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PubMedDate not supplied

Use of the theory of planned behavior to explain HRT decisions.

OBJECTIVE: To test the theory of planned behavior (TPB) and other variables to discriminate among women who have made various decisions about hormone replacement therapy (HRT). METHOD: An anonymous survey was completed by a diverse sample of 641 women employed at a community college. RESULTS: Survey response rate was 64.3%. Results from a discriminant analysis showed that HRT use was most strongly associated with perceived behavioral control and reliance on one's physician as a source of HRT information. CONCLUSIONS: The TPB is a useful framework for explaining HRT decisions in a period of uncertainty about risks and benefits of the therapy.

Adolescent↗

PubMed1986

Irreversible binding of pristinamycin IIA (streptogramin A) to ribosomes explains its "lasting damage" effect.

In vitro and in vivo studies are presented to test the hypothesis that the synergistic action of the pristinamycins is not due to a catalytic effect of pristinamycin IIA (PIIA) on the bacterial ribosome. We demonstrate that there is a proportionality between the quantity of PIIA bound on the ribosome and pristinamycin IA (PIA) retained by it. Moreover in vitro and in vivo experiments correlated to biological effects (growth and protein synthesis) demonstrate that pristinamycin IIA is tightly bound on 70S ribosome, which satisfactory explains the so called "lasting damage effect".

Anti-Bacterial Agents↗

PubMed2006

Does utilization of screening mammography explain racial and ethnic differences in breast cancer?

BACKGROUND: Reasons for persistent differences in breast cancer mortality rates among various racial and ethnic groups have been difficult to ascertain. OBJECTIVE: To determine reasons for disparities in breast cancer outcomes across racial and ethnic groups. DESIGN: Prospective cohort. SETTING: The authors pooled data from 7 mammography registries that participate in the National Cancer Institute-funded Breast Cancer Surveillance Consortium. Cancer diagnoses were ascertained through linkage with pathology databases; Surveillance, Epidemiology, and End Results programs; and state tumor registries. PARTICIPANTS: 1,010,515 women 40 years of age and older who had at least 1 mammogram between 1996 and 2002; 17,558 of these women had diagnosed breast cancer. MEASUREMENTS: Patterns of mammography and the probability of inadequate mammography screening were examined. The authors evaluated whether overall and advanced cancer rates were similar across racial and ethnic groups and whether these rates were affected by the use of mammography. RESULTS: African-American, Hispanic, Asian, and Native American women were more likely than white women to have received inadequate mammographic screening (relative risk, 1.2 [95% CI, 1.2 to 1.2], 1.3 [CI, 1.2 to 1.3], 1.4 [CI, 1.3 to 1.4], and 1.2 [CI, 1.1 to 1.2] respectively). African-American women were more likely than white, Asian, and Native American women to have large, advanced-stage, high-grade, and lymph node-positive tumors of the breast. The observed differences in advanced cancer rates between African American and white women were attenuated or eliminated after the cohort was stratified by screening history. Among women who were previously screened at intervals of 4 to 41 months, African-American women were no more likely to have large, advanced-stage tumors or lymph node involvement than white women with the same screening history. African-American women had higher rates of high-grade tumors than white women regardless of screening history. The lower rates of advanced cancer among Asian and Native American women persisted when the cohort was stratified by mammography history. LIMITATIONS: Results are based on a cohort of women who had received mammographic evaluations. CONCLUSIONS: African-American women are less likely to receive adequate mammographic screening than white women, which may explain the higher prevalence of advanced breast tumors among African-American women. Tumor characteristics may also contribute to differences in cancer outcomes because African-American women have higher-grade tumors than white women regardless of screening. These results suggest that adherence to recommended mammography screening intervals may reduce breast cancer mortality rates.

Adult↗

PubMed2000

The windlass mechanism of the foot. A mechanical model to explain pathology.

This article presents a mechanical model that can be used to understand the foot, to help develop methods of treatment of foot pathology, and to provide direction for future research in foot mechanics and pathology. The anatomy and mechanical function of the windlass mechanism of the foot are analyzed using principles of mechanical engineering. The principles of force couples and free-body diagrams are explained and then applied to the foot. The relationship of the windlass mechanism to plantar fasciitis or heel spur syndrome, hallux abducto valgus, and hallux limitus is discussed.

Biomechanical Phenomena↗

PubMedDate not supplied

Explaining solution focused therapy.

