Patient Demographics and Characteristics of Infection with Carbapenem-Resistant <i>Acinetobacter baumannii</i>in a Teaching Hospital from the United States

A characterization of the clinical demographic features of patients with infection caused Acinetobacter baumannii, and the antibiotyping of the isolates recovered from these patients was undertaken, with a special reference to carbapenem-resistant variants, and their risk factors. This study was conducted retrospectively from January 2010 to March 2011 at a 616-bed tertiary care university hospital. Sixty-four patients were identified. Clinical and microbiological data were analyzed for risk factors and demographic features to derive relative risk and odds ratio. We identified 100 A. baumannii from 64 patients during 15 months period. Significant risk factors were working age (18 - 60 years), male gender, hospital stay (>1 week but Pseudomonas aeruginosa, and Klebsiella pneumoniae were the significant co-infecting agents. The antibiogram demonstrated multidrug resistance in a majority of the isolates. Relative risk associated with ventilator, diabetes, and surgery was higher in repeat isolates than in first isolates and were multidrug resistant. Repeat isolates were more resistant that the first isolates to most anti-acinetobacter agents, but the overall crude mortality was not significant during this study period, and couldn’t correlated to the choice of treatment. In conclusion, a resistance against all clinically used carbapenems, and colistin is rapidly increasing in repeat isolates of A. baumannii;leaves narrow therapeutic options to treat multidrug-resistant and pandrug-resistant A. baumannii infection. For the first time we report rising incidence of colistin resistance by 20 percent in repeat isolates, and is worrisome for healthcare centers. A combination therapy should be adopted to treat such infection to avoid the emergence of colistin-resistant phenotypes in the United States.

Degenerative meniscus: Pathogenesis, diagnosis, and treatment options

The symptomatic degenerative meniscus continues to be a source of discomfort for a significant number of patients. With vascular penetration of less than onethird of the adult meniscus, healing potential in the setting of chronic degeneration remains low. Continued hoop and shear stresses upon the degenerative meniscus results in gross failure, often in the form of complex tears in the posterior horn and midbody. Patient history and physical examination are critical to determine the true source of pain, particularly with the significant incidence of simultaneous articular pathology. Joint line tenderness, a positive Mc Murray test, and mechanical catching or locking can be highly suggestive of a meniscal source of knee pain and dysfunction. Radiographs and magnetic resonance imaging are frequently utilized to examine for osteoarthritis and to verify the presence of meniscal tears, in addition to ruling out other sources of pain. Non-operative therapy focused on nonsteroidal anti-inflammatory drugs and physical therapy may be able to provide pain relief as well as improve mechanical function of the knee joint. For patients re-fractory to conservative therapy, arthroscopic partial meniscectomy can provide short-term gains regarding pain relief, especially when combined with an effective, regular physiotherapy program. Patients with clear mechanical symptoms and meniscal pathology may benefit from arthroscopic partial meniscectomy, but surgery is not a guaranteed success, especially with concomitant articular pathology. Ultimately, the long-term outcomes of either treatment arm provide similar results for most patients. Further study is needed regarding the short and long-term outcomes regarding conservative and surgical therapy, with a particular focus on the economic impact of treatment as well.

Effects of Meglumine Cyclic Adenylate Pretreatment on Systemic inflammatory Response Syndrome Induced by Lipopolysaccharide in Rats

Studies showed that the use of cyclic adenosine monophosphate(cAMP) substitutes or intracellular c AMP activators increased intracellular cAMP level, causing anti-inflammatory effects. This study was to investigate the effects of pretreatment with meglumine cyclic adenylate(MCA), a compound of meglumine and cAMP, on systemic inflammation induced by lipopolysaccharide(LPS) in rats. Eighteen adult male Sprague-Dawley rats were randomly divided into 3 groups(n=6 each): control group(NS group), LPS group(LPS group) and LPS with MCA pretreatment group(MCA group). Systemic inflammation was induced with LPS 10 mg/kg injected via the femoral vein in LPS and MCA groups. In MCA group, MCA 2 mg/kg was injected via the femoral vein 20 min before LPS injection, and the equal volume of normal saline was given in NS and LPS groups at the same time. Three hours after LPS injection, the blood samples were taken from the abdominal aorta for determination of plasma concentrations of TNF-α, IL-1, IL-6, IL-10, cAMP by ELISA and NF-κBp65 expression by Western blotting. The experimental results showed that inflammatory and antiinflammatory indices were increased in LPS group compared to NS group; inflammatory indices were declined and anti-inflammatory indices were increased in MCA group relative to LPS group. Our study suggested that MCA pretreatment may attenuate LPS-induced systemic inflammation.

