Multicenter Prospective Cohort Study of Renal Failure in Patients Treated with Colistin versus Polymyxin B

Nephrotoxicity is the main adverse effect of colistin and polymyxin B (PMB). It is not clear whether these two antibiotics are associated with different nephrotoxicity rates. We compared the incidences of renal failure (RF) in patients treated with colistimethate sodium (CMS) or PMB for ≥48 h. A multicenter prospective cohort study was performed that included patients aged ≥18 years. The primary outcome was renal failure (RF) according to Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) criteria. Multivariate analysis with a Cox regression model was performed. A total of 491 patients were included: 81 in the CMS group and 410 in the PMB group. The mean daily doses in milligrams per kilogram of body weight were 4.2 ± 1.3 and 2.4 ± 0.73 of colistin base activity and PMB, respectively. The overall incidence of RF was 16.9% (83 patients): 38.3% and 12.7% in the CMS and PMB groups, respectively (P < 0.001). In multivariate analysis, CMS therapy was an independent risk factor for RF (hazard ratio, 3.35; 95% confidence interval, 2.05 to 5.48; P < 0.001) along with intensive care unit admission, higher weight, older age, and bloodstream and intraabdominal infections. CMS was also independently associated with a higher risk of RF in various subgroup analyses. The incidence of RF was higher in the CMS group regardless of the patient baseline creatinine clearance. The development of RF during therapy was not associated with 30-day mortality in multivariate analysis. CMS was associated with significantly higher rates of RF than those of PMB. Further studies are required to confirm our findings in other patient populations.     

Recurrent enteric gallstone obstruction

Small bowel gallstone obstruction may recur, most often within a few days after surgery, due to an overlooked intraenteric stone or subsequent passage of another gallstone via the cholecystoenteric fistula. In the case reported herein there was a 6-month interval. A critical review of the radiologic signs of gallstone ileus is presented.     

Hemodynamic, pulmonary vascular, and myocardial abnormalities secondary to pharmacologic constriction of the fetal ductus arteriosus. A possible mechanism for persistent pulmonary hypertension and transient tricuspid insufficiency in the newborn infant.

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes. This resulted in a significant rise in the fetal pulmonary-to-systemic arterial mean blood pressure difference across the ductus arteriosus, presumably secondary to constriction of the ductus arteriosus. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of prostaglandin E1 (PGE1) into the fetal inferior vena cava. Fetal lungs from study and control animals were fixed by perfusion at measured pulmonary arterial mean blood pressure, and fifth-generation resistance vessels were studied. The medial width/external diameter ratio was significantly increased in the study vs the control lungs due to increased smooth muscle and decreased external diameter. In addition, study fetuses had acute degenerative myocardial changes in the tricuspid valve papillary muscles, the right ventricular free wall and the interventricular septum. Similar changes were not seen in control fetuses. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus, fetal pulmonary arterial hypertension, and right ventricular damage. If severe, this may cause rapid fetal death. If less severe, in the newborn infant, this mechanism may be one cause of persistent pulmonary hypertension due to vasoconstriction and increased pulmonary arterial smooth muscle and/or tricuspid insufficiency due to papillary muscle infarction.     

A recommended scale for cognitive screening in clinical trials of Parkinson's disease

Cognitive impairment is common in Parkinson's disease (PD). There is a critical need for a brief, standard cognitive screening measure for use in PD trials whose primary focus is not on cognition. The Parkinson Study Group (PSG) Cognitive/Psychiatric Working Group formed a Task Force to make recommendations for a cognitive scale that could screen for dementia and mild cognitive impairment in clinical trials of PD where cognition is not the primary outcome. This Task Force conducted a systematic literature search for cognitive assessments previously used in a PD population. Scales were then evaluated for their appropriateness to screen for cognitive deficits in clinical trials, including brief administration time (<15 minutes), assessment of the major cognitive domains, and potential to detect subtle cognitive impairment in PD. Five scales of global cognition met the predetermined screening criteria and were considered for review. Based on the Task Force's evaluation criteria the Montreal Cognitive Assessment (MoCA), appeared to be the most suitable measure. This Task Force recommends consideration of the MoCA as a minimum cognitive screening measure in clinical trials of PD where cognitive performance is not the primary outcome measure. The MoCA still requires further study of its diagnostic utility in PD populations but appears to be the most appropriate measure among the currently available brief cognitive assessments. Widespread adoption of a single instrument such as the MoCA in clinical trials can improve comparability between research studies on PD. © 2010 Movement Disorder Society     

Cyclical estrogen and free radical damage to the rabbit urinary bladder

Introduction and hypothesis  

There are a number of lower urinary tract dysfunctions (LUTD) that occur primarily in women. Our hypothesis is that cyclical estrogen will produce LUTD in part by the generation of free radicals and oxidative damage to cellular and subcellular membranes.     