Psychotherapies have tended to concentrate on clients' complaints in an attempt to overcome their problems: solution focused therapy, on the other hand, looks for their strengths, competencies and potentials, and enables them to recognise and build on them. The authors explain the basis of the therapy, then illustrate how it operates in practice with three short case studies.

Female↗

PubMed2001

Doing better with "bad kids": explaining the policy-research gap with conduct disorder in Canada.

Conduct disorder (severe and persistent antisocial behaviour in children and youth) is an important community mental health problem in Canada and has been the focus of considerable recent public policy debate. Good research evidence is available on effective (and ineffective) interventions for conduct disorder. Paradoxically, however, relatively little of the research evidence is incorporated into policy decision-making. There is a policy-research gap. An example (Hamilton, Ontario) is used to illustrate this gap. The gap is then explained using a framework for health policy analysis that incorporates values, institutional structures, and information. Values and institutional structures greatly outweigh research evidence in influencing current Canadian policy-making for the problem of conduct disorder. Possibilities for improving the situation are suggested.

Canada↗

PubMed1991

Explaining resource consumption among non-normal neonates.

The adoption by Medicare in 1983 of prospective payment using diagnosis-related groups (DRGs) has stimulated research to develop case-mix grouping schemes that more accurately predict resource consumption by patients. In this article, the authors explore a new method designed to improve case-mix classification for newborns through the use of birth weight in combination with DRGs to adjust the unexplained case-mix severity. Although the findings are developmental in nature, they reveal that the model significantly improves our ability to explain resource use.

Birth Weight↗

PubMed1999

The role of medical problems and behavioral risks in explaining patterns of prenatal care use among high-risk women.

OBJECTIVE: To examine the associations between maternal medical conditions and behavioral risks and the patterns of prenatal care use among high-risk women. DATA SOURCE/STUDY DESIGN: Data on over 25,000 high-risk deliveries to African American and white women using multinomial logistic regression to predict the odds of adequate-plus care relative to three other categories of care. DATA COLLECTION/EXTRACTION METHODS: Data were extracted from records maintained by the University of Florida/Shands Hospital maternity clinic on all deliveries between 1987 and 1994; records for white and for African American women were subset to examine racial differences in medical conditions, health behaviors, and patterns of prenatal care use. PRINCIPAL FINDINGS: Net of sociodemographic and fertility-related characteristics, African American and white women with late antepartum conditions and hypertension problems had significantly higher odds of receiving adequate-plus care, as well as no care or inadequate care, relative to adequate care. White women with gynecological disease and medical/surgical problems were significantly less likely to receive no care or inadequate care, as were African American women with gynecological disease. CONCLUSIONS: Maternal medical conditions explain much but not all of the adequate-plus prenatal care use. More than 13 percent of African American women and 20 percent of white women with no reported medical problems or behavioral risks used adequate-plus care. Additional research is needed to understand this excess use and its possibilities in mediating birth outcomes.

Adolescent↗

PubMed1999

Direct effects on antigen-presenting cells and T lymphocytes explain the adjuvanticity of a nontoxic cholera toxin mutant.

The present study has elucidated two distinct mechanisms that may explain how a mutant of cholera toxin (mCT), E112K, retains adjuvant effects though it lacks ADP-ribosyltransferase activity and associated toxicity. In the first mechanism, we show that mCT E112K, like native cholera toxin (nCT), enhances B7-2 expression, but, to some extent, also enhances B7-1 on Peyer's patch B cells and macrophages. Cocultivation of CD4+ T cells with E112K- or nCT-treated B cells and macrophages in the presence of anti-CD3 stimulation resulted in the induction of T cell-proliferative responses. Further, the responses were blocked by mAbs to B7-1 and/or B7-2; however, the effect of anti-B7-1 was minimal. In the second mechanism, addition of mCT E112K or nCT to anti-CD3 mAb-stimulated Peyer's patch CD4+ T cells inhibited proliferative responses, while recombinant CT-B subunit (rCT-B) did not. Analysis of cytokine responses showed that both mCT E112K and nCT preferentially inhibited IFN-gamma production. Interestingly, however, nCT, but not mCT E112K, induced apoptosis in CD4+ T cells activated via the TCR-CD3 complex. These results indicate that CT uses at least two pathways for inhibition of Th1 responses and that, while nCT induces cAMP accumulation that in turn leads to apoptosis in Th1-type cells, mCT E112K, which lacks ADP-ribosyltransferase activity, inhibits IFN-gamma synthesis by a separate mechanism. Thus, mCT E112K, like nCT, induces adjuvant responses via up-regulation of mainly B7-2 on APCs and through preferential inhibition of Th1-type CD4+ T cell responses in the absence of ADP-ribosyltransferase activity.

