Antimicrobial resistance and molecular epidemiological characteristics of clinical isolates of Staphylococcus aureus in Changsha area

Background  Increasing prevalence of Staphylococcus aureus (S. aureus), particularly methicillin-resistant S. aureus (MRSA) has been reported in China. In this study, we investigated the drug resistance characteristic, genetic background, and molecular epidemiological characteristic of S. aureus in Changsha.

Methods  Between January 2006 and December 2008, 293 clinical isolates of S. aureus were collected from 11 hospitals in Changsha and identified by the Vitek-2 system. All the isolates were verified as MRSA by PCR amplification of both femA and mecA genes. K-B disk method was used to test drug sensitivity of S. aureus to antibiotics. Pulsed-field gel electrophoresis (PFGE) was performed for genotypic and homologous analysis of 115 isolates randomly selected from the original 293 clinical S. aureus isolates.

Results  S. aureus was highly resistant to penicillin, ampicillin, erythromycin, and clindamycin with resistant rates of 96.6%, 96.6%, 77.1%, and 67.2% respectively. All the isolates were susceptible to tecoplanin, vancomycin, and linezolid. MRSA accounted for 64.8% (190/293) of all the S. aureus strains. The 115 S. aureus isolates were clustered into 39 PFGE types by PFGE typing, with 13 predominant patterns (designated types A to M) accounting for 89 isolates. The most prevalent PFGE type was type A (n=56, 48.7%) and 100.0% of type A strains were MRSA. PFGE type A included 13 subtypes, and the most prevalent subtype was subtype A1 (46.4%, 26/56). Strains with PFGE type A were isolated from eight hospitals (8/11), and both subtypes A1 and A4 strains were isolated in a university hospital.

Conclusions  Clinical isolates of S. aureus in Changsha were resistant to multiple traditional antibiotics. There was an outbreak of PFGE type A MRSA in this area and the A1 subtype was the predominant epidemic clone. Dissemination of the same clone was an important reason for the wide spread of MRSA.     

Significance of Aspergillus spp. isolation from lower respiratory tract samples for the diagnosis and prognosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease

Background  Chronic obstructive pulmonary diseases (COPD) is an emerging population at risk for invasive infection of Aspergillus. Isolation of Aspergillus from lower respiratory tract (LRT) samples is important for the diagnosis of invasive pulmonary aspergillosis (IPA). The purpose of this study was to investigate the value of Aspergillus isolation from LRT samples for the diagnosis and prognosis of IPA in COPD population.

Methods  Clinical record with Aspergillus spp. isolation in COPD and immunocompromised patients was reviewed in a retrospective study. Patients were categorized and compared according to their severity of illness (admitted to general ward or ICU) and immunological function (COPD or immunocompromised).

Results  Multivariate statistical analysis showed that, combined with Aspergillus spp. isolation, APACHE II scores >18, high cumulative doses of corticosteroids (>350 mg prednisone or equivalent dose) and more than four kinds of broad-spectrum antibiotics received in hospital may be predictors of IPA in COPD (OR=9.076, P=0.001; OR=4.073, P=0.026; OR=4.448, P=0.021, respectively). The incidence of IPA, overall mortality, mortality of patients with IPA and mortality of patients with Aspergillus spp. colonization were higher in COPD patients in ICU than in general ward, but were similar between COPD and immunocompromised patients.

Conclusions  Aspergillus spp. isolation from LRT in COPD may be of similar importance as in immunocompromised patients, and may indicate an increased diagnosis possibility of IPA and worse prognosis when these patients received corticosteroids, antibiotics, and need to admit to ICU. Aspergillus spp. isolation from LRT samples combined with certain risk factors may be useful in differentiating colonization from IPA and evaluating the prognosis of IPA in COPD patients.

     

Significance of Aspergillus spp. isolation from lower respiratory tract samples for the diagnosis and prognosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease

Background  Chronic obstructive pulmonary diseases (COPD) is an emerging population at risk for invasive infection of Aspergillus. Isolation of Aspergillus from lower respiratory tract (LRT) samples is important for the diagnosis of invasive pulmonary aspergillosis (IPA). The purpose of this study was to investigate the value of Aspergillus isolation from LRT samples for the diagnosis and prognosis of IPA in COPD population.

Methods  Clinical record with Aspergillus spp. isolation in COPD and immunocompromised patients was reviewed in a retrospective study. Patients were categorized and compared according to their severity of illness (admitted to general ward or ICU) and immunological function (COPD or immunocompromised).

