Effects of conjugated equine estrogens or raloxifene on lipid profile, coagulation and fibrinolysis factors in postmenopausal women.

OBJECTIVES: To compare the effect of conjugated equine estrogens (CEE) and raloxifene on lipid profile and hemostasis. MATERIALS AND METHODS: A double-blind, randomized and parallel study was performed with 90 healthy postmenopausal women, aged 54 +/- 5 years, divided into three groups and submitted to daily therapy with either CEE 0.625 mg, raloxifene 60 mg or placebo for 4 months. The lipid profile, coagulation and fibrinolytic factors were analyzed. RESULTS: CEE increased the levels of high density lipoprotein cholesterol (HDL-C) from 49.0 to 56.8 mg/dl (p < 0.001), very low density lipoprotein cholesterol (VLDL-C) from 17.2 to 22.3 mg/dl (p < 0.001), and triglycerides from 86.0 to 111.7 mg/dl (p < 0.001), and decreased the levels of low density lipoprotein cholesterol (LDL-C) from 121.0 to 106.5 mg/dl (p < 0.001). The only significant effect of raloxifene was an increase in the levels of HDL-C from 46.0 to 47.8 mg/dl (p = 0.019). There was no significant reduction in LDL-C, from 115.5 to 110.2 mg/dl (p = 0.06), VLDL-C, from 21.7 to 20.0 mg/dl (p = 0.201), and triglycerides, from 108 to 100 mg/dl (p = 0.201). CEE decreased the levels of fibrinogen, from 370.5 to 326.8 g/l (p = 0.039) and the levels of antithrombin III, from 99.5 to 93.2% (p < 0.001). Raloxifene decreased the levels of fibrinogen, from 354.7 to 302.0 g/l (p = 0.009) and the levels of antithrombin III, from 102.4 to 98.5% (p = 0.039). CEE increased levels of protein C from 103.7 to 115.3 mg/l (p < 0.001) and raloxifene did not change the levels of protein C (107.9 to 105.1 mg/l; p = 0.158). CEE decreased the antigen levels of tissue plasminogen activator (t-PA) from 8.8 to 6.8 U/ml (p < 0.001), and of plasminogen activator inhibitor (PAI-1) from 30.8 to 21.6 U/ml (p < 0.010), whereas raloxifene had no significant effect on either t-PA, from 9.6 to 9.2 U/ml (p = 0.235) or PAI-1 antigen levels, from 32.1 to 30.4 U/ml (p = 0.538). CONCLUSION Both CEE and raloxifene exert significant effects on the lipid and coagulation profile. CEE had a more significant effect on fibrinolysis than raloxifene. These effects may have a significant impact on the cardiovascular risk that needs to be confirmed in larger studies.     

Gallibacterium anatis-secreted metalloproteases degrade chicken IgG.

Gallibacterium anatis (previously named Pasteurella haemolytica-like) is considered a normal inhabitant of genital and upper respiratory tracts of healthy chickens, but it is also associated with different pathological conditions. Secreted metalloproteases from field and reference G. anatis cultures were obtained by methanol precipitation and were characterized. Proteins of molecular mass higher than 100 kDa showing proteolytic activity were observed in 10% polyacrylamide gels copolymerized with 1% bovine casein. They were active at alkaline pH, and inhibited by ethylenediamine tetraacetic acid. Their activity was stable at 50 degrees C, but partially inhibited at 60 degrees C, and totally inhibited at higher temperatures. Secreted proteins were able to degrade chicken IgG after 24 h of incubation, and cross-reacted with a polyclonal antibody against purified protease from Actinobacillus pleuropneumoniae. Secreted metalloproteases could play a role in infections caused by G. anatis.     

Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome

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Risk factors for rhabdomyolysis with simvastatin and atorvastatin.

OBJECTIVE: To assess the frequency of risk factors for rhabdomyolysis with simvastatin and atorvastatin in cases reported to the Australian Adverse Drug Reactions Advisory Committee (ADRAC). DESIGN: Reports meeting the definition of rhabdomyolysis were reviewed for risk factors including age > or = 70 years, dose > or = 40 mg, hepatic dysfunction, diabetes mellitus, hyperkalaemia, hypothyroidism and the use of concomitant interacting medications. RESULTS: Only one report associated with simvastatin and five reports associated with atorvastatin did not list any risk factors for rhabdomyolysis. Interacting medicines featured in 77% of reports of rhabdomyolysis associated with simvastatin and 44% of reports associated with atorvastatin. A comparison of the age profile for reports of atorvastatin- and simvastatin-associated rhabdomyolysis with that for all adverse drug reaction reports received, and for all reports of muscle disorders, suggested a trend towards an increasing risk of rhabdomyolysis with increasing age with simvastatin but not with atorvastatin. Similarly, comparing prescribed tablet strengths from Pharmaceutical Benefits Scheme data with the HMG-CoA reductase inhibitor ('statin') doses in reports of rhabdomyolysis suggested a dose-related risk with simvastatin, but a less increased risk with high-dose atorvastatin. CONCLUSION: Risk factors for rhabdomyolysis featured in nearly all of the reports of statin-associated rhabdomyolysis and the majority of reports listed multiple risk factors, although dependence on risk factors appeared to be stronger with simvastatin than atorvastatin. The multiplication of risk factors in patients taking simvastatin and atorvastatin should be minimised.     

Correction of head movement on PET studies: comparison of methods.

Head movement presents a continuing problem in PET studies. Head restraint minimizes movement but is unreliable, resulting in the need to develop alternative strategies. These include frame-by-frame (FBF) realignment or use of motion tracking (MT) during the scan to realign PET acquisition data. Here we present a comparative analysis of these 2 methods of motion correction. METHODS: Eight volunteers were examined at rest using (11)C-raclopride PET with the radioligand administered as a bolus followed by constant infusion to achieve steady state. Binding potential (BP) was estimated using the ratio method during 2 periods of the scan at steady state. Head movement was compensated by using coregistration between frames (FBF) and 3 methods using MT measurements of head position acquired with a commercially available optical tracking system. RESULTS: All methods of realignment improved test-retest reliability and noise characteristics of the raw data, with important consequences for the power to detect small changes in radiotracer binding, and the potential to reduce false-positive and false-negative results. MT methods were superior to FBF realignment using coregistration on some indices. CONCLUSION: Such methods have considerable potential to improve the reliability of PET data with important implications for the numbers of volunteers required to test hypotheses.     

Vaginal tape erosion following transobturator tape (TOT) operation for stress urinary incontinence.

Inorganic sling materials when used for treatment of urinary stress incontinence have a high success rate of achieving continence. They unfortunately attract the complication of vaginal tape erosion. When used for Transobturator tape procedure (TOT) we found the Obtape sling (Mentor-Porges, Le Plessis-Robinson, France) attracted a high rate of erosion, likely due to the tape properties. We describe a series of tape erosions with the Obtape sling, the presentation, conservative and surgical management with favourable rates of maintenance of continence. We suggest the use of larger pore sized tapes to decrease the occurrence of vaginal tape erosion.