Adjuvants, Immunologic↗

PubMed1999

[Do obstetric causes of death explain the differences in maternal mortality between France and Europe?].

In view of understanding why the level of maternal mortality is higher in France than in other European countries, a specific study of frequency and causes has been carried out in these 13 countries. Two different sources of data were used: the annual civil death data from national offices which are published by the WHO, and the MOMS data. It was hypothesized that the pattern of causes plays a role in the level of maternal mortality. This hypothesis was checked with results issuing from a European concerted action where deaths were classified by a European group of medical experts using identical criteria. There were apparently more cases of hemorrhage, direct obstetric causes, and indirect obstetric causes in France than in the other European countries. The higher level of indirect obstetric causes may be explained by stronger registration regulations for maternal deaths recently implemented in France. Due to the higher level of hemorrhage as cause of maternal death in France, we suggest in-depth research is needed in the near future to study prevalence and management of obstetrical hemorrhage in France.

Cause of Death↗

PubMed1999

Increased clearance explains lower plasma levels of tissue-type plasminogen activator by estradiol: evidence for potently enhanced mannose receptor expression in mice.

Several clinical studies have demonstrated an inverse relationship between circulating levels of estrogen and tissue-type plasminogen activator (t-PA). The present study was designed to test the hypothesis that estrogens lower plasma levels of t-PA by increasing its clearance from the bloodstream. 17alpha-Ethinyl estradiol (EE) treatment resulted in a significant increase in the clearance rate of recombinant human t-PA in mice (0.46 mL/min in treated mice v 0. 32 mL/min in controls; P <.01). The clearance of endogenous, bradykinin-released t-PA in rats was also significantly increased after EE treatment (area under the curve [AUC], 24.9 ng/mL. min in treated animals v 31.9 ng/mL. min in controls; P <.05). Two distinct t-PA clearance systems exist in vivo: the low-density lipoprotein receptor-related protein (LRP) on liver parenchymal cells and the mannose receptor on mainly liver endothelial cells. Inhibition of LRP by intravenous injection of receptor-associated protein (RAP) as a recombinant fusion protein with Salmonella japonicum glutathione S-transferase (GST) significantly retarded t-PA clearance in control mice (from 0.41 to 0.25 mL/min; n = 5, P <.001) and EE-treated mice (from 0.66 to 0.35 mL/min; n = 5, P <.005), but did not eliminate the difference in clearance capacity between the 2 experimental groups. Similar results were obtained in mice in which LRP was inhibited via overexpression of the RAP gene in liver by adenoviral gene transduction. In contrast, administration of mannan, a mannose receptor antagonist, resulted in identical clearances (0.22 mL/min in controls and 0.24 mL/min in EE-treated mice). Northern blot analysis showed a 6-fold increase in mannose receptor mRNA expression in the nonparenchymal liver cells of EE-treated mice, whereas the parenchymal LRP mRNA levels remained unchanged. These findings were confirmed at the protein level by ligand blotting and Western blotting analysis. Our results demonstrate that EE treatment results in increased plasma clearance rate of t-PA via induction of the mannose receptor and could explain for the inverse relationship between estrogen status and plasma t-PA concentrations as observed in humans.

Animals↗

PubMed1999

The importance of shared environmental influences in explaining the overlap between mother's parenting and sibling relationships: reply to Neale (1999)

This article addresses concerns raised by M. C. Neale (1999) in his commentary on the D. A. Bussell et al. (1999) Nonshared Environment in Adolescent Development (NEAD) study. These concerns fall into two categories: (a) model assumptions and sample design and (b) testing of alternative models. The validity of the assumptions of quantitative genetic models is a concern for all researchers in this area. Discussion of those assumptions in this reply is brief and focuses on those most relevant to the NEAD sample. The two alternative models proposed by Neale were designed to provide alternatives to the large shared environmental effect found in the original report of Bussell et al. Because these alternative models did not provide a better fit, the appropriateness of Bussell et al.'s basic model and the importance of shared environmental influences for explaining the association among family subsystems are supported.