Results  Multivariate statistical analysis showed that, combined with Aspergillus spp. isolation, APACHE II scores >18, high cumulative doses of corticosteroids (>350 mg prednisone or equivalent dose) and more than four kinds of broad-spectrum antibiotics received in hospital may be predictors of IPA in COPD (OR=9.076, P=0.001; OR=4.073, P=0.026; OR=4.448, P=0.021, respectively). The incidence of IPA, overall mortality, mortality of patients with IPA and mortality of patients with Aspergillus spp. colonization were higher in COPD patients in ICU than in general ward, but were similar between COPD and immunocompromised patients.

Conclusions  Aspergillus spp. isolation from LRT in COPD may be of similar importance as in immunocompromised patients, and may indicate an increased diagnosis possibility of IPA and worse prognosis when these patients received corticosteroids, antibiotics, and need to admit to ICU. Aspergillus spp. isolation from LRT samples combined with certain risk factors may be useful in differentiating colonization from IPA and evaluating the prognosis of IPA in COPD patients.

     

Effect of in-hospital medical complications on case fatality post-acute ischemic stroke: data from the China National Stroke Registry

Background  In-hospital medical complications are associated with poorer clinical outcomes for stroke patients after disease onset. However, few studies from China have reported the effect of these complications on the mortality of patients with acute ischemic stroke. In this prospective work, the China National Stroke Registry Study, we investigated the effect of medical complications on the case fatality of patients with acute ischemic stroke.   

Methods  From September 2007 to August 2008, we prospectively obtained the data of patients with acute stroke from 132 clinical centers in China. Medical complications, case fatality and other information recorded at baseline, during hospitalisation, and at 3, 6, and 12 months after stroke onset. Multivariable Logistic regression was performed to analyze the effect of medical complications on the case fatality of patients with acute ischemic stroke.

Results  There were 39 741 patients screened, 14 526 patients with acute ischemic stroke recruited, and 11 560 ischemic stroke patients without missing data identified during the 12-month follow-up. Of the 11 560 ischemic patients, 15.8% (1826) had in-hospital medical complications. The most common complication was pneumonia (1373; 11.9% of patients), followed by urinary tract infection and gastrointestinal bleeding. In comparison with patients without complications, stroke patients with complications had a significantly higher risk of death during their hospitalization, and at 3, 6 and 12 months post-stroke. Having any one in-hospital medical complication was an independent risk factor for death in patients with acute ischemic stroke during hospital period (adjusted OR=6.946; 95% CI 5.181 to 9.314), at 3 months (adjusted OR=3.843; 95% CI 3.221 to 4.584), 6 months (adjusted OR=3.492; 95% CI 2.970 to 4.106), and 12 months (adjusted OR= 3.511; 95% CI 3.021 to 4.080). Having multiple complications strongly increased the death risk of patients.

Conclusion  Short-term and long-term outcomes of acute stroke patients are affected by in-hospital medical complications.     

Current asthma control predicts future risk of asthma exacerbation: a 12-month prospective cohort study

Background  The performance of asthma control test (ACT) at baseline for predicting future risk of asthma exacerbation has not been previously demonstrated. This study was designed to explore the ability of the baseline ACT score to predict future risk of asthma exacerbation during a 12-month follow-up.

Methods  This post hoc analysis included data from a 12-month prospective cohort study in patients with asthma (n=290). The time to the first asthma exacerbation was analyzed and the association between baseline ACT scores and future risk of asthma exacerbation was calculated as adjusted odds ratio (OR) using Logistic regression models. Further, sensitivity and specificity were estimated at each cut-point of ACT scores for predicting asthma exacerbations.

Results  The subjects were divided into three groups, which were uncontrolled (U, n=128), partly-controlled (PC, n=111), and well controlled (C, n=51) asthma. After adjustment, the decreased ACT scores at baseline in the U and PC groups were associated with an increased probability of asthma exacerbations (OR 3.65 and OR 5.75, respectively), unplanned visits (OR 8.03 and OR 8.21, respectively) and emergency visits (OR 20.00 and OR 22.60, respectively) over a 12-month follow-up period. The time to the first asthma exacerbation was shorter in the groups with U and PC asthma (all P <0.05). The baseline ACT of 20 identified as the cut-point for screening the patients at high risk of asthma exacerbations had an increased sensitivity of over 90.0% but a lower specificity of about 30.0%.

Conclusion  Our findings indicate that the baseline ACT score with a high sensitivity could rule out patients at low risk of asthma exacerbations and predict future risk of asthma exacerbations in clinical practice.