Effects of epinephrine on angiogenesis-related gene expressions in cultured rat cardiomyocytes

Epinephrine is often used for the treatment of patients with heart failure, low cardiac output and cardiac arrest. It can acutely improve hemodynamic parameters; however, it does not seem to improve longer term clinical outcomes. Therefore, we hypothesized that epinephrine may induce unfavorable changes in gene expression of cardiomyocyte. Thus, we investigated effects of epinephrine exposure on the mediation or modulation of gene expression of cultured cardiomyocytes at a genome-wide scale. Our investigation revealed that exposure of cardiomyocytes to epinephrine in an in vitro environment can up-regulate the expression ofangiopoietin-2 gene （~ 2.1 times）, and down-regulate the gene expression of neuregulin 1 （-3.7 times）, plasminogen activator inhibitor-1 （-2.4 times） and SPARC-related modular calcium-binding protein-2 （-4.5 times）. These changes suggest that epinephrine exposure may induce inhibition of angiogenesis-related gene expressions in cultured rat cardiomyocytes. The precise clinical significance of these changes in gene expression, which was induced by epinephrine exposure, warrants further experimental and clinical investigations.

Novel case of Trevor's disease:Adult onset and later recurrence

Dysplasia epiphysealis hemimelica(DEH),or Trevor’s disease,is an osteocartilaginous epiphyseal overgrowth typically occurring in children.The literature reports6 adult cases and none describe recurrence requiring additional procedures.We present a new-onset proximal tibial DEH in an adult recurring approximately 3 years after open excision.A 39-year-old female presented with a history of right knee pain,swelling,and instability.Physical examination revealed a firm proximal tibial mass.Computed tomography(CT)imaging showed an exophytic,lobulated,sclerotic mass involving the anterolateral margin of the lateral tibial plateau.Magnetic resonance imaging was suggestive of an osteochondroma.The patient underwent curettage of the lesion due to its periarticular location.Histology revealed benign and reactive bone and cartilage consistent with periosteal chondroma.Two and a half years later,the patient presented with a firm,palpable mass larger than the initial lesion.CT revealed a lateral tibial plateau sclerotic mass consistent with recurrent intraarticular DEH.A complete excision was performed and histology showed sclerotic bone with overlying cartilage consistent with exostosis.DEH is a rare epiphyseal osteocartilaginous outgrowth frequently occurring in the long bones of children less than 8 years old.DEH resembles an osteochondroma due to its pediatric presentation and similar histologic appearance.Adultonset cases comprise less than 1%of reported cases.Recurrence rate after surgical intervention is unknown.Only 1 such case,occurring in a child,has been described.Clinicians contemplating operative treatment for DEH should note the potential for recurrence and consider complete excision.A follow-up period of several years may be warranted to identify recurrent lesions.

Establishing a quality indicator format for endoscopic ultrasound

AIM: To perform a quality control(QC) review of endoscopic ultrasound(EUS) with emphasis on current consensus established quality indicators. METHODS: A national quality control study of EUS was performed with expanded international comparison. Ten different healthcare institutions in Israel participated in coordination with University of Chicago Medical Center. Each Israeli center provided ten patient reports, compared with twenty reports from University of Chicago Medical Center. Quality indicator forms were prepared with sections to be completed before, during, and after EUS. Physician compliance to all listed indicators wasevaluated. Quality indicators were evaluated prior to, during, and after performing EUS. RESULTS: One hundred different EUS procedural reports were analyzed. The mean patient age was 59 years old. Indications for referral were mostly for pancreatic or biliary reasons. QC showed several strongly reported areas, including indications for EUS(97%), anesthesia given(94%), periprocedural pancreatic evaluation(87%), and an overall summary of the EUS examination(82%). Intermediately reported areas included patients' pertinent past medical history(71.7%), evaluation of the biliary tree(63%), and providing medical guidance about potential procedural adverse events, including pancreatitis and bleeding(52%). Half of the reports(50%) did not include a systemic organ evaluation. Other areas, including systematic reporting of screened organs(36%), description of fine needle aspiration(15%), tumor description via tumor-nodemetastasis(5%), and listing of adverse events(0%) were largely lacking from procedural documentation. CONCLUSION: Documenting specific EUS quality indicators including listing post-procedural recommendations may improve the quality and efficiency of future EUS examinations and subsequent patient follow-up.