Adolescent↗

PubMedDate not supplied

Severe local hypothermia from laparoscopic gas evaporative jet cooling: a mechanism to explain clinical observations.

BACKGROUND AND OBJECTIVES: Explanations for laparoscopic-induced hypothermia fail to explain clinical observations. It is possible that water evaporation occurs from the jet stream of gas inflation resulting in tissue surface super-cooling leading to tissue damage and drying. METHODS: Theoretical calculations based on thermal conductivity, mass transfer effects and heat flux considerations correlated closely with synthetic and tissue experiments. Thermocouple measurements at a rate of 15 data points per second were performed. RESULTS: Cooling rates of 10 to 25 degrees centigrade per second for high flow rates were found based on gas flow rate and effective size of gas delivery site. These rapid temperature drops extended beyond a 2 cm2 diameter. CONCLUSIONS: Evaporative cooling accounts for significant hypothermia. The cooling is dependent on the lack of water vapor in the gases currently used during laparoscopy. Cooling rates are independent of height from tissue and geometry of delivery port. Heating and hydrating the gas to a physiologic condition eliminates hypothermia and tissue dessication.

Culture Techniques↗

PubMed2000

A new physiologically based, segregated-flow model to explain route-dependent intestinal metabolism.

Processes of intestinal absorption, metabolism, and secretion must be considered simultaneously in viewing oral drug bioavailability. Existing models often fail to predict route-dependent intestinal metabolism, namely, little metabolism occurs after systemic dosing but notable metabolism exists after oral dosing. A physiologically based, Segregated-Flow Model (SFM) was developed to examine the influence of intestinal transport (absorption and exsorption), metabolism, flow, tissue-partitioning characteristics, and elimination in other organs on intestinal clearance, intestinal availability, and systemic bioavailability. For the SFM, blood flow to intestine was effectively segregated for the perfusion of two regions, with 10% reaching an absorptive layer-the enterocytes at the villus tips of the mucosa where metabolic enzymes and the P-glycoprotein reside, and the remaining 90% supplying the rest of the intestine (serosa and submucosa), a nonabsorptive layer. The traditional, physiologically-based model, which regards the intestine as a single, homogeneous compartment with all of the intestinal blood flow perfusing the tissue, was also examined for comparison. The analytical solutions under first order conditions were essentially identical for the SFM and traditional model, differing only in the flow rate to the absorptive/removal region. The presence of other elimination organs did not affect the intestinal clearance and bioavailability estimates, but reduced the percentage of dose metabolized by the intestine. For both models, intestinal availability was inversely related to the intrinsic clearances for intestinal metabolism and exsorption, and was additionally affected by both the rate constant for absorption and that denoting luminal loss when drug was exsorbed. However, the effect of secretion by P-glycoprotein became attenuated with rapid absorption. The difference in flow between models imparted a substantial influence on the intestinal clearance of flow-limited substrates, and the SFM predicted markedly higher extents of intestinal metabolism for oral over i.v. dosing. Thus, the SFM provides a physiological view of the intestine and explains the observation of route-dependent, intestinal metabolism.

Administration, Oral↗

PubMed2000

Considerations on pharmacodynamics and pharmacokinetics: can everything be explained by the extent of drug binding to its receptor?

It is frequently assumed that pharmacological responses depend solely on the extent of drug binding to its receptor according to the occupational theory. It is therefore presumed that the intensity of the effect is determined by drug concentration at its receptor site, yielding a unique concentration-effect relationship. However, when dependence, abstinence, and tolerance phenomena occur, as well as for pharmacological responses in vivo that are modulated by homeostatic mechanisms, the rate of drug input shifts the concentration-effect relationship. Hence, such responses cannot be explained on the sole basis of the extent of drug binding to its receptor. Information on the cellular and molecular processes involved in the generation of abstinence, dependence, and tolerance will undoubtedly result in the development of pharmacodynamic models allowing a satisfactory explanation of drug effects modulated by these phenomena. Notwithstanding, integrative physiology concepts are required to develop pharmacokinetic-pharmacodynamic models allowing the description of drug effects in an intact organism. It is therefore important to emphasize that integrative physiology cannot be neglected in pharmacology teaching and research, but should be considered as an equally valuable tool as molecular biology and other biomedical disciplines for the understanding of pharmacological effects.