     

Autologous bone marrow stem cell transplantation in critical limb ischemia: a meta-analysis of randomized controlled trials

Background  Amputation-free survival (AFS) has been recommended as the gold standard for evaluating No-Option Critical Limb Ischemia (NO-CLI) therapy. Early-phase clinical trials suggest that autologous bone-marrow derived cells (BMCs) transplantation may have a positive effect on patients with NO-CLI, especially decreasing the incidence of amputation. However, the BMCs therapeutic efficacy remains controversial and whether BMCs therapy is suitable for all CLI patients is unclear.

Methods  We conducted a meta-analysis using data from randomized controlled trials (RCTs) by comparing autologous BMCs therapy with controls in patients with critical limb ischemia, and the primary endpoint is the incidence of amputation. Pubmed, EBSCO and the Cochrane Central Register of Controlled Trials (to approximately July 25, 2012) were searched.

Results  Seven RCTs with 373 patients were enrolled in the meta-analysis. Because serious disease was the main reason leading to amputation in one trial, six studies with 333 patients were finally included in the meta-analysis. Pooling the data of the final six studies, we found that BMCs therapy significantly decreased the incidence of amputation in patients with CLI (odds ratio (OR), 0.37; 95% confidence interval (CI), 0.22 to 0.62; P=0.0002), and the efficacy had not significantly declined within 6 months after BMCs were transplanted; OR, 0.33; 95% CI, 0.16 to 0.70; P=0.004 within 6 months and OR, 0.30; 95% CI, 0.11 to 0.79; P=0.01 within 3 months. The rate of AFS after BMCs therapy was significantly increased in patients with Rutherford class 5 CLI (OR 3.28; 95% CI, 1.12 to 9.65; P=0.03), while there was no significant improvement in patients with Rutherford class 4 (OR 0.35; 95% CI, 0.05 to 2.33; P=0.28) compared with controls. The BMCs therapy also improved ulcer healing (OR, 5.83; 95% CI, 2.37 to 14.29; P=0.0001).

Conclusions  Our analysis suggests that autologous BMCs therapy has a beneficial effect in decreasing the incidence of amputation and the efficacy does not decrease significantly within 6 months after BMCs transplantation. Patients with Rutherford class 5 are suitable for BMCs therapy, while the efficiency in patients with Rutherford 4 needs further evaluation.

     

Risk factors for delayed graft function in cardiac death donor renal transplants

Background  Delayed graft function (DGF) is common in kidney transplants from organ donation after cardiac death (DCD) donors. It is associated with various factors. Determination of center-specific risk factors may help to reduce the incidence of DGF and improve the transplantation results. The aim of this study is to define risk factors of DGF after renal transplantation.

Methods  From March 2010 to June 2012, 56 cases of recipients who received DCD kidneys were selected. The subjects were divided into two groups: immediate graft function (IGF) and DGF groups. Transplantation factors of donors and recipients as well as early post-transplant results of recipients were compared between the two groups.

Results  On univariate analysis, preoperative dialysis time of recipients (P <0.001), type of dialysis (P=0.039), human leucocyte antigen (HLA) mismatch sites (P <0.001), the cause of brain death (P=0.027), body mass index (BMI) of donors (P <0.001), preoperative infection (P=0.002), preoperative serum creatinine of donors (P <0.001), norepinephrine used in donors (P <0.001), cardiopulmonary resuscitation (CPR) of donors (P <0.001), warm ischemia time (WIT) (P <0.001) and cold ischemia time (CIT) (P <0.001) showed significant differences. Recipients who experienced DGF had a longer hospital stay, and higher level of postoperative serum creatinine.

Conclusion  Multiple risk factors are associated with DGF, which had deleterious effects on the early post-transplant period.

     

Predictive factors improving survival after gastric and hepatic surgical treatment in gastric cancer patients with synchronous liver metastases

Background  The prognosis for patients with gastric cancer and synchronous liver metastases is very poor. However, a standard therapeutic strategy has not been well established. The clinical benefit and prognostic factors after hepatic surgical treatment for liver metastases from gastric cancer remain controversial.

Methods  Records of 105 patients who underwent gastrectomy regardless of hepatic surgical treatment for gastric cancer with synchronous liver-only metastases in our center between 1995 and 2010 were retrospectively reviewed.

