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At least 199 records · Page 11Linked to original sources
PubMed2005

The effects of aromatase inhibitors on lipids and thrombosis.

Oestrogen is known to influence blood lipid levels and though its cardioprotective effects are less clear than once thought, there remains concern that reduction of oestrogen levels during hormonal treatment for breast cancer may have an adverse effect on cardiovascular risk. While tamoxifen has been shown to improve lipid profiles, the aromatase inhibitors have a very different mode of action and do not possess the oestrogen-agonistic effects of tamoxifen. At present, there are few data on the effects of these agents on lipid profiles. Available data are mixed, but suggest that the different aromatase inhibitors have different effects on lipid profiles. Some studies show anastrozole as generally having little effect on lipids, while others have indicated adverse effects on lipid profiles/increased hypercholesterolaemia. Letrozole has been associated with adverse effects on lipid profiles in some studies, including BIG 1-98, but short-term data from randomised trials do not show increased cardiovascular morbidity. By contrast, exemestane, which has been studied in slightly more detail, may either have little effect or may be associated with slightly improved lipid profiles. In general, the changes have been small and are likely to be of little relevance in women with advanced breast cancer, but if these agents come to be used in early breast cancer, their impact on lipid profiles may become more important. Many studies are currently underway with the aromatase inhibitors, with safety assessments including monitoring lipid levels. The results of these studies are keenly awaited.

Aromatase Inhibitors↗
PubMed2005

Frequent analytical/experimental problems in lipase-mediated synthesis in solvent-free systems and how to avoid them.

Compared with chemical catalysis, enzymatic catalysis is a relatively new topic. Experimental work involving lipases deserves careful attention and accurate procedures still need to be implemented. A rapid but careful survey of published data immediately demonstrates that experiments performed under similar conditions with similar reagents have led to very different results. The aim of this work is to point out the importance of accurate and systematic procedures in order to ensure the reproducibility of experimental data. We strongly believe that different results found by different labs are due to problems detected in the procedures used. Quantification of the immobilisation efficiency of lipase on several supports through UV/visible methods and sampling methods used to obtain correct enzymatic activity values are specifically analysed. After a brief review which demonstrates the big discrepancies found in the literature, original data from Candida rugosa lipase adsorption on polypropylene powder and its use in the solvent-free synthesis of ethyl oleate are introduced in order to exemplify the difficulties found in these kinds of systems. Several procedures described in the literature are assayed and the accuracy of the results obtained is carefully analysed. The aim of the whole analysis performed is that it would be useful for any powdered solid to be used as a support for a lipase in a solvent-free system for any synthesis reaction, especially for those involving a volatile reagent. Throughout this contribution, special emphasis is placed on how catalytic reaction results using enzymes (free and immobilised) are reported so as to allow comparison between published data, something which is usually difficult since very different units are used and often complementary data are not included.

Catalysis↗
PubMed1993

Sexual dimorphism in relation to big-game hunting and economy in modern human populations.

Postcranial skeletal data from two recent Eskimo populations are used to test David Frayer's model of sexual dimorphism reduction in Europe between the Upper Paleolithic and Mesolithic. Frayer argued that a change from big-game hunting and adoption of new technology in the Mesolithic reduced selection for large body size in males and led to a reduction in skeletal sexual dimorphism. Though aspects of Frayer's work have been criticized in the literature, the association of big-game hunting and high sexual dimorphism is untested. This study employs univariate and multivariate analysis to test that association by examining sexual dimorphism of cranial and postcranial bones of two recent Alaskan Eskimo populations, one being big-game (whale and other large marine mammal) hunting people, and the second being salmon fishing, riverine people. While big-game hunting influences skeletal robusticity, it cannot be said to lead to greater sexual dimorphism generally. The two populations had different relative sexual dimorphism levels for different parts of the body. Notably, the big-game hunting (whaling) Eskimos had the lower multivariate dimorphism in the humerus, which could be expected to be the structure under greatest exertion by such hunting in males. While the exertions of the whale hunting economic activities led to high skeletal robusticity, as predicted by Frayer's model, this was true of the females as well as the males, resulting in low sexual dimorphism in some features. Females are half the sexual dimorphism equation, and they cannot be seen as constants in any model of economic behavior.

Alaska↗
PubMed1976

High-molecular IRI (big, big insulin) in islet cell adenoma.

