Cefoperazone-sulbactam and risk of coagulation disorders or bleeding: a retrospective cohort study

ABSTRACT

Objectives: Limited evidence has suggested that cefoperazone-sulbactam causes coagulation disorders and bleeding.

Methods: The authors conducted a retrospective study to compare patients receiving cefoperazone-sulbactam versus those treated with cefoperazone-tazobactam or ceftazidime. Propensity-score matching was used to explore whether treatment with cefoperazone-sulbactam increased the risk of prothrombin time (PT) prolongation, coagulation disorders, and bleeding, or decreased platelets (PLT).

Results: The cohort included 23,242 patients. Among patients receiving cefoperazone-sulbactam, the risk of PT prolongation, coagulation disorders, decreased PLT, and bleeding was 5.3%, 9.2%, 15.7%, and 4.2%, respectively. Propensity-score matching analyses suggested that cefoperazone-sulbactam increased the risk of PT prolongation (aOR 2.26, 95% CI 1.61–3.18), coagulation disorders (aOR 1.81, 95% CI 1.43–2.30), and decreased PLT (aOR 1.46, 95% CI 1.25–1.72), but not increase bleeding (aOR 1.05, 95% CI 0.79–1.40) compared with ceftazidime. Patients receiving cefoperazone-sulbactam had higher risk of PT prolongation (aOR 1.53, 95% CI 1.11–2.10), coagulation disorders (aOR 1.53, 95% CI 1.21–1.95), but not decreased PLT (aOR 0.93, 95% CI 0.81–1.07) or bleeding (aOR 1.11, 95% CI 0.87–1.42), compared with those receiving cefoperazone-tazobactam.

Conclusion: Cefoperazone-sulbactam may be associated with a higher risk of PT prolongation and coagulation disorders compared with cefoperazone-tazobactam and ceftazidime.     

Long-term vardenafil therapy improves hemodynamics in patients with pulmonary hypertension.

The phosphodiesterase-5 (PDE-5) inhibitor, sildenafil, has been reported to produce sustained pulmonary vasodilatation in patients with pulmonary hypertension (PH). Recently, vardenafil, a more potent and selective PDE-5 inhibitor than sildenafil, has been approved for the treatment of erectile dysfunction. However, the long-term effects of oral vardenafil in patients with PH are unknown. We studied five consecutive patients with PH; one with primary pulmonary hypertension, two with chronic pulmonary thromboembolism, one with Eisenmenger syndrome (ventricular septal defect) and one with secondary pulmonary hypertension after a ventricular septal defect closure operation. In an acute hemodynamic trial, vardenafil (5 mg) significantly decreased both the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) with an increase in cardiac output. In a chronic hemodynamic trial, the maintenance dose of vardenafil (10 to 15 mg) for 3 months significantly decreased the PVR, but not the SVR, with a 20.7% reduction of the PVR/ SVR ratio. Plasma brain natriuretic peptide (BNP) levels were also significantly decreased after 3 months. This pilot study demonstrates that long-term oral vardenafil therapy may be a safe and effective treatment for patients with PH.     

Risk factors and ankle brachial indexes in cerebral infarction combined with peripheral arterial disease