Results  The overall survival rate for the 105 patients was 42.1%, 17.2%, and 10.6% at 1, 2, and 3 years, respectively, with a median survival time of 11 months. Multivariate survival analysis revealed that the extent of lymphadenectomy (D) (P <0.001), lymph node metastases (P <0.001), extent of liver metastases (H) (P=0.008), and lymphovascular invasion (P=0.002) were significant independent prognostic factors for survival. Among patients who underwent D2 lymphadenectomy, those who underwent hepatic surgical treatment had a significantly improved survival compared with those who underwent gastrectomy alone (median survival, 24 vs. 12 months; P <0.001). However, hepatic surgical treatment was not a prognostic factor for patients who underwent D1 lymphadenectomy (median survival, 8 vs. 8 months; P=0.495). For the 35 patients who underwent gastrectomy plus hepatic surgical treatment, D2 lymphadenectomy (P <0.001), lymph node metastases (P=0.015), and extent of liver metastases (H1 vs. H2 and H3) (P=0.017) were independent significant prognostic factors for survival.

Conclusions  D2 lymphadenectomy plus hepatic surgical treatment may provide hope for long-term survival of judiciously selected patients with hepatic metastases from gastric cancer. Patients with a low degree of lymph node metastases and H1 liver metastases would make the most appropriate candidates. However, if D2 dissection cannot be achieved, hepatic surgical treatment is not recommended.

     

Routine use of a transanastomotic stent is unnecessary for hepatojejunostomy in liver transplantation

Background  The use of transanastomotic stents for Roux-en-Y hepatojejunostomy (RYHJ) in liver transplantation (LT) remains controversial. The aim of this retrospective study was to assess the role of transanastomotic stent for RYHJ in LT.

Methods  RYHJ for biliary reconstruction in LT was performed in 52 patients. Twenty-five patients had bile duct reconstruction by RYHJ with transanastomotic stents (S group), while 27 patients underwent the same procedure without transanastomotic stents (non-S group). The two groups were compared in terms of post-LT biliary complications and survival.

Results  The incidences of bile leakage, anastomotic stricture, non-anastomotic stricture, biliary sludge/lithiasis and biliary infection were 12% (3/25), 9.5% (2/21), 23.5% (4/17), 11.8% (2/17), and 24% (6/25), respectively in the S group, and 0, 0, 20.0% (5/25), 10.0% (2/20), and 16.7% (4/24), respectively in the non-S group. One and three year survival rates were 48.0% (12/25) and 34.0% (8/23), respectively, in the S group and 57.7% (15/26) and 38.9% (7/18), respectively, in the non-S group. There was no significant difference between the two groups in terms of the incidence of various biliary complications and survival (P >0.05).

Conclusion  The routine use of transanastomotic stents is not necessary for RYHJ for biliary reconstruction in LT

     

Detection of carboxyhemoglobin in patients with hepatic encephalopathy due to hepatitis B virus-related cirrhosis

Background  The heme oxygenase/carbon monoxide (HO/CO) system plays an important role in the development of hepatic fibrosis. The level of the HO/CO can be directly obtained by determining the carboxyhemoglobin (COHb) level. The aims of this study were to reveal the significance of COHb in patients with hepatitis B virus-related cirrhosis (HBC) complicated by hepatic encephalopathy (HE), and to further investigate the influence of the HO/CO pathway on the end-stage cirrhosis, hoping to find a reliable indicator to evaluate the course of HBC.

Methods  According to the diagnostic criteria, 63 HBC inpatients with HE were enrolled in group H. Patients regaining awareness with current therapies were categorized into group P-H. Comparisons were made with a control group (group N) consisting of 20 health volunteers. The levels of COHb, partial pressure of oxygen (PaO₂) and oxygen saturation (SaO₂) were determined by arterial blood gas analysis method. The incidences of hepatorenal syndrome (HRS), upper gastrointestinal bleeding, esophagogastric varices and spontaneous bacterial peritonitis (SBP) in group H were recorded. COHb levels in different groups were compared, and the correlations of COHb levels with HE grades (I, II, III, and IV), PaO₂, SaO₂ and hypoxemia were analyzed.

