Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia

Statin-ezetimibe combinations are a potentially advantageous therapeutic option for high-risk patients who need additional lowering of low-density lipoprotein cholesterol (LDL-C). These combinations may overcome some of the limitations of statin monotherapy by blocking both sources of cholesterol. Recently, a fixed-dose combination with atorvastatin, one of the most extensively studied statins, was approved and launched in several countries, including the USA. Depending on atorvastatin dose, this combination provides LDL-C reductions of 50-60%, triglyceride reductions of 30-40%, and high-density lipoprotein cholesterol (HDL-C) increases of 5-9%. Studies comparing the lipid-lowering efficacy of the atorvastatin-ezetimibe combination with the alternatives of statin dose titration or switching to a more potent statin consistently showed that combination therapy provided greater LDL-C reduction, translating into a greater proportion of patients achieving lipid goals. Simvastatin-ezetimibe combinations have been shown to reduce the incidence of major atherosclerotic events in several clinical settings to a magnitude that seems similar to that observed with statins for the same degree of absolute LDL-C lowering. The atorvastatin-ezetimibe combination has also been shown to induce the regression of coronary atherosclerosis measured by intravascular ultrasound in a significantly greater proportion of patients than atorvastatin alone. Atorvastatin-ezetimibe combinations are generally well tolerated. Previous concerns of a possible increase in the incidence of cancer with ezetimibe were dismissed in large trials with long follow-up periods. In this paper, we examine the rationale for an atorvastatin-ezetimibe combination, review the evidence supporting it, and discuss its potential role in the management of dyslipidemia.info:eu-repo/semantics/acceptedVersio

Importance of Cutaneous Changes in the Diagnosis of Neurological Diseases

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18F-FDG-PET/CT in diagnosis of Q fever endocarditis

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A lower bound on CNF encodings of the at-most-one constraint

Constraint "at most one" is a basic cardinality constraint which requires that at most one of its $n$ boolean inputs is set to $1$. This constraint is widely used when translating a problem into a conjunctive normal form (CNF) and we investigate its CNF encodings suitable for this purpose. An encoding differs from a CNF representation of a function in that it can use auxiliary variables. We are especially interested in propagation complete encodings which have the property that unit propagation is strong enough to enforce consistency on input variables. We show a lower bound on the number of clauses in any propagation complete encoding of the "at most one" constraint. The lower bound almost matches the size of the best known encodings. We also study an important case of 2-CNF encodings where we show a slightly better lower bound. The lower bound holds also for a related "exactly one" constraint.Comment: 38 pages, version 3 is significantly reorganized in order to improve readabilit

Síndroma Ovo-Ave na Criança:Um Caso Clínico

A síndroma ovo -ave é uma entidade clínica rara, em especial em idade pediátrica. Descreve -se o caso de criança de sexo masculino, 5 anos, que habita zona rural, com clínica sugestiva de alergia ao ovo e à carne de frango desde os 7 meses. Aos 2,5 anos apresenta queixas de asma brônquica, rinite alérgica e eczema atópico. Os testes cutâneos foram positivos para extractos de clara e gema de ovo. Dosearam -se IgE específi cas para clara e gema de ovo (>100 kU/L), carne de frango (1,0 kU/L), α -livetina (0,7 kU/L), penas de frango (15,3 kU/L). O estudo de immunoblotting evidenciou ligação de IgE a bandas com peso molecular entre 30-66 kDa e 32-45 kDa para clara e gema, respectivamente, 38/39/42 kDa para carne de frango e 33-45 kDa para penas de frango. Em doentes com alergia a carne de aves, expostos a factores ambientais de risco e sensibilização elevada a gema de ovo, dever -se -á suspeitar da síndroma ovo-ave

Extending the applicability of the dose addition model to the assessment of chemical mixtures of partial agonists by using a novel toxic unit extrapolation method