BACKGROUND: Ankle brachial index(ABI)is widely involved in researches and clinical application of peripheral vascular injury of patients with diabetes (DM);however ,the application in cerebral infarction(CI)is rare.OBJECTIVE: To investigate the possible risk factor of cerebral infarction plus peripheral arterial disease(PAD),compare metabolic characteristics of patients who having CI plus PAD or only having CI,and understand the significance of ABI on screening and diagnosing CI plus PAD of lower limb.DESIGN: Contrast observation based on CI patients.SETTING: Deparment of Neurology,Nanxishan Hospital of Guangxi Zhang Autonomous Region.PARTICIPANTS:A total of 124 CI patients were selected from Department of Neurology.Nanxishan Hospital of Guangxi Zhuang Autonomous Region from July 2005 to April 2006,including 72 males and 52 females aged from 45 to 88 years.All patients met the diagnostic criteria of cerebrovascular disease established by National Academic Conference of Cerebrovascular Diseases in 1995 and determined as cerebral infarction with MRI or CT examination.All patients provided informed consent.There were 46 cases(37.2%)with CI plus PAD and 78 cases(62.8%)only with CI.METHODS: Blood pressure of bilateral ankles and upper extremities was measured at plain clinostatism with DINAMAP blood pressure monitor(GE Company).The ratio between average systolic pressure of lateral ankle and average systolic pressure of both upper extremities was regarded as ABI.The normal ABI was equal to or more than 0.9.If ABI＜0.9 occurred at one side,patients were diagnosed as PAD.On the second morning after hospitalization,blood was collected to measure fasting blood glucose(FBG),2-hour postprandial blood glucose(PBG2h),glycosylated hemoglobin(HbAlc),triglycerides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C).Among them,blood glucose.lipid and other biochemical markers were measured with enzyme chemistry assay and HbA1c was measured with HbA1c meter based on high liquid phase.Measurement data and enumeration data were compared with t test and Chi-square test.and multiple factors were deat with Logistic regression analysis and multivariate linear regression analysis.MAIN OUTCOME MEASURES: Results of correlation between ABI and metabolic markers with multivariate linear regression analysis;risk factors of CI plus PAD with Logistic regression analysis;comparisons of metabolic markers between PAD and non-PAD patients.RESULTS:All 124 patients with acute CI were involved in the final analysis.①Comparisons of metabolic markers:Levels of serum LDL-C and uric acid(UA)were higher of PAD patients than those of non-PAD patients(t=2.051 9,3.339 1,P＜0.05);however,there were no significant differences among other metabolic markers(P＞0.05).②Results of multivariate linear regression analysis:PBG2h,LDL.C and UA were obvious correlation with ABI of posterior tibial artery of lower limb and dorsal pedis artery rpartial regression coefficient:-0.231 to-1.010,P＜0.05).③Risk factors of CI plus PAD with Logistic regression analysis:Age.Smoking history,sum of CI focus(≥3)and LDL-C were independent risk factor of CI plus PAD(OR=1.524-5.422,P＜0.05-0.01 ).CONCLUSION:①Levels of serum LDL-C and UA of patients with CI plus PAD are high.②ABI of lower limbs is correlation with PBG2h,LDL-C and UA.In addition,measuring ABI is beneficial for early diagnosing PAD of lower limbs of patients who have poorly controlled blood glucose,abnormal lipid and poor renal function.③Age,LDL-C and sum of CI focus(≥3)are independent risk factors of CI plus PAD.It is of significance for screening non-PAD patients to evaluate risk degrees and prognosis and select therapeutic methods based on ABI measurement.     

Experimental animal models of pancreatic carcinogenesis and metastasis

Pancreatic cancer is a lethal disease characterized by early metastasis, local invasion, and resistance to conventional therapies. To understand its etiology and eventually make prevention of it possible and effective, appropriate carcinogenesis models will certainly help us understand the effects of environmental and genetic elements on pancreatic carcinogenesis. The development of new treatment strategies to control cancer metastasis is of immediate urgency. Fulfillment of this task relies on our knowledge of the cellular and molecular biology of pancreatic cancer metastasis and the availability of biologically and clinically relevant model systems. Many of the existing pancreatic cancer carcinogenesis and metastasis animal models are described in this review. The advantages and disadvantages of each model and their clinical implications are discussed, and special attention is focused on experimental therapeutic strategies targeting pancreatic cancer metastasis.     

Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme.

Angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension. It is believed that treatment with an ARB increases the level of plasma angiotensin II (Ang II) because of a lack of negative feedback on renin activity. However, Ichikawa (Hypertens Res 2001; 24: 641-646) reported that long-term treatment of hypertensive patients with olmesartan resulted in a reduction in plasma Ang II level, though the mechanism was not determined. It has been reported that angiotensin 1-7 (Ang-(1-7)) potentiates the effect of bradykinin and acts as an angiotensin-converting enzyme (ACE) inhibitor. It is known that ACE2, which was discovered as a novel ACE-related carboxypeptidase in 2000, hydrolyzes Ang I to Ang-(1-9) and also Ang II to Ang-(1-7). It has recently been reported that olmesartan increases plasma Ang-(1-7) through an increase in ACE2 expression in rats with myocardial infarction. We hypothesized that over-expression of ACE2 may be related to a reduction in Ang II level and the cardioprotective effect of olmesartan. Administration of 0.5 mg/kg/day of olmesartan for 4 weeks to 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) significantly reduced blood pressure and left ventricular weight compared to those in SHRSP given a vehicle. Co-administration of olmesartan and (D-Ala7)-Ang-(1-7), a selective Ang-(1-7) antagonist, partially inhibited the effect of olmesartan on blood pressure and left ventricular weight. Interestingly, co-administration of (D-Ala7)-Ang-(1-7) with olmesartan significantly increased the plasma Ang II level (453.2+/-113.8 pg/ml) compared to olmesartan alone (144.9+/-27.0 pg/ml, p<0.05). Moreover, olmesartan significantly increased the cardiac ACE2 expression level compared to that in Wistar Kyoto rats and SHRSP treated with a vehicle. Olmesartan significantly improved cardiovascular remodeling and cardiac nitrite/ nitrate content, but co-administration of olmesartan and (D-Ala7)-Ang-(1-7) partially reversed this anti-remodeling effect and the increase in nitrite/nitrate. These findings suggest that olmesartan may exhibit an ACE inhibitory action in addition to an Ang II receptor blocking action, prevent an increase in Ang II level, and protect cardiovascular remodeling through an increase in cardiac nitric oxide production and endogenous Ang-(1-7) via over-expression of ACE2.     

膀胱移行细胞癌P16、P15、P14基因5＇CpG岛甲基化检测

目的 探讨P16、P15、P14基因5＇CpG岛在膀胱移行细胞癌中甲基化状态及其临床意义。方法 应用甲基化特异性PCR（methylation—specific PCR，MSP）方法检测40例膀胱移行细胞癌P16、P15、P14基因甲基化程度，χ^2检验分析其甲基化程度与膀胱癌病理分级分期间关系。结果 膀胱移行细胞癌P16、P15、P14 5＇CpG岛甲基化扩增阳性化率分别为27．5％、17．5％、35％，而正常膀胱组织中均未检测到三种基因5＇CpG岛甲基化。P16、P14基因甲基化与膀胱癌病理分级分期有显著性差异（P〈0．05），P15基因则没有显著性差异（P〉0．05）。结论 P16、P15、P14基因在膀胱癌组织中的甲基化率较高，三种抑癌基因5＇CpG岛异常高甲基化，在膀胱癌的发生、发展中具有重要作用。     

神经外科重症监护病房常见病原菌的分布与耐药性研究

目的调查珠江医院神经外科重症监护病房(ICU)病原菌的分布与耐药情况,分析ICU院内感染的发生原因,探讨防治对策。方法应用法国VITEKⅡ全自动细菌鉴定仪鉴定病原菌,用纸片扩散法检测药敏结果。结果神经外科ICU菌群主要以革兰阴性杆菌(71.6%)为主,鲍曼不动杆菌占16.7%,大肠埃希菌占15.7%,铜绿假单胞菌占13.7%,肺炎克雷伯菌占13.7%等。但葡萄球菌、粪肠球菌等阳性球菌(28.4%)也有增加的趋势。亚胺培南和头孢哌酮/舒巴坦仍保持最高抗菌活性,细菌的耐药率分别为15.3%和30.6%。结论我院神经外科ICU感染主要病原菌是革兰阴性杆菌,对常用抗菌药物耐药性较高,但革兰阳性球菌所占比例呈增高趋势。控制第二、三代头孢菌素以及制酸剂(质子泵抑制剂)的预防性用药,减少耐药菌株的产生,有针对性地使用抗生素是控制危重病人感染的有效措施。