Results  The COHb level in group P-H ((1.672±0.761)%) was significantly higher than that in group N ((0.983±0.231)%) (P <0.01), and the level in group H ((2.102±1.021)%) was significantly higher than groups P-H and N (P <0.01). A positive correlation was observed between the COHb concentration and the grade of HE (r_s=0.357, P=0.004). There were no significant differences of COHb levels between HE patients with and without complications such as esophagogastric varices ((2.302±1.072)% vs. (1.802±1.041)%, P >0.05) or the occurrence of SBP ((2.960±0.561)% vs. (2.030±1.021)%, P >0.05). Compared with HE patients with HRS, the level of COHb was significantly higher in HE patients without HRS ((2.502±1.073)% vs. (1.981±1.020)%, P=0.029). The COHb level had a negative correlation with PaO₂ (r=−0.335, P=0.007) while no statistically significant relationship was found with SaO₂ (r=−0.071, P >0.05). However, when the above two parameters met the diagnostic criteria of hypoxemia, the COHb concentration increased ((2.621±0.880)% vs. (1.910±0.931)%, P=0.011).

Conclusions  COHb is a potential candidate to estimate the severity and therapeutic effect of HE. The levels of COHb may be tissue-specific in cirrhotic patients with different complications.

     

真菌性角膜炎前房积脓的临床分析

Background  Hypopyon is common in eyes with fungal keratitis. The evaluation of the clinical features, culture results and the risk factors for hypopyon and of the possible correlation between hypopyon and the treatment outcome could be helpful for making treatment decisions.   

Methods  The medical records of 1066 inpatients (1069 eyes) with fungal keratitis seen at the Shandong Eye Institute from January 2000 to December 2009 were reviewed retrospectively for demographic features, risk factors, clinical characteristics, laboratory findings and treatment outcomes. The incidence of hypopyon, the fungal culture positivity for hypopyon, risk factors for hypopyon and the effect of hypopyon on the treatment and prognosis were determined. 

Results  We identified 1069 eyes with fungal keratitis. Of the 850 fungal culture-positive eyes, the Fusarium species was the most frequent (73.6%), followed by Alternaria (10.0%) and Aspergillus (9.0%). Upon admission, 562 (52.6%) eyes with hypopyon were identified. The hypopyon of 66 eyes was evaluated via fungal culturing, and 31 eyes (47.0%) were positive. A total of 194 eyes had ocular hypertension, and 172 (88.7%) of these eyes had hypopyon (P <0.001). Risk factors for incident hypopyon included long duration of symptoms (P <0.001), large lesion size (P <0.001) and infection caused by the Fusarium and Aspergillus species (P <0.001). The positivity of fungal culture for hypopyon was associated with duration of symptoms and lesion size. Surgical intervention was more common in cases with hypopyon (P <0.001). Hypopyon was a risk factor for the recurrence of fungal keratitis after corneal transplantation (P=0.002).

Conclusions  Hypopyon is common in patients with severe fungal keratitis and can cause ocular hypertension. About half of the hypopyon cases were positive based on fungal culture. Long duration of symptoms, large lesion size and infection with the Fusarium and Aspergillus species were risk factors for hypopyon. The presence of hypopyon increases the likelihood of surgical intervention.

     

Outcome of in vitro fertilization in endometriosis-associated infertility: a 5-year database cohort study

Background  Endometriosis affects natural fertility through various approaches, and in vitro fertilization (IVF) is a good treatment. But the IVF result of endometriosis patients is still under debate. We investigated the effect of endometriosis on IVF by analyzing the data from a single reproductive center.

Methods  A retrospective, database-searched cohort study was performed. Relevant information was collected from the electronic records of women who underwent IVF/intracytoplasmic sperm injection between January 2006 and December 2010 in the Assisted Reproductive Unit of Sir Run Run Shaw Hospital. Patients with endometriosis were enrolled the study group. The rest of the women formed the control group. The main outcome was the clinical pregnancy rate. Secondary outcomes were oocytes retrieved number, fertilization rate, high-quality embryo rate, number of high-quality embryo for embryo transplantation, and implantation embryo/high-quality embryo ratio (IE/HQE ratio). Comparisons were performed by the  c²-test and independent t-test.

Results  The endometriosis group (n=177) had a markedly lower oocytes retrieved number, fertilization rate, implantation rate, and clinical pregnancy rate (7.6±5.1, 63.6%, 27.7%, and 45.2%, respectively) compared with the non-endometriosis group (n=4267; 11.8±7.3, 68.4%, 36.2%, and 55.2%, respectively).  Stratified analysis showed that this difference was found in the subgroup younger than 35-years old, while only fertilization rate and implantation rate were different in the elder subgroup. The ratio of high-quality embryos transferred is lower in endometriosis group (53.7% vs. 71.8%, P <0.05), but there is no difference in IE/HQE ratio between two groups. There is no significant difference in fertilization rate, implantation rate, and clinical pregnancy rate between mild and severe endometriosis patients.