In agreement with data previously reported (Yalow and Berson 1973), after gel filtration of acid-ethanol extracts of islet cell adenomas (performed in 3 M acetic acid) 1.4% to 1.8% of total immunoreactive insulin (IRI) eluted ahead of proinsulin. The high-molecular IRI (HM-IRI) was, however, found to be heterogenous in size and consisted of at least three components, the major one having an estimated molecular weight of about 50,000. Under certain conditions, HM-IRI was partially dissociated into proinsulin- and insulin-like components. We conclude that HM-IRI does not represent a precursor of proinsulin and insulin, but probably a self-association product of the peptides or an association of insulin and proinsulin to other proteins extracted from tumor tissue.

Adenoma↗
PubMed1995

So what do you propose we use instead? A reply to Block.

Unfortunately, Block's brilliant critique is terribly biased, much like a legal brief that presents only one side of the issues at suit. It does not distinguish between the Big Five model of phenotypic personality attributes from alternative models of the causal underpinnings of personality differences. Ironically, it attempts to explain away the extensive evidence for the Big Five model as largely the result of data prestructuring, with no acknowledgement of the unique contribution of the lexical approach to minimizing such problems. Even more seriously, it omits a good deal of crucial evidence favorable to the Big Five model, including studies of Block's own Q-set and independent investigations of personality-related terms in other languages. Sadly, Block's closing suggestions provide little in the way of specific proposals for alternatives that he would have us use instead.

Factor Analysis, Statistical↗
PubMed2006

Cardiovascular safety profiles of aromatase inhibitors : a comparative review.

Third-generation aromatase inhibitors (AIs) are now being used for the adjuvant treatment of postmenopausal women with breast cancer, and are challenging tamoxifen, the previous 'gold standard' of care, in this setting. This review evaluates the potential clinical impact of anastrozole, letrozole and exemestane on the cardiovascular (CV) system of postmenopausal women with breast cancer. Some data for CV safety are available for AIs from the advanced disease setting; however, most derive from patients being treated for early disease. CV data on anastrozole for the treatment of early breast cancer were taken from the ATAC trial, in which anastrozole was compared with tamoxifen in the primary adjuvant setting, and the ABCSG trial 8/ARNO 95 combined analysis, in which switching to 3 years of anastrozole after 2 years of tamoxifen was compared with the standard 5 years of tamoxifen adjuvant therapy. Letrozole has been studied in the primary adjuvant setting and the adjuvant sequencing setting in the BIG 1-98 study, as well as in extended adjuvant endocrine therapy after 5 years of tamoxifen in the MA-17 trial. For exemestane, results were reviewed from the IES trial, in which switching to exemestane following 2-3 years of adjuvant tamoxifen was compared with continued tamoxifen treatment. All these trials clearly confirmed that all three AIs significantly reduce the risk of thromboembolic events compared with tamoxifen. Data on anastrozole versus tamoxifen from the ATAC trial (68 months' follow-up) showed a similar incidence of myocardial infarctions (MIs), CV deaths and overall deaths for both therapies; however, anastrozole appeared to be associated with a lower incidence of cerebrovascular events compared with tamoxifen. In addition, the ABCSG trial 8/ARNO 95 study reported no difference in terms of MIs for patients switching to anastrozole compared with patients continuing tamoxifen treatment. Data from BIG 1-98 (26 months' follow-up) suggested that primary adjuvant treatment with letrozole may be associated with a significantly greater incidence of CV events and a numerical increase of cerebrovascular and cardiac deaths compared with tamoxifen. However, no increase in CV events with letrozole was reported from the MA-17 trial. In the IES, updated data at 55 months' median follow up showed no significant difference in the incidence of MIs and cardiac deaths between patients who switched to exemestane compared with those who continued tamoxifen. In conclusion, a significantly reduced risk of thromboembolic disease was observed for all three AIs compared with tamoxifen. Anastrozole is, at this point, the only AI with a detailed benefit-risk profile from over 5 years' follow-up in the adjuvant setting. Thus far, no apparent CV-safety concerns have emerged. Preliminary data on letrozole and exemestane suggest that longer follow-up is needed for these two AIs before being able to fully assess their respective long-term CV toxicity profile. The present differences in CV-safety profiles suggest that third-generation AIs should not be considered as equivalents in clinical practice.

Aromatase Inhibitors↗
PubMed2004

Superiority of big endothelin-1 and endothelin-1 over natriuretic peptides in predicting survival in severe congestive heart failure: a 7-year follow-up study.