血清视黄醇结合蛋白4在妊娠糖尿病患者中显著升高

探讨中国汉族人群血清视黄醇结合蛋白4(RBP4)水平与妊娠糖尿病的关系.收集2005年7月至2007年12月在瑞金医院妇产科行常规产前检查的孕妇195例(妊娠糖尿病组99例,正常糖耐量组96例),同时收集65例非妊娠期健康育龄期妇女作为对照组,所有受试者均排除急慢性疾病,并统一用酶联免疫法检测血清RBP4水平.与非妊娠正常对照组相比,妊娠期妇女血清RBP4水平均明显升高,妊娠糖尿病患者血清RBP4水平较正常妊娠妇女显著升高[(43.04±1.85对33.84±2.17)ms/L,P<0.01].在妊娠期妇女中,多元逐步回归分析显示,胰岛素抵抗指数(HOMA-IR)和甘油三酯是血清RBP4水平升高的独市危险因素(r2=0.165).本研究结果提示,妊娠期妇女血清RBP4水平较非妊娠妇女显著升高,而与正常孕妇相比,妊娠糖尿病患者血清RBP4水平更高;在妊娠期妇女中胰岛素抵抗和甘油三酯水平与RBP4水平显著正相关.     

Silver exposure in developing zebrafish produces persistent synaptic and behavioral changes

Environmental silver exposures are increasing due to the use of silver nanoparticles, which exert antimicrobial actions by releasing Ag⁺, a suspected developmental neurotoxicant. We evaluated the long-term neurochemical and behavioral effects of embryonic Ag⁺ exposure in zebrafish at concentrations that had no overt effects on morphological development. Exposure to 0.03, 0.1 or 0.3 μM Ag⁺ during the first five days post-fertilization caused elevations in both dopamine and serotonin turnover in the adult zebrafish brain without affecting basal neurotransmitter levels. Consistent with these synaptic effects, Ag⁺-exposed fish showed a faster acquisition of avoidance behavior in a three-chamber test apparatus, without any change in response latency or overall swimming ability. Our results indicate that Ag⁺ is a developmental neurotoxicant that causes persistent neurobehavioral effects, reinforcing health concerns about Ag⁺ released from silver nanoparticles.     

High prevalence of OXA-143 and alteration of outer membrane proteins in carbapenem-resistant Acinetobacter spp. isolates in Brazil

Carbapenem resistance amongst Acinetobacter spp. has been increasing in the last decade. This study evaluated the outer membrane protein (OMP) profile and production of carbapenemases in 50 carbapenem-resistant Acinetobacter spp. isolates from bloodstream infections. Isolates were identified by API20NE. Minimum inhibitory concentrations (MICs) for carbapenems were determined by broth microdilution. Carbapenemases were studied by phenotypic tests, detection of their encoding gene by polymerase chain reaction (PCR) amplification, and imipenem hydrolysis. Nucleotide sequencing confirming the enzyme gene type was performed using MegaBACE 1000. The presence of OMPs was studied by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and PCR. Molecular typing was performed using pulsed-field gel electrophoresis (PFGE). All isolates were resistant to carbapenems. Moreover, 98% of the isolates were positive for the gene encoding the enzyme OXA-51-like, 18% were positive for OXA-23-like (only one isolate did not show the presence of the insertion sequence ISAba1 adjacent to this gene) and 76% were positive for OXA-143 enzyme. Five isolates (10%) showed the presence of the IMP-1 gene. Imipenem hydrolysing activity was detected in only three strains containing carbapenemase genes, comprising two isolates containing the bla(IMP) gene and one containing the bla(OXA-51/OXA-23-like) gene. The OMP of 43 kDa was altered in 17 of 25 strains studied, and this alteration was associated with a high meropenem MIC (256 μg/mL) in 5 of 7 strains without 43 kDa OMP. On the other hand, decreased OMP 33-36 kDa was found in five strains. The high prevalence of OXA-143 and alteration of OMPs might have been associated with a high level of carbapenem resistance.