Conclusions  Endometriosis patients suffer a decreasing IVF pregnancy rates mainly caused by reducing oocytes number and fertilization rate, regardless of the severity of the disease. Appropriate intracytoplasmic sperm injection manipulation might improve the outcomes of IVF.

     

法呢基转移酶在原发性肝癌中的表达

Background  Primary liver cancer (PLC) is a common malignant tumor. Over the past decade, although farnesyltransferase (FTase) has emerged as a significant target for anticancer therapies and has become a hotspot of cancer research, its exact mechanism of action remains unknown. The aim of this study was to investigate the expression of FTase in PLC and its role in the development of PLC.

Methods  Expression of FTase was detected by real-time fluorescent quantitative-polymerase chain reaction (FQ-PCR) in cancer and surrounding normal tissues from 32 patients with PLC.

Results  Expression of FTase mRNA in PLC was significantly higher than that in normal hepatic tissues (P <0.001). Overexpression of FTase was as high as 87.5%. The positive rate for FTase mRNA in the high tendency to metastatic recurrence group was obviously higher than that in the low tendency to metastatic recurrence group (P=0.02). The positive rate for FTase mRNA in patients with metastatic recurrence during postoperative follow-up was also significantly higher than that in those without metastatic recurrence (P=0.01).

Conclusions  The level of FTase mRNA expression in cancer tissues is much higher than in normal tissues. FTase may play an important role in the genesis and development of PLC and may be one of the reliable markers for the metastatic activity gained by liver tumor cells. FTase could be used clinically in predicting metastatic recurrence of PLC.     

Effect of anterior nucleus of thalamus stimulation on glucose metabolism in hippocampus of epileptic rats

Background  Electrical stimulation of the anterior nucleus of the thalamus (ANT) appears to be effective against seizures. In this study, we investigated changes in glucose metabolism during high-frequency stimulation of ANT in epileptic rats.

Methods  Three groups of rats were used: (1) a stimulation group (n=12), (2) a sham stimulation group (n=12) with seizures induced by stereotactic administration of kainic acid (KA), and (3) a control group (n=12) with sham surgery. Concentric bipolar electrodes were stereotaxically implanted unilaterally in the ANT. High-frequency stimulation was performed in each group except the sham stimulation group. Microdialysis probes were lowered into the CA3 region of the hippocampus unilaterally but bilaterally in the stimulation group. The concentrations of glucose, lactate, and pyruvate in dialysate samples were determined by an ISCUS microdialysis analyzer.

Results  The extracellular concentrations of lactate and lactate/pyruvate ratio (LPR) of epileptic rats were significantly higher than in control rats (P=0.020, P=0.001; respectively). However, no significant difference in the concentration of glucose and pyruvate was found between these groups (P >0.05). Electrical stimulation of ANT induced decreases in lactate and LPR in the ipsilateral hippocampus (KA injected) of the stimulation group (P <0.05), but it did not influence the glucose metabolism in the contralateral hippocampus (P >0.05).

Conclusions  This study demonstrated that the glycolysis was inhibited in the ipsilateral hippocampus of epileptic rats during electrical ANT stimulation. These findings may provide useful information for better understanding the mechanism of ANT-deep brain stimulation.

     

Steady-state pharmacokinetics of zidovudine in Chinese HIV-infected patients

Background  The pharmacokinetics of zidovudine (AZT) are possibly influenced by weight, age, sex, liver and renal functions, severity of disease, and ethnicity. Currently, little information is available on the steady-state pharmacokinetics of AZT in Chinese HIV-infected patients. The current study aimed to characterize the steady-state pharmacokinetics of AZT in a Chinese set-up.

Methods  Eleven Chinese HIV-infected patients were involved in the steady-state pharmacokinetic study. In total, 300 mg of AZT, as a part of combination therapy, was given to patients, and serial blood samples were collected for 12 hours. The samples were measured by a high-performance liquid chromatography (HPLC) assay, and the results were analyzed by both the non-compartment model and the one-compartment model.

Results  The C_max of AZT in Chinese patients was higher than that in non-Asian patients. The half-life of AZT, analyzed by the non-compartment model (P=0.02), in male patients ((1.02±0.22) hours) was shorter than that of AZT in female patients ((1.55±0.29) hours). The AZT clearance, analyzed by the one-compartment model (P=0.045), in male patients ((262.60±28.13) L/h) was higher than that in female patients ((195.85±60.51) L/h).