BACKGROUND: Plasma concentrations of atrial and brain natriuretic peptides (ANP, BNP), of their N-terminal pro-peptides, of endothelin-1 (ET-1), and big endothelin-1 (big ET-1) have diagnostic and prognostic significance in congestive heart failure (CHF). However, their respective values as a predictor of survival remain controversial and have never been directly compared in severe CHF. METHODS AND RESULTS: We analyzed, in 47 patients with severe CHF (New York Heart Association [NYHA] class III to IV; age 66 +/- 8 years, ejection fraction 20 +/- 6%), the prognostic performance of a panel of neurohormones and assays (N-terminal pro-ANP 1-25, 68-98 by radioimmunoassay [RIA], and 1-98 by enzyme-linked immunosorbent assay [ELISA], BNP by RIA and immunoradiometric assay [IRMA], N-terminal pro-BNP by Elisa, ET-1 by RIA, and big ET-1 by RIA and Elisa. Data were compared with 40 patients with mild to moderate CHF [NYHA I-II] and 30 healthy subjects. After a follow-up of 81 +/- 15 months, there were 34 deaths and 1 heart transplant. All neurohormones were significantly higher at baseline in patients with severe than in mild to moderate CHF or healthy subjects (all P < .001). Although all neurohormones but BNP IRMA were significant predictors of survival in univariate analysis, only big ET-1 RIA and ET-1 were independent predictors of survival (improvement chi(2): 7.5 and 4.6, P < .01 and P < .05). Using medians as cutpoints of big ET-1 RIA and ET-1, 2 severe CHF populations were defined with a different outcome (5-year survival: 55 versus 18%, P < .01). CONCLUSIONS: Big ET-1 and ET-1 are strong independent predictors of survival in patients with severe CHF and better for this purpose than natriuretic peptides or their pro-peptides. These markers allow easily to identify a population with a very high risk mortality eligible for more aggressive therapies.

Atrial Natriuretic Factor↗
PubMed2005

Locating the big five personality factors in the relate relationship evaluation measures.

Factor analyses of data from 400 students who completed the adjective section of the Relate relationship evaluation and similar descriptors from the measure of the "big five" factors of personality by Digman and Inouye indicated that all of the "big five" measures, surgency, agreeableness, conscientiousness, neuroticism, and openness, can be assessed as part of the Relate assessment.

Adolescent↗
PubMed1979

Influence of hydrogen ion concentration on bile acid induced acute gastric mucosal ulcerogenesis.

Aggressive treatment with H(2) receptor blocking agents and/or antacids has been advocated as effective prophylaxis against and treatment for "stress ulcer," based on the logical but infrequently tested assumption that the severity of the disease is critically determined by the concentration of intraluminal acid. The present study investigated this assumption in a model which employed topical acid, topical bile acid and mucosal ischemia to induce ulcerogenesis. With vascularized, chambered ex vivo wedges of canine proximal gastric wall, groups of animals were studied during three sequential periods using topical test solutions (TS) containing either 0 mM, 100 mM or 160 mM HCI. During period 1, mucosae were exposed to TS alone; during period 2, either to TS containing 1 mM sodium taurocholate (TC) or to TS and concomitant vasopressin infusion (VP); and during period 3, to TS + TC + VP. Parameters evaluated included net H(+) flux ( big up tri, openH(+)), aminopyrine clearance (AC), a measure of mucosal blood flow, net TC flux ( big up tri, openTC) and the lesion index, graded 0-5. The data indicate that in nonischemic mucosa exposed to constant [TC], AC was significantly increased, big up tri, openH(+) ("back-diffusion") increased as a linear function of [H(+)] and no lesions were observed. Under the same circumstances in ischemic mucosa, big up tri, openH(+) increased as linear function of [H(+)]. As a consequence, lesion severity was also a linear function of [H(+)]. big up tri, openTC was enhanced at low pH but bore no relation to the degree of mucosal damage induced. Assuming applicability of the model, these studies provide support for the use of H(2) receptor blocking agents and/or antacids to prevent or ameliorate "stress ulcer" disease.

Acute Disease↗
PubMed2001

[The current condition and research progress of normal wound repair and "un-controlled" wound repair].

OBJECTIVE: To describe the concept of "un-controlled wound repair" and review its current progress in basic research and clinical treatment. METHODS: The literature review and comprehensive analysis methods were used in this study. RESULTS: The results showed that the normal wound repair and "un-controlled" wound repair had made big progress in cellular, molecular and genetic levels in recent years and these progresses had enhanced the treatment progress in clinic. CONCLUSION: All data indicate that the wound repair is made a big progress both in basic and clinic fields. New high techniques, such as clone, biochip and stem cell and their use will promote the deep study of "un-controlled" wound repair.