Animals↗

PubMed2000

Hydroxychloroquine inhibits calcium signals in T cells: a new mechanism to explain its immunomodulatory properties.

Hydroxychloroquine (HCQ), a lysosomotropic amine, is an immunosuppressive agent presently being evaluated in bone marrow transplant patients to treat graft-versus-host disease. While its immunosuppressive properties have been attributed primarily to its ability to interfere with antigen processing, recent reports demonstrate HCQ also blocks T-cell activation in vitro. To more precisely define the T-cell inhibitory effects of HCQ, the authors evaluated T-cell antigen receptor (TCR) signaling events in a T-cell line pretreated with HCQ. In a concentration-dependent manner, HCQ inhibited anti-TCR-induced up-regulation of CD69 expression, a distal TCR signaling event. Proximal TCR signals, including inductive protein tyrosine phosphorylation, tyrosine phosphorylation of phospholipase C gamma1, and total inositol phosphate production, were unaffected by HCQ. Strikingly, anti-TCR-crosslinking-induced calcium mobilization was significantly inhibited by HCQ, particularly at the highest concentrations tested (100 micromol/L) in both T-cell lines and primary T cells. HCQ, in a dose-dependent fashion, also reduced a B-cell antigen receptor calcium signal, indicating this effect may be a general property of HCQ. Inhibition of the calcium signal correlated directly with a reduction in the size of thapsigargin-sensitive intracellular calcium stores in HCQ-treated cells. Together, these findings suggest that disruption of TCR-crosslinking-dependent calcium signaling provides an additional mechanism to explain the immunomodulatory properties of HCQ.

Antigens, CD↗

PubMed2000

Auto-catalysed progression of aneuploidy explains the Hayflick limit of cultured cells, carcinogen-induced tumours in mice, and the age distribution of human cancer.

Evidence continues to accumulate that aneuploidy, an imbalance in the number of chromosomes, is responsible for the characteristic phenotypes of cancer, including the abnormal cellular size and morphology of cancer cells, the appearance of tumour-associated antigens, as well as the high levels of membrane-bound and secreted proteins responsible for invasiveness and loss of contact inhibition. Aneuploidy has also been demonstrated to be the self-perpetuating source of the karyotypic instability of cancer cells. Here it is shown that the auto-catalysed progression of aneuploidy explains the kinetics of the finite lifetime of diploid cells in culture, the time course of the appearance of papillomas and carcinomas in benzo[a]pyrene-treated mice, and the age-dependence of human cancers. Modelling studies indicate that the ease of spontaneous transformation of mouse cells in culture may be due to a chaotic progression of aneuploidy. Conversely, the strong preference towards senescence and resistance to transformation of human cells in culture may be the result of a non-chaotic progression of aneuploidy. Finally, a method is proposed for quantifying the aneuploidogenic potencies of carcinogens.

Age Distribution↗

PubMed2000

Bias and Sampling Error of the Estimated Proportion of Genotypic Variance Explained by Quantitative Trait Loci Determined From Experimental Data in Maize Using Cross Validation and Validation With Independent Samples.

Cross validation (CV) was used to analyze the effects of different environments and different genotypic samples on estimates of the proportion of genotypic variance explained by QTL (p). Testcrosses of 344 F(3) maize lines grown in four environments were evaluated for a number of agronomic traits. In each of 200 replicated CV runs, this data set was subdivided into an estimation set (ES) and various test sets (TS). ES were used to map QTL and estimate p for each run (p(ES)) and its median (p(ES)) across all runs. The bias of these estimates was assessed by comparison with the median (p(TS.ES)) obtained from TS. We also used two independent validation samples derived from the same cross for further comparison. The median p(ES) showed a large upward bias compared to p(TS.ES). Environmental sampling generally had a smaller effect on the bias of p(ES) than genotypic sampling or both factors simultaneously. In independent validation, p(TS.ES) was on average only 50% of p(ES). A wide range among p(ES) reflected a large sampling error of these estimates. QTL frequency distributions and comparison of estimated QTL effects indicated a low precision of QTL localization and an upward bias in the absolute values of estimated QTL effects from ES. CV with data from three QTL studies reported in the literature yielded similar results as those obtained with maize testcrosses. We therefore recommend CV for obtaining asymptotically unbiased estimates of p and consequently a realistic assessment of the prospects of MAS.

Journal Article↗