Conclusion  The present study provides valuable information for the clinical practice of AZT-based highly active antiretroviral therapy in a Chinese set-up.

     

Effect of high-dose rosuvastatin loading before percutaneous coronary intervention in female patients with non-ST-segment elevation acute coronary syndrome

Background  Early loading statin therapy before percutaneous coronary intervention (PCI) is associated with reduced mortality and periprocedural myocardial injury. The aim of this study was to study the effect of rosuvastatin loading therapy before PCI in female patients with non-ST-segment elevation acute coronary syndrome (NSTEACS).

Methods  Consecutive 117 female patients with NSTEACS were randomly assigned to either the group of rosuvastatin loading before PCI (20 mg 12 hours before angioplasty procedure, with a further 10 mg dose 2 hours before procedure, the loading dose group, n=59) or the no rosuvastatin treatment group before PCI (control group, n=58). Periprocedural myocardial injury, periprocedural changes of high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-a in serum and the incidence of major adverse cardiac events (MACE) 3 months and 6 months later were assessed.

Results  The incidence of periprocedural myocardial injury was higher in control group than loading dose group (CKMB: 10.17% vs. 25.86% , P=0.027; Troponin I: 11.86% vs. 29.31%, P=0.019). MACE occurred in 1.69% of patients in loading dose group and 12.07% of those in control group 3 months after procedure (P=0.026), 3.39% vs. 17.24% at 6 months (P=0.014). The levels of hs-CRP, IL-1, IL-6, and TNF-a in serum were not significantly different between the two groups before PCI, but after PCI they were significantly higher in control group.

Conclusions  High-dose rosuvastatin loading before PCI significantly reduced periprocedural myocardial injury and periprocedural inflammation cytokines release and improved 3-month and 6-month clinical outcomes in female patients with NSTEACS who underwent PCI.     

Antimicrobial activity of linezolid combined with minocycline against vancomycin-resistant Enterococci

Background Vancomycin-resistant Enterococci (VRE) cause serious infections that are difficult to treat.We carried out this study to determine the mutant prevention concentration (MPC) of linezolid when...     

Characteristics of pulmonary inflammation in combined pulmonary fibrosis and emphysema

Background  The condition of concomitant upper lobe emphysema and lower lobe fibrosis as identified by computer tomography is known as combined pulmonary fibrosis and emphysema (CPFE). CPFE has distinct clinical characteristics compared with emphysema alone (EA) and idiopathic pulmonary fibrosis (IPF) without emphysema. However, the pulmonary inflammation characteristics of CPFE are not well known, and the differences between CPFE and the other two diseases with regards to pulmonary inflammation need to be explored. The pulmonary inflammatory characteristics were investigated in CPFE patients and compared with EA and IPF.

Methods  Fraction exhaled nitric oxide (Fe,NO) and differential cell counts, the concentrations of monokine induced by interferon gamma (MIG/CXCL9), interferon-inducible protein 10 (IP-10/CXCL10), and interferon-inducible T cell alpha chemoattractant (I-TAC/CXCL11) were measured in induced sputum obtained from subjects with CPFE (n=22), EA (n=22), IPF (n=14), and healthy volunteers (HV, n=12). In addition, immunohistochemistry was used to quantify the expression of nitric oxide synthases in alveolar macrophages in 23 lung tissues from patients and control subjects.

Results  The CPFE group had higher alveolar NO than subjects in the EA and HV groups (P=0.009, P=0.001, respectively) but not than the IPF group (P >0.05). Numbers of sputum eosinophils were significantly elevated in CPFE and IPF groups compared with the HV group (P=0.001, P=0.008). In contrast, eosinophil counts in EA group did not differ from those in the HV group. Compared with the EA and HV groups, the CPFE group had a lower concentration of I-TAC/CXCL11 in sputum supernatants (P=0.003, P=0.004). Immunoreactivity for inducible nitric oxide synthase (iNOS) was higher in the CPFE group than in the EA group (P=0.018).

Conclusions  The pulmonary inflammation of CPFE group is more similar to IPF group, while the distal airway inflammation is more significant in CPFE and IPF groups than in EA group. Lung eosinophil cell infiltration and high NOS expression in alveolar macrophage might participate in this pathogenesis.

     

Impact of different termination modes on atrial fibrillation termination in catheter ablation of persistent atrial fibrillation

Background  The optimal endpoint for catheter ablation of persistent atrial fibrillation (AF) remains ambiguous. This study investigated the impact of AF termination as a procedural endpoint and the termination mode on long-term clinical outcome.

