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.     

Adjuvant radiotherapy in carcinomas of the uterine cervix: the prognostic value of hemoglobin levels

Anemia has been associated with a poorer treatment response and reduced survival in women undergoing primary radiotherapy (RT) or radiochemotherapy for advanced cervical carcinoma. This study aimed to determine the influence of anemia on outcome in patients with cervical carcinoma undergoing adjuvant RT. Medical records were reviewed for 183 cervical cancer patients who had received adjuvant RT because of risk factors after radical surgery (n= 109) or inadequate primary surgery (simple hysterectomy; n= 74). Kaplan-Meier and Cox regression analyses were used to study hemoglobin levels before and during adjuvant RT in relation to recurrence-free and overall survival. Hemoglobin values > or =11 g/dL were considered normal, while those <11 g/dL indicated anemia. Hemoglobin levels before RT influenced significantly overall survival and recurrence-free survival across the whole group (overall survival--log rank(all patients)= 7.5; df = 1; P= 0.006). However, subgroup analysis showed that the observed difference was mainly due to the group of women who had undergone inadequate primary surgery (overall survival--log rank(inadequate surgery)= 10.8; df = 1; P= 0.001). Multifactorial regression analyses comparing hemoglobin before RT with grading and tumor stage confirmed the prognostic value of hemoglobin values. Maintaining normal hemoglobin values before and during adjuvant RT seems to be important, especially in patients who have had inappropriate simple hysterectomy, which may resemble a therapeutic situation.     

A theoretical model evaluating the angular distribution of luminescence emission in X-ray scintillating screens.

The aim of this study was to examine the angular distribution of the light emitted from radiation-excited scintillators in medical imaging detectors. This distribution diverges from Lambert's cosine law and affects the light emission efficiency of scintillators, hence it also affects the dose burden to the patient. In the present study, the angular distribution was theoretically modeled and was used to fit experimental data on various scintillator materials. Results of calculations revealed that the angular distribution is more directional than that predicted by Lambert's law. Divergence from this law is more pronounced for high values of light attenuation coefficient and thick scintillator layers (screens). This type of divergence reduces light emission efficiency and hence it increases the incident X-ray flux required for a given level of image brightness.     

Interleukin-6 -174 G/C promoter polymorphism and effects of fenofibrate and simvastatin on inflammatory markers in hypercholesterolemic patients.

To evaluate whether the interleukin-6 (IL-6) -174 G/C polymorphism might alter the effects of micronized fenofibrate or simvastatin therapy on inflammatory markers, we measured IL-6, C-reactive protein, CD40 ligand, adhesion molecules, P-selectin and monocyte chemoattractant protein-1 in hypercholesterolemic patients both before and after a 30-day treatment. Serum IL-6 levels were significantly higher in patients with the GC or CC genotypes (P=0.04). The presence of the C allele was associated with greater absolute reduction of IL-6 levels (P=0.04) following fenofibrate treatment. There was no significant association between the -174 G/C IL-6 polymorphism and the effects of simvastatin treatment. A relationship between the -174 G/C IL-6 polymorphism and the anti-inflammatory action of fenofibrate reported might be useful in the optimization of the treatment regimen in patients receiving this class of drugs.     

Cognitive impairment in heart failure.

Heart failure is reaching epidemic proportions in the United States, causing a constellation of disabling symptoms. Cognitive impairment in people with heart failure may be more common than previously known with multiple etiologies from both the disease process and the treatment. Exemplars from a research study are used to illustrate the perspective of heart failure patients. Given the critical importance of memory deficits on patient education, potential nursing interventions to address the issue of cognitive impairment are described.     

Improvement in the Appearance of Wrinkles with Topical Transforming Growth Factor β1 and l-Ascorbic Acid

BACKGROUND AND OBJECTIVE: Facial rhytides are a common cosmetic concern. Surgical treatment effects dramatic improvement; however, the associated risk and cost may be prohibitive. Recent focus is on developing topical products containing biologically active ingredients for at-home therapy. Our study examines the effects of a topical cream containing transforming growth factor-beta(1) (TGF-beta(1)), l-ascorbic acid, and Cimicifuga racemosa extract (CRS) (Topix Pharmaceuticals, North Amityville, NY, USA). MATERIALS AND METHODS: In the first arm of the study, 12 subjects were randomized to apply CRS to the left or right side of their face and a cream containing l-ascorbic acid and C. racemosa in silicone base (vitamin C [Vit C]) to the contralateral side twice daily for 3 months. In the second arm of the study, 20 subjects were randomized to apply CRS to the left or right side of their face and Tissue Nutrient Solution Recovery Complex (TNS) (SkinMedica, Carlsbad, CA, USA), a product containing a variety of growth factors including VEGF, PDGF-A, G-CSF, HGF, IL-6, IL-8, and TGF-beta(1) (Nouricel-MD) without l-ascorbic acid, C. racemosa extract, or silicone base, to the contralateral side of their face twice daily for 3 months. Digital photographs were scored by study-blinded physicians, and self-assessments were completed by all subjects at baseline and at the conclusion of the protocol. RESULTS: CRS and TNS were well tolerated, and all subjects completed the 3-month protocol for the CRS versus Vit C arm of the study. Physicians rated success in facial wrinkling scores on the CRS-treated side of the face for 27 of 31 subjects. Responders showed, on average, 21.7% improvement in physician-rated wrinkle scores. The mean improvement in the group of 31 patients as a whole was 12%. Eighteen of 31 subjects reported a noticeable improvement on their CRS-treated side. Both CRS and TNS demonstrate significant success between baseline and 3-month scores, and both growth factor products are superior to Vit C. Patients preferred CRS over TNS. CONCLUSION: CRS is effective in minimizing the appearance of facial rhytides. The success of the CRS product is largely attributable to the incorporation of TGF-beta(1).     

Modelling Germline Mosaicism and Different New Mutation Rates Simultaneously for Appropriate Risk Calculations in Families with Duchenne Muscular Dystrophy

For several genetic diseases two biological phenomena have been recognised as important: germline mosaicism; and different new mutation rates in males and females depending on mutation type. Both principles have been investigated separately and their influence on risk estimation in families has been exemplified in the literature. The aim of this paper is to present a general model that includes mosaicism and different new mutation rates. Mosaicism is introduced by defining additional alleles at the disease locus in combination with adapted segregation rules. Taking Duchenne muscular dystrophy as an example, we derive the conditions which have to be fulfilled for a population in mutation selection equilibrium. Our approach describes the model at the population level and not in individual subjects. This has the advantage of being able to use well known algorithms for the calculation of likelihoods in pedigrees, and to include additional diagnostic information such as marker genotypes and carrier deletion test results. We demonstrate the impact of the new model on a typical pedigree. In families where the patient is not available, the distinction between point mutations and deletions is important, since often molecular diagnostic tests for females can only screen for deletions. Negative deletion test results can now be included in the risk calculations.