Effects of milrinone on inflammatory response-related gene expressions in cultured rat cardiomyocytes

Congestive heart failure(CHF)is defined as a cardiac dysfunction leading to low cardiac output and inadequate tissue perfusion.Intravenous positive inotropes are used to increase myocardial contractility in hospitalized patients with advanced heart failure.Milrinone is a phosphodiesterase Ⅲ inhibitor and used most commonly for inotropic effect.The well-known PROMISE study investigated the effects of milrinone on mortality in patients with severe CHF,and concluded that long-term therapy with milrinone increased morbidity and mortality armong patients with advanced CHF.Previous studies have suggested that phosphodiesterase inhibitors can have potential effects on inflammatory pathways.Hence,we hypothesized that milrinone may alter inflammatory gene expressions in cardiomyocytes,thus leading to adverse clinical outcomes.We used rat cardiomyocyte cell line H9 C2 and studied the impact of exposing cardiomyocytes to milrinone(10 μmol/L)for 24 hours on inflammatory gene expressions.RNA extracted from cultured cardiomyocytes was used for whole rat genome gene expression assay(41 000 genes).The following changes in inflammatory response-related gene expressions were discovered.Genes with increased expressions included:THBS2(+ 9.98),MMP2(+3.47),DDIT3(+2.39),and ADORA3(+3.5).Genes with decreased expressions were:SPP1(-5.28)and CD14(-2.05).We found that the above mentioned gene expression changes seem to indicate that milrinone may hinder the inflammatory process which may potentially lead to adverse clinical outcomes.However,further in vivo and clinical investigations will be needed to illustrate the clinical relevance of these gene expression changes induced by milrinone.

Role of Oxidative Stress in Cardiac Allograft Vasculopathy

Cardiac Allograft Vasculopathy, an accelerated form of arterial occlusive disease, is the major cause of death in the long-term after heart transplantation. Multiple factors influence the initiation and progression of CAV. These include ischemia-reperfusion, dyslipidemia, insulin resistance, and hypertension due to the use of immunosuppressive agents, the direct effects of immunosuppressive agents on endothelial function, and viruses (CMV). Impaired endothelial function reflects abnormalities in the production or activity of several vasoactive substances. Disruption of the nitric oxide synthase (NOS) pathway leads to changes in vascular reactivity, structure, and interaction with circulating blood components. Since endothelium-derived nitric oxide (NO) suppresses vascular cell proliferation and vascular inflammation, a deficit in vascular NO facilitates development of CAV. The link between oxidative stress and CAV largely exists in the balance between free radical superoxide generation and NO production. This review focuses on identifying the oxidative stress factors affecting CAV.

Does Cyclosporine Down Regulate IL-17 in Cardiac Allograft Vasculopathy?

Background: Cardiac Allograft Vasculopathy (CAV) is characterized by vascular inflammation and intimal proliferation which results in luminal stenosis and myocardial infarction. During vascular inflammation elaboration of several cytokines and differential expression of growth factors have been noted. CAV remains the major threat to long-term graft survival. CD4 and CD8 T-cell subsets play a significant role in the development of transplant rejection. Chronic transplant rejection often leads to development of CAV. A new CD4 effector cell subset that produces IL-17 (Th17) has been shown to be up-regulated in the murine system in the setting of CAV. This study assesses the level of IL-17 in cardiac transplant patients with and without CAV as compared to nontransplanted controls. Methods: Levels of IL-17, IL-6, MCP-1 were measured by ELISA in plasma of four nontransplanted controls, nine cardiac allograft recipients with CAV (HT-GVD) and eight post transplant subjects without a diagnosis of CAV (HT-No GVD). All post transplant patients were immune suppressed with cyclosporine. HT-GVD patients were 1-15 years post transplant while HT-No GVD subjects were 1 - 10 years post transplant. Results: IL-17, MCP-1 and IL-6 were significantly down regulated in HT-GVD subjects compared to the HT-No GVD subjects (p 0.001) but not significant between controls and HT-No GVD (p = ns). Conclusions: A decrease in IL-17 in HT-GVD subjects as compared to HT-No GVD in the presence of cyclosporine treatment could be a consequence of down regulation of IL-6. It is likely that cyclosporine differentially regulates pro inflammatory molecules in the setting of graft vascular disease.

静脉麻醉药物的新进展

咪达唑仑、依托咪酯和丙泊酚是目前常用的静脉麻醉药，静脉麻醉药物的研发都与它们衔尾相随。修饰已知药物的分子结构来改良药性以及发掘新型静脉麻醉药物，始终是过去数十年来并行不悖的制药焦点。静脉麻醉药物的一般作用机制是：通过促进神经元通道开放、易化氯离子内流，