Methods  Two hundred and ninety-three patients who underwent stepwise ablation for persistent AF were categorized into the AF termination by ablation group and into the electrical cardioversion (CV) group. Subgroups were also analyzed based on different termination modes. Follow-up assessment included early recurrence and sinus rhythm (SR) maintenance.

Results  During initial ablation, 33 patients (11.3%) were directly converted to SR, 166 patients (56.7%) were converted to atrial tachycardia (AT) that subsequently restored SR with further ablation in 98 patients (33.4%), and a total of 162 patients (55.3%) underwent cardioversion due to persistent atrial arrhythmias. Comparison between termination by ablation and termination by cardioversion in patients exhibiting AF or AT revealed that no significant difference was observed in early recurrence (38.2% vs. 43.8%, P=0.328) and SR maintenance (67.2% vs. 59.8%, P=0.198) during the (23±7) months follow-up. Even after repeat ablation, the SR maintenance continued to exhibit no statistical difference in above two groups (72.5% vs. 70.4%, P=0.686). Further analysis of subgroups, however, demonstrated that patients with AF terminated directly to SR experienced better clinical outcomes than other subgroups (P <0.05). Furthermore, atrial arrhythmias present during ablation have been implicated in prediction of recurrence mode: AF or AT (P <0.05).

Conclusions  Termination as a procedural endpoint is not associated with favorable long-term SR maintenance in persistent AF. AF methods that convert arrhythmia directly to SR have, however, been linked with improved clinical outcomes, although conversions to AT may not be correlated. Atrial arrhythmias observed during the ablation may be used to predict the recurrence mode.

     

Three hours continuous injection of adenosine improved left ventricular function and infarct size in patients with ST-segment elevation myocardial infarction

Background  The definitive treatment for myocardial ischemia is reperfusion. However, reperfusion injury has the potential to cause additional reversible and irreversible damage to the myocardium. One likely candidate for a cardioprotection is adenosine. The present study aimed at investigating the effect of intravenous adenosine on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). 

Methods  Patients with STEMI within 12 hours from the onset of symptoms were randomized by 1:1:1 ratio to receive either adenosine 50 µg∙kg^-1∙min^-1 (low-dose group, n=31), or 70 µg∙kg^-1∙min^-1 (high-dose group, n=32), or saline 1 ml/min (control group, n=27) for three hours. Drugs were given to the patients immediately after the guide wire crossed the culprit lesion. Recurrence of no-reflow, TIMI flow grade (TFG) and TIMI myocardial perfusion grade (TMPG), and collateral circulation were recorded. The postoperative and preoperative ST segment elevation sum of 18-lead electrocardiogram (ECG) and their ratio (STsum-post/STsum-pre) were recorded, as well as the peak time and peak value of CK-MB enzyme. Serial cardiac echo and myocardial perfusion imaging were performed at 24 hours and 6 months post-stenting. The primary endpoint was left ventricular function, and infarct size. The secondary end-point was the occurrence of cardiac and non-cardiac death, non-fatal myocardial infarction, and heart failure.

Results  A total of 90 STEMI patients were studied. No-reflow immediately after stent procedure was seen in 11 (35.5%) patients in the control group, significantly different from 6.3% in the low-dose group or 3.7% in the high-dose group (both P=0.001). STsum-post/STsum-pre in the low-dose and high-dose groups was significantly different from the control group (low-dose group vs. control group, P=0.003 and high-dose group vs. control group, P=0.001), without a dose-dependent pattern (P=0.238). The peak value of CK-MB enzyme was significantly reduced in the high-dose group compared to the control group (P=0.024). Compared to the left ventricular ejection fraction (LVEF) in control group, LVEF in the low-dose group increased by 5.8% at 24 hours (P=0.012) and by 10.9% at 6 months (P=0.007), LVEF in the high-dose group increased by 9.5% at 24 hours (P=0.001) and by 10.0% at 6 months (P=0.001), respectively. Significant reduction of infarct size by 24.2% was detected in the high-dose group vs. low-dose or control groups (P=0.008). There was no significant difference regarding secondary endpoints at 6 months among the treated groups. Cardiac function by NYHA classification in both the low-dose and the high-dose groups was improved significantly (P=0.013, P=0.016).

Conclusion  Intravenous adenosine administration might significantly reduce the recurrence of no-reflow, with resultant improved left ventricular systolic function. High-dose adenosine was further associated with significant reduction of infarct size.