Cicatrix, Hypertrophic↗
PubMed2005

Spatial, temporal, and interspecies patterns in fine particulate matter in Texas.

The Big Bend Regional Aerosol and Visibility Observational (BRAVO) field study was conducted from July to October 1999 and was followed by several years of modeling and data analyses to examine the causes of haze at Big Bend National Park TX (BBNP). During BRAVO, daily speciated fine (diameter <2.5 microm) particulate concentrations were measured at 37 sites throughout Texas. At the primary receptor site, K-Bar Ranch, there were many additional measurements including a "high-sensitivity" version of the 24-hr fine particulate elemental data. The spatial, temporal, and interspecies patterns in these data are examined here to qualitatively investigate source regions and source types influencing the fine particulate concentrations in Texas with an emphasis on sources of sulfates, the largest contributor to fine mass and light extinction. Peak values of particulate sulfur (S) varied spatially and seasonally. Maximum S was in Northeast Texas during the summer, whereas peak S at BBNP was in the fall. Sulfate acidity at BBNP also varied by month. Sources of Se were evident in Northeast Texas and from the Carbón I and II plants. High S episodes at BBNP during BRAVO had several different trace element characteristics. Carbon concentrations at BBNP during BRAVO were probably mostly urban-related, with arrival from the Houston area likely. The Houston artificial tracer released during the second half of BRAVO was highly correlated with some carbon fractions. There was evidence of the influence of African dust at sites throughout Texas during the summer. Patterns in several trace elements were also examined. Vanadium was associated with air masses from Mexico. Lead concentrations in southern Texas have dropped dramatically over the past several years.

Air Pollutants↗
PubMed1978

[Radio-anatomical study of the main trunk of the middle cerebral artery (author's transl)].

This work corroborates anatomical data well known since G. Lazorthes about the main trunk of the middle cerebral artery. The data are interesting in various fields: Sylvian aneurysms, big sphenoïd ridge meningiomas, extra-intra cranial micro neurosurgical anastomoses. This work is based upon 280 angiographic pictures, 20 dissections of brain arteries and 12 plastic injections of the brain arterial vascular tree. The most important data to point out are variations of length and of division (no division, simple bifurcation, trifurcation or multiple divisions), variability in the central arteries and some rare anomalies like accessory middle cerebral arteries and duplication.

Cerebral Angiography↗
PubMed2006

[Controversial study results in relation to minimum volume standards].

Multiple studies have demonstrated positive associations between volume and treatment outcome, especially in complex procedures. However, using these results in determining volume standards in Germany keeps being problematic: often, there is a lack of specific German data on the volume and outcome of healthcare providers making the modeling of potential effects almost impossible. In addition, recent publications focusing on the methods that are typically used in analyzing these associations indicate that the significance of positive volume-outcome associations is limited. The methodological quality of most studies is rather low, and there is a high heterogeneity among them concerning study populations, case mix, study designs and analytical methods. Results on the single-hospital level show a high variation of outcome parameters. There are both good hospitals with low volumes and bad hospitals with high volumes. Using the "best guideline-based current procedures" seems to be of high importance for the good outcomes of small and big hospitals. Furthermore, studies have demonstrated that data on historical outcomes are a better predictor for good outcomes than hospital procedural volumes. Furthermore in some studies negative outcomes were shown to be related to high volumes at facilities with a high case load per staff member. These results suggest that a more sophisticated consideration of the methods and results of volume-outcome studies is required. Therefore, volume standards should continue to be cautiously applied and obligatorily accompanied by health services research.

Delivery of Health Care↗
PubMed1999

[Ultrasonic and CT diagnosis of large upper abdominal mass].

OBJECTIVE: To assess accuracy of ultrasonic (US) and CT diagnosis of big mass in the upper abdomen. METHODS: Data from 38 clinically and pathologically confirmed cases were retrospectively analyzed and accuracy of their preoperative US and CT diagnosis compared. RESULTS: US diagnosis was correct in 3 of 9 (33.3%) cases with a mass in the liver, in 16 of 21 (76.2%) cases with a mass in the adrenal gland and in 2 of 4 cases with a mass in the kidney. In contrast, CT diagnosis was correct in 2 of 9 (22.2%) cases with a mass in the liver, in 4 of 18 (22.2%) cases with a mass in the adrenal gland and none in a case with a mass in the kidney. In 4 cases with a mass in the spleen, neither US nor CT diagnosis was correct. CONCLUSION: Because organs in the upper abdomen are closely located with each other, correct imaging localization of big mass in this region is not without difficulty. In this series, accuracy of diagnosis with US and CT is comparable, but for localizing tumor in the adrenal gland, US imaging seems superior. US and CT are both incapable of accurately diagnosing large mass in the spleen.