This article has been made available through the Brunel Open Access Publishing Fund.Dose addition, a commonly used concept in toxicology for the prediction of chemical mixture effects, cannot readily be applied to mixtures of partial agonists with differing maximal effects. Due to its mathematical features, effect levels that exceed the maximal effect of the least efficacious compound present in the mixture, cannot be calculated. This poses problems when dealing with mixtures likely to be encountered in realistic assessment situations where chemicals often show differing maximal effects. To overcome this limitation, we developed a pragmatic solution that extrapolates the toxic units of partial agonists to effect levels beyond their maximal efficacy. We extrapolated different additivity expectations that reflect theoretically possible extremes and validated this approach with a mixture of 21 estrogenic chemicals in the E-Screen. This assay measures the proliferation of human epithelial breast cancers. We found that the dose-response curves of the estrogenic agents exhibited widely varying shapes, slopes and maximal effects, which made it necessary to extrapolate mixture responses above 14% proliferation. Our toxic unit extrapolation approach predicted all mixture responses accurately. It extends the applicability of dose addition to combinations of agents with differing saturating effects and removes an important bottleneck that has severely hampered the use of dose addition in the past. © 2014 Scholze et al

Combined use of a femtosecond laser and a microkeratome in obtaining thin grafts for Descemet stripping automated endothelial keratoplasty: an eye bank study

Purpose: To evaluate the use of a femtosecond laser combined with a microkeratome in the preparation of posterior corneal disks for Descemet stripping automated endothelial keratoplasty (DSAEK).
Methods: This experimental study involved ultrathin DSAEK tissue preparation of 22 donor corneas unsuitable for transplantation. The first cut was performed with an Intralase® FS60 laser and the second cut with a Moria CBm 300-µm microkeratome. The thickness of the first cut was modified for each cornea to obtain a final graft thickness of less than 110 µm. Precut and postcut central pachymetry were performed with an ultrasonic pachymeter. Central endothelial cell density (ECD) was calculated before and 24 hours after tissue preparation. 
Results: Final graft thickness was 105.0 ± 26.1 (SD) µm (range 65-117). The mean microkeratome head cut thickness was 324.5 ± 10.9 µm (range 310-345). Precut and postcut ECDs averaged 2250 ± 222 and 2093 ± 286 cells/mm2, respectively, representing 6.9% of cell loss. No corneas were perforated.
Conclusion: Femtosecond FS60 lasers and Moria CBm 300-µm microkeratomes can be used sequentially to prepare consistently thin DSAEK grafts with no irregular cuts or cornea perforations

Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways

Lung cancer is one of the most common cancers in the world with a high mortality rate. We analyzed 45 surgical samples of the adenocarcinoma, 13 with lymph node metastasis. APC, BCL2, chromogranin A, CK 5/6/18 (LP34), CK20, CK7, cyclin D1, EGFR, ERCC1, HER2, Ki67, LRP, MRP, P53, RB and TTF1 expressions were evaluated by immunohistochemistry (IHC). Higher Ki67, APC, ERCC1 expressions and lower TTF1 expression were identified in advanced stages (IIA and IIIA) of adenocarcinomas, which reflect a more aggressive, less differentiated, possibly a non-TRU adenocarcinoma. Acinar, micropapillary and BA/lepidic adenocarcinoma patterns were the most similar patterns and papillary was the most different pattern followed by solid pattern, according to expression of these markers. Different adenocarcinoma patterns are engaged with different molecular pathways for carcinogenesis, based on the differences of expression. Acinar, BA/lepidic and micropapillary showed higher TTF1 expression (type TRU), and papillary and solid patterns revealed less TTF1 expression, exhibiting a non-TRU/bronchial phenotype. Solid pattern revealed lower HER2 and higher EGFR and ERCC1 (this compared to papillary) expression; papillary higher HER2 and lower ERCC1 expressions; micropapillary higher RB expression; and acinar lower ERCC1 and higher EGFR expressions. Ciclin D1 seems to have more importance in acinar and BA/lepidic patterns than in micropapillary. ERCC1 protein expression in micropapillary, solid and BA/lepidic patterns may indicate DNA repair activation. Inhibition of apoptosis could be explained by BCL2 overexpression, present in all adenocarcinoma patterns. MRP-1 and LRP were overexpressed in all patterns, which may have implications for drug resistance. Further studies are needed to interpret these data regarding to therapy response in advanced staged bronchial-pulmonary carcinomas.info:eu-repo/semantics/publishedVersio