmpA (odds ratio [OR], 28.85), Acute Physiologic and Chronic Health Evaluation (APACHE) II score >or=20 (OR, 8.08), and septic shock (OR, 4.33) were statistically significant predictors of metastatic infection. Metastatic infection (OR, 6.73), severity of disease (APACHE II score >or=16; OR, 11.82), septic shock (OR, 8.30), acute respiratory failure (OR, 69.92), and gas formation revealed on imaging (OR, 13.26) predicted mortality. Pigtail drainage protected against both metastatic infection (OR, 0.25) and mortality (OR, 0.14). CONCLUSION: Management of primary liver abscess caused by K. pneumoniae with use of first-generation cephalosporins and percutaneous drainage was associated with low rates of mortality, metastatic infection, and complications. These rates are comparable to those reported for third-generation cephalosporins.

Association of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-4 in cerebrospinal fluid with blood-brain barrier dysfunction in patients with eosinophilic meningitis caused by Angiostrongylus cantonensis.

To evaluate possible blood-brain barrier (BBB) dysfunction caused by matrix metalloproteinase-9 (MMP-9) and its regulation by tissue inhibitors of metalloproteinase (TIMPs) in patients with eosinophilic meningitis caused by infection with Angiostrongylus cantonensis, 40 patients and 28 controls were included in this study. Concentrations of MMP-2, MMP-9, TIMP-1, and cerebrospinal fluid (CSF):serum albumin ratios (Q(Alb) values) were significantly increased in patients compared with controls. However, concentrations of TIMP-4 were significantly lower in patients. In contrast to MMP-2, proteolytic activity of MMP-9 detected by gelatin zymography was only observed in patients with eosinophilic meningitis. We detected higher levels of antibodies specific for A. cantonensis and higher Q(Alb) values and MMP-9 concentrations in CSF of patients with eosinophilic meningitis, Furthermore, the increase in the Q(Alb) value was significantly correlated with the increase in MMP-9 in patients. In parallel with CSF MMP-9, patients also showed an increase in CSF leukocyte counts. Gradual decreases in levels of Q(Alb), MMP-9, and TIMP-1 and increases in levels of TIMP-4 were observed in six patients during recovery from eosinophilic meningitis. These results suggest that the source of MMP-9 in CSF of patients with eosinophilic meningitis was probably associated with leukocytes migrating from peripheral blood to CSF. Activity of MMP-9 in CSF of patients could not be completely inhibited because of the decrease of TIMP-4, which may cause BBB dysfunction, as shown by higher Q(Alb) values in patients.

Cerebrospinal fluid hepatocyte growth factor level in meningitis.

BACKGROUND AND PURPOSE: Hepatocyte growth factor (HGF) is a multifunctional cytokine that has been found to be elevated in tuberculous and bacterial meningitis, but no evaluation has been undertaken of its usefulness in identifying various forms of aseptic meningitis. METHODS: In a retrospective study, the levels of HGF in the cerebrospinal fluid of 65 patients were measured prior to treatment. The association of HGF with non-infectious diseases and clinically or microbiologically proven bacterial, tuberculous, viral, fungal and parasitic meningitis was observed, along with its relation to other parameters of the cerebrospinal fluid. RESULTS: Forty six of the 65 patients (71%) were diagnosed as having meningitis. Cerebospinal fluid HGF level was significantly elevated in patients with meningitis compared with patients with non-infectious diseases (1501 vs 578 pg/mL; Mann-Whitney U test, p=0.001). The highest HGF level was found in bacterial meningitis (2699 pg/mL), followed by tuberculous meningitis (1540 pg/mL), viral meningitis (1431 pg/mL), fungal meningitis (714 pg/mL) and parasitic meningitis (174 pg/mL). There was no association between HGF level and other parameters of the cerebrospinal fluid (Pearson's correlation test). CONCLUSION: Cerebrospinal fluid HGF may offer additional information in the classification of meningitis. This may assist in patient management when no pathogen is cultured from the cerebrospinal fluid and when other parameters of the cerebrospinal fluid demonstrate equivocal results.

Antimicrobial resistance of rapidly growing mycobacteria in western Taiwan: SMART program 2002.

BACKGROUND/PURPOSE: To understand the resistance patterns of rapidly growing mycobacteria (RGM) in Taiwan, antimicrobial resistance of clinical isolates was determined as part of the SMART (Surveillance from Multicenter Antimicrobial Resistance in Taiwan) program. METHODS: During the period from January 2002 to December 2003, clinical isolates were collected from eight hospitals located on the west side of Taiwan and one reference laboratory. Broth microdilution minimum inhibitory concentrations of 11 antimicrobial agents were determined for 312 clinical isolates of RGM, including the Mycobacterium fortuitum group (110 isolates), Mycobacterium abscessus group (168 isolates), and Mycobacterium chelonae group (34 isolates). RESULTS: Nearly all of the RGM were susceptible to amikacin and ofloxacin (= 90%) and resistant to doxycycline (less than 3% susceptible). Tobramycin showed similar in vitro activity against the M. fortuitum and M. chelonae (77%) groups, but was less active against the M. abscessus group (58%). Ciprofloxacin was active mainly against M. fortuitum (95%). Nearly all RGM were resistant to erythromycin and doxycycline. However, around half of the RGM isolates remained susceptible to minocycline (50-54%). Clarithromycin was active against the M. abscessus group (53% susceptible), with a high rate of resistance in the M. chelonae (38% susceptible) and M. fortuitum (15% susceptible) group. Cefoxitin was more active against the M. fortuitum group (65%) than the other two RGM (40-44%), and les than 40% of the RGM isolates remained susceptible to imipenem (21-38%). CONCLUSION: The resistance of RGM in Taiwan is not as high as previously reported (notably for tobramycin, ciprofloxacin and cefoxitin), but reduction in the susceptibility rates of clarithromycin and imipenem for the M. fortuitum and M. abscessus groups demonstrates the importance of in vitro susceptibility testing of clinically important isolates, as susceptibility may differ in different geographical areas, even regionally, and over time.

Idiopathic Pulmonary Arterial Hypertension Was Diagnosed Initially by the Computed Tomographic Angiogram.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare and progressive disease with non-specific signs and symptoms. A 50-year-old woman with IPAH presented to the emergency department (ED) with a complaint of episodic dyspnea that had persisted for the previous two months. Based on the fi ndings of the initial chest computed tomographic angiography conducted in the ED, we suspected pulmonary hypertension. IPAH was eventually confi rmed following a series of investigations, including right heart catheterization. The history of this interesting case is reported with a review of the relevant literature.

Fish gambler's tenosynovitis caused by Mycobacterium marinum: environmental investigation of a fishing pond in Southern Taiwan.

We describe a patient with Mycobacterium marinum tenosynovitis associated with a fish spine injury acquired at a gambling fishing pond in southern Taiwan and identify the source of the infection. M. marinum was isolated from fishing ponds and underground water and wastewater at the site. The isolates shared the same pulsed-field gel electrophoresis pattern as the patient. M. marinum was not detected in 54 samples obtained from 27 fish. Mycobacterium gordonae was isolated from 24 samples collected from the fish. Mycobacterium abscessus was isolated from 3 fish samples (Lateolabrax japonicus 1 and Sciaenops ocellatus 2). M. abscessus and M. gordonae were isolated from all water samples. This investigation provides strong evidence that the predisposing factor for the M. marinum infection was with a fish spine injury acquired at a gambling fishing pond. The source of the infection was the contaminated pond water.