Abdominal Neoplasms↗
PubMed2000

Personality and job performance: the Big Five revisited.

Prior meta-analyses investigating the relation between the Big 5 personality dimensions and job performance have all contained a threat to construct validity, in that much of the data included within these analyses was not derived from actual Big 5 measures. In addition, these reviews did not address the relations between the Big 5 and contextual performance. Therefore, the present study sought to provide a meta-analytic estimate of the criterion-related validity of explicit Big 5 measures for predicting job performance and contextual performance. The results for job performance closely paralleled 2 of the previous meta-analyses, whereas analyses with contextual performance showed more complex relations among the Big 5 and performance. A more critical interpretation of the Big 5-performance relationship is presented, and suggestions for future research aimed at enhancing the validity of personality predictors are provided.

Humans↗
PubMed1999

Proteolytic processing of big endothelin-3 by the kell blood group protein.

Kell blood group protein shares a consensus sequence (H.E.X.X.H) with a large family of zinc-dependent endopeptidases. Kell has closest homology with neutral endopeptidase 24.11, endothelin converting enzyme-1 (ECE-1), and the PEX gene product that, as a group, comprise the M13 subfamily of mammalian neutral endopeptidases. The proteolytic activity of the M13 members, but not of Kell, has been previously demonstrated. A secreted form of wild-type Kell protein (s-Kell), devoid of the intracellular and transmembrane domains, was expressed in sf9 cells. As a negative control, an inactive mutant Kell protein (E582G) was expressed. As determined by N-terminal amino acid sequencing and mass spectrometry of the cleaved products, wild-type s-Kell, but not the control mutant protein, specifically cleaved big endothelin-3 (ET-3) at Trp(21)-Ile(22), yielding ET-3, and, to a much lesser extent, also cleaved big ET-1 and big ET-2 at Trp(21)-Val(22), yielding ET-1 and ET-2. Enzymatic activity was partially inhibited by phosphoramidon. s-Kell has an acidic pH optimum (pH 6.0 to 6.5). Like the recombinant protein, red blood cells of common Kell phenotype also preferentially process big ET-3, in contrast to Ko (null) cells that do not. These data demonstrate that the Kell blood group protein is a proteolytic enzyme that processes big ET-3, generating ET-3, a potent bioactive peptide with multiple biological roles.

Endothelin-3↗
PubMed1991

Phosphoramidon inhibits the intracellular conversion of big endothelin-1 to endothelin-1 in cultured endothelial cells.

Effects of various protease inhibitors on the conversion of big endothelin (ET)-1 to ET-1 in cultured endothelial cells were analyzed. A metal protease inhibitor, phosphoramidon, decreases the amount of ET-1 and increase that of big ET-1 released. This effect is dose-dependent and not nonspecific. When the contents of ET-1 and big ET-1 in the cells after culturing in the medium with or without phosphoramidon were measured, the ratio of ET-1: big ET-1 in the cells was 3.3 : 1 and phosphoramidon inverted the ratio in the cells to 1 : 3.5. These data strongly suggest that a phosphoramidon-sensitive protease converts big ET-1 to mature ET-1 intracellularly.

Animals↗
PubMedDate not supplied

Deceleration of age at menarche in Poland.

The purpose of this paper is to describe secular growth changes in age at menarche of girls in Poland during the past 40 years. For this purpose data obtained from four consecutive surveys conducted in 1955, 1966, 1978 and 1988 were analysed. Each cohort was selected from settlements: big cities, small towns (approximately 10,000 inhabitants) and villages. Data regarding schoolgirls aged 7-18 years were collected by the status quo method. It was found that after the continuous trend towards an earlier maturation of Polish girls from 1955 to 1978 a substantial slowing down, and even a reverse trend, was observed. The deceleration of the age at menarche is most marked among girls from small towns. The results seem to have been caused by the retardation of menarcheal age in social groups which in the previous examinations were the earliest maturers.

Adolescent↗